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Return to work (RTW) after cancer can be modulated by psychosocial factors, including a reordering of one's life values, with more emphasis on private life than work-life. This change in patients' outlook on work-life is however poorly understood.We used data from a French cohort (CANTO, NCT01993498) of women diagnosed with stage I-III primary breast cancer (BC) prospectively assessing life priorities between work and private life at diagnosis and 2 years after diagnosis. We identified women who reported a shift in life values toward private life, and we investigated the clinical, demographic, work-related, and psychosocial determinants of this change using logistic regressions.Overall, 46% (N = 1097) of the women had reordered their life priorities toward private life 2 years after diagnosis. The factors positively associated with this shift included being diagnosed with stage III BC, perceiving one's job as not very interesting, being an employee/clerk (vs. executive occupation), perceiving no support from the supervisor at baseline, perceiving negative interferences of cancer in daily life, and perceiving a positive impact from experiencing cancer. Depressive symptoms were negatively associated with this shift.After BC, there seems to be an important reordering of life values, with more emphasis on private life. This change is influenced by clinical determinants, but also by work-related and psychosocial factors.Stakeholders should consider this change in a patient's outlook on work-life as much as the classical physical late effects when designing post-BC programs to support RTW.

Abstract. Long-term adherence to adjuvant endocrine therapy (ET, tamoxifen and aromatase inhibitors) is paramount for patients with early-stage breast cancer. Adherence to adjuvant endocrine therapy is hampered by numerous side effects associated with sustained estrogen deprivation. We aimed to describe recent real-world patterns of therapy, patients’ discontinuations of ET, toxicities, quality of life (QoL) and to develop a predictive model of early ET discontinuation. Methods. We used the first 9595 patients of the French CANTO cohort (NCT01993498), to evaluate among 6238 premenopausal and postmenopausal patients with HR+/HER2- stage I-III BC, who were prescribed adjuvant ET: a. treatment patterns of adjuvant ET including change of ET prescription during the follow-up course b. ET-associated toxicities and c. impact on QoL. Independent variables included medical history and toxicities as measured by : Common Toxicity Criteria Adverse Events (CTCAE) v4, Patient-Reported Outcomes (PROs) including European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ-C30) and Breast Cancer Module (BR23), and Hospital Anxiety and Depression Scale (HADS). Treatment discontinuation and treatment change were determined on the basis of patient’s declaration and medical decisions reported in the CANTO eCRF. We used patient data at 4 months from therapy initiation to train and evaluate on a held-out test set a machine-learning model (gradient-boosted trees) that is predictive of time to early discontinuation i.e. permanent discontinuation before four years of additional therapy. Results. 4052 post-menopausal patients and 2186 premenopausal patients were included in this analysis. Median follow-up after ET initiation is 3 years and 2 months. 86% of post-menopausal patients were prescribed a non-steroidal AI initially and 92% of premenopausal patients received tamoxifen first. Discontinuation rate of the first adjuvant endocrine therapy at 1 year was 14% and 10% in premenopausal and post-menopausal patients, respectively. Among 741 post-menopausal and 340 premenopausal patients who started a second ET, discontinuation of the second prescribed adjuvant ET at 1 additional year of therapy is 30% in both populations. Patients who switched from a first adjuvant ET to a second or further one continued to have more treatment-related toxicities and associated decrements in QoL. Exclusions due to data completeness and outcome definition led to 5331 patients being used for the model (4264 in the training set and 1067 in the validation set). In that population, the permanent discontinuation rate at 3 years is 6%. Our prediction model of time to early discontinuation obtains a C-index of 0.78 in the held-out validation set. Conclusion. Tolerability and continued adherence to ET remains a challenge for many patients. Early discontinuation models may assist in identifying patients who are likely to interrupt their adjuvant ET. Adapted clinical management, including robust support and management of toxicities, as well as new and more tolerable adjuvant endocrine therapies may improve the clinical outcomes of these patients. Citation Format: Felix Balazard, Aurélie Bertaut, Élise Bordet, Stéphane Mulard, Julie Blanc, Nathalie Briot, Gautier Paux, Asma Dhaini Merimeche, Olivier Rigal, Charles Coutant, Marion Fournier, Christelle Jouannaud, Patrick Soulie, Florence Lerebours, Paul-Henri Cottu, Olivier Tredan, Laurence Vanlemmens, Christelle Levy, Marie-Ange Mouret-Reynier, Mario Campone, Keri J. S. Brady, Medha Sasane, Megan Rice, Catherine Coulouvrat, Anne-Laure Martin, Alexandra Jacquet, Ines Vaz-Luis, Christina Herold, Barbara Pistilli. Patterns of adjuvant endocrine therapy, discontinuations, toxicities and quality of life: Development of a model for early discontinuation using the CANTO cohort [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-13-08.

