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Background: Breast cancer (BC) management in older women requires an individual approach and is becoming increasingly topical given the aging population. Postoperative radiation therapy (RT) is a standard treatment of BC after breast-conserving-surgery in most patients but its relative benefit may be counteracted by potential side-effects, especially in elderly. The aim of this study was to assess acute and long-term radiation-induced toxicities and the impact of comorbidities on outcomes in the older women treated by RT for non-metastatic breast cancer. Materials and Methods: Women aged ≥ 70 years at diagnosis, who received exclusive or postoperative RT for primary non-metastatic breast cancer, including carcinoma in situ, between 2003 and 2009 were retrieved from the Institut Curie registry. We calculated the Charlson Comorbidity Index (CCI) for each patient and collected the cardiovascular risk factors other than age (hypertension, dyslipidemia, smoking status). We analyzed overall survival (OS), progression free survival (PFS) and acute and late toxicities according to the CTCAE (Common Terminology Criteria for Adverse Events) v3.0. Results: A total of 817 patients was included in this study. Median age at diagnosis was 76.6 years [70 – 93.3]. Most patients had HR+ (hormone-receptor positive) HER2- breast cancer (83.9 %). 517 patients (62.7%) had at least one cardiovascular risk factor. With a median follow-up of 6.7 years [0.5 - 13], OS at 5 years was 86.3% CI95%[83.8 - 88.8], and PFS was 84.5% CI95%[81.9 – 87.1]. OS at 5 years was statistically different according to the Charlson index: 90.2% CI95%[87.2 – 93.3] for a CCI of 0, 84.6 % CI95%[80.5 – 88.8] for a CCI of 1, and 78% CI95%[70.5 – 86.2] for a CCI ≥ 2 (p < 0.001, log-rank test), respectively. Similar results were found for PFS (p < 0.001, log-rank test). 22.6% of patients had no toxicity; of those who experienced toxicity, most was limited to grade I or II. Only five cases (0.6%) of radiation – induced pneumonitis were reported after a median time of 16.4 months (grade I, n = 1; grade II, n = 2). One case (0.1%) of myocardial ischemia was described 14.5 months after RT. Women older than 80 years were less likely to have acute dermatitis (OR = 0.62; CI95%[0.45 - 0.85]), long-term breast pain (OR = 0.31; CI95%[0.14 - 0.62]), and long-term breast deformation (OR = 0.63; CI95%[0.42 - 0.93]) compared to patients younger than 80 years. There was no significant association found between other cardiovascular risk factors and toxicities. Conclusion: Radiation therapy for breast cancer in the older women is well-tolerated. An extended follow-up is planned in order to assess toxicities at a longer time horizon. Further studies could be envisaged to assess the quality-of-life during and after RT for breast cancer in the older patient population. Citation Format: Cao KI, Salviat F, Fourquet A, Falcou M-C, Laki F, Beuzeboc P, Savignoni A, Bazire L, Poortmans P, Kirova YM. Tolerability and outcomes of radiation therapy for breast cancer in older women: A retrospective study in 817 patients [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 P2-11-20.

