179 results on '"Marc, Debled"'
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2. Abstract P4-07-24: Circulating tumor cells enumeration and Health Related Quality of Life of patients treated with first-line chemotherapy for HER2 negative metastatic breast cancer
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Jean-Yves Pierga, Oumar Billa, Sandrine Dabakuyo, Jérôme Lemonnier, Frédérique Berger, Olivier Trédan, William Jacot, Anthony Gonçalves, Marc Debled, Christelle Levy, Christelle Jouannaud, Marie-Ange Mouret-Reynier, Jean-Marc Ferrero, Florence Dalenc, Fatima-Zohra Toumi, Franck Bonnetain, Francois-Clement Bidard, and Shufang Renault more...
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Cancer Research ,Oncology - Abstract
Background: In patients with metastatic breast cancer (mBC), Circulating Tumor Cells (CTC) counts have a strong prognostic impact on progression free survival (PFS) and overall survival (OS). Changes 4 weeks after the start of a new line of therapy, inform on treatment efficacy. Despite improvements in systemic treatment, metastatic BC remains mainly uncurable with alteration of health-related quality of life (HRQOL) during the course of the disease. The aim of this work was to assess impact of clinical factors and biological factors as CTC on HRQOL. Methods: The French cohort COMET is a prospective study including first line HER2 negative patients receiving weekly paclitaxel and bevacizumab according to EMA approved combination. The aim of this cohort was to evaluate clinical, biological and radiological parameters associated with patients’ outcome (CTC, CEC, serum markers, ctDNA, pharmacogenomic polymorphisms, metabolomic parameters, visceral fat assessed by initial CTscan, serum estradiol level, and quality of life). HRQOL was assessed at baseline, at every cycle until progression and then every 3 months up to death using the EORTC QLQ-C30 questionnaire and its breast cancer specific module, the EORTC QLQ-BR23. Five dimensions of HRQOL were analyzed for the primary analyses: Global health status (GHS), physical functioning (PF), Emotional functioning (EF), fatigue (FA) and pain (PA). Time until definitive deterioration (TUDD) in HRQOL was defined as the interval between inclusion and the first decrease in HRQOL score ≥ 5 compared to baseline HRQOL score with no further improvement or in case of death. CTC counts were determined using the standard CellSearch system [Menarini Silicon Biosystems]. Results: Out of 510 patients included in COMET study, 432 patients with available HRQOL data were analyzed in this study. At baseline, patients reported a mean score for GHS of 57.6 (SD=22.7), for PF of 75.8 (23.2), for EF of 62.2 (25.8), for FA of 42.2 (29.60) and for PA of 38.1 (31.5). The Median TUDDs for the 5 targeted dimensions was 10.1 months [7.5-16.9] for GHS, 6.1 months [4.1-8.9] for PF, 21.6 [18.7-31.2] for EF, 10.8 [6.2-16.6] for FA and 13.6[10.1-22.5] months for PA. CTC counts were available in 261 patients at base line and in 229 patients after 4 weeks of treatment, before second cycle of chemotherapy. CTC high count was independent of main clinical and biological characteristics except lobular subtype. We confirmed the poor outcome of patients with high CTC count at base line and after one cycle of treatment with the threshold of > 4CTC/7.5 ml of blood. Out of the 5 dimensions of HRQOL, TUDD of EF was significantly correlated with a high CTC level at base line (p=0.0262) and even more with still an elevated count of CTC after one cycle of chemotherapy(p=0.0137). There was no association of CTC with the other dimensions of HRQOL. Conclusion: This is the first study ever reporting an analysis of QoL and CTC. We observed an association of high CTC count with one component of HRQOL scale. This suggests that CTC could be complementary to clinical factors that could influence HRQOL in HER2 negative metastatic BC treated with first line chemotherapy. Citation Format: Jean-Yves Pierga, Oumar Billa, Sandrine Dabakuyo, Jérôme Lemonnier, Frédérique Berger, Olivier Trédan, William Jacot, Anthony Gonçalves, Marc Debled, Christelle Levy, Christelle Jouannaud, Marie-Ange Mouret-Reynier, Jean-Marc Ferrero, Florence Dalenc, Fatima-Zohra Toumi, Franck Bonnetain, Francois-Clement Bidard, Shufang Renault. Circulating tumor cells enumeration and Health Related Quality of Life of patients treated with first-line chemotherapy for HER2 negative metastatic breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-24. more...
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- 2023
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3. Abstract P4-07-54: Health related quality of life of patients treated with bevacizumab and paclitaxel as first-line treatment for HER2 negative metastatic breast cancer: impact of clinical factors
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Oumar Billa, Sandrine Dabakuyo, Marion Chevrier, Franck Bonnetain, Isabelle Desmoulins, William Jacot, Olivier Trédan, Marc Debled, Christelle Levy, Anthony Gonçalves, Jean-Marc Ferrero, Florence Dalenc, Christelle Jouannaud, Marie-Ange Mouret-Reynier, Mireille Mousseau, Julien Grenier, Jean-Philippe Jacquin, Fatima-Zohra Toumi, Frédérique Berger, Jérôme Lemonnier, and Jean-Yves Pierga more...
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Cancer Research ,Oncology - Abstract
Background: Advances in screening and treatment have led to increase in breast cancer (BC) survival in recent years but prognoses for metastatic BC remain poor with poorer outcomes as health-related quality of life (HRQOL). Treatment as bevacizumab and paclitaxel for metastatic BC, although that can increase time to progression of disease, often carry toxicity and is not curative but rather palliative in intent with the goal to improve or maintain HRQOL. The aim of this work was to assess impact of clinical factors such as disease progression, toxicity on HRQOL. Methods: COMET study is a multicenter prospective single-arm cohort study in France whose main objective was to identify biological factor that could predict the clinical benefit of bevacizumab-paclitaxel combination therapy as first treatment in HER2 negative metastatic BC. HRQOL was assessed at baseline, at every cycle (every for 4 weeks) until progression and then every 3 months up to death using the EORTC QLQ-C30 questionnaire and its BC specific module, the EORTC QLQ-BR23. In this ancillary study, we targeted 5 dimensions HRQOL for the primary analyses: Global health status (GHS), physical functioning (PF), Emotional functioning (EF), fatigue (FA) and pain (PA). The primary endpoint was time until definitive deterioration (TUDD) in HRQOL scales that defined as time between inclusion and the first decrease HRQOL score ≥ 5 points compared to baseline score, with no further improvement of at least 5 points. Multivariable Cox model with time dependent covariate was performed to assess clinical factors associated with TUDD for each of the 5 target dimensions HRQOL. We performed 3 models for each dimension: model 1 including all covariate with p< 0.10 in univariable; model 2 including model 1 and adjusted on cancer subtype and model 3 included model 1 stratified by cancer subtype. P value < 0.01 were considered statistically significant. Results: Out of 510 patients included in COMET study, 432 patients with available HRQOL data were analyzed in this study. Median age at inclusion was 58 years (range: 29-83), and 24.4% of patients had triple negative tumor subtype. About 79 % of cancers were invasive ductal carcinoma and 43 % patients had least 3 metastasis sites at baseline. At baseline, patients reported a mean score for GHS of 57.6 (SD=22.7), for PF of 75.8 (23.2), for EF of 62.2 (25.8), for FA of 42.2 (29.60) and for PA of 38.1 (31.5). The Median TUDDs for the 5 targeted dimensions was 10.1 months [7.5-16.9] for GHS, 6.1 months [4.1-8.9] for PF, 21.6 [18.7-31.2] for EF, 10.8 [6.2-16.6] for FA and 13.6[10.1-22.5] months for PA. In multivariable analyses, Disease Progression was associated with TUDD of GHS (HR [99%CI] =2.4 [1.2-4.9] and TUDD of PF (2.1 [1.1-3.7]). After adjusted on cancer subtype, association persisted with TUDD of GHS (p=0.009). Performance Status was associated with TUDD of PF (1.6 [1.2-2.3]), and TUDD of Pain (1.6 [1.1-2.3]). Performance Status association with TUDD of PF continued after adjustment on cancer subtype (p=0.0003). Prior endocrine therapy was associated with TUDD of pain in patients with tumor with positive hormone receptor (HR+) (2.4 [1.2-4.7]). There was no factor associated with TUDD of EF and TUDD of FA. Conclusion: Results of this study have shown that among the 5 targeted dimensions HRQOL, Physical Functioning was deteriorated in the shortest time. Disease progression, base line performance status and prior endocrine therapy for HR+ subtype, are clinical factors that could influence HRQOL in HER2 negative metastatic BC treated with first line chemotherapy. Citation Format: Oumar Billa, Sandrine Dabakuyo, Marion Chevrier, Franck Bonnetain, Isabelle Desmoulins, William Jacot, Olivier Trédan, Marc Debled, Christelle Levy, Anthony Gonçalves, Jean-Marc Ferrero, Florence Dalenc, Christelle Jouannaud, Marie-Ange Mouret-Reynier, Mireille Mousseau, Julien Grenier, Jean-Philippe Jacquin, Fatima-Zohra Toumi, Frédérique Berger, Jérôme Lemonnier, Jean-Yves Pierga. Health related quality of life of patients treated with bevacizumab and paclitaxel as first-line treatment for HER2 negative metastatic breast cancer: impact of clinical factors [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-54. more...
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- 2023
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4. Clinical outcome of patients with isolated central nervous system progression on first-line pertuzumab and trastuzumab treatment for HER2-positive metastatic breast cancer in a real-life cohort
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Laetitia Collet, Lauriane Eberst, Gauthier Ludovic, Marc Debled, Loana Hrab, Marie-Ange Mouret-Reynier, Isabelle Desmoulins, Anthony Goncalves, Mario Campone, Jean-Marc Ferrero, Etienne Brain, Lionel Uwer, Jean-Christophe Eymard, Veronique Dieras, Gaetane Simon, Marianne Leheurteur, Florence Dalenc, Laurence Vanlemmens, Amelie Darlix, Monica Arnedos, and Thomas Bachelot more...
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Oncology ,Pharmacology (medical) ,Radiology, Nuclear Medicine and imaging ,General Medicine - Published
- 2023
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5. Abstract P1-03-04: Visceral fat area as a predictive factor in metastatic HER2 negative breast cancer patients treated by first line chemotherapy with weekly paclitaxel and bevacizumab
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Séverine Guiu, Boris Guiu, Marion Chevrier, Oumar Billa, Christelle Levy, Olivier Trédan, Isabelle Desmoulins, Marc Debled, Jean-Marc Ferrero, Christelle Jouannaud, Anthony Gonçalves, Maria Rios, Marie-Ange Mouret-Reynier, Frédérique Berger, Fatima-Zohra TOUMI, Jérôme Lemonnier, Jean-Yves Pierga, Sandrine Dabakuyo, and Sophie Gourgou more...
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Cancer Research ,Oncology - Abstract
Background Obesity has previously been correlated with poorer survival in both early and metastatic breast cancer. Adipose tissues release proangiogenic factors such as Insulin-like Growth Factor and Vascular Endothelial Growth Factor that may ultimately promote tumor growth. CTscan can be used to measure the visceral fat area (VFA) and the subcutaneous fat area (SFA) on the same section. High VFA has been shown to independently predict poorer outcome in patients given first-line bevacizumab-based treatment for metastatic colorectal cancer and metastatic renal cell carcinoma. The prospective multicenter COMET trial included metastatic HER2 negative breast cancer patients receiving bevacizumab and paclitaxel as fist-line chemotherapy. This study was designed to identify and validate reliable factors to predict benefit of bevacizumab and allow for a more personalized use of this antiangiogenic agent. Our aim was to evaluate the prognostic value of BMI (Body Mass Index), VFA and SFA in the COMET cohort and their impact on the quality of life. Patients and Methods Out of the 510 patients included in the COMET trial from 9/2012 to 3/2016, 480 received bevacizumab and paclitaxel as first-line treatment and 360 had available CTscan data. VFA and SFA were measured retrospectively on the CTscans performed before chemotherapy initiation, at the level of the umbilicus with the patient in the supine position. ImageJ software was used to measure pixels with densities in the -190 HU to -30 HU range in order to delineate the subcutaneous and visceral compartments and to compute the cross-sectional area of each in cm2. These measurements were performed by a radiologist blinded to patients’ characteristics and outcomes. For VFA and SFA, we used a threshold at the median value. VFA and SFA levels were tested for their association with progression-free survival (PFS) and overall survival (OS). The impact on quality of life was based on the Global Health Status, the Physical functioning, the Emotional functioning, Fatigue and Pain scores. Results The mean age at inclusion was 57 years (range: 28-83). At initial diagnosis, the main histological type was invasive ductal carcinoma (n = 247, 80.7%). Most patients had received prior neoadjuvant/adjuvant chemotherapy (n = 245, 68.1%) and a large majority (95.4%) had less than 3 metastatic sites. One hundred and forty patients (46.7%) had histological grade II and 41% had grade III tumors. The majority of the patients had positive hormone receptor tumor (n = 238, 79.3 %) and 62 (20.7%) had triple-negative tumor subtype. The median BMI was 24.7 (range : 17-46). After a median follow-up of 60.6 months (95%CI, 60-61.3), median PFS was 9.5 months (95CI, 8.6-10.3). There was no significant correlation between BMI (p = 0.69), VFA (p = 0.24) or SFA (p = 0.58) and PFS in the univariate analysis. The median OS was 29.6 months (95CI, 25.9-32.4). BMI, VFA and SFA were not correlated with OS. Out of the 360 patients, 328 had available data regarding the quality of life. There was no impact of the VFA or the SFA on the different quality of life scores. Conclusions In our prospective cohort of 360 patients with metastatic breast cancer receiving bevacizumab and paclitaxel as first-line treatment, high VFA or high SFA were not associated with a poorer survival. VFA and SFA had no impact on quality of life. Citation Format: Séverine Guiu, Boris Guiu, Marion Chevrier, Oumar Billa, Christelle Levy, Olivier Trédan, Isabelle Desmoulins, Marc Debled, Jean-Marc Ferrero, Christelle Jouannaud, Anthony Gonçalves, Maria Rios, Marie-Ange Mouret-Reynier, Frédérique Berger, Fatima-Zohra TOUMI, Jérôme Lemonnier, Jean-Yves Pierga, Sandrine Dabakuyo, Sophie Gourgou. Visceral fat area as a predictive factor in metastatic HER2 negative breast cancer patients treated by first line chemotherapy with weekly paclitaxel and bevacizumab [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-03-04. more...
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- 2023
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6. Impact of lobular versus ductal histology on overall survival in metastatic breast cancer: a French retrospective multicentre cohort study
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Florence Dalenc, Amélie Lusque, Thibault De La Motte Rouge, Barbara Pistilli, Etienne Brain, David Pasquier, Marc Debled, Jean-Christophe Thery, Anthony Gonçalves, Isabelle Desmoulins, Christelle Levy, Lionel Uwer, Jean-Marc Ferrero, Jean-Christophe Eymard, Marie-Ange Mouret-Reynier, Anne Patsouris, Jean-Sébastien Frenel, Thierry Petit, Michael Chevrot, Thomas Bachelot, Séverine Guiu, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA) more...
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Male ,Carcinoma, Lobular ,Cancer Research ,Oncology ,[SDV]Life Sciences [q-bio] ,Carcinoma, Ductal, Breast ,Humans ,Breast Neoplasms ,Female ,Prognosis ,Retrospective Studies - Abstract
The impact of the histological lobular subtype on overall survival (OS) in metastatic breast cancer (MBC) is still under debate, with very few data available.Using the French national multicentre Epidemiological Strategy and Medico Economics [ESME]) data platform, the primary objective was to compare the OS of patients with invasive lobular carcinoma (ILC) versus invasive ductal carcinoma (IDC) MBC, with adjustment on the main prognostic factors using two approaches: multivariable analysis and matching with a propensity score. Secondary objectives were to compare first-line progression-free survival (PFS1) and describe patients and tumour characteristics.Of the 16,703 patients with MBC in the ESME database, 13,111 met all inclusion criteria for the present analysis. One-thousand eight-hundred and four (13.8%) patients had ILC and 11.307 (86.2%) IDC. In the multivariable analysis, patients with ILC had a worse OS [hazard ratio (HR): 1.31; 95%CI 1.20-1.42; p 0.0001] and a worse PFS1 (HR: 1.15; 95%CI 1.07-1.22; p 0.0001) as compared with those with IDC, independently of hormone receptor and HER2 status. Interestingly, OS was better (HR 0.79; 95% confidence interval [CI] 0.64-0.98; p = 0.0302), worse (HR: 1.17; 95%CI 1.08-1.27; p = 0.0001) or similar (HR: 0.88; 95%CI 0.67-1.15; p = 0.3455) in patients with ILC with triple-negative, hormone receptor-positive/HER2-negative and HER2-positive MBC, respectively, compared with patients with IDC.Lobular histology is an independent adverse prognostic factor among women with MBC. ILC MBC could be considered a specific entity. Dedicated prospective studies are needed to tailor the management of these patients. more...
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- 2022
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7. Abstract P2-07-10: Germline BRCA screening for locally advanced breast cancer treated by neoadjuvant chemotherapy: Defining a subgroup with high rate of mutation and local relapses
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Nicolas Sevenet, Christine Tunon de Lara, Jeanne Leroux, Françoise Bonnet, Marc Debled, Delfine Lafon, Emmanuelle Barouk-Simonet, Marion Fournier, Adeline Petit, Virginie Bubien, Nathalie Quenel-Tueux, Véronique Brouste, and Gaëtan MacGrogan more...