Background Palbociclib is indicated for the treatment of hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC), in combination with endocrine therapy. Emerging real-life data suggest that the efficacy of a palbociclib-based therapy is highly conserved. We report the Institut Curie hospital experience. Patients and methods We retrospectively reviewed all patients with HR + HER2- ABC treated with a palbociclib-based therapy as first or second line for ABC, with an initial prescription from November 2016 to December 2018. Clinical, laboratory and imaging data were retrieved from electronic records. Data lock was December 31st, 2019. Descriptive analyses, univariate and multivariate Cox regression analyses were performed. Results We included 310 consecutive patients. Median age was 61.8 years old. Palbociclib was prescribed in first line in 225 patients (72.6%). Before palbociclib-based therapy initiation, 122 patients (39.3%) were endocrine naive, 96 (31.0%) endocrine sensitive and 92 (29.7%) endocrine resistant. Median follow-up was 20.7 months. Median progression free survival (PFS) was 23.4 months (95%CI: 21.6-NR) in endocrine naive patients, 22.7 months (95%CI: 14.7-NR) in endocrine sensitive, and 13.4 months (95%CI: 10.7–20.8) in endocrine resistant. At 12 months from the initiation of palbociclib, 94.5% of patients were alive. By multivariate analysis, poor prognosis factors for PFS were identified in the endocrine naive/sensitive population: initial ECOG status 2, previous endocrine therapy for ABC, 3 metastatic sites or more. Toxicity profile was similar to previously published data. Conclusion In a non-selected population of patients with HR + HER2- ABC, the efficacy and safety data are strikingly similar to those previously reported., Highlights • Efficacy of palbociclib in advanced breast cancer in real-life is very close to that from the pivotal trials. • Long-term follow-up of patients treated with palbociclib show no cumulative adverse events.

Background: Nowadays, the assessment of health related quality of life (HRQOL) in women with breast cancer (BC) has become very important, with the improvement of their prognosis and the growing number of BC survivors. HRQOL is therefore a main endpoint in cancer therapeutic care and its improvement should be an important goal of BC treatment. The aim of this study was to assess HRQOL at the end of acute treatment in BC patients using data of the multicenter prospective French CANTO cohort. Methods: CANTO (NCT 01993498) is a multicenter prospective observational study (26 centers in France) whose main objective is to study the chronic toxicities of anticancer treatments in 12,000 women with localized stages I to III BC. HRQOL was assessed at baseline and at the end of acute treatments (surgery +/- radiotherapy +/- chemotherapy) using the EORTC-QLQ-C30 questionnaire and its BC specific module, the EORTC-QLQ-BR23 questionnaire. The EORTC-QLQ-C30 is composed of 30 items which allow generating 15 scales which are: 5 functional scales, 8 symptom scales, a global health status and a financial difficulties scale. The EORTC-QLQ-BR23 comprises 23 items and contains 4 functional scales and 4 symptoms scales. The minimal clinically important change score (MCID) was defined as a mean difference of at least 10 points in HRQOL scores between the baseline and the end of acute treatments (M0). Mixed linear model was used to assess the determinants of HRQOL For the dimensions with MCID. Results: from March 2012 to December 2014, 5801 BC patients were included in the CANTO cohort. The mean age at diagnostic was 57 years (SD=11.5) and 22.1 % of patients was single. Ninety percent of women had a good performance status and 79 % did not have comorbidities. Most of patients underwent surgery (99.7%), among which 77% by conservative surgery, and respectively 90.3 % were treated with radiotherapy, 80.2 % with hormone therapy and 53.3 with chemotherapy. Out of 23 dimensions, treatments for the disease did not impact the HRQOL of patients for global health status and 17 others dimensions of the QLQ-C30 and QLQ-BR23. However, with the means change score (MD) over 10 points, body image functional scale (MD= -14, p Conclusion: Results of this study did not show an impact of acute treatments for early stage BC on global health status of patients. The most affected dimensions, by the treatments, were body image, pain, breast symptoms, arm symptoms and upset by hair loss. Overweight, anxiety, depression, education level, hormonal status and chemotherapy were the main determinant of HRQOL. Citation Format: Oumar Billa, Olivia Dialla, Sarah Dauchy, Barbara Pistilli, Paul-Henri Cottu, Anne Lesur, Florence Lerebour, Olivier Tredan, Laurence Vanlemmens, Christelle Jouannaud, Christelle Levy, Charles Cecile, Anne Laure Martin, Sibille Everhard, Florence Joly, Charles Coutant, Fabrice Andre, Patrick Arveux, Sandrine Dabakuyo-Yonli. Health related quality of life at the end of acute treatments for early stage breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-17-04.

