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Purpose: EGFR is frequently overexpressed in cervical cancer, suggesting EGFR blockade as a promising treatment approach. Cetuximab, an anti EGFR antibody, used conjointly with radiochemotherapy, was feasible in first-line treatment of cervix carcinoma limited to the pelvis.Experimental Design: This randomized phase II trial enrolled 78 FIGO stage IB2–IIIB cervical cancer patients to either cisplatin-based radiochemotherapy alone (arm B, n = 38) or conjointly with a 6-week course of weekly cetuximab (arm A, n = 40). Brachytherapy was given to the pelvic mass. Primary endpoint was disease-free survival (DFS) at 2 years. EGFR expression and targeted sequencing were performed in 54 of 78 patients.Results: Cetuximab over a 6-week period did not improve DFS at 24 months. At 31 months median follow-up, DFS was not significantly different (P = 0.18). Complete response at 4 to 6 months was strongly predictive for excellent DFS (log-rank test; P < 0.001). PIK3CA, KRAS, and STK11 mutations were observed in 22%, 4%, and 2% of patients, respectively. No tumor with a PI3K pathway mutation showed complete response (0/8 in arm A and 0/6 in arm B), whereas 14 of 52 (27%) tumors without mutations did (P = 0.021). PI3K pathway-mutated tumors showed a trend toward poorer DFS (P = 0.06) following cetuximab (8/22) as compared with those following standard treatment only (6/18).Conclusions: Similar to patients with head and neck cancer, patients with cervical cancer showed no gain in DFS at 2 years following a combined treatment of cetuximab with radiochemotherapy. Although treatment tolerance and compliance were satisfactory, it remains to be demonstrated whether maintenance therapy with cetuximab could be beneficial in selected patient groups. Clin Cancer Res; 21(11); 2530–7. ©2015 AACR.

supplementary table 4. Multivariate analysis for Complete Clinical Response and Figo stage

supplementary table 2. Protocol�defined treatment�related Adverse Events

supplementary table 3. Response evaluation at 2 time points

supplementary table 1. Radiotherapy and Chemotherapy Treatment dose and Surgery

Background. Preclinical works have suggested that conventional cytotoxic chemotherapies may increase the number of cancer stem cells. Angiogenesis inhibition has been described in vitro to have an impact on stem cells proliferation. We developed a proof of concept clinical trial to explore Bevacizumab-chemotherapy activity on breast cancer stem cells for patients treated in the neoadjuvant setting. Patients and Methods. Breast cancer patients requiring preoperative chemotherapy were included in this open-label, randomized, prospective, multicentre phase II trial. All received FEC-docetaxel combination for a maximum of 8 cycles, and patients randomized in the experimental arm received concomitant Bevacizumab (15 mg/kg Q3W). The primary endpoint was to describe aldehyde dehydrogenase (ALDH1, identified by immunohistochemistry) positive tumour cells rate before treatment and after the 4th cycle. Secondary objectives included safety, pathological complete response (pCR) rate, disease-free survival (DFS), relapse-free survival (RFS), and overall survival (OS). Results. Seventy-five patients were included from March 2010 to July 2012, including 50 in the experimental arm. More than 80% of patients received all planned chemotherapy cycles. ALDH1 expression could be assessed both before treatment and after the fourth cycle of chemotherapy for 32 patients. The absence of a significant increase (> 5%) in ALDH1+ cells rate after chemotherapy was demonstrated in the Bevacizumab arm (n=19, Median=-0.125, one-sided 95%CI=[-∞-0], p=0.001).Yet, the same was observed in the control arm (n=13, Median=-0.25, one-sided 95%CI=[-∞-0],, p=0.006). Grade 3 or 4 adverse events, including haematological, digestive, and cutaneous disorders, were observed for 94% of the patients in the experimental arm and 88% in the control arm. A non-significant increase in pCR was observed in the Bevacizumab arm (OR=2.24, 95CI [0.77-6.54], p=0.14), but survival was not improved (OS: p=0.89 for the whole cohort; DFS: p=0.45; and RFS: p=0.68 for non-metastatic cases) . ALDH1 status at inclusion was not correlated to efficacy. Conclusions. We observed that the rate of ALDH1+ tumour cells did not increase after Bevacizumab-based chemotherapy. However, as similar results were observed with chemotherapy only, Bevacizumab impact on breast cancer stem cells cannot be confirmed. Citation Format: Sabatier R, Charafe-Jauffret E, Pierga J-Y, Curé H, Lambaudie E, Houvenaeghel G, Ginestier C, Sfumato P, Extra J-M, Gonçalves A. AVASTEM – Stem cells inhibition by bevacizumab in combination with neoadjuvant chemotherapy for locally advanced breast cancers: A prospective proof of concept randomized phase II trial [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 P2-10-02.

The phase II AVASTEM trial explored the impact of chemotherapy-bevacizumab combination on breast cancer stem cells in the neoadjuvant setting. We aimed to identify biological features associated with preoperative chemotherapy efficacy and prognosis by analyses of circulating tumor cells (CTCs) and bevacizumab pharmacokinetics (PK). The main objective was to assess the prognostic (relapse-free survival and overall survival) and predictive (pathological complete response, pCR) values of CTCs (CellSearch technology) and bevacizumab PK (ELISA). Seventy-five patients were included. Out of them 50 received bevacizumab-chemotherapy and 25 received chemotherapy alone. CTC results were available for 60 patients and PK data for 29 patients in the experimental arm. The absence of CTC at inclusion was correlated to better outcome. Five-years overall survival (OS) was 91% for CTC-negative patients vs. 54% for CTC-positive cases (HR = 6.21, 95%CI (1.75&ndash, 22.06), p = 0.001, log-rank test). Similar results were observed for RFS with 5 y-RFS of 78% vs. 44% (HR = 3.51, 95%CI (1.17&ndash, 10.52), p = 0.017, log-rank test). However, CTC status at baseline was not predictive of pCR (p = 0.74). CTC status after one cycle was not a significant prognostic factor (HR = 1.56, 95%CI (0.19&ndash, 12.67), p = 0.68 for OS and HR = 2.76, 95%CI (0.60&ndash, 12.61), p = 0.17 for RFS, log-rank test). Bevacizumab serum levels could not predict pCR and survival. PK values were not associated with treatment-related toxicities. In conclusion, CTCs detection at baseline is a prognostic marker for breast cancer receiving a neoadjuvant chemotherapy-bevacizumab combination independently of tumor response.