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Cancer Research ,Oncology - Abstract
Introduction: Neoadjuvant chemotherapy (NAC) is proposed for locally advanced breast cancer (LABC) to increase the breast conservative treatment (BCT). In France, mastectomy is the risk-reducing prophylactic surgical strategy only for pre-symptomatic germline BRCA-mutated (gBRCAm) patients. On the other hand, BCT is proposed to all patients following NAC based on clinical response, even for patients do not demonstrating germline BRCA mutation. Moreover, in the case of BRCA mutation, local recurrence risk is higher in the BCT group (23%) vs mastectomy (5%). The aim of this retrospective one-institution analysis is to evaluate if the knowledge of gBRCAm status impact shared surgical decision between surgeons and patients. Patients and methods: Inclusion criteria were: (i) patients treated for unilateral LABC, T2-4, N≥0, M0 by NAC, and (ii) patients who underwent germline BRCA screening. BRCA screening, using targeted next-generation screening, was carried out either during NAC (rapid process) or after surgery. Deleterious mutations were confirmed using Sanger sequencing before passing on the results to the clinical geneticist. Some gBRCAm patients from Olympia clinical trial study were also included. Patients were followed-up over a long term for overall survival (OS), local recurrence (LR) and disease-free recurrence interval (DRFI). Chi-square, Fischer test and T-test and Wilcoxon test were used to generate statistical descriptive analysis. Results: Between 2007 and 2015, 988 women were treated for LABC at our institution. Among them, 151 patients underwent clinical genetic testing for gBRCAm based on these criteria: young age at diagnosis or familial history of breast or ovarian cancer or histological characteristics as grade 2/3, Her2-3+ or basal like. A total of 125 patients were included in the study; 27 patients had germline mutations (MT group) and no mutations were detected in 98 patients (WT). Significant differences between the two groups (MT vs WT) were observed for - Intrinsic tumor subtypes basal like (64.3% vs 42.5%, p=0.0432) - ER are more often negative (21.4% vs 46.8%, p=0.0165). Among the 29 patients who underwent germline screening during NAC and eligible for BCT, all the patients with gBRCAm choose mastectomy (100%). Among the 96 patients with screening mutation after breast cancer treatment, 6 of the 19 patients with gBRCAm had a mastectomy (28%). In the 25 gBRCAm patients, 15 had a BCT and 11 a mastectomy. In the 98 wtBRCA patients, 70 had a BCT and 28 a mastectomy. After a follow-up of 76.8 months of 83 patients with BCT, we observed 9 LR, 7% in the WT group and 30.8% in the MT group. The median delay of disease recurrence is 40.8 months [22-113]. According DRFI and OS, there is not statistically difference between the WT and the MT group, at 3 years and 5 years of follow up. Discussion: In this selected subgroup of patients, gBRCAm rate is higher (21%) than the rate based on familial criteria for BRCA testing (12%). Regarding the rationale for BCT or mastectomy procedure in LABC and pre-symptomatic gBRCAm patients, this study led us to establish mastectomy as the sole risk-reducing strategy surgery procedure for gBRCAm patients. Moreover, 100% gBRCAm patients chose mastectomy; the mastectomy rate was lower when the patient was unaware of their BRCA status (26%). The LR rate was higher in the gBRCAm vs wtBRCA with a statistical difference. In LABC patients with high genetic risk, the knowledge of mutation status could influence patients’ and surgeons’ choice of surgery. In case of gBRCAm status, mastectomy is recommended to decrease LR risk Citation Format: Nicolas Sevenet, Christine Tunon de Lara, Jeanne Leroux, Françoise Bonnet, Marc Debled, Delfine Lafon, Emmanuelle Barouk-Simonet, Marion Fournier, Adeline Petit, Virginie Bubien, Nathalie Quenel-Tueux, Véronique Brouste, Gaëtan MacGrogan. Germline BRCA screening for locally advanced breast cancer treated by neoadjuvant chemotherapy: Defining a subgroup with high rate of mutation and local relapses [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-07-10. more...
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- 2022
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8. Abstract P1-18-19: Long term results with everolimus in advanced hormone receptor positive breast cancer in a multicenter national real world observational study (ESME)
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Hélène Francois-Martin, Audrey Lardy-Cleaud, Barbara Pistilli, Christelle Levy, Véronique Diéras, Jean-Sébastien Frenel, Séverine Guiu, Marie-Ange Mouret-Reynier, Audrey Mailliez, Jean-Christophe Eymard, Thierry Petit, Mony Ung, Isabelle Desmoulins, Paule Augereau, Thomas Bachelot, Lionel Uwer, Marc Debled, Jean-Marc Ferrero, Corinne Veyret, Antony Goncalves, Michael Chevrot, and Paul H Cottu more...
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Cancer Research ,Oncology - Abstract
Background The everolimus (EVE)-exemestane combination has been included in the International guidelines for metastatic HR+/HER2- breast cancer (mBC) since the results of the Bolero-2 trial. Marketing authorization has been granted in France in July 2012. A first report of the UNICANCER Epidemiological Strategy and Medical Economics (ESME) Research program described the real world use of everolimus therapy (ESMO 2017, #266). We report here updated data with long-term overall survival (OS) analyses, focusing on patients treated from 2012 onwards. Methods All patients (pts) who initiated treatment for a newly diagnosed mBC between 2008 and 2017 in all 18 French Comprehensive Cancer Centers have been included in the real life ESME database, which collects retrospective data using a clinical trial-like methodology. The primary endpoint of the present report was overall survival in pts who received everolimus. In order to adjust for differences between groups (EVE treated vs non EVE treated patients), we analyzed the impact of everolimus on OS and PFS by using a propensity score and inverse probability of treatment weighting (IPTW) sensitivity analyses, built with relevant cancer-related clinical variables in relation to survival and allocation of treatment. Those analyses were performed by line 1, 2 or 3 of treatment for mBC. Results The ESME program included 23,698 pts of whom 1897 with HR+/HER2- mBC received at least 1 dose of EVE and were diagnosed after 2012. Median age was 63 y (22-103). EVE pts were slightly younger than non-EVE pts (25.9% and 23.7% under 52 y, respectively, p=0.0574). EVE treated pts had more frequent non visceral metastases (52.3% vs 47.9%) and bone only metastases (38.5% vs 31.3%) at metastatic diagnosis, and less symptoms at mBC diagnosis (42.4% vs 47.5%) than non-EVE pts (all p values HR (CI95%)p value12 months OS EVE vs not (unadjusted Kaplan Meier)Line 10.34 (0.16-072).005497% vs 93%Line 20.34 (0.22-0.52) Citation Format: Hélène Francois-Martin, Audrey Lardy-Cleaud, Barbara Pistilli, Christelle Levy, Véronique Diéras, Jean-Sébastien Frenel, Séverine Guiu, Marie-Ange Mouret-Reynier, Audrey Mailliez, Jean-Christophe Eymard, Thierry Petit, Mony Ung, Isabelle Desmoulins, Paule Augereau, Thomas Bachelot, Lionel Uwer, Marc Debled, Jean-Marc Ferrero, Corinne Veyret, Antony Goncalves, Michael Chevrot, Paul H Cottu. Long term results with everolimus in advanced hormone receptor positive breast cancer in a multicenter national real world observational study (ESME) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-18-19. more...
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- 2022
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9. Everolimus Added to Adjuvant Endocrine Therapy in Patients With High-Risk Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Primary Breast Cancer
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Thomas Bachelot, Paul Cottu, Sylvie Chabaud, Florence Dalenc, Djelila Allouache, Suzette Delaloge, Jean-Philippe Jacquin, Julien Grenier, Laurence Venat Bouvet, Apurna Jegannathen, Mario Campone, Francesco Del Piano, Marc Debled, Anne-Claire Hardy-Bessard, Sylvie Giacchetti, Marie-Ange Mouret-Reynier, Philippe Barthelemy, Laure Kaluzinski, Audrey Mailliez, Eric Legouffe, Matthew Sephton, Judith Bliss, Jean-Luc Canon, Frederique Penault-Llorca, Jerome Lemonnier, David Cameron, Fabrice Andre, Rhodia Opérations, RHODIA, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Centre Léon Bérard [Lyon], Department of Medical Oncology, Institut Curie, Paris 75248, France, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Service Oncologie Médicale [Saint Priest en Jarez], Institut de Cancérologie Lucien Neuwirth [Saint Priest en Jarez], Laboratoire de Biologie du Développement (LBD), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Institut Bergonié [Bordeaux], Centre Armoricain de Radiothérapie, d'Imagerie médicale et d'Oncologie [Plérin, Saint-Brieuc] (CARIO), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), ChemBioPharm, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Service d'hématologie et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), Qingdao Agricultural University Qingdao, Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), CRLCC Paul Papin, Université Catholique de Louvain = Catholic University of Louvain (UCL), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), École des Hautes Études en Santé Publique [EHESP] (EHESP), Laboratoire d'Ergonomie et d'Épidémiologie en Santé au Travail (LEEST), Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), and PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Institut de Veille Sanitaire (INVS) more...
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Cancer Research ,MESH: Xenograft Model Antitumor Assays ,Receptor, ErbB-2 ,[SDV]Life Sciences [q-bio] ,H3K27me3 ,JMJD3 ,Breast Neoplasms ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,MESH: Everolimus ,Disease-Free Survival ,AR status ,GSK-J4 ,Double-Blind Method ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,asymptomatic ,MESH: Double-Blind Method ,Everolimus ,epidrugs ,COVID ,Prostate cancer ,MESH: Humans ,epigenetics ,Cancer patients ,MESH: Receptor, ErbB-2 ,MESH: Antineoplastic Combined Chemotherapy Protocols ,xenografts ,Oncology ,Chemotherapy, Adjuvant ,MESH: Chemotherapy, Adjuvant ,MESH: Pyrimidines ,MESH: Disease-Free Survival ,Female ,MESH: Female ,MESH: Breast Neoplasms - Abstract
PURPOSE Everolimus, an oral inhibitor of the mammalian target of rapamycin, improves progression-free survival in combination with endocrine therapy (ET) in postmenopausal women with aromatase inhibitor–resistant metastatic breast cancer. However, the benefit of adding everolimus to ET in the adjuvant setting in early breast cancer is unknown. PATIENTS AND METHODS In this randomized double-blind phase III study, women with high-risk, hormone receptor–positive, human epidermal growth factor receptor 2–negative primary breast cancer were randomly assigned to everolimus or placebo for 2 years combined with standard ET. Stratification factors included ET agent, receipt of neoadjuvant versus adjuvant chemotherapy, progesterone receptor status, duration of ET before random assignment, and lymph node involvement. The primary end point was disease-free survival (DFS). The trial is registered with ClinicalTrials.gov (identifier: NCT01805271 ). RESULTS Between June 2013 and March 2020, 1,278 patients were randomly allocated to receive everolimus or placebo. At the first interim analysis, the trial was stopped for futility and a full analysis undertaken once data snapshot complete. One hundred forty-seven patients have had a DFS event reported and at 3 years, DFS did not differ between patients who received ET plus everolimus (88% [95% CI, 85 to 91]) or ET plus placebo (89% [95% CI, 86 to 91; hazard ratio, 0.95; 95% CI, 0.69 to 1.32; P = .77]). Grade ≥ 3 adverse events were reported in 22.9% of patients (29.9% with everolimus v 15.9% with placebo, P < .001). 53.4% everolimus-treated patients permanently discontinued experimental treatment early compared with placebo-treated 22.3%. CONCLUSION Among high-risk patients, everolimus added to adjuvant ET did not improve DFS. Tolerability was a concern, with more than half of patients stopping everolimus before study completion. Everolimus cannot be recommended in the adjuvant setting. more...
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- 2022
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10. Abstract PS14-07: Ribociclib + letrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2−) advanced breast cancer (ABC) and central nervous system metastases: Subgroup analysis of the phase IIIb CompLEEment-1 trial
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L. Menon-Singh, Paul Cottu, Michelino De Laurentiis, Luigi Coltelli, Nadia Califaretti, Shekar Patil, François Duhoux, Ella Evron, Marc Debled, Javier Salvador Bofill, Paolo Marchetti, Katie Zhou, and J. Wu more...
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Cancer Research ,business.industry ,Letrozole ,Central nervous system ,Cancer ,Subgroup analysis ,Ribociclib ,medicine.disease ,medicine.anatomical_structure ,Oncology ,Hormone receptor ,medicine ,Cancer research ,In patient ,business ,Human Epidermal Growth Factor Receptor 2 ,medicine.drug - Abstract
Background: Approximately 10-30% of patients (pts) with metastatic breast cancer (BC) are diagnosed with central nervous system (CNS) metastases, which are a major cause of morbidity and mortality, and are associated with a poor prognosis. Due to improving diagnostics and treatments in BC, and therefore longer pt survival, more CNS metastases in breast cancer pts are readily detected. However, pts with CNS metastases are often excluded from clinical trials. Ribociclib (RIB), an oral, selective cyclin-dependent kinase 4/6 inhibitor, is approved for use in combination with endocrine therapy (ET) in women with HR+, HER2- ABC. Here, we present a subgroup analysis of pts with CNS metastases at baseline from the Core Phase of CompLEEment-1 (NCT02941926), a Phase IIIb trial of RIB in combination with letrozole (LET) in pts with HR+, HER2- ABC. The eligibility criteria for this study allowed a broader and more diverse pt population than those of previous Phase III trials of RIB + LET, to reflect a typical real-world clinical setting. Methods: CompLEEment-1 included women of any menopausal status and men with HR+, HER2- ABC treated with ≤1 line of prior chemotherapy and no prior hormonal therapy for advanced disease. Pts received RIB (600 mg QD, 3 weeks on/1 week off) in combination with LET (2.5 mg QD, continuous). Men and premenopausal women received a luteinizing hormone-releasing hormone agonist (3.6 mg goserelin or 7.5 mg leuprolide, Q28D). This subgroup analysis assessed the primary outcomes (safety and tolerability) and secondary outcomes of time to progression (TTP), overall response rate (ORR), and clinical benefit rate (CBR) in pts with CNS metastases. Results: At the data cutoff date (November 8, 2019), 51 pts with CNS metastases (1.57%; total pt population N = 3,246) had been evaluated: median age was 56.0 years, 30 (58.8%) pts were postmenopausal, and ECOG PS Citation Format: Paul Cottu, Michelino De Laurentiis, Paolo Marchetti, Luigi Coltelli, Nadia Califaretti, Marc Debled, Shekar Patil, Ella Evron, Francois Duhoux, Lakshmi Menon-Singh, Jiwen Wu, Katie Zhou, Javier Salvador Bofill. Ribociclib + letrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2−) advanced breast cancer (ABC) and central nervous system metastases: Subgroup analysis of the phase IIIb CompLEEment-1 trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-07. more...
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- 2021
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11. Abstract PS7-46: Enrollment of older metastatic breast cancer patients in clinical trials
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Michaël Chevrot, Capucine Baldini, Jean-Christophe Eymard, Isabelle Desmoulins, Matthieu Carton, David Pasquier, Jean-Sebastien Frenel, Thomas Bachelot, William Jacot, Jean-Marc Ferrero, Anne Patsouris, Lionel Uwer, Marie-Ange Mouret-Reynier, Anthony Gonçalves, Christelle Levy, Thibault De La Motte Rouge, Marc Debled, Michael Bringuier, C. Courtinard, Olivier Rigal, Thierry Petit, and Florence Dalenc more...
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Cancer Research ,medicine.medical_specialty ,Proportional hazards model ,business.industry ,Cancer ,Context (language use) ,medicine.disease ,Metastatic breast cancer ,Metastasis ,Clinical trial ,Clinical research ,Breast cancer ,Oncology ,Internal medicine ,medicine ,business - Abstract
Background: About 40% of breast cancer cases occur in women 65 years old (yo) or older and 20% in women over 75 yo. These numbers are expected to increase in the near future. Ironically, older patients remain underrepresented in clinical trials with no improvement in the past decade, although they may present different efficacy/toxicity profiles compared with younger adults. In this context, real life cohorts may bring valuable insight to identify potential barriers to recruitment of older patients with metastatic breast cancer (MBC) in clinical trials. Methods: We used the national Epidemio-Strategy and Medical Economics (ESME) MBC Data Platform, a multi-center real life database using a retrospective data collection process in 18 French Cancer Centers. Cases selected were adult patients with MBC whose first metastasis was treated between January 1st, 2008 and December 31st, 2016. We selected MBC women over 70 yo at the time of MBC diagnosis, with at least one line of systemic treatment and no other cancer in the 5 years before MBC. The primary objective was to describe factors associated with enrollment in clinical trials in older patients, using a multivariable Cox model. Factors included in this model were age (continuous, and by class), period (2008-2011 vs 2012-2016), phenotype (ER+, HER2+, or ER- HER2-), ECOG Performance Status (PS), treatment, metastatic sites (brain, visceral, nodes/bone only) and number, and volume of hospital activity. No geriatric description could be extracted from the database. Results: There were 5846 patients ≥70yo (median age 77) and 15892 patients < 70 yo. Of the older ones, 245 (4.2%) were enrolled in a clinical trial in first line compared with 1602 (10%) for younger ones. Most of the older patients in this cohort (66%) had ER+ HER2+ disease, half had visceral metastases (< 3 metastatic sites in 82%). Median follow-up of older patients was 46.3 months; 95%CI 44.8-49.0. Cause of death was related to disease in 1155 (33.9%) older patients, and related to another cause or unknown in 2156 (63.3%), data were missing for 2441 patients. Median overall survival (OS) was 34.1 months in the older population, 95%CI 32.9-35.4, and specific overall survival was 70.8 months, 95%CI 66.3-80.0. Significant factors identified in the multivariable analysis for enrollment in 1st line treatment clinical trial ≥70 are shown in table. Volume of activity was not identified as one. By multivariate analysis, participation of older patients to a clinical trial was associated with an increased OS (HR 0.7; 95% CI 0.6-0.8) but not with a better breast cancer specific survival (HR 0.94; 95%CI 0.68-1.29). Conclusions: In this large real-life database, few older MBC patients were enrolled in a trial compared with younger ones. Factors associated with such participation to clinical research were younger age (< 80 yo), good PS, HER2+ disease, and investigational treatment consisting of chemotherapy or targeted therapy. There was a small improvement in accruing older patients between 2007-2011 and 2012-2016 (2.6% versus 5.5%). Most of these factors raise questions on drug availability and perceived potential benefits by investigators and medical teams. Accrual of older patients with cancer in other disease types should be more encouraged. VariableOR95%CIAge vs 70-75 75-80 80-85 85+0.74 0.47 0.170.54-1 0.31-0.71 0.06-0.37MBC diagnosis period vs 2008-2011 2012-20161.671.23-2.27Phenotype vs Others HER2+1.761.26-2.45PS vs 0 1 2-40.71 0.150.5-1 0.08-0.26Treatment4.88 5.253.08-7.9 3.48-8.14Chemotherapy vs others4.883.08-7.9Targeted treatment vs others5.253.48-8.14 Citation Format: Michael Bringuier, Matthieu Carton, Christelle Levy, Anne Patsouris, David Pasquier, Marc Debled, Olivier Rigal, William Jacot, Anthony Gonçalves, Isabelle Desmoulins, Thibault De La Motte Rouge, Thomas Bachelot, Jean-Marc Ferrero, Jean-Christophe Eymard, Florence Dalenc, Marie-Ange Mouret-Reynier, Thierry Petit, Michael Chevrot, Coralie Courtinard, Lionel Uwer, Jean-Sebastien Frenel, Capucine Baldini. Enrollment of older metastatic breast cancer patients in clinical trials [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-46. more...