Background: The cyclin-dependent kinase (CDK)4/6 inhibitor RIBO is approved in combination with an aromatase inhibitor (AI) for HR+, HER2– ABC in postmenopausal women with no prior therapy for ABC, based on the MONALEESA-2 trial (Hortobagyi et al. NEJM 2016). Although a high proportion of patients with HR+, HER2– ABC are >65 years of age, older patients are often under-represented in clinical trials. Furthermore, treatment decisions may be complicated by comorbidities, functional status, and concurrent medications. Here, we report early safety results for patients ≥65 years of age enrolled in CompLEEment-1, an open-label, phase 3b trial evaluating RIBO+LET as first-line endocrine-based therapy in an expanded patient population. Methods: Patients with HR+, HER2– ABC, ≤1 line of prior chemotherapy (CT), and no prior endocrine therapy for ABC received RIBO (600 mg/day, 3 weeks on/1 week off) + LET (2.5 mg/day); men and premenopausal women received concomitant goserelin (3.6-mg subcutaneous implant every 28 days). The primary outcome was safety and tolerability. A pre-planned interim analysis was conducted ˜15 months after first patient first visit. Results: Of the first 1,008 patients enrolled who completed 56 days of follow-up or discontinued before the data cut-off date, 377 were ≥65 years of age. Of these, 157 (41.6%) were 65- Conclusions: Initial safety results from CompLEEment-1, from the first 56 days of follow-up, demonstrate the tolerability of RIBO+LET in older patients, consistent with the overall patient population. NCT02941926. Citation Format: Ring A, Borstnar S, Ferreira A, Azim HA, Cottu P, Lu J, Martin M, Zamagni C, Beck JT, Zhou K, Wu J, Menon L, De Laurentiis M. Ribociclib (RIBO) + letrozole (LET) in older patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2–negative (HER2–) advanced breast cancer (ABC): Preliminary subgroup results from the phase 3b CompLEEment-1 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 P6-18-16.