Background There is no large prospective trial assessing mid-term adverse effects of adjuvant chemotherapy. In order to address this question, we developed CANTO (CANcer TOxicities - NCT01993498 - http://etudecanto.org/), a prospective trial dedicated to the quantification of side effects after treatment for patients with early breast cancer and to develop predictors of such toxicities. The aim of this presentation is to assess chemotherapy (CT) practice and to report toxicities that persist 3-6 months after CT. Methods CANTO is a prospective study enrolling newly diagnosed invasive cT0-cT3, cN0-3, M0 breast cancer patients (pts) of 26 French comprehensive cancer centers. The study has included 10 500 patients at the time of submission. Pts are assessed at diagnosis, 3-6, 12, 36, 48 and 60 months after treatment completion. CANTO collects >100 items related to toxicities. In the current study, we focus on the first set of data available from the trial (1st database lock, n=6090). We here assess CT practice and toxicities at 3 months. Results Information about (neo)adjuvant CT (NACT/ACT) is available in 5805 pts (96%). Median age at diagnosis was 57y (22-93). Pts had HR+/HER2-, HER2+ or triple negative (TN) tumors in 74%, 15% and 11% of cases. Ki67 was assessed in 70%, and genomic tests in 1% of pts, respectively. Overall, 3074 pts (53%) received CT, either adjuvant (ACT: 76%) or neoadjuvant (NACT: 24%). ACT/NACT pts (84%) received a sequential anthracyclines–taxanes based 6 courses CT schedule. CT was administered in 44.7%, 87.2% and 92.3% of HR+/HER2+/TN tumors, respectively. ACT was administered in 73.2% of pT2+ pts (vs 36.0% in pT0-1 – p We focus here on clinically most relevant patient reported symptoms at 3 m (any grade). side effects at 3m no CT (%)CT (%)p valuePain76.682.1 Pain complaint was recorded in 3596 pts (97.2% of pts with available data), with a median value of 4 on the VAS (range 1-10). In ACT/NACT pts, muscle and joint pain were predominant. Neurological symptoms were seen in 3024 pts (59%), the most frequent pertaining to cognitive disorder (attention trouble, CT: 61.2% vs noCT: 56% - p=.06) and peripheral neuropathy (overall 31%). Paresthesias and sensory neuropathy were much more frequent in CT vs noCT pts: respectively 37.3% vs 20.3% and 25.7% vs 12.8% (both p Conclusions In this real life, prospective cohort, CT is frequently prescribed and appears in good compliance with current guidelines. Overall, symptoms burden at treatment completion is strikingly high, and much higher in pts receiving CT. A special attention should be given to pain and neurological symptoms. Dedicated questionnaires and sub-studies will explore in depth these side effects. Extended analyses of CT practice and toxicities will be presented. Citation Format: Cottu PH, Amar Y, Pistilli B, Bonsang-Kitzis H, Lesur A, Lerebours F, Vanlemmens L, Tredan O, Levy C, Jouannaud C, Fournier M, Soulie P, Rigal O, Giacchetti S, Arnaud A, Arsene O, Savignoni A, Mesleard C, Andre F, Arveux P. CANTOCHEM: Analysis of chemotherapy practice and early side effects in the 6090 first patients from the prospective CANTO cohort [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 P6-12-18.

Background About 20% of breast cancer (BC) patients will develop distant metastases. HER2-positive (HER2+) disease is associated with poorer prognosis. However, outcome of HER2+ BC patients has dramatically improved since the use of trastuzumab. Although most HER2+ metastatic BC (MBC) patients will eventually develop progressive disease within one year of trastuzumab-based treatment, some are long-term responders (LTR). Few data on these patients are available. Methods The primary objective was to assess overall survival (OS) of HER2+ MBC patients treated with trastuzumab as 1st-line at the Institut Curie, based on institution-specific data included in the French Epidemiological Strategy and Medical Economics (ESME) program for MBC patients established in 2014 by Unicancer. Long-term responders (LTR) were defined as having a non-progressive disease for at least 2 years under 1st-line trastuzumab. Secondary objectives included progression-free survival (PFS), disease-free interval (DFI), prediction factors for LTR status by univariate and multivariate analysis: characteristics of patients (age, BMI, menopausal status), of primary tumour (e.g. hormone receptor (HR) status), of treatment (e.g. endocrine therapy, partner for trastuzumab combination), number and type of metastases. Results From 2008 to 2014, 2990 MBC patients were identified in the Curie-ESME MBC database. Of these, 460 had HER2+ disease. Sixteen patients with second primary malignancy were excluded. Of the 444 remaining patients, 340 received 1st-line trastuzumab and could be analyzed. With a 42.5-month median follow-up time, the mean age at metastatic diagnosis was 55.7 years, 59.4% had a HR-positive disease and 43.2% had de novo metastases or occurring within 6 months after adjuvant treatment. DFI was >24 months in 47.9% of patients, and 78.5% received 1st-line trastuzumab combined with taxane-based chemotherapy (CT). In 87 patients (25.6%) classified as LTR, median PFS was 56.2 months (CI95% 41.53-not reached) vs. 10.9 months in non-LTR (CI95% 9.46-11.8). Median OS in LTR is not reached versus 44.3 months in non-LTR (CI95% 37.9-49.1). Median age, menopausal status, BMI, pathological characteristics and treatment for primary BC were similar in both groups. The following factors were predictive of LTR status by univariate analysis: number of metastatic sites ( 3, p=0.022); endocrine treatment for metastatic disease (p=0.002); absence of central nervous system metastases (p=0.035); and taxane-based 1st- line CT (p=0.032). In multivariate analysis, only number of metastatic sites and taxane-based 1st-line CT were predictive of LTR status. In contrast, age, DFI, visceral disease, and adjuvant trastuzumab-based treatment did not influence outcome. Although not statistically significant, HR+ status was more frequent in LTR versus non-LTR patients (66.7% versus 56.9%). Conclusions With a median follow-up of 42.5 months, we found that more than 95% of LTR to 1st-line trastuzumab were still alive and could achieve a median PFS longer than 4.6 years. Although some clinical factors are clearly associated with better outcome, further investigations are needed to identify the mechanisms of resistance or sensitivity to trastuzumab. Citation Format: Kaczmarek E, Saint-Martin C, Pierga J-Y, Brain E, Rouzier R, Dubot C, Savignoni A, Mouret-Fourme E, Simon G, Carton M, Lerebours F. Long-term survival in HER2-positive metastatic breast cancer treated with first-line trastuzumab: Real-life results from the Curie ESME database [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 P5-21-14.