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- 2021
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12. Abstract PD10-08: Outcomes of germline BRCA carriers versus non-carriers in the french national metastatic breast cancer ESME cohort 2008-2016
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Audrey Mailliez, Suzette Delaloge, Marie-Ange Mouret-Reynier, Jean-Marc Ferrero, Gaëtane Simon, Jean-Sebastien Frenel, Amélie Lusque, Thibault De La Motte Rouge, Laurence Gladieff, Olivier Caron, Thierry Petit, A. Gonçalves, Luc Cabel, Jean-Christophe Eymard, Marc Debled, and Véronique D'Hondt more...
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Internal medicine ,Cohort ,medicine ,business ,medicine.disease ,Metastatic breast cancer ,Germline - Abstract
BACKGROUND: Approximately 5% of breast cancer (BC) patients (pts) carry a deleterious germline BRCA mutation (gBRCAm). Retrospective studies suggest that overall survival (OS) is equivalent between gBRCAm carriers and non-carriers with metastatic BC (MBC). We aimed to use the large ESME multicentre national MBC database to compare outcomes of gBRCAm carriers, gBRCA wild-type (WT) and not tested (NT) pts. METHODS: We used the large ESME MBC database (NCT03275311), a unique national cohort of all consecutive pts who initiated a first-line treatment for MBC between 2008 and 2016 in one of the 18 French Comprehensive Cancer Centers. All pts with data available regarding gBRCA testing were selected for the present analysis. 26 pts with non-BRCA germline mutations were classified in the WT group. The primary endpoint was OS from date of treatment initiation in the 3 groups of patients: gBRCAm, gBRCA WT and gBRCA NT.Secondary endpoints were progression-free survival under first line treatment (PFS1), clinical and biological characteristics of the 3 groups and prognostic factors for OS. Multivariable analyses included the main known prognostic factors (age at MBC, MBC subtype, disease-free interval, presence of visceral disease, number of metastatic sites). They were conducted using Cox proportional analyses. RESULTS: 20624 pts were included in this analysis (414 gBRCAm, 1710 WT, 18500 gBRCA NT). Pts and disease characteristics are summarized in table 1. As expected, patients with gBRCAm were younger and had a higher rate of TNBC and G3 tumors. Median follow-up was 50.5 months (95%CI 49.7-51.5). Non-adjusted median OS was 30.6 months [21.9-34.3] in the gBRCAm group, 35.8 [32.2-37.8] in the WT and 39.3 [38.3-40.3] in NT groups. Median PFS1 was 7.9 months [6.6-9.3] in the gBRCAm group, 7.8 [7.3-8.5] in the WT and 9.7 months [ 9.5-10.0] in the NT groups. In multivariable analyses, OS and PFS were not significantly different between MBC patients with gBRCA and others (respective HRs 1.01 [0.88;1.17], p=0.87 and 0.94 [0.84;1.06], p=0.31). CONCLUSION: In this large scale real-life ESME MBC database analysis, outcomes of gBRCAm carriers with MBC do not differ from non carriers or not tested subgroups, when adjusted for other prognostic factors. Table 1: characteristics of patients and diseasegBRCAm. gBRCA WT. gBRCA NT Pvalue (chi-2)N = 414 N = 1710 N = 18500 Age (years) median [range]45 [23-82]48 [20- 88]61 [22-103]p Citation Format: Audrey Mailliez, Veronique D'Hondt, Amelie Lusque, Olivier Caron, Luc Cabel, Antony Goncalves, Marc Debled, Laurence Gladieff, Jean-Marc Ferrero, Thierry Petit, Marie-Ange Mouret-Reynier, Jean-Christophe Eymard, Jean-Sébastien Frenel, Thibault De La Motte Rouge, Gaëtane Simon, Suzette Delaloge. Outcomes of germline BRCA carriers versus non-carriers in the french national metastatic breast cancer ESME cohort 2008-2016 [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD10-08. more...
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- 2021
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13. Early Locoregional Breast Surgery and Survival in de novo Metastatic Breast Cancer in the Multicenter National ESME Cohort
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Jean-François Honart, Elvire Pons-Tostivint, Thierry Petit, Clémentine Jankowski, Sophie Guillermet, Amélie Lusque, Gaëtane Simon, Marc Debled, Jean-Marc Ferrero, Thomas Bachelot, Audrey Mailliez, Marian Gutowski, Léa Leufflen, Brigitte De La Lande, Nicolas Pouget, Mario Campone, Marianne Leheurteur, Jean-Christophe Eymard, Olivier Villacroux, Frédéric Marchal, Anthony Gonçalves, Jean-Sebastien Frenel, Judicaël Hotton, and Christelle Levy more...
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Oncology ,medicine.medical_specialty ,Chemotherapy ,Proportional hazards model ,business.industry ,Breast surgery ,medicine.medical_treatment ,Cancer ,medicine.disease ,Metastatic breast cancer ,Radiation therapy ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,Cohort ,medicine ,030211 gastroenterology & hepatology ,Surgery ,Primary breast cancer ,business - Abstract
OBJECTIVE The aim was to evaluate the impact of local surgery performed during the year following metastatic breast cancer (MBC) diagnosis on patients' outcomes from a large real-life cohort. SUMMARY BACKGROUND DATA Locoregional treatment for patients with MBC at the time of diagnosis remains debated. METHODS Women with newly diagnosed, de novo stage IV MBC and who started MBC treatment between January 2008 and December 2014 in one of the 18 French Comprehensive Cancer Centers were included (NCT03275311). The impact of local surgery performed during the first year on overall survival (OS) and progression-free survival (PFS) was evaluated by the Cox proportional hazards model in a 12 month-landmark analysis. RESULTS Out of 16,703 patients in the ESME database, 1,977 had stage IV MBC at diagnosis, were alive and progression-free at 12 months and eligible for this study. Among them, 530 (26.8%) had received primary breast cancer surgery within 12 months. A greater proportion of patients who received surgery had less than 3 metastatic sites than the no-surgery group (90.8% vs 78.2%, p < 0.0001). Surgery within 12 months was associated with treatment with chemotherapy, HER2-targeted therapy (89.1% vs 69.6%, p < 0.0001) and locoregional radiotherapy (81.7% vs 32.5%, p < 0.0001). Multivariable analyses showed that surgery performed within 12 months was associated with longer OS and PFS (adjusted HR [95%CI] = 0.75 [0.61 - 0.92] and 0.72 [0.63 - 0.83], respectively), which were also affected by pattern and number of metastatic sites, histological subtype and age. CONCLUSIONS In the large ESME cohort, surgery within one year after de novo MBC diagnosis was associated with a significantly better OS and PFS. more...
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14. Durvalumab compared to maintenance chemotherapy in metastatic breast cancer: the randomized phase II SAFIR02-BREAST IMMUNO trial
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Tifenn Lharidon, J C Théry, Marie-Ange Mouret Reynier, Philippe Barthélémy, Thomas Filleron, Francesco Del Piano, Marc Debled, Christelle Levy, Monica Arnedos, Alexandra Jacquet, Xavier Tchiknavorian, Florence Dalenc, Alicia Tran-Dien, Anthony Gonçalves, Jean-Marc Ferrero, Fabrice Andre, Mario Campone, Ivan Bièche, Benjamin Verret, Ingrid Garberis, Amélie Lusque, Florence Coussy, Etienne Rouleau, C. Lefeuvre-Plesse, Marie-Paule Sablin, Alice Mege, Marta Jimenez, William Jacot, Benoit You, Thomas Bachelot, Nicolas Isambert, and Julien Adam more...
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,education.field_of_study ,Durvalumab ,business.industry ,BRCA mutation ,Population ,Cancer ,General Medicine ,medicine.disease ,Metastatic breast cancer ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Breast cancer ,Maintenance therapy ,030220 oncology & carcinogenesis ,Internal medicine ,Medicine ,Progression-free survival ,business ,education - Abstract
The impact of single-agent antibodies against programmed death-ligand 1 (PD-L1) as maintenance therapy is unknown in patients with metastatic breast cancer. The SAFIR02-BREAST IMMUNO substudy included patients with human epidermal growth factor receptor type 2 (Her2)-negative metastatic breast cancer whose disease did not progress after six to eight cycles of chemotherapy. Patients (n = 199) were randomized to either durvalumab (10 mg kg−1 every 2 weeks) or maintenance chemotherapy. In the overall population, durvalumab did not improve progression-free survival (adjusted hazard ratio (HR): 1.40, 95% confidence interval (CI): 1.00–1.96; P = 0.047) or overall survival (OS; adjusted HR: 0.84, 95% CI: 0.54–1.29; P = 0.423). In an exploratory subgroup analysis, durvalumab improved OS in patients with triple-negative breast cancer (TNBC; n = 82; HR: 0.54, 95% CI: 0.30–0.97, P = 0.0377). Exploratory analysis showed that the HR of death was 0.37 (95% CI: 0.12–1.13) for patients with PD-L1+ TNBC (n = 32) and 0.49 (95% CI: 0.18–1.34) for those with PD-L1− TNBC (n = 29). In patients with TNBC, exploratory analyses showed that the HR for durvalumab efficacy (OS) was 0.18 (95% CI: 0.05–0.71; log-rank test, P = 0.0059) in patients with CD274 gain/amplification (n = 23) and 1.12 (95% CI: 0.42–2.99; log-rank test, P = 0.8139) in patients with CD274 normal/loss (n = 32). Tumor infiltration by lymphocytes (CD8, FoxP3 and CD103 expressions) and homologous recombination deficiency did not predict sensitivity to durvalumab in exploratory analyses. This latter finding should be interpreted with caution since only one patient presented a germline BRCA mutation. The present study provides a rationale to evaluate single-agent durvalumab in maintenance therapy in patients with TNBC. Exploratory analyses identified CD274 amplification as a potential biomarker of sensitivity. Maintenance chemotherapy was more effective than durvalumab in patients with hormone receptor-positive and Her2-negative disease. Exploratory analyses from the phase 2 randomized SAFIR02-IMMUNO trial identify biomarkers associated with improved outcomes to durvalumab as compared to maintenance chemotherapy in patients with triple-negative breast cancer. more...
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- 2021
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15. Real-world evidence of the management and prognosis of young women (⩽40 years) with de novo metastatic breast cancer
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Amélie Mallet, Amélie Lusque, Christelle Levy, Barbara Pistilli, Etienne Brain, David Pasquier, Marc Debled, Jean Christophe Thery, Anthony Gonçalves, Isabelle Desmoulins, Thibault De La Motte Rouge, Christelle Faure, Jean Marc Ferrero, Jean Christophe Eymard, Marie Ange Mouret-Reynier, Anne Patsouris, Paul Cottu, Florence Dalenc, Thierry Petit, Olivier Payen, Lionel Uwer, Séverine Guiu, Jean Sébastien Frenel, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA) more...
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Oncology ,[SDV]Life Sciences [q-bio] ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: Breast cancer (BC) in young women merits a specific approach given the associated fertility, genetic and psychosocial issues. De novo metastatic breast cancer (MBC) in young women is an even more serious condition, with limited data available. Methods: We evaluated management of women aged ⩽40 years with de novo MBC in a real-life national multicentre cohort of 22,463 patients treated between 2008 and 2016 (NCT0327531). Our primary objective was to compare overall survival (OS) in young women versus women aged 41–69 years. The secondary objectives were to compare first-line progression-free survival (PFS1) and to describe treatment patterns. Results: Of the 4524 women included, 598 (13%) were ⩽40 years. Median age at MBC diagnosis was 36 years (range = 20–40). Compared with women aged 41–69 years, young women had more grade III tumours (49% versus 35.7%, p Conclusion: De novo MBC affects a significant proportion of young women. A subgroup of these patients achieves long OS and merits multidisciplinary care. more...
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- 2022
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16. Neoadjuvant chemotherapy and radiotherapy for locally advanced breast cancer: Safety and efficacy of reverse sequence compared to standard technique?
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Mathilde Maire, Marc Debled, Adeline Petit, Marion Fournier, Gaëtan Macgrogan, Nathalie Quenel-Thueux, Hélène Charitansky, Simone Mathoulin-Pelissier, Hervé Bonnefoi, and Christine Tunon de Lara
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Oncology ,Mammaplasty ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Surgery ,Breast Neoplasms ,Female ,General Medicine ,Mastectomy ,Neoadjuvant Therapy ,Retrospective Studies - Abstract
The reverse sequence of neoadjuvant chemotherapy, preoperative radiotherapy, mastectomy then immediate breast reconstruction is currently proposed for selected patients with locally advanced breast cancer. Few studies have compared it to the standard sequence of neoadjuvant chemotherapy, mastectomy and radiotherapy with or without differed reconstruction. Our study compares overall (OS) and recurrence-free (RFS) survivals of breast cancer patients treated with reverse sequence compared to the standard technique.In this retrospective, single center study at a Comprehensive Cancer Center in France, patients were included if: female, agelt;65y, had received neoadjuvant chemotherapy, mastectomy and radiotherapy, and were M0. Outcomes for patients treated by reverse sequence (RS) are compared to those for patients treated by standard sequence (ST). Data was collected from medical records.From January 2009 to April 2018, 222 eligible patients were treated, 46 by RS and 176 by ST. Mean follow-up was 61.7 months. Five-year OS and RFS did not differ between groups. 5-yr OS: 88.4% 95%CI [74.1-95.0] for RS and 81.5% 95%CI [74.0-87.0] for ST (P = 0.4412); 5-yr RFS: 78.3% 95%CI [61.9-88.3] for RS and 70.1% 95%CI [62.2-76.7] for ST (P = 0.3003). Overall treatment time was significantly shorter in the RS group, and the rate of severe surgical complications did not differ between groups.For locally advanced breast cancer patients with an indication for radiation therapy the reverse sequence offers similar safety and efficacy results as the standard treatment while allowing immediate breast reconstruction. However, careful patient selection is necessary, particularly with regard to preoperative lymph node invasion. more...
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- 2021
17. Long-Term Results with Everolimus in Advanced Hormone Receptor Positive Breast Cancer in a Multicenter National Real-World Observational Study
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Hélène François-Martin, Audrey Lardy-Cléaud, Barbara Pistilli, Christelle Levy, Véronique Diéras, Jean-Sébastien Frenel, Séverine Guiu, Marie-Ange Mouret-Reynier, Audrey Mailliez, Jean-Christophe Eymard, Thierry Petit, Mony Ung, Isabelle Desmoulins, Paule Augereau, Thomas Bachelot, Lionel Uwer, Marc Debled, Jean-Marc Ferrero, Florian Clatot, Anthony Goncalves, Michael Chevrot, Sylvie Chabaud, and Paul Cottu more...
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Cancer Research ,advanced luminal breast cancer ,real-world data ,Oncology ,overall survival ,everolimus - Abstract
Everolimus is the first oral targeted therapy widely used in advanced HR+/HER2− breast cancer. We sought to evaluate the impact of everolimus-based therapy on overall survival in the ESME-MBC database, a national metastatic breast cancer cohort that collects retrospective data using clinical trial-like methodology including quality assessments. We compared 1693 patients having received everolimus to 5928 patients not exposed to everolimus in the same period. Overall survival was evaluated according to treatment line, and a propensity score with the inverse probability of treatment weighting method was built to adjust for differences between groups. Crude and landmark overall survival analyses were all compatible with a benefit from everolimus-based therapy. Adjusted hazard ratios for overall survival were 0.34 (95% CI: 0.16–0.72, p = 0.0054), 0.34 (95% CI: 0.22–0.52, p < 0.0001), and 0.23 (95% CI: 0.14–0.36, p < 0.0001) for patients treated with everolimus in line 1, 2, and 3 and beyond, respectively. No clinically relevant benefit on progression-free survival was observed. Causes for everolimus discontinuation were progressive disease (56.2%), adverse events (27.7%), and other miscellaneous reasons. Despite the limitations inherent to such retrospective studies, these results suggest that adding everolimus-based therapy to the therapeutic sequences in patients with advanced HR+/HER2− breast cancer may favorably affect overall survival. more...
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- 2023
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18. Progression-free survival on endocrine therapy, before or after chemotherapy, in hormone receptor-positive HER2-negative metastatic breast cancer
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Audrey Mailliez, Marie Alexandre, Marie Chaix, Fanny Le Du, C. Courtinard, Thomas Bachelot, Audrey Lardy-Cleaud, Marc Debled, Jean-Christophe Eymard, Marie-Ange Mouret-Reynier, Maxime Fontanilles, Florence Lerebours, Florence Dalenc, Alessandro Viansone, Anthony Gonçalves, Jean-Marc Ferrero, Pauline Corbaux, Thierry Petit, Christelle Levy, Jean-Sebastien Frenel, Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM) more...
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Oncology ,Endocrine therapy ,Cancer Research ,medicine.medical_specialty ,Receptor, ErbB-2 ,medicine.medical_treatment ,Breast Neoplasms ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Chemotherapy ,030212 general & internal medicine ,Progression-free survival ,Retrospective Studies ,business.industry ,Cancer ,Real-word data ,medicine.disease ,Metastatic breast cancer ,Hormones ,3. Good health ,Hormone receptor ,HR+/HER2− ,030220 oncology & carcinogenesis ,Cohort ,Female ,Advanced breast cancer ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,business - Abstract
PURPOSE: A major question when treating HR+/HER2- metastatic breast cancer (MBC) is whether early introduction of chemotherapy (CT) increases endocrine resistance. We aimed to describe progression-free survival (PFS) under first endocrine therapy (ET) depending on whether given before or after CT in a large nationwide cohort, in the pre-CDK era. METHODS: The real-life retrospective ESME database includes all patients with MBC whose first-line treatment was initiated between 2008 and 2014 in one of the 18 French Comprehensive Cancer Centres. Our primary objective was to compare PFS from start of first ET in patients with HR+/HER2- MBC who received ET or CT first. RESULTS: We identified 6293 patients who received at least one ET line during their first two therapeutic lines for MBC. As first-line therapy, 3832 (60.9%) received ET alone (ET1 1st group), whilst 2461 (39.1%) received CT, including 2024 patients (32.2%) with maintenance ET after CT (ET1 after CT group). Median PFS under first ET was 12.4 months (95% CI 11.9-13.1) in ET 1st group vs. 12.6 months in ET1 after CT group (95% CI 12.1-13.4), HR 0.96 (95% CI 0.90-1.01, P = 0.1277). CONCLUSIONS: PFS under first ET appears identical whether prescribed before or after chemotherapy. These data suggest chemotherapy does not promote endocrine resistance. more...