Background: Fatigue is a multidimensional symptom. It is recognised as one of the most burdensome and long-lasting adverse effects of cancer and cancer treatment. We aimed to characterise long-term fatigue trajectories among breast cancer survivors. Methods: We performed a detailed longitudinal analysis of fatigue using a large ongoing national prospective clinical study (CANcer TOxicity, NCT01993498) of patients with stage I–III breast cancer treated from 2012–2015. Fatigue was assessed at diagnosis (baseline), year-one, -two, and -four post-diagnosis. Baseline clinical, socio-demographic, behavioural, tumour- and treatment-related characteristics were available. Trajectories of fatigue and risk factors of trajectory-group membership were identified by iterative estimates of group-based trajectory models and multivariable logistic regression. Findings: Three trajectory-groups were identified for severe global fatigue (N=4173). Twenty-one per cent of patients were in the "High" risk group, having a risk estimate of severe global fatigue of 94·8% [95% confidence interval (CI) 86·6–100·0] at diagnosis and 64·8% [95% CI 59·2–70·1] at year four; 19% of patients clustered in the "Deteriorating" group with a risk estimate of severe global fatigue of 13·8% [95% CI 6·7%–20·9%] at diagnosis and 64·5% [95% CI 57·3–71·8] at year four; and 60% were in the “Low” risk group with a risk estimate of 3·6% [95% CI 2·5–4·7] at diagnosis and 9·6% [95% CI 7·5–11·7] at year four). The distinct dimensions of fatigue clustered in different trajectory groups than those identified by severe global fatigue, being differentially impacted by socio-demographic, clinical, and treatment-related factors. Interpretation: Our findings highlight the multidimensional nature of cancer-related fatigue and the complexity of its risk factors. This study helps to identify patients with increased risk of severe fatigue and to inform personalised interventions to ameliorate this problem. Funding: Susan G. Komen, French Foundation for Cancer Research, Foundation Gustave Roussy, and French Government (Agence Nationale de la recherche [ANR]). Declaration of Interest: None to declare. Ethical Approval: All study participants provided informed consent, and the national regulatory and ethics committee approved the study (ID-RCB:2011-A01095-36,11-039).

Background Treatment strategies for metastatic breast cancer (MBC) have made great strides over the past 10 years. Real-world data allow us to evaluate the actual benefit of new treatments. ESME (Epidemio-Strategy-Medico-Economical)-MBC, a nationwide observational cohort (NCT03275311), gathers data of all consecutive MBC patients who initiated their treatment in 18 French Cancer Centres since 2008. Patients and methods We evaluated overall survival (OS) in the whole cohort (N = 20 446) and among subtypes: hormone receptor positive, human epidermal growth factor 2 negative (HR+/HER2−; N = 13 590), HER2+ (N = 3919), and triple-negative breast cancer (TNBC; N = 2937). We performed multivariable analyses including year of MBC diagnosis as one of the covariates, to assess the potential OS improvement over time, and we described exposure to newly released drugs at any time during MBC history by year of diagnosis (YOD). Results The median follow-up of the whole cohort was 65.5 months (95% CI 64.6-66.7). Year of metastatic diagnosis appears as a strong independent prognostic factor for OS [Year 2016 HR 0.89 (95% CI 0.82-0.97); P = 0.009, using 2008 as reference]. This effect is driven by the HER2+ subcohort, where it is dramatic [Year 2016 HR 0.52 (95% CI 0.42-0.66); P < 0.001, using 2008 as reference]. YOD had, however, no sustained impact on OS among patients with TNBC [Year 2016 HR 0.93 (95% CI 0.77-1.11); P = 0.41, using 2008 as reference] nor among those with HR+/HER2– MBC [Year 2016 HR 1.02 (95% CI 0.91-1.13); P = 0.41, using 2008 as reference]. While exposure to newly released anti-HER2 therapies appeared very high (e.g. >70% of patients received pertuzumab from 2016 onwards), use of everolimus or eribulin was recorded in less than one-third of HR+/HER2– and TNBC cohorts, respectively, whatever YOD. Conclusion OS has dramatically improved among HER2+ MBC patients, probably in association with the release of several major HER2-directed therapies, whose penetrance was high. This trend was not observed in the other subtypes, but the impact of CDK4/6 inhibitors cannot yet be assessed., Highlights • OS of HER2+ MBC patients keeps improving over time [Year 2016 HR 0.52 (95% CI 0.42-0.66); P < 0.001, using 2008 as reference]. • This effect seems timely related to the release of drugs demonstrated to improve survival in clinical trials. • OS gains observed in real life among HER2+ MBC patients are at least equivalent to those observed in clinical trials. • YOD had no sustained impact on OS among patients with TNBC and luminal MBC. • The impact of CDK4/6 inhibitors cannot yet be assessed in this cohort.