Purpose: To report the results of a randomised study comparing the efficacy of Hydrosorb® versus control (water based spray) in the topical treatment of grade 1 and 2 radiation dermatitis in population of patients treated for early stage breast cancer (BC) with normo fractionated radiotherapy (RT). Patients and Methods: Breast cancer patients with grade 1-2 radio-induced dermatitis during normo fractionated postoperative radiotherapy were eligible (according to the CTCAE v3 scale). They were randomised to receive either Hydrosorb® (A) or water based spray (B). The primary endpoint was local treatment failure defined as interruption of radiotherapy because of skin radiotoxicity or and/or change of local cares for skin alteration. Secondary endpoints were the evaluation of skin colorimetry, pain, and quality of life. Pain was assessed according to two classes with a VAS cut-off of 2. Results: Two-hundred seventy eight patients were enrolled (A = 142, B = 136). There were 186 successfully treated patients (82 in Hydrosorb® arm, and 74 in the control arm). There were 60 "failures" in the Hydrosorb® arm, and 62 in the control arm (p = 0.72), but mostly without interruption of the radiotherapy. Twenty-four patients stopped the radiotherapy treatment for local cares (16 in Hydrosorb®, arm and 8 in control arm). No risk factors were associated with failure to local treatment. The average absolute reduction of colorimetric levels between day 28 and day 0 was 4 in the Hydrosorb®, and 4.2 in the water spray groups, respectively (p = 0.36). Forty-eight patients in the Hydrosorb® arm had a VAS > 2 versus 51 patients in the placebo arm, i.e. 34% and 38%, respectively (p = 0.45). A significant reduction of pain was observed on D7 (p = 0.04) and D21 (p = 0.01) in the Hydrosorb® arm. Sixty patients in the Hydrosorb® arm and 55 patients in the placebo arm had moderately to severely altered quality of life (p = 0.76). Conclusions: The present study showed no significant difference between Hydrosorb® and simple water spray in the treatment of acute radio-induced dermatitis even if there was a trend to an improvement in pain at the first weeks after the treatment. Systematic prevention measures and modern breast cancer radiotherapy techniques now allow excellent tolerability, but the place of topical treatment to optimize this tolerability has yet to be defined. Citation Format: Bazire L, Fromentin I, Diallo A, de Lalande B, Pernin V, Dendale R, Fourquet A, Savignoni A, Kirova Y. Hydrosorb® versus control (water based spray) in the management of radio-induced skin toxicity: Results of multicentre controlled randomized trial. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-12-16.