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- 2021
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19. Prognostic value of CEC count in HER2-negative metastatic breast cancer patients treated with bevacizumab and chemotherapy: a prospective validation study (UCBG COMET)
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Christelle Levy, Marie-Ange Mouret-Reynier, Veronique Lorgis, Jean-Yves Pierga, Jérôme Lemonnier, Antoine Vasseur, François-Clément Bidard, Elisabeth Luporsi, Alexia Savignoni, Marie-Laure Tanguy, Marc Debled, Anthony Gonçalves, Jean-Marc Ferrero, Coraline Dubot, Christelle Jouannaud, William Jacot, Olivier Tredan, Luc Cabel, Florence Dalenc, Marion Chevrier, Institut Curie [Paris], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Dept Med Oncol, Centre Léon Bérard [Lyon], Département d'Oncologie Médicale [Institut Curie, Paris], Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'Oncologie Médicale, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Service d'Oncologie médicale [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut Jean Godinot [Reims], UNICANCER, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Institut Claudius Regaud, UNICANCER [Paris], Department of Biostatistics, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département de Biostatistique, Santé Publique et Information Médicale [CHU Pitié-Salpêtrière] (BIOSPIM ), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP) more...
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Male ,0301 basic medicine ,Oncology ,Cancer Research ,Multivariate analysis ,Physiology ,[SDV]Life Sciences [q-bio] ,medicine.medical_treatment ,Clinical Biochemistry ,Cell Count ,Biomarkers, Pharmacological ,Breast cancer ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,Prospective Studies ,Neoplasm Metastasis ,skin and connective tissue diseases ,Middle Aged ,Neoplastic Cells, Circulating ,Prognosis ,Metastatic breast cancer ,3. Good health ,Bevacizumab ,030220 oncology & carcinogenesis ,cardiovascular system ,Female ,medicine.drug ,Validation study ,medicine.medical_specialty ,Circulating endothelial cell ,Breast Neoplasms ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Breast Neoplasms, Male ,03 medical and health sciences ,Predictive Value of Tests ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Aged ,Chemotherapy ,Performance status ,business.industry ,Endothelial Cells ,Genes, erbB-2 ,medicine.disease ,030104 developmental biology ,business ,Circulating endothelial cells - Abstract
Proof of concept studies has reported that circulating endothelial cell (CEC) count may be associated with the outcome of HER2-negative metastatic breast cancer (mBC) patients treated by chemotherapy and the anti-VEGF antibody bevacizumab. We report the results obtained in an independent prospective validation cohort (COMET study, NCT01745757). The main baseline criteria were HER2-negative mBC, performance status 0–2 and no prior chemotherapy for metastatic disease. CECs were detected by CellSearch® from 4 ml of blood at baseline and after 4 weeks of weekly paclitaxel and bevacizumab therapy. CEC counts (considered both as a continuous variable and using the previously described 20 CEC/4 ml cutoff) were associated with clinical characteristics and progression-free survival (PFS). CEC count was obtained in 251 patients at baseline and in 207 patients at 4 weeks. Median baseline CEC count was 22 CEC/4 ml (range 0–2231). Baseline CEC counts were associated with performance status (p = 0.02). No statistically significant change in CEC counts was observed between baseline and 4 weeks of therapy. High baseline CEC count was associated with shorter PFS in univariate and multivariate analyses (continuous: p more...
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- 2019
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20. Impact of breast cancer molecular subtypes on the incidence, kinetics and prognosis of central nervous system metastases in a large multicentre real-life cohort
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Thomas Bachelot, Mathieu Robain, Christelle Levy, Marc Debled, Florence Dalenc, Véronique Diéras, Christelle Jouannaud, Michaël Chevrot, David Pasquier, Lionel Uwer, I. Lecouillard, Julien Fraisse, William Jacot, Jean Marc Ferrero, Paul Cottu, Anthony Gonçalves, Mario Campone, Marie Ange Mouret-Reynier, Amélie Darlix, Etienne Brain, Suzette Delaloge, Guillaume Louvel, Marianne Leheurteur, Paule Augereau, Thierry Petit, and Jean-David Fumet more...
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Receptor, ErbB-2 ,Nervous System Neoplasms ,Central nervous system ,Triple Negative Breast Neoplasms ,Kaplan-Meier Estimate ,Gastroenterology ,Disease-Free Survival ,Article ,Breast Neoplasms, Male ,Metastasis ,Young Adult ,03 medical and health sciences ,Breast cancer ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Neoplasm Metastasis ,Young adult ,skin and connective tissue diseases ,Aged ,030304 developmental biology ,Aged, 80 and over ,0303 health sciences ,business.industry ,Incidence (epidemiology) ,Middle Aged ,Prognosis ,medicine.disease ,Metastatic breast cancer ,Clinical trial ,Kinetics ,medicine.anatomical_structure ,Oncology ,Outcomes research ,Hormone receptor ,030220 oncology & carcinogenesis ,Neurological manifestations ,Cohort ,Female ,business - Abstract
Background Metastatic breast cancer (MBC) behaviour differs depending on hormone receptors (HR) and human epidermal growth factor receptor (HER2) statuses. Methods The kinetics of central nervous system (CNS) metastases (CNS metastasis-free survival, CNSM-FS) and subsequent patient’s prognosis (overall survival, OS) according to the molecular subtype were retrospectively assessed in 16703 MBC patients of the ESME nationwide multicentre MBC database (Kaplan–Meier method). Results CNS metastases occurred in 4118 patients (24.6%) (7.2% at MBC diagnosis and 17.5% later during follow-up). Tumours were HER2−/HR+ (45.3%), HER2+/HR+ (14.5%), HER2+/HR− (14.9%) and triple negative (25.4%). Median age at CNS metastasis diagnosis was 58.1 years (range: 22.8–92.0). The median CNSM-FS was 10.8 months (95% CI: 16.5–17.9) among patients who developed CNS metastases. Molecular subtype was independently associated with CNSM-FS (HR = 3.45, 95% CI: 3.18–3.75, triple-negative and HER2−/HR+ tumours). After a 30-month follow-up, median OS after CNS metastasis diagnosis was 7.9 months (95% CI: 7.2–8.4). OS was independently associated with subtypes: median OS was 18.9 months (HR = 0.57, 95% CI: 0.50–0.64) for HER2+/HR+ , 13.1 months (HR = 0.72, 95% CI: 0.65–0.81) for HER2+/HR−, 4.4 months (HR = 1.55, 95% CI: 1.42–1.69) for triple-negative and 7.1 months for HER2−/HR+ patients (p Conclusions Tumour molecular subtypes strongly impact incidence, kinetics and prognosis of CNS metastases in MBC patients. Clinical trial registration NCT03275311. more...
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- 2019
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21. Real‐life activity of eribulin mesylate among metastatic breast cancer patients in the multicenter national observational ESME program
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Audrey Mailliez, Jean-Marc Ferrero, Marie Chaix, Julien Fraisse, Mathieu Robain, Sophie Gourgou, Paul Cottu, Anthony Gonçalves, Claudia Lefeuvre, Marc Debled, Séverine Guiu, Jean-Christophe Eymard, Christelle Levy, C. Courtinard, Mario Campone, Marianne Leheurteur, Pierre-Etienne Heudel, William Jacot, Lionel Uwer, Barbara Pistilli, Florence Dalenc, Thierry Petit, Marie-Ange Mouret-Reynier, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut du Cancer de Montpellier (ICM), CRLC Val d'Aurelle-Paul Lamarque, CRLCC Val d'Aurelle - Paul Lamarque, Centre Léon Bérard [Lyon], Université de Montpellier (UM), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Gustave Roussy (IGR), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Institut Bergonié [Bordeaux], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), CRLCC Eugène Marquis (CRLCC), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut Jean Godinot [Reims], Centre Paul Strauss, CRLCC Paul Strauss, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Institut Curie [Paris], Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), and Université Lille Nord de France (COMUE)-UNICANCER more...
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Oncology ,Cancer Research ,medicine.medical_specialty ,Receptor, ErbB-2 ,[SDV]Life Sciences [q-bio] ,medicine.medical_treatment ,Population ,Antineoplastic Agents ,Breast Neoplasms ,Disease-Free Survival ,law.invention ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Breast cancer ,real-life cohort ,Randomized controlled trial ,law ,Internal medicine ,Humans ,Medicine ,Furans ,education ,eribulin ,Aged ,Retrospective Studies ,Chemotherapy ,education.field_of_study ,business.industry ,Ketones ,Middle Aged ,medicine.disease ,Metastatic breast cancer ,Progression-Free Survival ,3. Good health ,chemistry ,030220 oncology & carcinogenesis ,Concomitant ,Cohort ,Female ,metastatic breast cancer ,business ,Eribulin - Abstract
International audience; Eribulin mesylate (EM) was recently approved for metastatic breast cancer (MBC) chemotherapy (CT) in late lines by the FDA, with debated results in second line. We evaluated outcomes in breast cancer patients receiving EM as second, third and fourth line in a national real-life cohort of 16,703 consecutive MBC patients initiating their first metastatic therapeutic line between 2008 and 2014. Primary and secondary objectives were overall survival (OS) and progression-free survival (PFS). An imbalance was seen for HER2+ tumors and concomitant anti-HER2 targeted therapies use, we thus performed a subanalysis in HER2- patients. PFS and OS were significantly better in EM patients in third and fourth lines, compared to "Other chemotherapies" patients (PFS: 4.14 vs. 3.02 months, p = 0.0010; 3.61 vs. 2.53 months, p = 0.0102, third and fourth-line; OS: 11.27 vs. 7.65 months, p = 0.0001; 10.91 vs. 5.95 months, p more...
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- 2019
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22. Enrollment of Older Metastatic Breast Cancer Patients in First Line Clinical Trials: 9-Year Experience of the Large-Scale Real-Life Multicenter French ESME Cohort
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Alessandro Viansone, Matthieu Carton, Marc Debled, Capucine Baldini, Jean-Marc Ferrero, A. Goncalves, Jean-Christophe Eymard, Jean-Sebastien Frenel, Anne Patsouris, Michaël Chevrot, Thibault De La Motte Rouge, Thierry Petit, C. Courtinard, Lionel Uwer, Mony Ung, Michael Bringuier, Christelle Levy, Thomas Bachelot, Isabelle Desmoulins, Marie-Ange Mouret-Reynier, Olivier Rigal, David Pasquier, and William Jacot more...
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Clinical trial ,Oncology ,medicine.medical_specialty ,Scale (ratio) ,business.industry ,Internal medicine ,First line ,Cohort ,Medicine ,business ,medicine.disease ,Metastatic breast cancer - Abstract
Purpose: Older cancer patients are underrepresented in clinical trials. We aimed to understand barriers to clinical trial recruitment in women aged 70 years old (yo) or over with metastatic breast cancer (MBC).Methods: We used the national Epidemio-Strategy and Medical Economics MBC Data Platform, a French multi-center real life database. We selected MBC women over 70yo, without central nervous system metastases, with at least one line of systemic treatment, between January 1st, 2008 and December 31st, 2016, and had no other cancer in the 5 years before MBC. The primary objective was to evaluate the proportion of patients enrolled in clinical trials according to their age. Secondary objective was to identify variables associated with enrollment.Results: 5552 women were aged ≥ 70 (median 74yo; IQR72-77). 14611 were less than 70. Of the older ones, 239 (4%) were enrolled in a clinical trial during first line of treatment, compared with 1529 (10.5%) for younger ones. Multivariable analysis of variables predicting for enrollment during first line of treatment in older patients were younger age (OR 0.50 [95%CI; 0.33-0.76] for the 80-85yo class; OR 0.17 [95%CI; 0.06-0.39] for the 85yo and more class), good ECOG Performance Status (PS 0-1) (OR 0.15 [95%CI; 0.08-0.27] for the PS 2-4 class), HER2+ disease (OR 1.78 [95%CI; 1.27-2.48]), type of treatment (chemotherapy/targeted therapy/immunotherapy OR 5.01 [95%CI; 3.13-8.18]), and period (OR 1.65 [95%CI; 1.22–2.26] for 2012-2016, compared to 2008-2011).Conclusions: In this large database, few older MBC patients were enrolled in a trial compared with younger ones. more...
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- 2021
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23. Abstract P4-05-02: Impact of hormone receptor status on clinicopathological characteristics and outcomes among HER2-positive metastatic breast cancer patients in the ESME database
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Luc Cabel, Matthieu Carton, Veronique Dieras, Thierry Petit, Severine Guiu, Corinne Veyret, Anthony Goncalves, Lionel Uwer, Paule Augereau, Jean-Marc Ferrero, Christelle Levy, Florence Dalenc, Isabelle Desmoulins, Marie Ange Mouret-Reynier, Marc Debled, Thomas Bachelot, Jean-Christophe Eymard, Barbara Pistilli, Jean Sebastien Frenel, Michael Chevrot, Audrey Mailliez, and Marcela Carausu more...
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Cancer Research ,Oncology - Abstract
Introduction. Evidence suggests that human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) patients have different clinical characteristics and outcomes according to the hormone receptor (HR) status. We aimed to evaluate the impact of HR status in this population extracted from a large real-world database. Methods. We performed a retrospective analysis of HER2+ MBC patients (pts) included in the real world ESME MBC database (NCT03275311) between 2008 and 2017. Descriptive statistics, the Kaplan-Meier method and Cox proportional hazards models were used to report characteristics, outcomes and prognostic factors. Results. Of 4,145 HER2+ MBC pts eligible for our analysis, 1,449 (35%) had HR-negative (HR-), while 2,696 (65%) had HR-positive (HR+) tumors. Pts with HR- tumors had metastases earlier (median 9.3 vs 28.0 mo from primary cancer), had more often de novo MBC (47.6% vs 38.1%), grade III tumors (50.9% vs 33.6%), visceral metastases (70.9% vs 60.8%) and less often bone only disease (8.4% vs 21.1%) compared to those with HR+ tumors, all p Cox multivariable model for overall survival in patients with HER2-positive MBCCategoriesNHazard ratio95% CIp valueTumor gradeGrade I/II17711 Citation Format: Luc Cabel, Matthieu Carton, Veronique Dieras, Thierry Petit, Severine Guiu, Corinne Veyret, Anthony Goncalves, Lionel Uwer, Paule Augereau, Jean-Marc Ferrero, Christelle Levy, Florence Dalenc, Isabelle Desmoulins, Marie Ange Mouret-Reynier, Marc Debled, Thomas Bachelot, Jean-Christophe Eymard, Barbara Pistilli, Jean Sebastien Frenel, Michael Chevrot, Audrey Mailliez, Marcela Carausu. Impact of hormone receptor status on clinicopathological characteristics and outcomes among HER2-positive metastatic breast cancer patients in the ESME database [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-05-02. more...
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- 2022
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24. Breast cancer patients treated with intrathecal therapy for leptomeningeal metastases in a large real-life database
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Lionel Uwer, Paule Augereau, Thierry Petit, Matthieu Carton, C. Levy, L. Larrouquere, Luc Cabel, M.-A. Mouret-Reynier, Florence Dalenc, M. Carausu, C. Lefeuvre-Plesse, Michaël Chevrot, Amélie Darlix, M. Campone, Benjamin Verret, A. Gonçalves, Jean-David Fumet, M. Leheurteur, Marc Debled, C. Courtinard, J-M Ferrero, Christelle Jouannaud, David Pasquier, Institut Curie [Paris], Institut du Cancer de Montpellier (ICM), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Institut Bergonié [Bordeaux], UNICANCER, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Claudius Regaud, Institut Gustave Roussy (IGR), Département de médecine oncologique [Gustave Roussy], Centre René Gauducheau [Saint-Herblain] (CRLCC Nantes-Atlantique), Centre Régional de Lutte Contre le Cancer Nantes-Atlantique, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), Université Côte d'Azur (UCA)-UNICANCER, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Centre Eugène Marquis (CRLCC), Centre Paul Strauss, CRLCC Paul Strauss, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Institut Jean Godinot [Reims], Centre Léon Bérard [Lyon], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lille-UNICANCER, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UNICANCER-Université Côte d'Azur (UCA), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), and Admin, Oskar more...
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Cancer Research ,Population ,Breast Neoplasms ,computer.software_genre ,03 medical and health sciences ,intrathecal therapy ,0302 clinical medicine ,Breast cancer ,breast cancer ,leptomeningeal metastasis ,cohort study ,Medicine ,Humans ,Breast ,education ,Survival rate ,Original Research ,education.field_of_study ,Database ,business.industry ,Proportional hazards model ,Mortality rate ,Hazard ratio ,Middle Aged ,medicine.disease ,Prognosis ,Metastatic breast cancer ,3. Good health ,Oncology ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,030220 oncology & carcinogenesis ,Concomitant ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Female ,Neoplasm Recurrence, Local ,business ,computer ,Meningeal Carcinomatosis ,030217 neurology & neurosurgery - Abstract
Background Leptomeningeal metastasis (LM) is a rare complication of metastatic breast cancer (MBC), with high morbidity/mortality rates. Our study aimed to describe the largest-to-date real-life population of MBC patients treated with intrathecal (IT) therapy and to evaluate prognostic models. Methods The Epidemiological Strategy and Medical Economics (ESME) MBC database (NCT03275311) includes all consecutive patients who have initiated treatment for MBC since 2008. Overall survival (OS) of patients treated with IT therapy was estimated using the Kaplan–Meier method. Prognostic models were constructed using Cox proportional hazards models. Performance was evaluated using C-index and calibration plots. Results Of the 22 266 patients included in the database between 2008 and 2016, 312 received IT therapy and were selected for our analysis. Compared with non-IT-treated patients, IT-treated patients were younger at MBC relapse (median age: 52 years versus 61 years) and more often had lobular histology (23.4% versus 12.7%) or triple-negative subtype (24.7% versus 13.3%) (all P < 0.001). Median OS was 4.5 months [95% confidence interval (CI) 3.8-5.6] and 1-year survival rate was 25.6%. Significant prognostic factors associated with poorer outcome on multivariable analysis were triple-negative subtype (hazard ratio 1.81, 95% CI 1.32-2.47), treatment line ≥3 (hazard ratio 1.88, 95% CI 1.30-2.73), ≥3 other metastatic sites (hazard ratio 1.33, 95% CI 1.01-1.74) and IT cytarabine or thiotepa versus methotrexate (hazard ratio 1.68, 95% CI 1.28-2.22), while concomitant systemic therapy was associated with better OS (hazard ratio 0.47, 95% CI 0.35-0.62) (all P < 0.001). We validated two previously published prognostic scores, the Curie score and the Breast-graded prognostic assessment, both with C-index of 0.57. Conclusions MBC patients with LM treated with IT therapy have a poor prognosis. We could identify a subgroup of patients with better prognosis, when concomitant systemic therapy and IT methotrexate were used., Highlights • The outcome of BC patients with IT-treated LM is poor, with a median OS of 4.5 months. • Concomitant systemic therapy may improve the outcome in IT-treated patients. • Patients treated with IT methotrexate had better outcome than those treated with IT cytarabine/thiotepa. • The Curie and Breast-graded prognostic assessment scores were prognostic for IT-treated patients. more...