The prospective multicenter COMET trial followed a cohort of 306 consecutive metastatic breast cancer patients receiving bevacizumab and paclitaxel as first-line chemotherapy. This study was intended to identify and validate reliable biomarkers to better predict bevacizumab treatment outcomes and allow for a more personalized use of this antiangiogenic agent. To that end, we aimed to establish risk scores for survival prognosis dichotomization based on classic clinico-pathological criteria combined or not with single nucleotide polymorphisms (SNPs). The genomic DNA of 306 patients was extracted and a panel of 13 SNPs, covering seven genes previously documented to be potentially involved in drug response, were analyzed by means of high-throughput genotyping. In receiver operating characteristic (ROC) analyses, the hazard model based on a triple-negative cancer phenotype variable, combined with specific SNPs in VEGFA (rs833061), VEGFR1 (rs9582036) and VEGFR2 (rs1870377), had the highest predictive value. The overall survival hazard ratio of patients assigned to the poor prognosis group based on this model was 3.21 (95% CI (2.33&ndash, 4.42), p &lt, 0.001). We propose that combining this pharmacogenetic approach with classical clinico-pathological characteristics could markedly improve clinical decision-making for breast cancer patients receiving bevacizumab-based therapy.

Background Palbociclib is a CDK4/6 inhibitor with demonstrated efficacy and safety in combination with endocrine therapy in advanced luminal breast cancer (LBC). We evaluated the respective efficacy and safety of chemotherapy and letrozole–palbociclib (LETPAL) combination as neoadjuvant treatment in patients with high-risk LBC. Patients and methods NeoPAL (UCBG10/4, NCT02400567) is a randomised, parallel, non-comparative phase II study. Patients with ER-positive, HER2-negative, Prosigna®-defined luminal B, or luminal A and node-positive, stage II–III breast cancer, not candidate for breast-conserving surgery, were randomly assigned to either letrozole (2.5 mg daily) and palbociclib (125 mg daily, 3 weeks/4) during 19 weeks, or to FEC100 (5FU 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2)×3 21-day courses followed by docetaxel 100 mg/m2×3 21-day courses. Primary end point was residual cancer burden (RCB 0–I rate). Secondary end points included clinical response, proliferation-based markers, and safety. Results Overall, 106 patients were randomised [median Prosigna® ROR Score 71 (22–93)]. RCB 0–I was observed in four and eight patients in LETPAL [7.7% (95% CI 0.4–14.9)] and chemotherapy [15.7% (95% CI 5.7–25.7)] arms, respectively. Pathological complete response rates were 3.8% and 5.9%. Clinical response (75%) and breast-conserving surgery rates (69%) were similar in both arms. Preoperative Endocrine Prognostic Index 0 scores (breast cancer-specific survival) were observed in 17.6% and 8.0% of patients in LETPAL and chemotherapy arms, respectively. Safety profile was as expected, with 2 versus 17 serious adverse events (including 11 grade 4 serious AEs in the chemotherapy arm). Conclusion LETPAL combination was associated with poor pathological response but encouraging clinical and biomarker responses in Prosigna®-defined high-risk LBC. Contemporary chemotherapy regimen was associated with poor pathological and biomarker responses, with a much less favourable safety profile. LETPAL combination might represent an alternative to chemotherapy in early high-risk LBC. Clinical Trial Number NCT02400567.