International audience; Cancer management in the elderly is often considered as suboptimal, highly variable, and rarely evidence-based. Data are needed to understand decision-making processes in this population. A survey was performed in France to describe decision-making in gynaecologic patients over 70. It followed a three-step method: (1) 101 representative physicians questioned about treatment decision criteria; (2) simplified individual data were collected; (3) as well as detailed data patients receiving chemotherapy. This analysis refers to breast cancer subgroup of patients. Main decision criteria were performance status, comorbidities, and renal function. In adjuvant setting, the main concern was life expectancy, whereas it was quality of life in metastatic setting. Of the 631 patients entered in the simplified analysis, 41% had been evaluated by a geriatrician, 67% received chemotherapy. In the detailed analysis, patients older than 75 were more likely to receive a monochemotherapy and to be treated with weekly/divided dose. In adjuvant setting, respectively, 19, 55, and 26% of the patients were treated with regimen validated in the elderly, validated in a younger population, and not validated. A G-CSF was prescribed in 48% of the patients, as primary prophylaxis in 78 and in 41% of patients with a risk of febrile neutropenia \textless 10%. Geriatric covariates become an increasing concern in the decision-making process. This survey also suggests an insufficient use of validated chemotherapy regimens. To date, age remains a risk factor for heterogeneity in oncologic practice justifying a persistent effort for elaborating and disclosing specific recommendations.

Preclinical works have suggested cytotoxic chemotherapies may increase the number of cancer stem cells (CSC) whereas angiogenesis inhibition may decrease CSC proliferation. We developed a proof of concept clinical trial to explore bevacizumab activity on breast CSC. Breast cancer patients requiring preoperative chemotherapy were included in this open-label, randomized, prospective, multicenter phase II trial. All received FEC-docetaxel combination, and patients randomized in the experimental arm received concomitant bevacizumab. The primary endpoint was to describe ALDH1 (Aldehyde dehydrogenase 1) positive tumor cells rate before treatment and after the fourth cycle. Secondary objectives included safety, pathological complete response (pCR) rate, disease-free survival (DFS), relapse-free survival (RFS), and overall survival (OS). Seventy-five patients were included. ALDH1+ cells rate increase was below the predefined 5% threshold in both arms for the 32 patients with two time points available. Grade 3 or 4 adverse events rates were similar in both arms. A non-significant increase in pCR was observed in the bevacizumab arm (42.6% vs. 18.2%, p = 0.06), but survival was not improved (OS: p = 0.89; DFS: p = 0.45; and RFS: p = 0.68). The increase of ALDH1+ tumor cells rate after bevacizumab-based chemotherapy was less than 5%. However, as similar results were observed with chemotherapy alone, bevacizumab impact on breast CSC cells cannot be confirmed.

Objective To determine the possible effect of two homeopathic medicines, Ruta graveolens 5CH and Rhus toxicodendron 9CH, in the prevention of aromatase inhibitor (AI) associated joint pain and/or stiffness in women with early, hormone-receptor positive, breast cancer. Methods This prospective, unrandomized observational study was carried out between April and October 2014. Women were recruited in two groups, according to which of the two study centres they attended: one receiving homeopathy in addition to standard treatment (group H) and a control group, receiving standard treatment (group C). All women were treated with an AI. In addition, women in group H also took Ruta graveolens 5CH and Rhus toxicodendron 9CH (5 granules, twice a day) up to 7 days before starting AI treatment. The homeopathic medicines were continued for 3 months. Demographic and clinical data were recorded using a self-assessment questionnaire at inclusion (T0) and 3 months (T3). Primary evaluation criteria were the evolution of scores for joint pain and stiffness, the impact of pain on sleep and analgesic consumption in the two groups after 3 months of treatment. Results Forty patients (mean age 64.9 ± 8.1 years) were recruited, 20 in each group. Two-thirds of the patients had joint pain before starting AI treatment. There was a significant difference in the evolution of mean composite pain score between T0 and T3 in the two groups (−1.3 in group H vs. +3.4 in group C; p = 0.0001). The individual components of the pain score (frequency, intensity and number of sites of pain) also decreased significantly in group H. Nine patients in group C (45%) vs. 1 (5%) in group H increased their analgesic consumption between T0 and T3 (p = 0.0076). After 3 months of treatment, joint pain had a worse impact on sleep in patients in group C (35% vs. 0% of patients; p = 0.0083). The differences observed in the evolution of morning and daytime stiffness between the two groups were smaller (p = 0.053 and p = 0.33, respectively), with the exception of time necessary for the disappearance of morning stiffness which was greater in group C (37.7 ± 23.0 vs. 17.9 ± 20.1 min; p = 0.0173). Conclusion These preliminary results suggest that treatment with Ruta graveolens 5CH and Rhus toxicodendron 9CH may decrease joint pain/stiffness in breast cancer patients treated with AIs. A larger-scale randomized study is required to confirm these results.

International audience; Estrogen receptor-, progesterone receptor- and HER2-negative breast cancers, also known as triple-negative breast cancers (TNBCs), have poor prognoses and are refractory to current therapeutic agents, including epidermal growth factor receptor (EGFR) inhibitors. Resistance to anti-EGFR therapeutic agents is often associated with sustained kinase phosphorylation, which promotes EGFR activation and translocation to the nucleus and prevents these agents from acting on their targets. The mechanisms underlying this resistance have not been fully elucidated. In addition, the IL-17E receptor is overexpressed in TNBC tumors and is associated with a poor prognosis. We have previously reported that IL-17E promotes TNBC resistance to anti-mitotic therapies. Here, we investigated whether IL-17E promotes TNBC resistance to anti-EGFR therapeutic agents by exploring the link between the IL-17E/IL-17E receptor axis and EGF signaling. We found that IL-17E, similarly to EGF, activates the EGFR in TNBC cells that are resistant to EGFR inhibitors. It also activates the PYK-2, Src and STAT3 kinases, which are essential for EGFR activation and nuclear translocation. IL-17E binds its specific receptor, IL-17RA/IL17RB, on these TNBC cells and synergizes with the EGF signaling pathway, thereby inducing Src-dependent EGFR transactivation and pSTAT3 and pEGFR translocation to the nucleus. Collectively, our data indicate that the IL-17E/IL-17E receptor axis may underlie TNBC resistance to EGFR inhibitors and suggest that inhibiting IL-17E or its receptor in combination with EGFR inhibitor administration may improve TNBC management.

Purpose: EGFR is frequently overexpressed in cervical cancer, suggesting EGFR blockade as a promising treatment approach. Cetuximab, an anti EGFR antibody, used conjointly with radiochemotherapy, was feasible in first-line treatment of cervix carcinoma limited to the pelvis. Experimental Design: This randomized phase II trial enrolled 78 FIGO stage IB2–IIIB cervical cancer patients to either cisplatin-based radiochemotherapy alone (arm B, n = 38) or conjointly with a 6-week course of weekly cetuximab (arm A, n = 40). Brachytherapy was given to the pelvic mass. Primary endpoint was disease-free survival (DFS) at 2 years. EGFR expression and targeted sequencing were performed in 54 of 78 patients. Results: Cetuximab over a 6-week period did not improve DFS at 24 months. At 31 months median follow-up, DFS was not significantly different (P = 0.18). Complete response at 4 to 6 months was strongly predictive for excellent DFS (log-rank test; P < 0.001). PIK3CA, KRAS, and STK11 mutations were observed in 22%, 4%, and 2% of patients, respectively. No tumor with a PI3K pathway mutation showed complete response (0/8 in arm A and 0/6 in arm B), whereas 14 of 52 (27%) tumors without mutations did (P = 0.021). PI3K pathway-mutated tumors showed a trend toward poorer DFS (P = 0.06) following cetuximab (8/22) as compared with those following standard treatment only (6/18). Conclusions: Similar to patients with head and neck cancer, patients with cervical cancer showed no gain in DFS at 2 years following a combined treatment of cetuximab with radiochemotherapy. Although treatment tolerance and compliance were satisfactory, it remains to be demonstrated whether maintenance therapy with cetuximab could be beneficial in selected patient groups. Clin Cancer Res; 21(11); 2530–7. ©2015 AACR.