BACKGROUND: The benefit of chemotherapy for patients with estrogen receptor(ER)+ HER2- breast cancers is an ongoing question. The evaluation of the tumor's proliferation by Ki67 may guide the indication but no consensual predictive cut-off has been set yet. MATERIALS AND METHODS: This study included women with a first ER+HER2- invasive breast cancer treated by primary surgery between 2003 and 2008. Data was collected prospectively. Ki67 cut-off was sequentially set each 1% from 5% to 30%. For each threshold, the interaction between Ki67 and adjuvant chemotherapy was integrated in a multivariate Cox model to determine when it became statistically significant in predicting distant-disease free survival (DDFS). Using different Ki67 cut-offs, we also compared DDFS of patients who had or not an indication of chemotherapy, depending on whether they actually received it or not. RESULTS: Among the 3221 breast cancers, median Ki67 was 10%, with a mean of 15% (S.D = 14). Ki67 was an independent prognosis factor whether the cut-off was set to 14% or to 20% (p CONCLUSION: In ER+ HER2- breast cancers, a Ki67 level of expression >= 20% was predictive of benefit from adjuvant chemotherapy. A threshold at 14% was not as discriminant. Based on this large cohort study, we recommend the use of a cut-off at 20% to decide whether patientes with ER positive tumors should receive chemotherapy or not/. Citation Format: Rouzier R, Rossi L, Lerebours F, Savignoni A, Falcou M-C, Bonneau C, Pierga J-Y, Guinebretière J-M. Ki67 cut-off point to predict the benefit of adjuvant chemotherapy in ER+ HER2- breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-63.

Background: Despite of therapeutics progress in advanced breast cancer, brain metastases occurrence remain a frequent and delicate situation. The efficacy of whole-brain radiation therapy (WBRT), still considered as the standard local treatment in case of multiple brain metastases, is limited. Recently, several phase II studies have shown some efficacy of the association of WBRT and temozolomide (TMZ), an oral alkylating agent already known as a radiosensitizer, with improved brain control rate (44 to 96%). Patients with breast cancer were underrepresented and none of these trials have studied this combined treatment issue in this specific population. The aim of this study was to assess the efficacy and safety of WBRT combined with temozolomide in the treatment of brain metastases from breast cancer. Materials and Methods: A prospective randomized multicenter phase II study was developed, using a modified two-stage Fleming design. Patients with newly diagnosed intraparenchymal brain metastases from breast cancer, not suitable for surgery nor radiosurgery, were included. All patients received conformational WBRT (3 Gy x 10 to 30 Gy). They were randomized to WBRT plus concomitant TMZ administered 75 mg/m2/day during radiation period versus WBRT alone. The primary endpoint was radiologic objective response at six weeks after the end of treatment, defined as a partial or complete response on systematic brain MRI (WHO modified criteria). We also evaluated neurologic symptoms, tolerance, safety, progression free survival (PFS) and overall survival (OS) as secondary endpoints. A longer clinical-brain MRI follow-up was planned, each three months during a two-year period. All of the patients gave their written informed consent to be part of the study, which was approved by the local committee. Results: One hundred patients were enrolled between February 2008 and December 2010 (50 in the WBRT + TMZ arm, 50 in the WBRT arm). The median age was 55 [29 -79]. Eighty (80) patients had brain metastases as single secondary localization. About one third of patients had a triple negative breast cancer subtype (38,3% in the association arm and 35,71% in the WBRT alone arm). There were 26,7% and 14,6% of HER2 positive subtype respectively. The median follow-up was 30 months [range 6-60]. At six months from brain metastases diagnosis (three months after the end of the treatment), objective response rate seems better in the WBRT + TMZ arm: 52% versus 40% in the arm WBRT alone but was not statistically significant (p = 0,54). No complete response was observed. In the WBRT + TMZ group, median PFS and OS at six-months were respectively 55,6% [range 46-7 – 66,0] and 67,7% [range 59,1 – 77,6]. No improvement in neurologic symptoms was noticed. In multivariate analysis, initial TNM status was significantly correlated with PFS and OS. The concurrent use of TMZ with WBRT was well-tolerated. The most frequent upper grade II acute toxicity was reversible leucopenia in the association arm. Conclusion: The addition of temozolomide to WBRT in patients with brain metastases from breast cancer did not improve local control or survival at six months follow-up. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-11-01.