Purpose To determine the 3 years late toxicity among patients with non-metastatic breast cancer who received concurrent bevacizumab and locoregional radiotherapy. Material and methods This is a single-arm, multicentre, prospective study, of the toxicity of adjuvant concomitant association of bevacizumab and radiotherapy in patients with breast cancer. Toxicity was assessed by the Common Terminology Criteria for Adverse Events version 3.0 during the radiotherapy and follow-up clinics at 12 and 36 months after its completion. The study was designed to evaluate the toxicity at one year, 3 years and 5 years. Results Sixty-four patients were included from October 2007 to August 2010. All of them received concurrent adjuvant radiotherapy and bevacizumab (in 24 cases after primary systemic treatment). All patients received non-fractionated radiotherapy to breast or chest wall with or without irradiation of regional lymph nodes. Early toxicity has been previously reported. Median follow-up was 46.4 months (range: 18–77 months). Median age was 53 years old (range: 23–68 years). The 3-years overall survival was 93% (range: 87–100%). Evaluation of the toxicity at 3 years was available for 67% of the patients. There was a low rate of toxicity: 14% grade 1 pain, 9% grade 1 fibrosis, 2% grade 1 telangiectasia, 2% grade 1 paresis, 7% grade 1 lymphedema and 2% grade 3 lymphedema. No grade 4 toxicity was observed. No patient had a left ventricular ejection fraction below 50% at 3 years. Conclusions Concurrent bevacizumab with locoregional radiotherapy is associated with acceptable 3-years toxicity in patients with breast cancer.

Background In early breast cancer (BC), there has been a trend to escalate endocrine therapy (ET) and to de-escalate chemotherapy (CT). However, the impact of ET versus CT on the quality of life (QoL) of early BC patients is unknown. Here, we characterize the independent contribution of ET and CT on patient-reported outcomes (PROs) at 2 years after diagnosis. Patients and methods We prospectively collected PROs in 4262 eligible patients using the European Organization for Research and Treatment of Cancer QLQ-C30/BR23 questionnaires inside CANTO trial (NCT01993498). The primary outcome was the C30 summary score (C30-SumSc) at 2 years after diagnosis. Results From eligible patients, 37.2% were premenopausal and 62.8% postmenopausal; 81.9% received ET and 52.8% CT. In the overall cohort, QoL worsened by 2 years after diagnosis in multiple functions and symptoms; exceptions included emotional function and future perspective, which improved over time. ET (Pint = 0.004), but not CT (Pint = 0.924), had a persistent negative impact on the C30-SumSc. In addition, ET negatively impacted role and social function, pain, insomnia, systemic therapy side-effects, breast symptoms and further limited emotional function and future perspective recovery. Although CT had no impact on the C30-SumSc at 2-years it was associated with deteriorated physical and cognitive function, dyspnea, financial difficulties, body image and breast symptoms. We found a differential effect of treatment by menopausal status; in premenopausal patients, CT, despite only a non-significant trend for deteriorated C30-SumSc (Pint = 0.100), was more frequently associated with QoL domains deterioration than ET, whereas in postmenopausal patients, ET was more frequently associated with QoL deterioration, namely using the C30-SumSc (Pint = 0.004). Conclusion(s) QoL deterioration persisted at 2 years after diagnosis with different trajectories by treatment received. ET, but not CT, had a major detrimental impact on C30-SumSc, especially in postmenopausal women. These findings highlight the need to properly select patients for adjuvant ET escalation.