Objective: Neoadjuvant chemotherapy (NACT) allows for a more frequent use of breast-conservative surgery; it is also an in vivo model of individual tumor sensitivity which permits to determine new prognostic factors to personalize the therapeutic approach. Methods: Between 2000 and 2012, 318 patients with primary invasive breast cancer were treated with a median of 6 cycles of NACT; they received either an anthracycline-based FEC 100 protocol (31.1%), or anthracyclines + taxanes (53.5%), with trastuzumab if indicated (15.4%). Results: After a median follow-up of 44.2 months, the pathological complete response rate according to the classification of Chevallier et al. [Am J Clin Oncol 1993;16:223-228] was 19.3%, and overall (OS) and disease-free survival (DFS) at 10 years were 60.2 and 69.6%, respectively. Univariate analyses demonstrated that the Residual Disease in Breast and Nodes (RDBN) index was the most significant prognostic factor for OS (p = 0.0082) and DFS (p = 0.0022), and multivariate analyses mainly revealed that the residual tumor size, residual involved node number and post-chemotherapy Scarff-Bloom-Richardson (SBR) grading were the most significant prognostic factors. Conclusions: In a cohort of patients who were all homogeneously treated with some of the most common drugs for breast cancer, we demonstrate that NACT may provide additional prognostic factors and confirm the RDBN index. As this index allows for the prediction of survival with different breast cancer subtypes, we suggest that it should be calculated routinely to help clinicians to select patients who need adjuvant treatments.

Background: Decrease of circulating tumor cells (CTC) during treatment is an independent prognostic factor in metastatic breast cancer (MBC). We specifically evaluated the impact of CTC on brain metastasis outcome. Methods: HER2-positive MBC with brain metastasis not previously treated with whole-brain radiotherapy received firstline combination of lapatinib and capecitabine in a phase II study. CTC were detected at baseline and day 21 (CellSearch). Results: Median follow-up of the 44 analyzed patients was 21.2 months. The central nervous system objective response (CNS-OR) rate was 66%. At baseline, 20 of 41 assessable patients for CTC (49%) had ≥1 CTC (range 1–301, median 3) and 9 (22%) had ≥5 CTC. At day 21, 7 of 38 patients (18%) had ≥ 1C TC (P = 0.006, versus baseline), and CTC had disappeared in 11 patients. CNS-OR rate was significantly higher in patients with no CTC at day 21 [25 of 31 (80%) versus 2 of 7 (29%), P= 0.01]. The 1-year overall survival rate was 83.9% in patients with no CTC at day 21 versus 42.9% in patients with ≥ 1C TC (P= 0.02). Conclusions: This is the first report showing a correlation between CNS metastasis response, outcome and early CTC clearance under targeted treatment of HER2+ MBC. Clinical Trials number: NCT00967031.

Despite the fact that CNB has been progressively replaced by FNAC in the investigation of nonpalpable lesions or microcalcifications without a clinical or radiological mass lesion, FNAC has yet a role in palpable lesions provided it is associated with the triple diagnosis and experienced cytologist. In these conditions, FNAC is a safe, effective, economical, and accurate technique for breast cancer evaluation. Numerous literature reviews and meta-analyses illustrated the advantages and disadvantages of both methods CNB and FNAC. The difference does not seem significant when noninformative and unsatisfactory FNAC was excluded. Recently, cytological methods using liquid-based cytology (LBC) technology improve immunocytological and molecular tests with the same efficiency as classical immunohistochemistry. The indications of FNAC were, for palpable lesions, relative contraindication of CNB (elderly or frailty), staging of multiple nodules in conjunction or not with CNB, staging of lymph node status, newly appearing lesion in patient under neoadjuvant treatment, decreasing of anxiety with a rapid diagnosis, evaluation of biomarkers and new biomarkers, and chronological evaluation of biomarker following the neoadjuvant therapy response.

Over-expression of MUC1/CD227 is observed in 90% of breast tumors. Classical morphologic description and semi-quantitative digital measurement of MUC1 were performed from immunohistochemical stained slides of 123 routine histological samples. Measures of MUC1 expression showed statistical differences between non tumoral (NT) breast tissue and Ductal Carcinoma In Situ (DCIS) or infiltrating carcinoma (IC), p

Summary Background Brain metastases occur in 30–50% of patients with metastatic HER2-positive breast cancer. In the case of diffuse brain metastases, treatment is based on whole brain radiotherapy (WBRT). Few systemic options are available. We aimed to investigate the combination of lapatinib plus capecitabine for the treatment of previously untreated brain metastases from HER2-positive breast cancer. Methods In this single-arm phase 2, open-label, multicentre study, eligible patients had HER2-positive metastatic breast cancer with brain metastases not previously treated with WBRT, capecitabine, or lapatinib. Tretament was given in 21 day cycles: patients received lapatinib (1250 mg, orally) every day and capecitabine (2000 mg/m 2 , orally) from day 1 to day 14. The primary endpoint was the proportion of patients with an objective CNS response, defined as a 50% or greater volumetric reduction of CNS lesions in the absence of increased steroid use, progressive neurological symptoms, and progressive extra-CNS disease. All responses had to be confirmed 4 weeks after initial response. Efficacy analyses included all patients who received the study drugs and were assessable for efficacy criteria. This trial is registered with ClinicalTrials.gov, number NCT00967031. Findings Between April 15, 2009, to Aug 2, 2010, we enrolled 45 patients, 44 (98%) of whom were assessable for efficacy, with a median follow-up of 21·2 months (range 2·2–27·6). 29 patients had an objective CNS response (65·9%, 95% CI 50·1–79·5); all were partial responses. Of all 45 treated patients, 22 (49%) had grade 3 or grade 4 treatment-related adverse events, of which the most common were diarrhoea in nine (20%) patients and hand-foot syndrome in nine (20%) patients. 14 (31%) patients had at least one severe adverse event; treatment was discontinued because of toxicity in four patients. No toxic deaths occurred. Interpretation The combination of lapatinib and capecitabine is active as first-line treatment of brain metastases from HER2-positive breast cancer. A phase 3 trial is warranted. Funding GlaxoSmithKline-France and UNICANCER.