Background: To identify ER+ve ERBB2-ve ductal T1T2N0 carcinomas associated with a poor prognosis remains challenging. We have previously demonstrated that the number of chromosomal breakpoints assessed by CGH could be a marker of worse outcome for breast carcinomas. Our aim was to validate the CGH based signature in a series of luminal ductal and T1T2 N0 carcinoma patients with long-term clinical follow-up. Patients and methods: We analyzed 214 patients treated for an invasive ductal ER+ve ERBB2-ve carcinomas, smaller than 30mm. The training set was composed of 109 patients (10.9 years of median follow-up; 30 cases associated with a metastatic event within less than 4 years/79 control cases with no metastastic event at 5 years) and the validation set of 105 patients (10.5 years of median follow-up; 30 relapses including contra-lateral breast carcinomas, loco-regional relapses and 8 metastatic events). None of the patient received adjuvant chemotherapy. 16 received an adjuvant hormonotherapy (10 in the training and 6 in the validation groups). We genotyped the sample set with the SNP6.0 affymetrix array. After RMA normalisation using Genotyping console, segmentation was performed according to the Zhang and Siegmund maximum method. In the training data set, the number of breakpoints was assessed, linked to outcome and the threshold optimising the sensitivity and specificity was determined (ROC curve). The threshold prognostic value was then tested on the validation series (Kaplan Meier analysis, log rank test, determination of relative risk and its confidence interval with a Cox model). Results: In the training set, median numbers of breakpoints were 7 in cases that experienced a metastatic event after more than 5 years and 40.5 in cases that experienced a metastatic event in less than 4 years. The threshold (Younden index ) was 34 breakpoints with a sensitivity of 0.57 and a specificity of 0.94 (AUC: 0.81[0.71;0.91]). In the validation set, the outcome of patients with more than 34 breakpoints was poorer than that of patients with less than 34 breakpoints (34 breakpoints: 11 events out of 22 patients with a median time to progression of 108 months; p34 versus 34 breakpoints: 4 events out of 22 patients with a median time to progression of 108 months; p=0.009 (logrank test); RR: 5.29 [1.32; 21.26]). Conclusion: We demonstated that patients with T1T2 ( Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-01.

Introduction: AdjuvantOnline is a web-based application designed to provide 10 years survival probability patients with breast cancer. Few validation studies have underlined some limitations, particularly an overestimation of the prognosis among certain subgroups of patients. Moreover, several predictors such as HER2 over expression status and proliferation markers have not been assessed in Adjuvant! original study. We provide the validation of AdjuvantOnline algorithm on two breast cancer datasets collected from two large European cancer centres, and we determined whether the accuracy of AdjuvantOnline is improved by others well known prognostic factors. Material and Methods: The French data set is composed of 456 women with early breast cancer, treated at the Institut Curie between 1995 and 1996. The dutch data set is composed of 295 women less that 52 years treated at the Netherlands Cancer Institute between 1984 and 1995. Agreement between observation and Adjuvant! prediction was checked by testing that the calibration slope was equal to 1. Logistic models were performed to evaluate whether risk factors adds significant prognostic information, including AdjuvantOnline a priori information as an offset. Results: Ten years survival status was known for 383 patients in the French data set and 247 patients in the Dutch data set. Adjuvant! prediction was globally well calibrated in the French data set (observed survival 86%, predicted survival 85%), but was overestimated in high grade, HER2 positive and Ki67 > 20% subgroups. HER2 status, Mitotic Index, Ki67 and treatment type were strongly associated with 10-year survival, even considering AdjuvantOnline a priori information. In the Dutch data set, the overall 10-year survival was overestimated by AdjuvantOnline (observed 66%, predicted 79%), particularly in patients less than 40 years old. Conclusion: AdjuvantOnline needs to be updated to adjust overoptimistic results in young and high grade patients, and should consider candidates, such as Ki67, HER2 and Mitotic Index. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-13.