Introduction Les resultats de l’essai KATHERINE ont demontre un beneficie de Kadcyla® administre en adjuvant sur la survie sans maladie invasive (iDFS) compare a l’Herceptin®, chez des patientes atteintes d’un cancer du sein precoce HER2+ et ayant presente une maladie residuelle invasive au niveau du sein et/ou des ganglions (non-pathological Complete Response, non-pCR) apres traitement neoadjuvant conventionnel. Dans ce contexte, une etude observationnelle (KADor) a ete mise en place afin d’obtenir des donnees sur les caracteristiques et les modalites de prise en charge de ces patientes en France ainsi qu’une estimation de leur nombre. Objectifs L’objectif principal de l’etude etait de decrire les modalites de prise en charge, entre 2014 et 2018, des patientes presentant un cancer du sein HER2+ et relevant d’un traitement medical neoadjuvant initie en 2014. L’estimation de la population cible, de la proportion de patientes non-pCR et de l’iDFS ont ete evaluees en objectifs secondaires. Methodes Etude francaise, observationnelle, retrospective et multicentrique conduite sur les patientes atteintes d’un cancer du sein precoce HER2+ ayant initie un traitement neoadjuvant a base d’Herceptin® en 2014 suivi d’une chirurgie. Un registre a ete mis en place a partir des dossiers patients en vue de recueillir l’exhaustivite des patientes prises en charge dans les centres participants, puis une cohorte de suivi incluant les patientes traitees en adjuvant a base d’Herceptin®. Un redressement a ete applique afin d’assurer la representativite des centres au niveau national. La taille de la population cible nationale a ete estimee par un modele de Poisson base sur les donnees des centres actifs et permettant de predire l’effectif des patientes non-pCR en France metropolitaine. Resultats Sur les 460 centres hospitaliers francais (public/prive) sollicites, 57 ont participe a l’etude. La representativite geographique et par type de centre etait globalement assuree, puis controlee par le redressement. Les populations du registre et de la cohorte etaient respectivement de 306 et 301 patientes. L’âge moyen des patientes incluses dans la cohorte etait de 52 ans (± 12,6). Selon les classifications T (taille de la tumeur) et N (atteinte ganglionnaire) de la tumeur primitive au diagnostic, les patientes etaient majoritairement T2N0 (22,9 %), T2N1 (22,2 %) et T3N1 (13,3 %). Pres de 60 % des patientes presentaient des recepteurs hormonaux. Plus de la moitie (57,1 %) des patientes etaient non-pCR. Le nombre moyen de cycles d’Herceptin® etait de 13,2 cycles avec un intervalle de confiance a 95 % (IC95 %) de [12,8–13,6]. L’hormonotherapie a ete administree a 47,5 % des patientes avec IC 95 % [41,9 %–53,1 %]. A 36 mois, le taux d’iDFS etait estime a 84,1 % avec IC 95 % [79,1 %–87,9 %] sur l’ensemble de la cohorte et respectivement 88,1 % avec IC95 % [80,7 %–92,8 %] chez les patientes pCR et 81,0 % avec IC95 % [73,8 %–86,4 %] chez les non-pCR. Le nombre potentiel de nouvelles patientes sur un an, en France, atteintes d’un cancer du sein precoce HER2+ traitees a base d’Herceptin® en neoadjuvant suivi d’une chirurgie a ete estime a 2015 patientes avec IC95 % [1516–2871]. Parmi elles, le nombre de patientes non-pCR a ete estime a 1152 avec IC95 % [867–1642]. Conclusion L’etude KADor a permis de decrire en vie reelle la prise en charge therapeutique des patientes atteintes d’un cancer du sein precoce HER2+ ayant initie un traitement neoadjuvant a base d’Herceptin® en France suivi d’une chirurgie et d’un traitement adjuvant egalement a base d’Herceptin®. Ces resultats revelent une adequation entre la pratique courante et les recommandations de prise en charge.

Background The NEOSPHERE trial suggested that pertuzumab (P) added to a combination of docetaxel and trastuzumab (T) as a neoadjuvant therapy in HER2 positive breast cancer (HER2+ BC) patients (pts) significantly enhances pathological complete response (pCR) rates. Here, we report our institution experience, focusing on stage III tumors. Methods We reviewed clinical and pathological response (residual cancer burden, RCB) in 355 HER2+ BC treated between 2010 and 2017 with neoadjuvant chemotherapy combined with T (n = 291) or TP (n = 64). Results were adjusted according to clinical stage, hormone receptors (HR) status, and chemotherapy regimen. In a subset of 157 pts matched on clinical TNM stage and HR expression (T, n = 98; TP, n = 59), a baseline pathological biomarker analysis was performed to assess TILs, PTEN, FOXP3 and PD-L1 expression. Results Among 355 patients, tumor clinical stages were T3 -T4 for 40% vs. 72% of T and TP pts (p Conclusions This retrospective study did not suggest any benefit of neoadjuvant TP dual HER2 blockade regarding pathological response for stage III HER2+ BC. Baseline pathological expressions of PTEN, FOXP3, TILs, PD-L1 did not correlate with pathological response. Legal entity responsible for the study Institut Curie. Funding Institut Curie. Disclosure All authors have declared no conflicts of interest.