International audience; PURPOSE:Anemia affects most patients treated for cancer by chemotherapy. It is a known major contributor to fatigue and loss of quality of life and is likely to have a negative effect on prognosis and mortality from cancer. The main purpose of this study was to characterize the management of anemia and iron deficiency in a French oncology day-care center.METHODS:A retrospective study was conducted between May and November 2012 in the oncology day unit of the Jean Godinot Cancer Center (France). The 133 patients included were all over the age of 18 and being treated by chemotherapy and had mild, moderate, or severe anemia.RESULTS:Over half (58%) the patients were shown to be receiving no specific treatment for anemia. Iron balance was assessed in 71 patients and iron deficiency diagnosed in 37. Stepwise logistic regression showed that patients with severe to moderate anemia were nearly four times more likely to have an iron balance assessment than those with mild anemia (OR, 3.78; 95% CI, 1.84-7.76; P = 0.0003). Classical logistic regression shows that older patients (≥70) are three times less likely to have an iron balance assessment than patients

Background: Decrease of CTC level during treatment in MBC has been reported as an independent prognostic and predictive factor of patients’ outcome. Monitoring CTC in addition to clinical response criteria is currently evaluated in early clinical trials in various cancer types. We sought to evaluate the clinical interest of peripheral blood CTC for patients included in the LANDSCAPE study which assessed the efficacy of upfront systemic treatment with L+C for newly diagnosed brain metastasis. Methods: This analysis is a preplanned secondary endpoint of the LANDSCAPE study. Eligible pts had HER2+ MBC with BM not previously treated with WBR, C or L. Pts received L1250 mg/day and C2000 mg/m2/day, days 1–14, every 21 days. The primary endpoint was a centrally assessed CNS objective response (CNS-OR) defined as a ≥50% volumetric reduction of CNS lesions in the absence of increasing steroid use, progressive neurologic symptoms or progressive extra-CNS disease. CTC were detected in 7.5 ml of blood using the CellSearchSystem™, combining EpCAM immunomagnetic selection (IMS) followed by anti-cytokeratin (A45B/B3) fluorescently staining for CTC at baseline and at day (D) 21, before cycle 2. Results: From 04/2009 to 08/2010, 45 pts were enrolled, 41 were evaluable for CTC at baseline and 38 at D21. Median age was 56 (range 35 to 79). PS was >1 only in 2 pts. At baseline, 20/41 (48.8%) pts had ≥ 1CTC and 9 (22%) ≥ 5CTC (range 1–301, median 3). CTC were detected in pts with (18/37) or without disease outside SNC (2/6) (p=0.63). At a median follow-up of 10 months (range 2.9−16.5), median TTP was 6.0 months [95% CI 4.9; 7.4] vs. 4.3 [2.8; 5.9] months for pts without and with CTC at baseline respectively (p=0.14). After 21 days of treatment, a disappearance of CTC was observed in 11pts (31%). At D21, only 7 (18.4%) pts had ≥ 1CTC and 3 (8%) ≥ 5 CTC (p=0.006, D21 vs. baseline). In 43 evaluable pts, CNS-OR rate was 67% (95%CI 51–81), with a median time from inclusion to response of 1.8 month. Absence of CTC was not correlated with CNS-OR rate at baseline (17/21 (81%) vs. 11/19 (58%), NS). Strikingly, remaining positivity for CTC at D 21 (≥ 1CTC) was correlated with a poor response rate in CNS: 2/6 (33.3%) vs. 25/31 (80.6%) in pts with 0 CTC, p=0.03. Conclusions: Early decrease (at D 21) in CTC level is correlated with a high response rate in newly diagnosed BM to L + C and underlines the predictive value of this blood marker in MBC pts even for brain metastasis. Longer follow-up is needed to assess its prognostic value under antiHER2 targeted therapy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-06-12.

Resume Entre le 1 er fevrier 2010 et le 1 er mai 2010, une enquete postale a ete realisee en Champagne et dans le departement de l’Aisne aupres de 1 957 medecins generalistes (MG) repertories par les conseils departementaux de l’Ordre des medecins. Un seul envoi a ete realise et 705 medecins ont retourne le questionnaire rempli. Le taux de retour a ete de 36,6 %. Les medecins generalistes ont precise clairement la place qu’ils souhaitaient occuper dans la prise en charge du patient cancereux : depistage et prevention, diagnostic precoce et orientation du patient, suivi per- et post-therapeutique et accompagnement en phase terminale. Les principales difficultes observees etaient la lourdeur de la charge morale, le manque de temps et le ressenti d’une formation post-universitaire inadaptee. La mauvaise communication avec les cancerologues et la faiblesse des structures cancerologiques de proximite ont ete relevees par 24 % des generalistes. Cependant, il est clair que ce sont les generalistes les plus motives par la cancerologie qui ont repondu. L’enquete permet toutefois de cibler des besoins specifiques en formation pour le suivi a domicile des effets secondaires des therapeutiques actuelles et l’ensemble de la phase terminale et des soins de support. Les benefices theoriques retires par les patients porteurs de cancers sont evoques et discutes. Des propositions concretes visant a donner des perspectives d’actions de terrain pour les MG, assorties d’evaluations d’etape, sont envisagees.

La candidose oropharyngee (COP) est une pathologie frequente en cancerologie. Son impact est sous-estime par rapport aux traitements qui la favorisent: chimiotherapie, radiotherapie, corticoides. Des specialistes multidisciplinaires (oncologues, mycologues, infectiologues, ORL, stomatologues) se sont reunis pour elaborer des recommandations de prise en charge diagnostique et therapeutique de la COP selon une methodologie bien etablie et detaillee dans l’article. Trois populations ont ete etudiees: patientes traitees pour un cancer du sein, patients traites pour un cancer ORL et patients âges traites pour un cancer. Les grands principes issus de cette reflexion sont la recherche de facteurs favorisants, l’examen systematique et precis de la cavite buccale (le diagnostic de la COP est clinique) et la mise en route immediate d’un traitement antifongique qui doit prendre en compte l’augmentation des candidas non albicans et des candidas albicans resistants au fluconazole. Le traitement de premiere intention de la COP est local, et ce n’est qu’en cas d’echec d’un traitement bien conduit dont l’observance aura ete controlee qu’un prelevement mycologique est a envisager.

PET is a crucial technique in molecular imaging, allowing in vivo assessment and localization of pathological processes, thanks to its ability to detect very small amounts of radioactive molecules. This is of particular interest in oncology where abnormal metabolism or synthesis in tumor cells but also various tumor characteristics can be studied using this nuclear medicine technique. FDG is currently the most widely used tracer, nowadays essential in the management of various malignancies, with large applications in diagnosis, initial assessment, therapy monitoring, and recurrence detection. The combination of anatomical information provided by PET/CT further increased its interest. Beyond its spread use in daily practice, future applications of PET will involve other tracers than FDG and develop research applications in humans as well as in small animals.

Background Variable rates of HER2 protein overexpression and gene amplification have been reported in advanced ovarian cancers (AOC). Trastuzumab, tested only as a single agent, has been shown to achieve 7% response in heavily pretreated patients with AOC with 3+ and 2+ HER2 immunostaining by immunohistochemistry (IHC). The GINECO trial explored the combination of trastuzumab with paclitaxel and carboplatin in patients with resistant AOC (< 6 months) and HER2 gene amplification.