Histone synthesis and chromatin assembly are mainly associated with DNA replication and are thus intimately involved in cell cycle regulation. The expression of key components involved in these events in human cells was studied in relation to cell-proliferative status. Among several chromatin assembly factors, chromatin assembly factor (CAF)-1 stood out as the most discriminating marker of the proliferative state. We show, using both immunofluorescence and Western blot analysis, that the expression of both CAF-1 large subunits, p150 and p60, is massively down-regulated during quiescence in several cell lines. Upon exit from the quiescent state, the CAF-1 subunits are re-expressed early, before DNA replication. The amounts of either total or chromatin-associated pools of CAF-1 proteins correlate directly with cell proliferation. Regulation of CAF-1 expression is partly controlled at the RNA level, as shown by quantitative reverse transcription-PCR and Northern blot experiments. Biological material from benign and malignant human breast tumors analyzed by immunocytochemistry and immunohistochemistry exhibits a strong positive correlation between CAF-1 p60 expression and the following proliferation markers: S-phase fraction (r = 0.84, P < 0.0001); Ki-67 (r = 0.94, P < 0.0001); and proliferating cell nuclear antigen (r = 0.95, P = 0.0001). We discuss the advantages of using CAF-1 to assess cell proliferation. High CAF-1 p60 levels are also shown to be associated with various prognostic factors. Our data highlight the precise association of CAF-1 expression with the proliferative state and validate the use of this factor as a useful proliferation marker and prognostic indicator in malignant and benign breast lesions.

Introduction: To determine whether the levels of expression of 17 candidate genes were associated with locoregional control after breast conserving treatments of early-stage breast cancers in young, premenopausal women.Methods: Gene expression was measured using RT-PCR in the breast tumors of a series of 53 young (≤40 years), premenopausal patients. All treatments consisted in primary breast conserving surgery followed by whole-breast radiotherapy (+/- regional lymph nodes) with or without systemic treatments (chemotherapy +/- hormone-therapy). The median follow-up was 10 years.Results: The 10-year locoregional recurrence rate was 70% (95% CI 57%-87%). In univariate analysis, no clinical/pathological prognostic factors were found to be significantly associated with a decreased loco-regional control. Expression of three genes was found to be significantly associated with an increased loco-regional recurrence rate: low estrogen receptor beta, low aromatase, high GATA3. Two others were associated with only a trend (p Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6035.

Purpose: To determine whether exclusive radiotherapy (ERT) could be an option after complete clinical response (cCR) to neoadjuvant chemotherapy (NCT) for early breast cancers (EBC).Patients and methods: Between 1985 and 1999, 1477 patients received NCT for EBC considered to be too large for primary conservative surgery. Of 165 patients with cCR, 65 were treated by breast surgery (with radiotherapy) and 100 by ERT.Results: The two groups were comparable in terms of baseline characteristics, except for larger initial tumor sizes in the ERT group. There were no significant differences in overall, disease-free and metastasis-free survivals. Five-year and 10-year overall survivals were 91% and 77% in the no surgery group and 82% and 79% in the surgery group, respectively (p = 0.9). However, a non-significant trend towards higher locoregional recurrence rates (LRR) was observed in the no surgery group (31% vs. 17% at 10 years; p = 0.06). In patients with complete responses on mammography and/or ultrasound, LRR were not significantly different (p = 0.45, 10-year LRR: 21% in surgery vs. 26% in ERT). No significant differences were observed in terms of the rate of cutaneous, cardiac or pulmonary toxicities.Conclusion: Omission of breast surgery in patients who achieved cCR to NCT was not associated with an increased risk of distant metastases or death. However a trend towards an increased risk of locoregional recurrence was observed in the ERT group. Imaging modalities appear to be essential to monitor chemotherapy response and possibly select patients in whom ERT can be proposed. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4108.