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- 2021
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25. 314P Efficacy of taxane rechallenge in early metastatic relapse of HER2-negative breast cancer patients previously treated with taxane
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Gaëtane Simon, C. Levy, Thomas Bachelot, M.A. Mouret Reynier, J.-C. Eymard, Lionel Uwer, A. Vasseur, T. de La Motte Rouge, Luc Cabel, Thomas Grinda, Florence Dalenc, A. Gonçalves, Isabelle Desmoulins, Matthieu Carton, Séverine Guiu, Paule Augereau, Thierry Petit, Laurence Vanlemmens, Marc Debled, and M. Robert more...
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Oncology ,medicine.medical_specialty ,Taxane ,Breast cancer ,business.industry ,Internal medicine ,HER2 negative ,medicine ,Hematology ,medicine.disease ,Previously treated ,business - Published
- 2021
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26. 231P Prognosis and efficacy of frontline treatment for HR+ HER2- metastatic breast cancer occurring in gBRCA1/2 carriers
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M. Leheurteur, Michaël Chevrot, Lionel Uwer, Luc Cabel, Thomas Bachelot, Anne Patsouris, Audrey Mailliez, William Jacot, J-M Ferrero, Thierry Petit, J.-C. Eymard, C. Levy, T. de La Motte Rouge, M.A. Mouret Reynier, Amélie Lusque, Suzette Delaloge, J-S. Frenel, Isabelle Desmoulins, Marc Debled, and A. Gonçalves more...
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Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,Hematology ,medicine.disease ,business ,Metastatic breast cancer - Published
- 2021
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27. Multimodal liquid biopsy for early monitoring and outcome prediction of chemotherapy in metastatic breast cancer
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Charlotte Proudhon, Jérôme Lemonnier, Anthony Gonçalves, Frédérique Berger, Shufang Renault, Jean-Yves Pierga, François-Clément Bidard, Marie-Laure Tanguy, Christelle Levy, Marc Debled, Isabelle Desmoulins, Elodie Girard, Sylvain Baulande, Coraline Dubot, Christelle Jouannaud, Amanda Bortolini Silveira, Caroline Hego, Benoit Albaud, William Jacot, Maria Rios, Jean-Marc Ferrero, Florence Dalenc, Olivier Tredan, Marie-Ange Mouret-Reynier, Aurore Rampanou, CIC1428 IGR-CURIE, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris-Saclay, Institut Curie [Paris], Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Léon Bérard [Lyon], Departement d'Oncologie médicale [Paris], Institut du Cancer de Montpellier (ICM), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département d'oncologie médicale, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut Jean Godinot [Reims], UNICANCER, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Génétique et Biologie du Développement, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Paris Cité (UPCité), ANR-10-EQPX-0031,FIT,Internet du Futur (des Objets)(2010), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), COLO, Mouniati, Internet du Futur (des Objets) - - FIT2010 - ANR-10-EQPX-0031 - EQPX - VALID, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID, Institut Curie [Saint-Cloud], Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Paris (UP) more...
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Oncology ,medicine.medical_specialty ,Bevacizumab ,medicine.medical_treatment ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Predictive markers ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Circulating tumor cell ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Internal medicine ,medicine ,Pharmacology (medical) ,Radiology, Nuclear Medicine and imaging ,Liquid biopsy ,RC254-282 ,030304 developmental biology ,0303 health sciences ,Chemotherapy ,business.industry ,GATA3 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Metastatic breast cancer ,3. Good health ,030220 oncology & carcinogenesis ,[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,Outcome prediction ,business ,medicine.drug - Abstract
Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) are two cancer-derived blood biomarkers that inform on patient prognosis and treatment efficacy in breast cancer. We prospectively evaluated the clinical validity of quantifying both CTCs (CellSearch) and ctDNA (targeted next-generation sequencing). Their combined value as prognostic and early monitoring markers was assessed in 198 HER2-negative metastatic breast cancer patients. All patients were included in the prospective multicenter UCBG study COMET (NCT01745757) and treated by first-line chemotherapy with weekly paclitaxel and bevacizumab. Blood samples were obtained at baseline and before the second cycle of chemotherapy. At baseline, CTCs and ctDNA were respectively detected in 72 and 74% of patients and were moderately correlated (Kendall’s τ = 0.3). Only 26 (13%) patients had neither detectable ctDNA nor CTCs. Variants were most frequently observed in TP53 and PIK3CA genes. KMT2C/MLL3 variants detected in ctDNA were significantly associated with a lower CTC count, while the opposite trend was seen with GATA3 alterations. Both CTC and ctDNA levels at baseline and after four weeks of treatment were correlated with survival. For progression-free and overall survival, the best multivariate prognostic model included tumor subtype (triple negative vs other), grade (grade 3 vs other), ctDNA variant allele frequency (VAF) at baseline (per 10% increase), and CTC count at four weeks (≥5CTC/7.5 mL). Overall, this study demonstrates that CTCs and ctDNA have nonoverlapping detection profiles and complementary prognostic values in metastatic breast cancer patients. A comprehensive liquid-biopsy approach may involve simultaneous detection of ctDNA and CTCs. more...
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- 2021
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28. Evolution of overall survival and receipt of new therapies by subtype among 20 446 metastatic breast cancer patients in the 2008-2017 ESME cohort
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Thomas Grinda, Marc Debled, Thomas Bachelot, Magali Lacroix-Triki, Paul-Henri Cottu, Audrey Mailliez, Anne Patsouris, Lionel Uwer, Thierry Petit, Isabelle Desmoulins, M. Robain, A. Gonçalves, Etienne Brain, Florence Dalenc, D. Perol, C. Courtinard, Suzette Delaloge, Véronique Diéras, C. Levy, Elise Deluche, C. Blaye, M.-A. Mouret-Reynier, Christelle Jouannaud, William Jacot, Alison Antoine, J-M Ferrero, Florian Clatot, Institut Gustave Roussy (IGR), Centre Léon Bérard [Lyon], Institut du Cancer de Montpellier (ICM), Institut Bergonié [Bordeaux], UNICANCER, Institut Curie [Paris], Centre Eugène Marquis (CRLCC), Institut Claudius Regaud, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), Université Côte d'Azur (UCA)-UNICANCER, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Centre Paul Strauss, CRLCC Paul Strauss, Institut Jean Godinot [Reims], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de médecine oncologique [Gustave Roussy], Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lille-UNICANCER, Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), and UNICANCER-Université Côte d'Azur (UCA) more...
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Oncology ,Cancer Research ,medicine.medical_specialty ,Receptor, ErbB-2 ,overall survival ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Triple Negative Breast Neoplasms ,Cohort Studies ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Breast cancer ,Internal medicine ,HER2 ,Medicine ,Humans ,030212 general & internal medicine ,real-life ,skin and connective tissue diseases ,Retrospective Studies ,Original Research ,Everolimus ,Epidermal Growth Factor ,new drugs ,business.industry ,Cancer ,medicine.disease ,Metastatic breast cancer ,Penetrance ,3. Good health ,chemistry ,030220 oncology & carcinogenesis ,Cohort ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Pertuzumab ,metastatic breast cancer ,business ,medicine.drug ,Eribulin - Abstract
Background Treatment strategies for metastatic breast cancer (MBC) have made great strides over the past 10 years. Real-world data allow us to evaluate the actual benefit of new treatments. ESME (Epidemio-Strategy-Medico-Economical)-MBC, a nationwide observational cohort (NCT03275311), gathers data of all consecutive MBC patients who initiated their treatment in 18 French Cancer Centres since 2008. Patients and methods We evaluated overall survival (OS) in the whole cohort (N = 20 446) and among subtypes: hormone receptor positive, human epidermal growth factor 2 negative (HR+/HER2−; N = 13 590), HER2+ (N = 3919), and triple-negative breast cancer (TNBC; N = 2937). We performed multivariable analyses including year of MBC diagnosis as one of the covariates, to assess the potential OS improvement over time, and we described exposure to newly released drugs at any time during MBC history by year of diagnosis (YOD). Results The median follow-up of the whole cohort was 65.5 months (95% CI 64.6-66.7). Year of metastatic diagnosis appears as a strong independent prognostic factor for OS [Year 2016 HR 0.89 (95% CI 0.82-0.97); P = 0.009, using 2008 as reference]. This effect is driven by the HER2+ subcohort, where it is dramatic [Year 2016 HR 0.52 (95% CI 0.42-0.66); P < 0.001, using 2008 as reference]. YOD had, however, no sustained impact on OS among patients with TNBC [Year 2016 HR 0.93 (95% CI 0.77-1.11); P = 0.41, using 2008 as reference] nor among those with HR+/HER2– MBC [Year 2016 HR 1.02 (95% CI 0.91-1.13); P = 0.41, using 2008 as reference]. While exposure to newly released anti-HER2 therapies appeared very high (e.g. >70% of patients received pertuzumab from 2016 onwards), use of everolimus or eribulin was recorded in less than one-third of HR+/HER2– and TNBC cohorts, respectively, whatever YOD. Conclusion OS has dramatically improved among HER2+ MBC patients, probably in association with the release of several major HER2-directed therapies, whose penetrance was high. This trend was not observed in the other subtypes, but the impact of CDK4/6 inhibitors cannot yet be assessed., Highlights • OS of HER2+ MBC patients keeps improving over time [Year 2016 HR 0.52 (95% CI 0.42-0.66); P < 0.001, using 2008 as reference]. • This effect seems timely related to the release of drugs demonstrated to improve survival in clinical trials. • OS gains observed in real life among HER2+ MBC patients are at least equivalent to those observed in clinical trials. • YOD had no sustained impact on OS among patients with TNBC and luminal MBC. • The impact of CDK4/6 inhibitors cannot yet be assessed in this cohort. more...
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- 2020
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29. VEGF-Related Germinal Polymorphisms May Identify a Subgroup of Breast Cancer Patients with Favorable Outcome under Bevacizumab-Based Therapy-A Message from COMET, a French Unicancer Multicentric Study
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Coraline Dubot, Nathalie Ebran, Emmanuel Chamorey, Marco Merlano, Jocelyn Gal, Anthony Gonçalves, Paul-Henri Cottu, Isabelle Desmoulins, Jean-Yves Pierga, Jean-Marc Ferrero, Gilles Romieu, Olivier Tredan, Etienne Brain, Marie-Christine Etienne-Grimaldi, Marc Debled, Julia Gilhodes, Gérard Milano, Laurence Llorca, Jérôme Lemonnier, and Patrick Brest more...
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Bevacizumab ,precision medicine ,overall survival ,lcsh:Medicine ,lcsh:RS1-441 ,Pharmaceutical Science ,SNP ,Single-nucleotide polymorphism ,bevacizumab ,Article ,lcsh:Pharmacy and materia medica ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,breast cancer ,Internal medicine ,Drug Discovery ,Medicine ,pharmacogenetics ,business.industry ,lcsh:R ,Hazard ratio ,Cancer ,medicine.disease ,Metastatic breast cancer ,VEGF ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cohort ,Molecular Medicine ,business ,Pharmacogenetics ,medicine.drug - Abstract
The prospective multicenter COMET trial followed a cohort of 306 consecutive metastatic breast cancer patients receiving bevacizumab and paclitaxel as first-line chemotherapy. This study was intended to identify and validate reliable biomarkers to better predict bevacizumab treatment outcomes and allow for a more personalized use of this antiangiogenic agent. To that end, we aimed to establish risk scores for survival prognosis dichotomization based on classic clinico-pathological criteria combined or not with single nucleotide polymorphisms (SNPs). The genomic DNA of 306 patients was extracted and a panel of 13 SNPs, covering seven genes previously documented to be potentially involved in drug response, were analyzed by means of high-throughput genotyping. In receiver operating characteristic (ROC) analyses, the hazard model based on a triple-negative cancer phenotype variable, combined with specific SNPs in VEGFA (rs833061), VEGFR1 (rs9582036) and VEGFR2 (rs1870377), had the highest predictive value. The overall survival hazard ratio of patients assigned to the poor prognosis group based on this model was 3.21 (95% CI (2.33&ndash, 4.42), p <, 0.001). We propose that combining this pharmacogenetic approach with classical clinico-pathological characteristics could markedly improve clinical decision-making for breast cancer patients receiving bevacizumab-based therapy. more...
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- 2020
30. Abstract P5-09-07: Risk reducing strategy in germline BRCA mutated patients with locally advanced breast cancer. Establishing mastectomy as a preventing procedure of local recurrence
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C. Tunon de Lara, Marc Debled, V Bubien, P. Lagarde, Michel Longy, M. Fournier, E Barrouk-Simonet, Simone Mathoulin-Pélissier, J Leroux, T Esnaud, F Chassaigne, C. Breton-Callu, Gaëtan MacGrogan, H. Charitansky, A. Petit, N Quenel-Tueux, Nicolas Sevenet, and Françoise Bonnet more...
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Locally advanced ,medicine.disease ,Germline ,Breast cancer ,Internal medicine ,medicine ,business ,Mastectomy - Abstract
Introduction Neoadjuvant chemotherapy (NAC) is proposed for locally advanced breast cancer (LABC) to increase the breast conservative treatment (BCT). In France, mastectomy is the risk-reducing prophylactic surgical strategy only for pre-symptomatic germline BRCA-mutated (gBRCAm) patients. On the other hand, BCT is proposed to all patients following NAC based on clinical response, regardless the gBRCAm status. The aim of this retrospective study is to evaluate the risk of local recurrence (LR) according to BRCA status. Patients and methods Inclusion criteria were: (i) patients treated for unilateral LABC, T2-3, N≥0, M0 by NAC, and (ii) patients who underwent germline BRCA screening. , using targeted next-generation screening, was carried out either during NAC (rapid process) or after surgery. Deleterious mutations were confirmed using Sanger sequencing before passing on the results to the clinical geneticist. Some gBRCAm patients from Olympia study were also included. Patients were followed-up over a long term for overall survival, LR and disease-free survival. Chi-square and Fischer test were used to generate statistical comparison. Results Between 2007 and 2015, 988 women were treated for LABC at our institution. Among them, 151 patients underwent clinical genetic testing for gBRCAm based on these criteria: young age at diagnosis or familial history of breast or ovarian cancer or histological characteristics as grade 2/3, Her2-3+ or basal like. A total of 122 patients were included in the study; 28 patients had gBRCAm status and no mutations were detected in 94 patients (wtBRCA). Significant differences between the two groups (gBRCAm vs wtBRCA) were observed for Mean age, (36.7 vs 40.1y (p=0.0032) , Intrinsic tumor subtypes basal like (64.3% vs 42.5%, p=0.0432) ER are more often negative (21.4% vs 46.8%, p=0.0165). Among the 30 patients who underwent BRCA screening during NAC and eligible for BCT, 8 of the 9 patients with gBRCAm choose mastectomy (88%). Among the 92 patients with screening mutation after breast cancer treatment, 5 of the 19 patients with gBRCAm had a mastectomy (28%). In the 28 gBRCAm patients, 15 had a BCT and 13 a mastectomy. In the 94 wtBRCA patients, 67 had a BCT and 27 a mastectomy. After a follow-up of 4.32 years, we observed 8 relapses, 5 LRs after BCT and 3 contro-lateral relapses. Of the 5 LRs, 3 came from 15 gBRCAm with BCT and 2 of the 67 wtBRCA (p=0.0403). Discussion In this selected subgroup of patients, gBRCAm rate is higher (23%) than the rate based on familial criteria for BRCA testing (12%). Regarding the rationale for BCT or mastectomy procedure in LABC and pre-symptomatic gBRCAm patients, this study led us to establish mastectomy as risk-reducing strategy in a sole surgery procedure for gBRCAm patients. Moreover, 88% gBRCAm patients chose mastectomy; the mastectomy rate was lower when the patient was unaware of their BRCA status (26%). The LR rate was higher in the gBRCAm vs wtBRCA with a statistical difference. In LABC patients with high genetic risk, the knowledge of mutation status could influence patients' and surgeons' choice of surgery. In case of gBRCAm status, mastectomy is recommended to decrease LR risk. Citation Format: Tunon de Lara C, Leroux J, Bonnet F, Debled M, Barrouk-Simonet E, Quenel-Tueux N, Lagarde P, Chassaigne F, Esnaud T, Fournier M, Bubien V, Breton-Callu C, Charitansky H, Petit A, Mathoulin-Pelissier S, Macgrogan G, Longy M, Sevenet N. Risk reducing strategy in germline BRCA mutated patients with locally advanced breast cancer. Establishing mastectomy as a preventing procedure of local recurrence [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-09-07. more...
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- 2019
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31. Abstract GS2-07: PHARE randomized trial final results comparing 6 to 12 months of trastuzumab in adjuvant early breast cancer
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Stéphanie Catala, Laetitia Gambotti, C. Faure Mercier, L. Venat-Bouvet, Xavier Pivot, Sophie Paget-Bailly, Iris Pauporté, J-M Grouin, Christelle Jouannaud, J-Y Pierga, Julie Henriques, Maria Rios, David Khayat, Gilles Romieu, P. Kerbrat, Thomas Bachelot, P. Fumoleau, Daniel Serin, Marc Espié, Marc Debled, Sophie Abadie-Lacourtoisie, J.P. Jacquin, Alain Lortholary, and L. Cany more...