Purpose There is a need for new agents to treat metastatic breast cancer (MBC) in patients for whom anthracycline therapy has failed or is contraindicated. This study was conducted to assess the efficacy and safety of the novel antineoplastic, the epothilone B analog ixabepilone, in patients with MBC previously treated with an adjuvant anthracycline. Patients and Methods Patients were age ≥ 18 years and had received a prior anthracycline-based regimen as adjuvant treatment. Ixabepilone as first-line metastatic chemotherapy was administered as a 40 mg/m2 intravenous infusion during 3 hours every 3 weeks. The primary efficacy end point was objective response rate (ORR). Secondary efficacy end points included duration of response, time to response, time to progression, and survival. Results All 65 patients were assessable for response. Their median age was 52 years (range, 33 to 80 years). ORR was 41.5% (95% CI, 29.4% to 54.4%), median duration of response was 8.2 months (95% CI, 5.7 to 10.2 months), and median time to response was 6 weeks (range, 5 to 17 weeks). Median survival was 22.0 months (95% CI, 15.6 to 27.0 months). Treatment-related adverse events were manageable and mostly grades 1/2: the most common of these (other than alopecia) was mild to moderate neuropathy, which was primarily sensory and mostly reversible in nature. Conclusion Ixabepilone is efficacious and has a predictable and manageable safety profile in women with MBC previously treated with an adjuvant anthracycline.

Author Summary Background. Neoadjuvant treatment provides a unique opportunity to evaluate individual tumor sensitivity. This study evaluated whether a response-guided strategy could improve clinical outcome compared with a standard treatment. Methods. Overall, 264 previously untreated stage II–III operable breast cancer patients were randomized to receive either standard treatment (arm A, n = 131), consisting of fluorouracil, epirubicin, and cyclophosphamide (FEC100: 500, 100, and 500 mg/m2, respectively, for 3 cycles) followed by docetaxel (100 mg/m2 for 3 cycles), or adapted treatment (arm B, n = 133), beginning with 2 cycles of FEC100 and switching to docetaxel if tumor size decreased by Results. Similar results were observed for clinical response (objective response was 54% vs 56%, p = .18), breast conservation surgery (BCS; 67% vs 68%, p = .97), and pathological complete response rate (Chevallier classification: 14% vs 11%, p = .68; Statloff classification: 16% vs 13%, p = .82) between arms A and B. Similar toxicities were observed, even with unbalanced numbers of FEC100 and docetaxel courses. Conclusion. Adapted and standard treatments had similar results in terms of tumor response, BCS rate, and tolerability. Further survival outcome data are expected.

Background The objective of this phase II study was to attempt to maximize response and survival in patients with bulky, operable breast cancer by combining sequential neoadjuvant docetaxel to a semi-intensive anthracycline- based regimen. Patients and Methods Eligible patients (N = 53) were included to receive 4 cycles of docetaxel, followed by a maximum of 4 cycles of TNCF (THP [theprubican]—doxorubicin/vinorelbine/cyclophosphamide/5-fluorouracil) every 21 days before definitive surgery and radiation therapy. Results After a median number of 4 cycles of docetaxel and 2 cycles of TNCF, the overall clinical response rate was 81.1%, including a 13.2% complete remission rate and only 2 incidences of progressive disease. Breast conservation was achieved in 87% of patients. According to Chevallier classification, a pathologic complete response in breast and axilla was confirmed in 6 patients (11.3%) and in 9 patients (17%) using the Sataloff's classification. The important myelosuppression observed in this trial was expected but limited by the prophylactic use of growth factors. After a median follow-up of 40.4 months, only 5 recurrences were documented, with a median time to first recurrence of 12.8 months. Conclusion Despite disappointing results of this trial for pathologic complete response rate, possibly because of the order of drug administration, clinical response, breast conservation, and survival were optimized.

Summary The clinical benefits of endocrine therapy for patients with hormonosensitive breast cancer are well established. For many years, five years’ treatment with tamoxifen was the gold standard of adjuvant treatment. The recent development of new endocrine agents provides physicians with the opportunity to take a more effective therapeutic approach. Nevertheless, the success of neoadjuvant endocrine therapy is much more recent and less frequently reported in the literature. This article reviews the studies published on neoadjuvant endocrine treatment (tamoxifen and aromatase inhibitors). According to the literature, neoadjuvant endocrine therapy seems to be effective and well tolerated. The newer generation of aromatase inhibitors (letrozole, anastrozole, exemestane) appear to result in better overall response rates and more conservative surgery than tamoxifen. Patients with an ER Allred score of 6 and over are most likely to respond and gain clinical benefit. The optimal duration of neoadjuvant therapy has not yet been investigated in detail. These preliminary results are interesting and should be confirmed by further studies.

Prognostic factors are used to help clinical decision-making in selecting the appropriate treatment for individual patients. The purpose of this retrospective study was to identify one or more factors associated with overall survival (OS) and disease-free survival (DFS), in 710 patients with operable breast cancer, subjected to neoadjuvant chemotherapy followed by surgery, radiotherapy and adjuvant treatments. At a median follow-up of 7.6 years, univariate analysis showed that pathological complete response (pCR) was significantly related to survival (p < 0.003), as well as accepted prognostic factors, as SBR and MSBR grades, hormonal receptors or node involvement at surgery, who remained significant in our study (p < 0.001). The revised Nottingham prognostic index (NPI) and related indices (BGI, MNPI and MBGI) were also significantly associated to survival (p < 0.003). In multivariate analysis, node involvement and MSBR grade remained prognostic factors for OS and DFS (p < 0.0003 and p < 0.02, respectively). The MNPI and pCR were significantly related with OS (p = 0.04) and pts with hormonal receptor-positive tumours had a better DFS than others (p = 0.004). Among all clinical and pathological parameters, axillary dissection after neoadjuvant chemotherapy is still important to determine node involvement, a major prognostic factor. Moreover, MSBR grade seemed to be more accurate and predictive of long-term outcome than the standard SBR grade. It is concluded that, outside any other 'biological' factor, residual disease in breast and nodes must be strongly considered after an induction chemotherapy so as to choose adjuvant treatment for the individual patient.

Nitrosoureas possess some anti-tumor activity as a single agent in metastatic melanoma (MM). In a phase II trial, we evaluated the anti-tumor effects of cystemustine chemotherapy, a new nitrosourea, as a second-line treatment. Patients were required to have histologic evidence of disseminated MM and had failed in first-line chemotherapy. Treatment comprised cystemustine given at a dose of 60 mg/m 2 every 2 weeks by a 15-min infusion. From February 1997 to September 1999, 22 patients (median age 66 years) were enrolled and were assessable. Two complete responses, one partial response, three stable diseases and 16 progressions were observed, giving an overall response rate of 13.6%. Median duration of response was 10 months (range 4-63). Median survival of responders and non-responders was 11 and 4 months, respectively. However, hematological toxicity, particularly thrombopenia, was a limiting factor for one-third of patients. We conclude that cystemustine at 60 mg/m 2 is active in patients who progressed after one line of chemotherapy in advanced disease, and offers the possibility of complete responses and long durations of these responses.