Purpose: To assess anti tumor activity of sequential epirubicin/cyclophosphamide followed by docetaxel with the randomized addition of celecoxib In Her2-ve patients or trastuzumab in Her2+ve patients versus no additional treatment, in terms of pathological complete response (pCR), defined as absence of residual invasive breast carcinoma and of nodal involvement.Patients and methods: 340 patients with stage II and III breast adenocarcinoma, with tumors ineligible for breast conservative surgery received 8 sequential 3 weekly cycles with epirubicin (75mg/m2)-cyclophosphamide (750mg/m2) for 4 cycles followed by docetaxel (100 mg/m2) for 4 cycles. According to HER2 status (IHC + FISH) they were randomized to receive together with docetaxel, in HER2 negative group (220 patients) celecoxib 800 mg/day during cycles 5-8 or no additional treatment and in HER2 positive group (120 patients) trastuzumab (8mg/kg then 6mg/kg) infused together with docetaxel or no additional treatment. All patients except eight with HER2+ tumor received adjuvant trastuzumab for a cumulative duration of 12 months.Results: In the HER2 negative group, pCR (grade 1 and 2 of Chevallier's classification) was observed in 11.5% and 13% of patients treated without and with neoadjuvant Celecoxib respectively. In the HER2+ group, pCR rate reached 26% in those having received neoadjuvant trastuzumab versus 19% in the others. There was no cardiac toxicity and no toxic death. Triple negative breast cancers experience the highest pCR rate of 30%.Conclusion: It is the first report on the effect of the addition of celecoxib to chemotherapy in neoadjuvant setting in breast cancer, showing that celecoxib does not improve the pCR rate. Addition of trastuzumab does, yet not to the extent reported with a protracted co-administration before surgery. Expression of hormonal receptors appears to be the major prognosticator for pCR. Molecular studies of gene expression profiling should allow improving such prediction.Supported by PHRC AOM/2OO2/02117, Pfizer inc., Roche, sanofi-aventis.ISRCTN10059974 Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5054.

Abstract #5132 Purpose: This study aimed to evaluate the skin and heart toxicities of a concurrent adjuvant trastuzumab (T) and radiotherapy (RT) for breast cancer (BC), especially in the case of IMC irradiation. Patients and methods: Prospective study of 57 pts treated at the Institut Curie between 02/2004 and 01/2007 by concurrent T-RT for non-metastatic BC. The perfusion of trastuzumab started either with or after chemotherapy (CT). RT, started at least 4 weeks after the completion of anthracycline-based chemotherapy, consisted of either whole breast (+/- boost) or chest wall normo-fractionated irradiation. When indicated the internal mammary chain (IMC) and supra/infra-clavicular lymph nodes were also irradiated. Left ventricular ejection fractions (LEVF), assessed at baseline, before start of RT (pre-RT), after completion of RT and then every 4-6 months with either echocardiography or multiple gated acquisition scanning, were considered normal if ≥50% or stated so by the cardiologist. A normal LVEF at baseline was one of the inclusion criteria. Skin toxicity was evaluated using CTCAEV3. Results: Median age was 49 years (25-80). CT with anthracycline was administered in 84% (48 pts) with either doxorubicine for 6 pts (median total dose 300 mg/m²) or epirubicine for 42 pts (median total dose 300mg/m²). All but one patient (treated weekly) received T every three weeks (8mg/kg followed by 6mg/kg) for a median duration of 12 months (6-33). The treated breast was the left one in 46% (26 pts). The IMC was irradiated in 88% (50 pts). Median follow-up for LVEF assessment was 13 months (2-33). LVEF at pre-RT were normal in 55 pts (100%, 2 Missing Data), at post-RT in 56 pts (98%, no MD) and at last follow-up in 54 pts (95%, no MD). Overall, there were 2 grade 0, 44 grade I, 11 grade II skin reactions. For the 27 patients with a skin toxicity assessment after 6months, late skin toxicity was grade 0 in 22 pts, grade 1 in 4, grade 2 in 1. There was no skin toxicity graded higher than 2. Conclusion: In this preliminary study of BC patients treated with T-RT with, in most cases, anthracycline-based CT and IMC irradiation, there was no significant increase in the rate of abnormal LVEF after concurrent T-RT and the skin toxicity was acceptable in routine. More patients and a longer follow-up are needed to ascertain that this regimen remains safe. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5132.

Abstract #1081 Background: The purpose of this study was to identify a genomic signature of early metastatic recurrence, in order to predict accurately breast carcinomas clinical outcome and to select patients with node negative and small tumor size ( Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1081.