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Population ,Context (language use) ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Randomized controlled trial ,law ,Trastuzumab ,Internal medicine ,Adjuvant therapy ,Medicine ,skin and connective tissue diseases ,education ,education.field_of_study ,business.industry ,Hazard ratio ,Cancer ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,business ,medicine.drug - Abstract
Since 2005, 12 months of trastuzumab added to chemotherapy alone is the standard of care in patients with HER2-positive breast cancer. PHARE ('Protocol for Herceptin® as Adjuvant therapy with Reduced Exposure') is the first trial comparing a reduction of adjuvant trastuzumab versus the standard 12 months. In 2012, the first analysis failed to prove that 6-months was non-inferior to 12-months of adjuvant trastuzumab (NCT00381901). The current presentation reports the final analysis. Methods: The trial was sponsored by the French National Cancer Institute (INCa) (www.e-cancer.fr), and approved by central Ethical Committee on May 15th 2006. Patients with HER2-positive early breast cancer were randomly assigned between 12 and 6 months of adjuvant trastuzumab duration. The randomization was stratified by concomitant or sequential trastuzumab administration with chemotherapy, estrogen receptor (ER) status and center. The primary objective was non-inferiority of 6- versus 12-months arms in the intent to treat population, in terms of disease-free survival (DFS) with a pre-specified hazard margin of 1.15. Overall Survival (OS) and metastasis free survival (MFS) were secondary endpoints. Results: A total of 3380 patients were randomized, their median age was 54 years (21-86). Patients and disease characteristics were well balanced between the two arms. No involved axillary node was observed in 54.5% of cases, 41.7% of tumors were ER negative. At a median follow-up of 7.5 years, 704 events counting for DFS were observed. Between the 12- and 6-months arms, the adjusted Hazard Ratio (HR) for DFS rates was 1.08 (95%CI: 0.93-1.25; p=0.39) favoring the longer exposure. The 1.15 margin of non-inferiority was included in the 95%CI. No heterogeneity in terms of treatment effect was observed, no significant difference for trastuzumab duration effects was found in any subgroups.For OS and MFS, the adjusted HR were 1.13 (95%CI 0.92-1.39) and 1.15 (95%CI 0.96-1.37), respectively. Conclusion: The choice of the non-inferiority margin will remain inherently a subject of controversy especially in the context of oncology trials where the primary outcome is survival and the least additional death could be considered unacceptable questioning the very feasibility of such trials. Nevertheless, PHARE failed to show that 6 months of adjuvant trastuzumab was non-inferior to 12 months. The standard of care should remain 12 months of adjuvant trastuzumab. Citation Format: Pivot X, Romieu G, Debled M, Pierga J-Y, Kerbrat P, Bachelot T, Espie M, Lortholary A, Fumoleau P, Serin D, Jacquin J-P, Jouannaud C, Rios M, Abadie-Lacourtoisie S, Venat-Bouvet L, Cany L, Catala S, Khayat D, Gambotti L, Pauporte I, Faure Mercier C, Paget-Bailly S, Henriques J, Grouin J-M. PHARE randomized trial final results comparing 6 to 12 months of trastuzumab in adjuvant early breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS2-07. more...
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- 2019
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32. Abstract P5-17-04: Metastatic inflammatory breast cancer: Clinical features and outcomes in the national, multicentric, real-life ESME cohort
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Lionel Uwer, Christelle Jouannaud, M. Campone, Florence Dalenc, J-M Ferrero, Bruno Coudert, A. Gonçalves, Audrey Lardy-Cleaud, François Bertucci, Audrey Mailliez, Gaëtane Simon, Barbara Pistilli, Florence Lerebours, Thomas Bachelot, Patrice Viens, M. Robain, T. de La Motte Rouge, A. Monneur, Marc Debled, C. Levy, M.-A. Mouret-Reynier, Séverine Guiu, Paule Augereau, Thierry Petit, M. Leheurteur, and PH Cottu more...
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Incidence (epidemiology) ,Cancer ,Multimodal therapy ,medicine.disease ,Primary tumor ,Inflammatory breast cancer ,Metastasis ,Breast cancer ,Internal medicine ,Medicine ,Disseminated disease ,skin and connective tissue diseases ,business - Abstract
Background:Primary inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer. Survival of IBC patients has been improved by multimodal therapy. However 5-year overall survival (OS) still remains close to 50-60%, due to high risk of disseminated disease. Given the low incidence, prognosis of metastatic cases stages is poorly described. Methods:This study aimed to describe OS of IBC (T4d AJCC TNM classification) with upfront or recurrent metastatic disease compared with non-IBC patients in the ESME database (N=16,702 patients). OS was calculated from the diagnosis of metastasis to the date of death (from any cause), or censored to date of latest news. Secondary objectives included progression-free survival (PFS). Results:From 2008 to 2014, 7,465 patients with diagnosis of MBC and known clinical status of their primary tumor (T) were identified, including 582 IBC (T4d) and 6,883 non-IBC. As expected, metastatic IBC was associated with pejorative features compared to non-IBC, with less hormonal receptors-positive tumors (44% vs 65.6%), more HER2-positive (30% vs 18.6%) or triple-negative (25.9% vs 15.8%) cases (p Compared with non-IBC, synchronous metastatic IBC showed worse median OS and PFS (39.9 months [95%CI 34.2-45.3] vs 48.4 months [95%CI 46.3-50.8], p=0.0035; 10 months [95%CI 8.8-12.7] vs 14.5 months [95%CI 13.6-15.7], p=0.0027, respectively. Similar results were obtained in metachronous metastatic cases (20.01 months [95%CI 17.1-21.2] vs 32.8 months [95%CI 31.5-34.3], p Conclusion:In this large national and multicentric study, IBC is a major and independent factor associated with adverse outcome in metastatic setting. Of note, the independent adverse impact on PFS identified in this study may suggest a lower sensitivity of metastatic IBC to available therapeutics. However, results seem to improve in the last years. Detailed analysis according to phenotype will be available. Citation Format: Monneur A, Bertucci F, Lardy-Cleaud A, Augereau P, Debled M, Levy C, Mouret-Reynier MA, Coudert B, Mailliez A, Bachelot T, Ferrero J-M, Guiu S, Uwer L, Campone M, Cottu P, Jouannaud C, De la Motte Rouge T, Leheurteur M, Petit T, Pistilli B, Dalenc F, Simon G, Robain M, Viens P, Lerebours F, Gonçalves A. Metastatic inflammatory breast cancer: Clinical features and outcomes in the national, multicentric, real-life ESME cohort [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-17-04. more...
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- 2019
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33. Contemporary outcomes of metastatic breast cancer among 22,000 women from the multicentre ESME cohort 2008–2016
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Laurence Vanlemmens, Marc Debled, Magali Lacroix-Triki, Christelle Levy, David Pérol, Lionel Uwer, Elise Deluche, Véronique Diéras, Thierry Petit, Veronique Lorgis, Thomas Bachelot, Simone Mathoulin-Pélissier, Anne Patsouris, Mathieu Robain, Jean Marc Ferrero, Marie Ange Mouret-Reynier, C. Courtinard, Florence Dalenc, Etienne Brain, Alison Antoine, C. Lefeuvre-Plesse, Marianne Leheurteur, Christelle Jouannaud, William Jacot, Anthony Gonçalves, Suzette Delaloge, Audrey Lardy-Cleaud, CHU Limoges, Oncogénèse et progression tumorale, Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Léon Bérard [Lyon], Medical Oncology Department, Salah Azaiz Institute, Department of Medical Oncology [Saint-Cloud], Institut Curie [Saint-Cloud], Service d'Oncologie Médicale, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Claudius Regaud, Senescence Escape and Soluble Markers of Cancer Progression (CRCINA-ÉQUIPE 12), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Service d'Oncologie médicale [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Department of Medical Oncology, CRLCC Eugène Marquis (CRLCC), Plateforme de génétique moléculaire des cancers d'Aquitaine, Centre Paul Strauss, CRLCC Paul Strauss, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), CRLCC Haute Normandie-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Département de Biologie et de Pathologie, Department of Biostatistics, Institut Curie [Paris], Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Université de Lille-UNICANCER more...
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,[SDV]Life Sciences [q-bio] ,Real life ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,03 medical and health sciences ,0302 clinical medicine ,Medical economics ,Internal medicine ,HER2 ,Epidemiology ,Overall survival ,medicine ,skin and connective tissue diseases ,Observational database ,Subtypes ,business.industry ,Cancer ,medicine.disease ,Metastatic breast cancer ,Confidence interval ,3. Good health ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cohort ,business - Abstract
Aim Real-world data inform the outcome comparisons and help the development of new therapeutic strategies. To this end, we aimed to describe the full characteristics and outcomes in the Epidemiological Strategy and Medical Economics (ESME) cohort, a large national contemporary observational database of patients with metastatic breast cancer (MBC). Methods Women aged ≥18 years with newly diagnosed MBC and who initiated MBC treatment between January 2008 and December 2016 in one of the 18 French Comprehensive Cancer Centers (N = 22,109) were included. We assessed the full patients’ characteristics, first-line treatments, overall survival (OS) and first-line progression-free survival, as well as updated prognostic factors in the whole cohort and among the 3 major subtypes: hormone receptor positive and HER2-negative (HR+/HER2−, n = 13,656), HER2-positive (HER2+, n = 4017) and triple-negative (n = 2963) tumours. Results The median OS of the whole cohort was 39.5 months (95% confidence interval [CI], 38.7–40.3). Five-year OS was 33.8%. OS differed significantly between the 3 subtypes (p Conclusions The ESME program represents a unique large-scale real-life cohort on MBC. This study highlights important situations of high medical need within MBC patients. Database registration clinicaltrials.gov Identifier NCT032753. more...
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- 2020
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34. Abstract PD9-08: Prognostic value of EndoPredict test in patients screened for UNIRAD, a UCBG randomized, double blind, phase III international trial evaluating the addition of everolimus (EVE) to adjuvant hormone therapy (HT) in women with high risk HR+, HER2- early breast cancer (eBC)
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Frederique Penault-Llorca, Florence Dalenc, Sylvie Chabaud, Paul Cottu, Djelila Allouache, David Cameron, Jean-Philippe Jacquin, Julien Grenier, Laurence Venat Bouvet, Apurna Jegannathen, Mario Campone, Francesco Del Piano, Marc Debled, Anne-Claire Hardy-Bessard, Sylvie Giacchetti, Philippe Barthelemy, Laure Kaluzinski, Audrey Mailliez, Marie-Ange Mouret-Reynier, Eric Legouffe, Anne Cayre, Mathilde Martinez, Catherine Delbaldo, Delphine Mollon-Grange, E. Jane Macaskill, Matthew Sephton, Laëtitia Stefani, Blaha Belgadi, Matthew Winter, Hubert Orfeuvre, Magali Lacroix-Triki, Herve Bonnefoi, Judith Bliss, Jean-Luc Canon, Jerome Lemonnier, Fabrice Andre, and Thomas Bachelot more...
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Cancer Research ,Oncology - Abstract
Background: The double blind randomized UNIRAD trial (NCT01805271) showed no evidence that adding Everolimus (EVE) to adjuvant endocrine therapy (EHT) for high-risk early breast cancer (BC) improved 3-year disease-free survival (iDFS) compared with EHT alone. In this trial, high risk was defined by any T and either ≥4N+, or ≥1N+ after neoadjuvant treatment, or ≥1N+ and EPclin high risk (EPCH) score ≥3.3. This sub analysis is aimed to verify prognostic added value of EndoPredict test results on outcomes in patients screened for the UNIRAD study.. Material and methods: From May 2015 to March 2020, 777 patients were screened with the EndoPredict test. Complete results were obtained for 767 of them. 662 pts were classified as EPCH and 429 were randomized in UNIRAD. 233 pts with EPCH and 105 pts with EPclin low risk (EPCL) were not randomized but followed up for iDFS. Statistical analysis: Kaplan-Meier estimates the association of the integrated molecular-clinico-pathologic EPclin score, and the 12-gene molecular EP score, with iDFS (primary endpoint) and dMFS (secondary endpoint). Independent prognostic added value of EPclin score was tested in a multivariate Cox model after adjusting on tumor characteristics (Grade and T, N). A two-sided p-value less than 0.05 considered as statistically significant, 95% confidence intervals reported with HR. Results: Median follow-up of the cohort was 36.6 mo (0-69) since EndoPredict test. As for the whole population, there was no significant difference in iDFS between treatment arms in the randomized EPCH group. On the other hand, EPclin was an independent prognostic factor for iDFS. 36 mo relapse rate from testing for patients in the EPCL group and the EPCH group was 0% and 7%, respectively (HR supposing continuous EPclin score: 2.36, 95%CI: 1.7-3.3, p < .0001). This difference remained significant when assessed in a cox model with tumor size, number of positive nodes and tumor grade (HR: 1.96, 95%CI: 1.32-2.9, p=0.0008). Furthermore, EPclin results was independently correlated to distant metastatic free survival: 36 mo dMFS for patient in the EPCL and EPCH group was 100% and 94%, respectively (adjusted HR: 2.13, 95%CI:11.3-3.4, p = .0014). Of interest when assessing prognostic of patients within quartiles of EPclin Score ( Citation Format: Frederique Penault-Llorca, Florence Dalenc, Sylvie Chabaud, Paul Cottu, Djelila Allouache, David Cameron, Jean-Philippe Jacquin, Julien Grenier, Laurence Venat Bouvet, Apurna Jegannathen, Mario Campone, Francesco Del Piano, Marc Debled, Anne-Claire Hardy-Bessard, Sylvie Giacchetti, Philippe Barthelemy, Laure Kaluzinski, Audrey Mailliez, Marie-Ange Mouret-Reynier, Eric Legouffe, Anne Cayre, Mathilde Martinez, Catherine Delbaldo, Delphine Mollon-Grange, E. Jane Macaskill, Matthew Sephton, Laëtitia Stefani, Blaha Belgadi, Matthew Winter, Hubert Orfeuvre, Magali Lacroix-Triki, Herve Bonnefoi, Judith Bliss, Jean-Luc Canon, Jerome Lemonnier, Fabrice Andre, Thomas Bachelot. Prognostic value of EndoPredict test in patients screened for UNIRAD, a UCBG randomized, double blind, phase III international trial evaluating the addition of everolimus (EVE) to adjuvant hormone therapy (HT) in women with high risk HR+, HER2- early breast cancer (eBC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD9-08. more...
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- 2022
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35. Clinicopathological characteristics and prognosis of breast cancer patients with isolated central nervous system metastases in the multicentre ESME database
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Marcela Carausu, Matthieu Carton, Luc Cabel, Anne Patsouris, Christelle Levy, Benjamin Verret, David Pasquier, Marc Debled, Anthony Gonçalves, Isabelle Desmoulins, Isabelle Lecouillard, Thomas Bachelot, Jean-Marc Ferrero, Jean-Christophe Eymard, Marie-Ange Mouret-Reynier, Michaël Chevrot, Eleonora De Maio, Lionel Uwer, Jean-Sébastien Frenel, Marianne Leheurteur, Thierry Petit, Amélie Darlix, Laurence Bozec, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA) more...
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Oncology ,[SDV]Life Sciences [q-bio] - Abstract
Background: As a result of progress in diagnosis and treatment, there is a growing prevalence of metastatic breast cancer (MBC) with isolated CNS metastases. This study describes the largest-to-date real-life cohort of this clinical setting and compares it to other clinical presentations. Methods: We retrospectively analysed the French Epidemiological Strategy and Medical Economics (ESME) MBC database including patients who initiated treatment for MBC between 2008 and 2016. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Descriptive statistics and multivariate Cox model were used. Results: Of 22,266 patients, 647 (2.9%) and 929 (4.2%) patients had isolated first-site CNS metastases or combined with extra-CNS metastases, with longer OS for the group with isolated CNS metastases (16.9 versus 13.9 months, adjusted HR = 1.69 (95% CI: 1.50–1.91), p Conclusions: Patients with isolated CNS metastases at MBC diagnosis represent a distinct population for which the role of systemic therapy needs to be further investigated in prospective studies. more...
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- 2022
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36. Efficacy of everolimus in patients with HR+/HER2- high risk early stage breast cancer
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PH Cottu, J-P. Jacquin, Sylvie Chabaud, M. Campone, J. Grenier, Marc Debled, E. Brain, D. Allouache, Thomas Bachelot, David Cameron, F. Del Piano, Sylvie Giacchetti, Jérôme Lemonnier, Judith M Bliss, M. Brunt, L. Venat Bouvet, Florence Dalenc, Fabrice Andre, J-L Canon, and A-C. Hardy Bessard more...