Metastatic breast cancer (MBC) is incurable in most cases. While multiple treatments are available, the median survival is still approximately 2 years. We planned to assess the apparent impact of taxanes and aromatase inhibitors (letrozole, anastrozole, and exemestane) on the survival of 857 MBC patients for more than 30 years. Patients classed into decades by metastatic disease onset date did not survive significantly longer in recent years. This does not exclude some marked improvements with time: 1) in the same period, the disease-free interval for MO patients increased progressively and significantly with time; 2) the overall relapse ratio in MO patients was 20% lower in the 1990-2000 decade compared with 1980-1990; 3) since 1995, treatment for metastasis has been significantly lighter with periods of chemotherapy separated by hormonotherapy or observation in the case of negative receptors. Analyzing individual therapies, availability of taxanes since 1994 did not result in a significant increase of the overall survival. Conversely, receiving hormonotherapy was an important prognostic factor of the overall survival. Three groups were classified according to hormone therapy: group 1--tamoxifen, group 2--aromatase inhibitors, group 3--a combination of tamoxifen then aromatase inhibitors. The combination of tamoxifen then aromatase inhibitors favored a survival improvement from metastasis appearance to death compared with aromatase inhibitors alone and with tamoxifen alone. The sequential treatment of tamoxifen then aromatase inhibitors is presently discussed as a possible standard when used as adjuvant treatment. This sequential effect could also constitute a valuable concept for metastatic patients.

Influence of stress on immunity and pathogenesis relates to corticotropic axis: hypothalamus-hypophysis-surrenals (HHS). Its over-stimulation due to traumas during early childhood or before birth seems to generate brain abnormalities such as reduction of hippocampus volume. More typical of adult age, hypothalamus-pineal gland axis (HP), responsible for melatonin production, may be impaired because of chronic stress, mainly through sleep disturbances or addictive behaviours. Old age has been reported to produce same impairments. Circadian cycle of melatonin is closely related to immune functions and its disturbance seems to induce, among populations undergoing frequent changes of life rhythm, a significant raise of cancer incidence: night shift workers, air pilots... Stress then seems enable to increase cancer risk through its negative impact on HHS and HP axis and therefore on immunity. Immunotherapy, which was an interesting solution considering this, has not yield yet expected results. Upstream, other ways have been successfully investigated in prospective randomised trials, such as psychotherapeutic treatments, with positive effects on cellular immunity and survival. The ability to condition immune responses in animals allows thinking that hypnotherapy could also be used along with standard treatments.

Resume La melatonine est une petite molecule lipophile, secretee essentiellement dans la glande pineale. La synthese de cette hormone suit un rythme circadien avec un pic vers les 2–3 heures du matin. La melatonine possede de nombreux recepteurs dans l'organisme ce qui lui confere des fonctions multiples telles que la resynchronisation des rythmes biologiques, l'induction du sommeil, la vasoregulation mais aussi l'immunomodulation. De nombreuses experiences realisees dans ce domaine ont permis de decouvrir differentes interactions entre la melatonine et le systeme immunitaire, et surtout le lien qui existe entre la melatonine et la lutte anticancereuse de l'organisme via le systeme immunitaire. Des essais de phase II chez l'homme rapportent une diminution de la thrombocytopenie, une amelioration du taux de certaines cytokines et une augmentation de la reponse objective chez des patients atteints de cancer. Afin de confirmer et d'approfondir ces resultats, nous nous proposons de realiser un essai de phase II randomise melatonine versus placebo chez des patientes atteintes de cancers du sein metastatiques apres deux lignes de traitement.

We have investigated new drug combinations of potential clinical value for treatment of hormone-refractory prostate cancer. Combinations of paclitaxel, carboplatin and mitoxantrone, and combinations of these three drugs with compounds targeting important pathways for cancer progression, 13-cis-retinoic acid and chelerythrine, were assessed. The drugs combinations were incubated for 72 h in steroid-free conditions with two androgen-independent cell lines, DU145 and PC3. Cytotoxicity assay was performed using resazurin and Hoescht 33342. Synergism and antagonism were measured by the combination index, and calculated for each combination by the median-effect method. All six compounds exhibited cytotoxic effects when tested alone. Paclitaxel exhibited the highest and 13-cis-retinoic acid the lowest effect on both cell lines. Paclitaxel demonstrated synergism or additivity with 13-cis-retinoic acid in both cell lines, whereas antagonistic effects were observed when it was tested in combination with carboplatin. Chelerythrine showed additive effects with mitoxantrone in both cell lines and with paclitaxel in PC3 cells. Our results suggest that combination of paclitaxel and 13-cis-retinoic acid, and of chelerythrine with mitoxantrone and paclitaxel, may have clinical value for the treatment of hormone-refractory prostate cancer.

La chimiotherapie neoadjuvante du cancer du sein correspond a l’utilisation d’un traitement cytostatique systemique avant le traitement locoregional (chirurgie et/ou radiotherapie). Initiee dans les annees 1970 pour le traitement des formes localement avancees et/ou inflammatoires, la chimiotherapie d’induction s’est etendue au debut des annees 1980 aux cancers dits operables, de taille superieure a 3 cm et/ou de position centrale afin de permettre une chirurgie conservatrice plus frequente. Cet objectif est obtenu dans environ 75 % des cas sans augmentation du risque de rechute locale et sans effet deletere sur la survie globale, malgre le retard du traitement locoregional. La chimiotherapie neo–adjuvante a bien sur evolue au fur et a mesure de l’avenement des drogues majeures du cancer du sein que sont les anthracyclines, la vinorelbine et les taxanes. Mais a ce jour, aucun protocole ne s’est impose comme un standard inconteste. Toutefois, il semble que l’obtention d’une reponse complete clinique soit le meilleur garant pour eviter la rechute. Et cela semble ne pouvoir s’observer qu’apres 6 cycles, voire 8 cycles de chimiotherapie combinant au minimum 2 des 3 drogues majeures du traitement du cancer du sein dont le docetaxel qui parait, aujourd’hui, avoir une place incontournable surtout lorsqu’il est utilise en sequentiel apres un traitement a base d’anthracyclines en dehors de toute contre–indication cardiaque.

Un des atouts de la chimiotherapie neo-adjuvante est de permettre l’evaluation de la chimiosensibilite tumorale in vivo. La maladie residuelle evaluee apres chimiotherapie neo–adjuvante par le biais de la reponse histopathologique, le grade SBR, l’envahissement ganglionnaire ou par d’autres facteurs comme le grade NPI, semble etre un indicateur puissant de la chimioresistance du cancer du sein. Son evaluation doit se substituer aux parametres pronostiques classiques disponibles avant le traitement et permet, d’une maniere generale, d’identifier des sousgroupes de patients de pronostic plus ou moins favorable, pour lequel un traitement adjuvant adapte pourrait etre administre. En cas de non–reponse a la chimiotherapie prescrite, il est maintenant possible d’en tenir compte pour administrer d’autres medicaments antitumoraux « sans resistance croisee » avec les precedents. L’influence sur la survie d’une adaptation therapeutique durant la chimiotherapie neo–adjuvante reste cependant a evaluer.