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Oncology ,medicine.medical_specialty ,Everolimus ,business.industry ,Hematology ,medicine.disease ,Breast cancer ,Internal medicine ,medicine ,In patient ,Stage (cooking) ,business ,medicine.drug - Published
- 2021
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37. Abstract P5-21-11: Benefit from palbociclib and fulvestrant based on previous fulvestrant and/or everolimus treatment. Based on a cohort of over 200 patients treated in a French compassionate program
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P Rusquec, C Lebreton, Monica Arnedos, Thomas Bachelot, Paule Augereau, G. Emile, M Morelle, J Aires, J-S. Frenel, Bianca Cheaib, Marc Debled, E. Jacquet, and Christine Levy
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Oncology ,Cancer Research ,education.field_of_study ,medicine.medical_specialty ,Univariate analysis ,Everolimus ,Fulvestrant ,business.industry ,Population ,Context (language use) ,Palbociclib ,medicine.disease ,Breast cancer ,Internal medicine ,medicine ,education ,business ,Survival analysis ,medicine.drug - Abstract
Background: CDK4/6 inhibitors have been approved in the recent years for the treatment of advanced hormone receptor-positive breast cancer. For patients with resistance to previous endocrine therapy, the approval is based on the results of the PALOMA-3 trial testing palbociclib in addition to fulvestrant observing a progression-free survival (PFS) of 9.2 months. Nevertheless, in this study no previous treatment with fulvestrant was allowed and no information had been reported of efficacy after everolimus administration. Patients and methods: We collected information from patients treated with palbociclib + fulvestrant in the context of a French compassionate access. We aimed at determining the benefit of this treatment in a real population to provide information about PFS in non-selected patients as well as efficacy of palbociclib and fulvestrant in patients previously treated with fulvestrant and/or everolimus. Median PFS were assessed by Kaplan-Meier survival analysis and compared with log-rank test. Results: 206 patients were identified from 5 institutions. Mean age at treatment was 61 years (range 28 – 85). 55% presented with visceral disease. Lines at where palbociclib + fulvestrant treatment was administered were as follows: 1% 1st line, 8.3% 2nd line, 19.4% 3rd line, 13.6% 4th line, 10.2% 5th lignes and the remaining 47.6% had received ≥6 lines (median: 5 lines, range 1 to 15). A total of 48% patients had previously been treated with fulvestrant. In a subsample of patient where the information was available (n=146), 67.8% patients had received everolimus in combination with endocrine therapy before palbociclib administration. A total of 77 patients were still on treatment. Median PFS on fulvestrant-palbociclib treatment at the date of data cut-off was of 5.46 months (95% CI; 4.6 to 6.6 months). In a univariate analysis, there were no significant differences in median PFS for patients treated or not with previous fulvestrant, suggesting a potential effect of palbociclib to recover sensitivity to fulvestrant (4.7 months for previous fulvestrant treatment [95% CI 4.07 - 6.3 months] vs 6.1 months for no previous fulvestrant [95% CI; 6.3 - 8.02 months], p=0.3559). Similarly, in the subsample of n=146 patients where information about previous everolimus treatment was available at data cut-off, benefit from palbociclib-fulvestrant was not affected by previous everolimus treatment (median PFS 4.8 months for previously treated [95% CI; 4.01 -7.8 months] vs 5.4 months for the untreated everolimus group [95% CI; 4.07 - 9.59 months], p=0.374). Conclusions: Fulvestrant-palbociclib in the real life is associated with a median PFS of 5.5 months, which is below the results provided in the PALOMA-3 trial, reflecting a much more advanced population. Importantly, neither previous everolimus treatment nor fulvestrant therapy affected benefit from fulvestrant-palbociclib in this population in univariate analyses suggesting a potential recovery of fulvestrant sensitivity with CDK4/6 inhibition. Results from multivariate analyses and more detailed information about patients' characteristics and benefit from previous therapies will be provided. Citation Format: Arnedos M, Rusquec P, Morelle M, Lebreton C, Jacquet E, Emile G, Aires J, Debled M, Frenel J-S, Augereau P, Cheaib B, Levy C, Bachelot T. Benefit from palbociclib and fulvestrant based on previous fulvestrant and/or everolimus treatment. Based on a cohort of over 200 patients treated in a French compassionate program [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-21-11. more...
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- 2018
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38. Abstract P3-12-10: First 6-month report of the longitudinal PHACS study (<u>P</u>harmacology and <u>H</u>ormonotherapy (HT) for <u>A</u>djuvant breast <u>C</u>ancer (BC) <u>S</u>tudy, NCT01127295)
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D Molnar-Stanciu, Etienne Chatelut, H Laharie-Mineur, E Suc, N. Dohollou, L. Venat-Bouvet, C Ferrer, H. Roche, D Franck, Frédéric Pinguet, P Marquet, Sandrine Lavau-Denes, C. Massabeau, Jacques Robert, Alexandre Evrard, V Mauries, Florence Dalenc, Marc Debled, Thomas Filleron, and William Jacot more...
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Cancer Research ,education.field_of_study ,business.industry ,Letrozole ,Population ,Cancer ,Anastrozole ,Pharmacology ,medicine.disease ,chemistry.chemical_compound ,Breast cancer ,Oncology ,Exemestane ,chemistry ,Pharmacodynamics ,Medicine ,business ,education ,Tamoxifen ,medicine.drug - Abstract
Background: BC is a hormone-dependent disease for 75% of pts. HT is used in both adjuvant and metastatic settings for hormone–receptor (HR) positive tumors. In adjuvant situation, a 5-year HT period at least is recommended. Side-effects (SE) frequently alter quality of life and compliance, reducing the well-known benefits in risks of relapses and specific deaths. Underlying mechanisms are well understood for estrogen deprivation-induced events such as hot flashes, but little is known on arthralgia under aromatase inhibitors (AI). So, pharmacogenomics (PG), pharmacokinetics (PK), potential medications interactions are of value to explain individual drugs exposures, possible related side-effects and compliance to treatment. Methods: We performed a prospective, multicenter, longitudinal study registering early clinical outcomes and SE during the first 3 years of adjuvant HT with tamoxifen (T) or AI. All tumors expressed at least one HR (>10%). The choice of HT molecule and one-drug or sequential treatment were left to the investigator. Pts were followed every 6 months with clinical examination by the referent oncologist and PK sampling each time. Biologic research consisted in PG investigations of different genes involved in the PK and pharmacodynamics of T and AI (95 SNPs) at baseline. SE, concurrent medications and compliance were registered by both the pts on a diary card and the physician. Evaluation was done only on new occurrence or increased grade of symptoms. Results: This first report focuses on characteristics of the population and the results after the 6 first months of treatment. Between June 2010 and October 2014, 23 centers recruited 2000 pts. 23 were excluded leaving 1977 fully evaluable women; 879 (44%) started with T, 1098 (55%) with AI (554 letrozole (L), 390 anastrozole (A), 154 exemestane (E)). 56% of them had previously received chemotherapy, 96% radiotherapy and 8% trastuzumab. Main characteristics were well balanced between the 2 classes of drugs; T was given mainly for pre- or perimenopausal pts. Most frequent co-morbidities were hypertension (8% T, 31% AI) and dyslipidemia or diabetes (T 11%, AI 26%). To note, almost 30% of pts described arthralgias at entrance and 37% had hot flashes. At 6 months, 122 pts (6%; 43 T, 79 AI) had stopped treatment mainly for toxicity (11 T; 12 AI), progression or death (7 T; 4 IA), personal reasons (15 T; 37AI); 4 asked for changing T and 52 AI (equally for the 3 drugs). All these events were significantly more frequent for AI pts (p=0.042) and with E within the AI class (p Main changes in onset or increased intensity of symptoms concerned hot flushes with all drugs (30%), asthenia (20%), insomnia (20%), weight gain (17%), arthralgias (15% for T, 30% for AI), thrombotic events (24 of which 11 with T). 3 grade3 SAE HT-related were reported. Biological data are reported in 2 other abst. (M. White-Koning. abst.#850248, F. Thomas, abst.#851525). Conclusions: These preliminary data on the first 6-months exposure to HT on adjuvant setting in the real-life confirm early rates of withdraws and toxicities. Longer follow-up and subsequent PK analysis should help to understand persistent side-effects and reasons for non-compliance to adjuvant HT. Citation Format: Roché H, Venat-Bouvet L, Debled M, Jacot W, Suc E, Dalenc F, Molnar-Stanciu D, Dohollou N, Franck D, Ferrer C, Laharie-Mineur H, Lavau-Denes S, Massabeau C, Mauries V, Robert J, Pinguet F, Marquet P, Evrard A, Chatelut E, Filleron T. First 6-month report of the longitudinal PHACS study (Pharmacology and Hormonotherapy (HT) for Adjuvant breast Cancer (BC) Study, NCT01127295) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-12-10. more...
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- 2018
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39. Abstract P6-14-02: Real-life activity of eribulin among metastatic breast cancer patients in the multicenter national observational ESME program
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A. Gonçalves, Christine Levy, J-M Ferrero, M. Campone, M. Leheurteur, M. Robain, Claudia Lefeuvre, Audrey Mailliez, Marc Debled, Lionel Uwer, PH Cottu, M-A Mouret-Reynier, Barbara Pistilli, J-C Eymard, William Jacot, Florence Dalenc, M. Chaix, C. Courtinard, P-E. Heudel, S Gourgou, Séverine Guiu, Julien Fraisse, and Thierry Petit more...
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0301 basic medicine ,Oncology ,Cancer Research ,Chemotherapy ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Cancer ,medicine.disease ,Metastatic breast cancer ,Clinical trial ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,0302 clinical medicine ,Breast cancer ,chemistry ,030220 oncology & carcinogenesis ,Internal medicine ,Propensity score matching ,medicine ,Clinical endpoint ,business ,Eribulin - Abstract
Background: In 2014, UNICANCER (composed of 18 French Comprehensive Cancer Centers) launched the Epidemiological Strategy and Medical Economics (ESME) program to investigate real-world data in solid tumors. Real-world data give the opportunity to assess for the activity of specific drugs outside clinical trials. Eribulin is approved for pre-treated metastatic breast cancer (MBC). Marketing authorization has been granted in France in July 2012. However few data are available regarding its efficacy in real life. We evaluated eribulin use as second and third line of chemotherapy in MBC patients from the ESME database. Methods: Data from all newly diagnosed MBC patients having initiated at least one treatment between Jan. 2008 and Dec. 2014 are included in the ESME database. Data were collected retrospectively using a clinical trial-like methodology. Primary endpoint was overall survival (OS), defined from the starting date of second or third line chemotherapy (eribulin versus other chemotherapy). Progression-free survival (PFS) was calculated as a secondary endpoint. Results: Of 16,703 MBC patients included in the ESME database, 7,412 received at least 2 lines of chemotherapy: eribulin/other chemotherapy, total 1,966/5,446, second line 363/5,446, third line 654/2,669. Depending on second or third line chemotherapy use classification, median age was 59 years (range 20-97) and 58 year (range 21 – 94), triple negative tumors accounted for 20% and 19% of cases, and median follow-up reached 26 months and 22 months respectively. Table reports median OS and PFS, according to lines and type of chemotherapy. OS eribulin (months)OS other chemotherapy (months)pPFS Eribulin (months)PFS other chemotherapy (months)pSecond line12.4 (11.3-15.1)11.8 (11.3-12.3)0.4654.1 (3.7-4.9)4.1 (4.0-4.3)0.9225Third line10.3 (9.3-11.5)7.7 (7.3-8.0) Supportive analyses (using a propensity score for adjustment and as a matching factor for nested case–control analyses) and sensitivity analyses will be available for full presentation at the meeting. Conclusion: In this large-scale real-life setting, MBC patients treated with third line eribulin showed an improved OS and PFS compared with those receiving another chemotherapy. The difference was not statistically significant for second line treatment. Citation Format: Jacot W, Heudel P-E, Fraisse J, Gourgou S, Guiu S, Dalenc F, Pistilli B, Campone M, Levy C, Debled M, Leheurteur M, Chaix M, Lefeuvre C, Goncalves A, Uwer L, Ferrero J-M, Eymard J-C, Petit T, Mouret-Reynier M-A, Courtinard C, Cottu P, Robain M, Mailliez A. Real-life activity of eribulin among metastatic breast cancer patients in the multicenter national observational ESME program [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-14-02. more...
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- 2018
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40. LBA11 Individual patient data meta-analysis of 5 non-inferiority RCTs of reduced duration single agent adjuvant trastuzumab in the treatment of HER2 positive early breast cancer
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Xavier Pivot, David G. Cox, C. Faure-Mercier, Jacinta Abraham, Janet A. Dunn, V. Georgoulias, Roberto D'Amico, Heikki Joensuu, Valentina Guarneri, Pierfranco Conte, Helena M. Earl, Marc Debled, Louise Hiller, David Miles, T. Huttunen, Andrew M Wardley, Henrik Lindman, David Cameron, Judith Fraser, and Gilles Romieu more...
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Oncology ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Hematology ,Patient data ,Non inferiority ,Trastuzumab ,Meta-analysis ,Internal medicine ,medicine ,Single agent ,Duration (project management) ,business ,Adjuvant ,Early breast cancer ,medicine.drug - Published
- 2021
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41. Optimal duration of adjuvant chemotherapy for high-risk node-negative (N–) breast cancer patients: 6-year results of the prospective randomised multicentre phase III UNICANCER-PACS 05 trial (UCBG-0106)
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Maria Rios, Daniel Serin, Etienne Brain, Marie-Josèphe Foucher-Goudier, Henri Roché, Magali Edel, Thomas Bachelot, Mario Campone, Lise Roca, Pierre Kerbrat, Alain Marre, Alain Lortholary, Christelle Levy, Marc Debled, Patrice Viens, Jérôme Lemonnier, Isabelle Desmoulins, Marie-Ange Mourret-Reynier, Remy Delva, Bernard Asselain, and Anne-Laure Martin more...
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Adult ,Oncology ,Cancer Research ,medicine.medical_specialty ,Adolescent ,Receptor, ErbB-2 ,Breast surgery ,medicine.medical_treatment ,Breast Neoplasms ,Kaplan-Meier Estimate ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Risk Factors ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Prospective Studies ,030212 general & internal medicine ,Prospective cohort study ,Cyclophosphamide ,Aged ,Epirubicin ,business.industry ,Hazard ratio ,Axillary Lymph Node Dissection ,Middle Aged ,Sentinel node ,medicine.disease ,Tumor Burden ,Clinical trial ,Treatment Outcome ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Female ,Fluorouracil ,France ,business ,medicine.drug - Abstract
Purpose Optimal duration of adjuvant chemotherapy in the treatment of early-stage breast cancer remained to be investigated rigorously for the standard regimens in widespread use in North America (doxorubicin/cyclophosphamide, AC) and Europe (5-fluorouracil/epirubicin/cyclophosphamide, FEC). Whether six cycles of FEC 100 present an advantage, or not, compared with only four cycles was tested directly in a phase III prospective multicentre trial. Patients and methods Between 2002 and 2006, 1515 women between 18 and 65°years of age, with node negative N(−) high-risk early-stage breast cancer, were included in the study following breast surgery and axillary lymph node dissection or procedure by sentinel node technique. Inclusion in the study required tumour size T ≥ 1 cm and at least one of the high-risk factors: T > 2 cm, negative oestrogen receptor/progesterone receptor (ER– and PR–), Scarff-Bloom-Richardson (SBR) grade II or III and age ≤ 35°years. Patients were randomly assigned to either six FEC 100 (Arm A) or four FEC 100 (Arm B). The trial was powered to detect an absolute difference ≥6% in disease-free survival (DFS) at 5°years. Results At 6.1°years median follow-up, with 91 (12%) events recorded in Arm A versus 106 (14%) in Arm B, no statistically significant risk increase was associated with four versus six FEC 100: DFS (hazard ratio (HR) = 1.18; CI 95% [0.89–1.56], P = .24) and overall survival (OS) (HR = 1.39; CI 95% [0.91–2.13], P = .12). Conclusion Differences in chemotherapy duration did not induce notably different outcomes in our cohort of high-risk patients. Clinical trial registry number NCT00055679 , Agence National de Securite du Medicament (ANSM) – France. more...
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- 2017
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42. Cholesterol, Cholesterol-Lowering Medication Use, and Breast Cancer Outcome in the BIG 1-98 Study
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Judy Garber, Richard D. Gelber, Thomas P. Ahern, Manuela Rabaglio, Alan S. Coates, Marco Colleoni, István Láng, Roger von Moos, Anita Giobbie-Hurder, Ian E. Smith, Karen N. Price, Beat Thürlimann, Aron Goldhirsch, Marc Debled, Bent Ejlertsen, Meredith M. Regan, and Signe Borgquist more...
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Hypercholesterolemia ,Estrogen receptor ,Breast Neoplasms ,Mastectomy, Segmental ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Double-Blind Method ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Nitriles ,medicine ,Humans ,Endocrine system ,Cumulative incidence ,610 Medicine & health ,Aged ,Proportional Hazards Models ,Gynecology ,Proportional hazards model ,business.industry ,Anticholesteremic Agents ,Letrozole ,Hazard ratio ,Middle Aged ,Triazoles ,medicine.disease ,Tamoxifen ,Cholesterol ,030104 developmental biology ,Receptors, Estrogen ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Female ,Radiotherapy, Adjuvant ,Neoplasm Recurrence, Local ,Receptors, Progesterone ,business ,Follow-Up Studies ,medicine.drug - Abstract
Purpose Cholesterol-lowering medication (CLM) has been reported to have a role in preventing breast cancer recurrence. CLM may attenuate signaling through the estrogen receptor by reducing levels of the estrogenic cholesterol metabolite 27-hydroxycholesterol. The impact of endocrine treatment on cholesterol levels and hypercholesterolemia per se may counteract the intended effect of aromatase inhibitors. Patients and Methods The Breast International Group (BIG) conducted a randomized, phase III, double-blind trial, BIG 1-98, which enrolled 8,010 postmenopausal women with early-stage, hormone receptor–positive invasive breast cancer from 1998 to 2003. Systemic levels of total cholesterol and use of CLM were measured at study entry and every 6 months up to 5.5 years. Cumulative incidence functions were used to describe the initiation of CLM in the presence of competing risks. Marginal structural Cox proportional hazards modeling investigated the relationships between initiation of CLM during endocrine therapy and outcome. Three time-to-event end points were considered: disease-free-survival, breast cancer–free interval, and distant recurrence–free interval. Results Cholesterol levels were reduced during tamoxifen therapy. Of 789 patients who initiated CLM during endocrine therapy, the majority came from the letrozole monotherapy arm (n = 318), followed by sequential tamoxifen-letrozole (n = 189), letrozole-tamoxifen (n = 176), and tamoxifen monotherapy (n = 106). Initiation of CLM during endocrine therapy was related to improved disease-free-survival (hazard ratio [HR], 0.79; 95% CI, 0.66 to 0.95; P = .01), breast cancer–free interval (HR, 0.76; 95% CI, 0.60 to 0.97; P = .02), and distant recurrence–free interval (HR, 0.74; 95% CI, 0.56 to 0.97; P = .03). Conclusion Cholesterol-lowering medication during adjuvant endocrine therapy may have a role in preventing breast cancer recurrence in hormone receptor–positive early-stage breast cancer. We recommend that these observational results be addressed in prospective randomized trials. more...
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- 2017
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43. Expression of Gastrin-Releasing Peptide Receptor in Breast Cancer and Its Association with Pathologic, Biologic, and Clinical Parameters: A Study of 1,432 Primary Tumors
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Clément Morgat, Hervé Bonnefoi, Elif Hindié, Nicolas Sevenet, Véronique Brouste, Gaëtan MacGrogan, Philippe Fernandez, Valérie Vélasco, and Marc Debled
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Adult ,Male ,Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Estrogen receptor ,Breast Neoplasms ,Lower risk ,030218 nuclear medicine & medical imaging ,Targeted therapy ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Cell Line, Tumor ,Internal medicine ,medicine ,Gastrin-releasing peptide receptor ,Humans ,Radiology, Nuclear Medicine and imaging ,Univariate analysis ,Tissue microarray ,business.industry ,Prognosis ,medicine.disease ,Gene Expression Regulation, Neoplastic ,Receptors, Bombesin ,Receptors, Estrogen ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,Immunohistochemistry ,Female ,business - Abstract
A growing body of evidence suggests that gastrin-releasing peptide receptor (GRPR) might be a valuable target in breast cancer. To understand which patients can be potential candidates for GRPR-based imaging or targeted therapy, we screened invasive breast cancers by immunohistochemistry for the presence and intensity of GRPR expression. Methods: We explored a tissue microarray of 1,432 primary breast tumors from patients who underwent surgery between 2000 and 2005 at Institut Bergonie, without prior neoadjuvant treatment. We studied associations between GRPR expression and clinical, pathologic, and biologic parameters. The association between GRPR expression and distant metastasis-free interval was also examined. Results: GRPR overexpression was found in 75.8% of the 1,432 tumors and was most strongly associated with estrogen receptor (ER) positivity (GRPR was high in 83.2% of ER-positive and 12% of ER-negative tumors; P < 0.00001). When molecular subtypes of breast cancer were considered, GRPR was overexpressed in 86.2% of luminal A-like tumors, 70.5% of luminal B-like human epidermal growth factor receptor 2 (HER2)-negative tumors, 82.8% of luminal B-like HER2-positive tumors, 21.3% of HER2-enriched tumors, and 7.8% of triple-negative tumors. Importantly, when breast tumors overexpressed GRPR, high GRPR expression was also found in metastatic lymph nodes in 94.6% of cases. Primary tumors with high GRPR expression were associated with lower risk of distant metastases at follow-up in univariate analysis (Log-rank P = 0.0084) but not in multivariate analysis. Hence, the prognostic impact of GRPR was lost when examined within specific molecular subtypes. Conclusion: Because GRPR is overexpressed in a high percentage of ER-positive tumors, GRPR targeting offers wide perspectives for imaging and treatment in patients with ER-positive breast cancer, using recently developed radiolabeled GRPR ligands. more...
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- 2017
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44. 279MO Divergent evolution of overall survival across metastatic breast cancer (MBC) subtypes in the nationwide ESME real life cohort 2008-2016
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A. Antoine, Véronique Diéras, Marc Debled, J-M Ferrero, M. Robain, Etienne Brain, D. Perol, Florian Clatot, William Jacot, M.A. Mouret Reynier, Isabelle Desmoulins, C. Levy, Florence Dalenc, Audrey Mailliez, Lionel Uwer, Thomas Bachelot, Anne Patsouris, A. Gonçalves, Paul-Henri Cottu, and Suzette Delaloge more...
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Divergent evolution ,Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,Cohort ,medicine ,Overall survival ,Hematology ,medicine.disease ,business ,Metastatic breast cancer - Published
- 2020
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45. Predictive factors of 5-year relapse-free survival in HR+/HER2- breast cancer patients treated with neoadjuvant endocrine therapy: pooled analysis of two phase 2 trials
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B Sigal, Christel Breton-Callu, Emmanuelle Fourme, Laurence Venat-Bouvet, Jérôme Lemonnier, N Quenel-Tueux, Thibault De La Motte Rouge, Jean-Yves Pierga, Marie-Ange Mouret-Reynier, Simone Mathoulin-Pélissier, Thomas Bachelot, Florence Lerebours, Hervé Bonnefoi, Véronique Becette, Gaëtan MacGrogan, Sofia Rivera, Marina Pulido, Christine Tunon de Lara, Marc Debled, Florence Dalenc, Département d'Oncologie Médicale [Centre René-Huguenin, Saint-Cloud], Hôpital René HUGUENIN (Saint-Cloud), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de Veille Sanitaire, Institut national de veille sanitaire, Service d'Oncologie Médicale, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Validation et identification de nouvelles cibles en oncologie (VINCO), UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Radiothérapie Moléculaire et Innovation Thérapeutique (RaMo-IT), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Service de Chirurgie, Institut Curie [Paris], Service d'Oncologie médicale [CHU Limoges], CHU Limoges, Plateforme de génétique moléculaire des cancers d'Aquitaine, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Eugène Marquis (CRLCC), Institut Claudius Regaud, Oncogénèse et progression tumorale, Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER [Paris], and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC) more...
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Oncology ,Cancer Research ,medicine.medical_specialty ,Time Factors ,Multivariate analysis ,[SDV]Life Sciences [q-bio] ,education ,Phases of clinical research ,Anastrozole ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Breast Neoplasms ,Article ,03 medical and health sciences ,Breast cancer ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Endocrine system ,030212 general & internal medicine ,Pathological ,Aged ,Univariate analysis ,Fulvestrant ,business.industry ,EPICENE ,Prognosis ,medicine.disease ,Survival Analysis ,Neoadjuvant Therapy ,3. Good health ,Risk factors ,030220 oncology & carcinogenesis ,Female ,business ,medicine.drug - Abstract
Background Few data are available on survival and predictive factors in early breast cancer (BC) patients treated with neoadjuvant endocrine therapy (NET). Methods This is a pooled analysis of two multicentre, randomised non-comparative phase 2 clinical trials evaluating neoadjuvant anastrozole and fulvestrant efficacy for postmenopausal HR+/HER2- breast cancer patients: HORGEN (NCT00871858) and CARMINA02 (NCT00629616) studies. Results In total, 236 patients were included in CARMINA02 and HORGEN trials. Modified intention-to-treat analysis was available for 217 patients. Median follow-up was 65.2 months. Relapse-free survival (RFS) and overall survival (OS) at 5 years were 83.7% (95% CI: 77.9–88) and 92.7% (95% CI: 88.2–95.6), respectively, with no difference between treatment arms. On univariate analysis, tumour staging (T2 vs T3–4; p = 0.0001), Ki-67 at surgery (≤10% vs >10%; p = 0.0093), pathological tumour size (pT1–2 vs pT3–4; p = 0.0012) and node status (pN negative vs positive; p = 0.007), adjuvant chemotherapy (p = 0.0167) and PEPI score (PEPI group I + II vs III; p = 0.0004) were associated with RFS. No events were observed in patients with pathological response according to the Sataloff classification. Multivariate analysis showed that preoperative endocrine prognostic index (PEPI) group III was associated with significantly worse RFS (p = 0.0069, hazard ratio = 3.33 (95% CI: 1.39–7.98)). Conclusions Postmenopausal HR+/HER2- breast cancer patients receiving NET generally have a favourable outcome. The PEPI score identifies a subset of patients of poorer prognosis who are candidates for further additional treatment. more...
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- 2020
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46. Factors Affecting Tamoxifen Metabolism in Patients With Breast Cancer: Preliminary Results of the French PHACS Study
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Jacques Robert, Alicja Puszkiel, Alexandre Evrard, Etienne Chatelut, Florence Dalenc, Marc Debled, Fabienne Thomas, Caroline Delmas, Laurence Venat-Bouvet, Isabelle Sillet-Bach, Henri Roché, Thomas Filleron, Christelle Vachoux, Etienne Suc, Cécile Arellano, Jean-Christophe Boyer, Valérie Le Morvan, Melanie White-Koning, William Jacot, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biochimie [CHRU Nîmes], Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Bergonié - CRLCC Bordeaux, CRLCC Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Oncologie médicale [CHU Limoges], CHU Limoges, Clinique Saint Jean Languedoc, Centre Hospitalier Brive-la-Gaillarde, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Bergonié [Bordeaux], UNICANCER, Institut Claudius Regaud, and Clinique Saint-Jean Languedoc [Toulouse] (CSJL) more...
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Oncology ,Adult ,medicine.medical_specialty ,CYP2D6 ,CYP2B6 ,Antineoplastic Agents, Hormonal ,Genotype ,Breast Neoplasms ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,CYP2C19 ,030226 pharmacology & pharmacy ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Pharmacokinetics ,Cytochrome P-450 Enzyme System ,Internal medicine ,medicine ,Cytochrome P-450 CYP3A ,Humans ,Pharmacology (medical) ,Prospective Studies ,skin and connective tissue diseases ,Aged ,Pharmacology ,CYP3A4 ,business.industry ,Middle Aged ,medicine.disease ,3. Good health ,Cytochrome P-450 CYP2B6 ,Tamoxifen ,Cytochrome P-450 CYP2D6 ,Pharmacogenetics ,030220 oncology & carcinogenesis ,Cytochrome P-450 CYP2C19 Inhibitors ,Female ,business ,medicine.drug - Abstract
International audience; In addition to the effect of cytochrome P450 (CYP) 2D6 genetic polymorphisms, the metabolism of tamoxifen may be impacted by other factors with possible consequences on therapeutic outcome (efficacy and toxicity). This analysis focused on the pharmacokinetic (PK)-pharmacogenetic evaluation of tamoxifen in 730 patients with adjuvant breast cancer included in a prospective multicenter study. Plasma concentrations of tamoxifen and six major metabolites, the genotype for 63 single-nucleotide polymorphisms, and comedications were obtained 6 months after treatment initiation. Plasma concentrations of endoxifen were significantly associated with CYP2D6 diplotype (P more...
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- 2019
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47. UCBG 2-04: Long-term results of the PACS 04 trial evaluating adjuvant epirubicin plus docetaxel in node-positive breast cancer and trastuzumab in the human epidermal growth factor receptor 2-positive subgroup
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Jean-Luc Canon, Veronique D'Hondt, Marc Debled, N. Dohollou, Mario Campone, Fanny Le Du, Suzette Delaloge, Jérôme Lemonnier, Jean-Yves Pierga, H. Orfeuvre, D. Serin, Etienne Brain, Lise Roca, Gilles Piot, Anthony Gonçalves, Jean-Marc Ferrero, Anne-Claire Hardy-Bessard, Christelle Levy, Maria Rios, Florence Dalenc, Henri Roché, and Isabelle Desmoulins more...
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0301 basic medicine ,Oncology ,Adult ,Bridged-Ring Compounds ,Cancer Research ,medicine.medical_specialty ,Receptor, ErbB-2 ,Population ,Breast Neoplasms ,Docetaxel ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Trastuzumab ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Anthracyclines ,skin and connective tissue diseases ,education ,neoplasms ,Aged ,Epirubicin ,education.field_of_study ,business.industry ,Hazard ratio ,Middle Aged ,medicine.disease ,Regimen ,030104 developmental biology ,030220 oncology & carcinogenesis ,Concomitant ,Female ,Taxoids ,business ,medicine.drug - Abstract
Purpose We conducted a double-randomised phase III trial to evaluate a concomitant taxane-anthracycline regimen in node-positive breast cancer and the efficacy of trastuzumab in the human epidermal growth factor receptor 2 (HER2)–positive subpopulation. Methods A total of 3010 patients with node-positive breast cancer were randomly assigned to receive 6 cycles of 500 mg/m2 of fluorouracil, 100 mg/m2 of epirubicin and 500 mg/m2 of cyclophosphamide (FEC) or 75 mg/m2 of epirubicin and 75 mg/m2 of docetaxel (ED). Patients with HER2-positive tumours were secondary randomly assigned to either trastuzumab or observation. The primary end-point was disease-free survival (DFS) in the two chemotherapy arms. Results After a 115-month median follow-up, DFS was not significantly better in the ED arm (DFS: 70%, 95% confidence interval [CI]: 67–72) than in the FEC arm (DFS: 68%, 95% CI: 65–70; hazard ratio [HR] = 0.88, 95% CI: 0.77–1.01; p = 0.064). The OS was not different between FEC (OS: 80%, 95% CI: 78–83) and ED (OS: 81%, 95% CI: 79–83); HR = 0.97, 95% CI: 0.81–1.16; p = 0.729). ED appeared more toxic. In the 528 HER2-positive subset, there was trend for a higher DFS, in the intention-to-treat population, in the trastuzumab arm (DFS: 68%, 95% CI: 61–74) than in the observation arm (DFS: 60%, 95% CI: 54–66; HR = 0.77, 95% CI: 0.57–1.03; p = 0.079). In the per-protocol population, DFS was significantly higher in the trastuzumab arm (DFS: 70%, 95% CI: 63–76) than in the observation arm (DFS: 59%, 95% CI: 53–65; HR = 0.69, 95% CI: 0.51–0.94; p = 0.0156). The OS was not different between these 2 arms. Conclusion This study did not show superiority of the concomitant anthracycline-taxane arm which was more toxic in high-risk node-positive breast cancer patients. Long-term results of the HER2-positive subpopulation are in line with those of the other adjuvant trastuzumab trials but quantitatively less pronounced mostly because of lack of power. more...
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- 2019
48. Residual cancer burden index and tumor-infiltrating lymphocyte subtypes in triple-negative breast cancer after neoadjuvant chemotherapy
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Christine Tunon de Lara, Houda Ben Rejeb, Marc Debled, Clémence Pinard, Elodie Richard, Valérie Velasco, Stéphanie Hoppe, Gaëtan MacGrogan, Véronique Brouste, and Hervé Bonnefoi
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Neoplasm, Residual ,medicine.medical_treatment ,Antineoplastic Agents ,Triple Negative Breast Neoplasms ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Lymphocytes, Tumor-Infiltrating ,Drug Therapy ,Internal medicine ,medicine ,Tumor Microenvironment ,Humans ,Pathological ,Triple-negative breast cancer ,Chemotherapy ,Univariate analysis ,Tumor microenvironment ,Tumor-infiltrating lymphocytes ,business.industry ,Hazard ratio ,medicine.disease ,Prognosis ,Survival Analysis ,Neoadjuvant Therapy ,030104 developmental biology ,Treatment Outcome ,030220 oncology & carcinogenesis ,Female ,business ,Biomarkers - Abstract
There is a need to refine the prognosis of triple-negative breast cancer (TNBC) patients after neoadjuvant chemotherapy (NAC) and to study the influence of the tumor microenvironment. We evaluated the prognostic value of pathological and immune markers in TNBC with residual disease (RD) after NAC. In a series of 186 TNBC patients treated by NAC, we assessed the prognostic value of the Residual Cancer Burden (RCB) index. In 109 patients with RD, we studied the impact of clinicopathological features and tumor immune response in the residual tumor on overall survival (OS) and distant recurrence-free interval (DRFI). In the whole group, the OS and DRFI, at 3 years, were statistically different between the different classes of RCB (P = 0.0004 and P more...
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- 2019
49. Assessment of the efficacy of successive endocrine therapies in hormone receptor-positive and HER2-negative metastatic breast cancer: a real-life multicentre national study
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Laurence Vanlemmens, Olivia Le Saux, Marc Debled, Véronique D'Hondt, Christelle Levy, Jean-Marc Ferrero, Veronique Lorgis, Sylvie Chabaud, Mathias Breton, Paul Cottu, Sophie Frank, Marianne Leheurteur, Mathieu Robain, Delphine Berchery, Audrey Lardy-Cleaud, Marie Ange Mouret-Reynier, C. Courtinard, Barbara Pistilli, Damien Parent, Lionel Uwer, Lilian Laborde, Geneviève Perrocheau, Michel Velten, and Thomas Bachelot more...
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0301 basic medicine ,Oncology ,Adult ,Cancer Research ,medicine.medical_specialty ,Time Factors ,Antineoplastic Agents, Hormonal ,Receptor, ErbB-2 ,medicine.medical_treatment ,Breast Neoplasms ,Risk Assessment ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Breast cancer ,Risk Factors ,Internal medicine ,Epidemiology ,medicine ,Biomarkers, Tumor ,Humans ,Neoplasm Metastasis ,Aged ,Retrospective Studies ,Aged, 80 and over ,Chemotherapy ,business.industry ,Cancer ,Middle Aged ,medicine.disease ,Metastatic breast cancer ,Confidence interval ,Progression-Free Survival ,Clinical trial ,030104 developmental biology ,Receptors, Estrogen ,030220 oncology & carcinogenesis ,Cohort ,Disease Progression ,Female ,France ,business ,Receptors, Progesterone - Abstract
For luminal metastatic breast cancer (MBC), endocrine therapy (ET) is the recommended initial treatment before chemotherapy. Our objective was to evaluate the efficacy of multiple ET lines in a real-life study.The Breast Cancer Epidemiological Strategy and Medical Economics (ESME) project analysed data from all patients with systemic treatment for MBC initiated between 2008 and 2014 in one of the 18 French Comprehensive Cancer Centres. The primary end-point was the successive progression-free survival (PFS) evaluation.The ESME research programme included 9921 patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2) negative (HER2-) MBC. Before any chemotherapy, 4195 (43.4%), 1252 (29.8%) and 279 (6.6%) patients received one, two or three ET ± targeted therapy, respectively. The median PFS for first-, second- and third-line ET ± targeted therapy was 11.5 (95% confidence interval [CI], 10.8-12.1), 5.8 (95% CI, 5.3-6.1) and 5.5 (95% CI, 4.6-6.3) months, respectively. In a multivariate analysis, time from diagnosis to metastatic recurrence (P 0.0001), presence of symptoms at metastatic relapse (P = 0.01), number of metastatic sites (P = 0.0003) and their localisation (P 0.0001) were prognostic factors for PFS1. Duration of previous PFS was the only prognostic factor for subsequent PFS (10% threshold). Ten percent of the patients showed long-term response to ET, with a total treatment duration before chemotherapy ≥43.6 months.Median PFS in our HR+/HER2- real-life cohort is similar to median first-line PFS reported in clinical trials, regardless of ET used as second- and third-line treatment. Despite the international consensus on early initiation of ET, the latter is not prescribed in most of the cases. Patients with a low tumour burden may achieve prolonged response on ET. more...
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- 2019
50. Corrigendum to ‘VP1-2021: Efficacy of everolimus in patients with HR+/HER2- high risk early stage breast cancer’
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Thomas Bachelot, J. Grenier, PH Cottu, M. Campone, Sylvie Chabaud, A.-C. Hardy Bessard, J-L Canon, Sylvie Giacchetti, F. Del Piano, Marc Debled, J.P. Jacquin, Judith M Bliss, E. Brain, Florence Dalenc, Fabrice Andre, Jérôme Lemonnier, M. Brunt, L. Venat Bouvet, D. Allouache, and David Cameron more...
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Oncology ,medicine.medical_specialty ,Everolimus ,business.industry ,Hematology ,medicine.disease ,Annals ,Breast cancer ,Internal medicine ,medicine ,In patient ,Stage (cooking) ,business ,medicine.drug - Published
- 2021
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