Treating patients with anthracycline- and taxane-pretreated metastatic breast cancer (MBC) represents a significant challenge to oncologists. The tumour-activated oral fluoropyrimidine, capecitabine, is the only treatment approved for these patients. Our study evaluated the efficacy, safety and impact on quality of life (QOL) of capecitabine in this setting. Patients (n=126) with anthracycline- and taxane-pretreated metastatic breast cancer received capecitabine 1250 mg/m 2 twice daily, days 1–14, followed by a 7-day rest period. Median time to progression was 4.9 months (95% Confidence Interval (CI): 4.0–6.4). Thirty-five patients (28%) achieved an objective response (95% CI: 20–36%), including five (4%) complete responses. Median overall survival was 15.2 months (95% CI: 13.5–19.6 months). Capecitabine demonstrated a favourable safety profile, with a low incidence of treatmentrelated grade 3/4 adverse events. The most common adverse events were hand–foot syndrome and gastrointestinal effects. QOL assessment showed that capecitabine treatment was associated with an increase in mean Global Health Score. Capecitabine is active, well tolerated and improves the QOL of patients with anthracycline- and taxane-pretreated metastatic breast cancer. Based on the consistently high activity demonstrated in clinical trials, capecitabine has become the reference treatment in this setting. # 2003 Elsevier Ltd. All rights reserved.

The Nottingham prognostic index (NPI), based on tumour size in breast, node involvement and Scarff–Bloom–Richardson (SBR) grading, has been shown to constitute a definitive prognostic factor of primary operable breast cancer in the adjuvant setting. We performed a retrospective study to evaluate the prognostic value of this index in 163 patients after neoadjuvant chemotherapy. Secondly, we examined the influence on survival of a revised NPI, only based on residual tumour size in breast and SBR grading in 228 patients, and consequently called breast grading index (BGI). The prognostic value of these two indices was also evaluated by replacing the SBR grade with the MSBR grade, a French modified SBR grading; the modified NPI (MNPI) and modified BGI (MBGI) were, respectively, obtained in 153 and 222 patients. At a median follow-up of 9.3 years, survival was significantly related to these four indices (P

Docetaxel (Taxotere), alone or in combination with other anticancer agents, has proven efficacy in the first- and second-line treatment of metastatic breast cancer. This phase II study investigated the efficacy and tolerability of docetaxel as neoadjuvant chemotherapy in women with stage II-III primary operable breast cancer. Patients (n=88) were treated with six cycles of docetaxel at 100 mg m(-2) every 21 days, followed by definitive surgery and radiotherapy. After six cycles of docetaxel, the overall clinical response rate was 68.4% (CI 95%: 58.1-78.7%), including 19.0% complete remissions. Breast conservation was achieved in 72.4% of patients. A high pathological complete response (pCR) rate in breast was confirmed in 15 patients (19.8% (CI 95%: 10.8-28.8%)) on Chevallier's classification restricted to breast and in 27 patients (35.5% (CI 95%: 24.7-46.3%)) on Sataloff's classification. After a median follow-up of 30.8 months, 19 recurrences were documented with a median time to first recurrence of 17.3 months. Patients with stage III tumours had more recurrences than patients with stage II tumours (P=0.02). The principal toxicity of docetaxel is myelosuppression and 70.5% of patients developed grade III or IV neutropenia with 13.6% developing neutropenic sepsis. There was no case of severe cardiac toxicity, thrombocytopenia or any other serious adverse events. In conclusion, neoadjuvant docetaxel induces a high pCR and breast-conservation rate. Docetaxel monotherapy is a highly effective regimen that merits formal comparison with currently used combination regimens in a randomised phase III study.

PURPOSE: To study tolerability and efficacy of an intensified chronomodulated schedule of fluorouracil (5-FU) and l-folinic acid (l-FA) as first-line treatment of metastatic colorectal cancer, 5-FU was given near individually determined dose-limiting toxicity in a multicenter phase II trial. PATIENTS AND METHODS: One hundred patients (68 men and 32 women, median age 62 years, World Health Organization performance status ≤ 2) with previously untreated and inoperable metastases received chronomodulated daily infusion of 5-FU/l-FA (from 10:00 pm to 10:00 am with peak at 4:00 am). 5-FU dose was escalated from 900 to 1,100 mg/m2/d with fixed dose of l-FA at 150 mg/m2/d for 4 days every 14 days. RESULTS: 5-FU dose escalation was achieved in 66% of the patients. Grade 3 to 4 toxicities mainly consisted of nausea or vomiting (14% of patients and 1.5% of courses), hand-foot syndrome (38% of patients and 8% of courses), mucositis (26% of patients and 4% of courses), and diarrhea (21% of patients and 2.3% of courses). Objective response rate (ORR) was 41% (95% confidence interval, 31.5% to 50.5%). Twenty patients underwent metastases surgery; among these, 12 had a complete resection. Median progression-free survival was 7 months. Median survival was 17 months; 28% of the patients were alive at 2 years and 18.6% at 3 years. CONCLUSION: The ORR achieved with intensified chronomodulated delivery of 5-FU/l-FA was nearly twice as high as that earlier obtained by our cooperative group using less intensive 5-FU/FA chronotherapy.

Age is a risk factor for chemo-induced febrile neutropenia (FN). According to ASCO guidelines, granulocyte colony-stimulating factor (G-CSF) use should be considered for regimens leading to a 10- to 20-percent risk of FN.A survey was undertaken describing the prescription of G-CSF in routine practices by 101 French physicians for 791 patients ≥70 years, having breast or gynaecological cancers, and receiving chemotherapy.G-CSF was prescribed in 51% of the cases. A primary prophylaxis was prescribed in 90%, 59% and 36% of patients receiving regimens presenting a FN-risk of ≥20%, 10-20% and10%, respectively. Covariates associated with the use of G-CSF were adjuvant chemotherapy, 3- or 4-weekly regimens, and geriatric assessment. Validated risk factors of FN were rarely considered.The prescription of G-CSF was multi-factorial. The estimation of FN risk was mainly based on physician's experience, explaining differences between guidelines and routine practice.

Aims. The differences between the 2007 and the 2013 ASCO/CAP HER2 guidelines have been compared. We also discussed the potential consequences in our pathological practice.Material and Methodology. 189 HER2 fluorescence in situ hybridisation (FISH) tests were performed from 1016 preliminary HER2 immunohistochemical tests (IHC). All cases were reviewed and reclassed following the 2007 and 2013 ASCO/CAP recommendations.Results. The 2013 version decreased false-negative IHC (3/118 versus 1/54,P=ns) and created more 2+ IHC (40/186 versus 89/186,P=0.001) or more 3+ IHC (9/186 versus 39/186,P=0.001). One false-positive IHC was described for the 2013 version (0/9 versus 1/39,P=ns). Equivocal FISH was reduced (8/186 versus 2/186,P=ns). An estimation based on our data for 1000 patients showed a rise of our FISH tests for the control of 2+ IHC (180 tests for the 2007 version versus 274 tests for the 2013 version or FISH work overflow is +52%) and for the control of 2+/3+ IHC (300 for the 2007 version versus 475 for the 2013 version or FISH work overflow is +58%).Conclusions. The new 2013 ASCO/CAP guidelines have detected more HER2 positive cases but have increased the number of FISH tests.

Resume Introduction. – Le tamoxifene est un anti-estrogene triphenylethylenique de synthese utilise dans le traitement du cancer du sein. Les effets indesirables de ce medicament derive du diethylstilboestrol proviennent de son action agoniste partielle des estrogenes : ces effets « paradoxaux » concernent essentiellement l’uterus avec une augmentation du risque de cancer de l’endometre. Exegese. – Les auteurs rapportent deux cas cliniques de sarcome uterin survenu chez des femmes menopausees prenant du tamoxifene, a la dose conventionnelle de 20 mg/j depuis 38 et 42 mois, comme traitement hormonal adjuvant d’un cancer du sein. Il sˈagissait d’un leiomyosarcome et d’un sarcome stromal, tous les deux asymptomatiques decouverts lors d’un examen echographique transvaginale systematique. Conclusion. – A cote des nombreux adenocarcinomes endometriaux developpes sous tamoxifene, generalement bien differencies et reveles par des metrorragies, des tumeurs plus rares et plus agressives ont ete ponctuellement observees sans distinction d’un lien etiopathogenique particulier. Les modalites de surveillance du tamoxifene ne font pas encore l’objet d’un consensus. Dans les deux cas presentes ici, le sarcome uterin a ete detecte par echographie en l’absence de metrorragies post-menopausiques. Nous restons partisans d’un examen gynecologique avec echographie endovaginale une fois par an chez les patientes prenant du tamoxifene pour cancer du sein.

Resume Introduction. – Le syndrome de Stewart-Treves a ete defini par les auteurs eponymes comme un lymphangiosarcome cutane survenant sur un lymphœdeme chronique du bras apres mastectomie suivie ou non dˈirradiation. Exegese. – Le cas rapporte correspondait a un angiosarcome cutane, d’expression clinique nodulaire violacee, developpe sur un lymphœdeme du membre superieur neuf ans apres une mammectomie radicale avec curage ganglionnaire axillaire pour cancer du sein completee dˈune radiotherapie externe au cobalt. Les tests immunohistochimiques ont permis d’eliminer l’hypothese d’une metastase cutaneobrachiale d’origine mammaire et d’affirmer la nature vasculaire sarcomateuse de la tumeur. Conclusion. – Les cas de syndrome de Stewart-Treves devraient se rarefier avec le declin des mastectomies (supra-)radicales, les methodes de recherche du ganglion axillaire sentinelle et la systematisation des mesures de prophylaxie du lymphœdeme brachial sequellaire.

Purpose This trial evaluated the efficacy of maintenance erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, after first-line chemotherapy. Patients and Methods Eligible patients had high-risk International Federation of Gynecology and Obstetrics stage I or stage II to IV epithelial ovarian, primary peritoneal, or fallopian tube cancer and were not selected for EGFR expression. All patients underwent first-line platinum-based chemotherapy (CT) and showed no signs of progression at the end of CT. Patients were randomly assigned to maintenance erlotinib 150 mg orally daily for 2 years or to observation. EGFR immunohistochemistry (IHC), fluorescent in situ hybridization (FISH), and mutation analyses were performed in 318 patients. Results Between October 2005 and February 2008, 835 patients were randomly assigned (median follow-up, 51 months). Twenty-six percent of the patients stopped erlotinib as a result of adverse effects (of these, 67% were due to rash). For erlotinib and observation, respectively, the median progression-free survival was 12.7 and 12.4 months (hazard ratio [HR], 1.05; 95% CI, 0.90 to 1.23), and the median overall survival was 50.8 and 59.1 months (HR, 0.99; 95% CI, 0.81 to 1.20 months), respectively. No subgroup could be identified with improved effect of erlotinib, based on IHC or FISH for EGFR, or mutations in genes related to the EGFR pathway, or on rash during erlotinib therapy. However, patients with a positive FISH EGFR score had a worse overall survival (46.1 months) than those with a negative score (67.0 months; HR, 1.56; 95% CI, 1.01 to 2.40; P = .044). Global health/quality-of-life scores showed a significant difference during the first year (P = .0102) in favor of the observation arm. Conclusion Maintenance erlotinib after first-line treatment in ovarian cancer did not improve progression-free or overall survival.

The proinflammatory cytokine Interleukin 17A (hereafter named IL–17A) or IL-17A producing cells are elevated in breast tumors environment and correlate with poor prognosis. Increased IL-17A is associated with ER(−) or triple negative tumors and reduced Disease Free Survival. However, the pathophysiological role of IL-17A in breast cancer remains unclear although several studies suggested its involvement in cancer cell dissemination. Here we demonstrated that a subset of breast tumors is infiltrated with IL-17A-producing cells. Increased IL-17A seems mainly associated to ER(−) and triple negative/basal-like tumors. Isolation of tumor infiltrating T lymphocytes (TILs) from breast cancer biopsies revealed that these cells secreted significant amounts of IL-17A. We further established that recombinant IL-17A recruits the MAPK pathway by upregulating phosphorylated ERK1/2 in human breast cancer cell lines thereby promoting proliferation and resistance to conventional chemotherapeutic agents such as docetaxel. We also confirmed here that recombinant IL-17A stimulates migration and invasion of breast cancer cells as previously reported. Importantly, TILs also induced tumor cell proliferation, chemoresistance and migration and treatment with IL-17A-neutralizing antibodies abrogated these effects. Altogether these results demonstrated the pathophysiological role of IL-17A-producing cell infiltrate in a subset of breast cancers. Therefore, IL-17A appears as potential therapeutic target for breast cancer.

The preservation of erythrocytes is important during cytostatic chemotherapy. To study the synergistic effect of GM-CSF plus G-CSF on the red blood recovery, we looked at the kinetics of red blood cells, total reticulocytes and High Fluorescence Reticulocytes (HFR) from peripheral blood of 26 breast cancer patients, between 2 cycles of chemotherapy. After four days of TNCF (Thp-doxorubicin, Vinorelbine, Cyclophosphamide, Fluorouracil) treatment, 12 patients received either GM-CSF or G-CSF (D5-D16) and 14 received both of them (GM-CSF, D5-D14 and G-CSF, D10-D14). Our results showed a significantly lesser RBC decrease for patients receiving both CSFs versus only one CSF (p < 0.05). This greater RBC preservation was explained by the increase of HFR and total reticulocytes from D12 to D17 in the peripheral blood of patients receiving the two CSFs, with significantly values greater than that of patients receiving one CSF (p < 0.01) it showed that the synergistic GM-CSFplus G-CSF effect observed previously on PBPC results in a positive effect on erythroid lineage. GM-CSF plus G-CSF association exhibit in vivo multilineage (myeloid and erythroid) activity showing the interest to use different cytokines in combination to obtain a better hematological recovery after induction chemotherapy as well as a better quality of PBPC mobilization for transplantation after high-dose chemotherapy.