Purpose Several studies showed a breast cancer downstaging due to screening. A first national survey was conducted in France in 2001–2002 to evaluate in the current clinical practice the clinicopathological features and treatments of 1049 firstly operated breast cancers. In order to assess the impact of the national screening program implemented in all regions in France in 2004, a new survey was performed in 2007–2008. Material The new survey included 1433 firstly operated breast cancers prospectively collected. These new data were compared to the results of the first national survey. Results According to TN classification, we found in the second survey T0: 27.6%, T1: 48.6%, T2: 21.3%, T3T4: 3.8% and Tx: 0.7%. Infiltrating ductal and lobular carcinomas represented 80% and 13% of tumours. Hormone receptors were positive in 85.3% and Her-2 overexpressed in 12.4% of tumours (83.9% and 20.6% in the first survey); 68.2% and 32% were pN0 and pN1-3. Lumpectomy and mastectomy were performed in 77% and 23% of the cases. Axillary dissection, sentinel node biopsy or both were performed in 42.6%, 41% and 16.4% of the cases, respectively. Radiotherapy, chemotherapy, hormonotherapy and trastuzumab were given to 93%, 51%, 83% and 9.3% of the patients. Compared with the results from the first survey, we found an increase of infraclinical lesions (T0 from 8.4 to 27.6%) and a wide decrease of pN+ rate (from 44% to 32%). The mastectomy rate was constant (23%), as well as radiotherapy use, whereas chemotherapy use decreased from 62.8 to 55.6%. Conclusion A complete national screening coverage clearly provides a favourable modification of breast cancer clinicopathological features. Both locoregional and adjuvant treatments were greatly downscaled.

Background The role of tumor-infiltrating lymphocytes (TILs) in breast cancer has been extensively studied over the last decade. High TILs levels have been associated with pathological response rate in the neoadjuvant setting and with better outcomes in the adjuvant setting. However, little attention has been paid to changes in TILs and residual TIL levels after neoadjuvant chemotherapy (NAC). We investigated TIL levels before, after chemotherapy, and their dynamics during treatment; and we assessed the correlation of these levels with response to NAC and prognosis. Materials and methods We identified 175 patients with primary HER2-positive breast cancers receiving NAC+/− trastuzumab between 2002 and 2011. Microbiopsy specimens and paired surgical samples were evaluated for stromal lymphocyte infiltration. Univariate and multivariate analyses were carried out to assess the association of clinical and pathological factors with pathological complete response (pCR) and disease-free survival. Results Baseline TIL levels were not significantly associated with pCR. TIL levels decreased during treatment in 78% of the patients. The magnitude of the decrease was strongly associated with pCR. After chemotherapy, TIL levels were high in tumors displaying aggressive patterns (high residual cancer burden score, mitotic index >22, tumor cellularity >5%). In the population with residual disease, TIL levels >25% at the end of NAC were significantly associated with an adverse outcome (TILs >25%, HR = 7.98, P = 0.009) after multivariate analyses including BMI, post-NAC mitotic index and tumor grade. Conclusion A decrease in TIL levels during chemotherapy was positively associated with response to treatment. In tumor failing to achieve pCR, post-NAC lymphocytic infiltration was associated with higher residual tumor burden and adverse clinical outcome. Further studies are required to characterize immune infiltration in residual disease to identify candidates who could benefit from second-line therapy trials including immune checkpoint inhibitors.

Background CNS metastases are a risk in pts with breast cancer, with brain metastases diagnosed in 10-20% of pts. RIB, an oral, selective CDK4/6 inhibitor, is approved for use in combination with endocrine therapy (ET) in women with HR+, HER2– ABC in multiple countries. Here, we present a subgroup analysis of pts with CNS metastases from CompLEEment-1 (NCT02941926), an open-label, phase 3b trial evaluating RIB + LET as first-line therapy in an expanded population. Methods Pts (N = 3,246) with HR+, HER2– ABC and no prior ET for ABC received RIB (600 mg/day, 3 weeks on/1 week off) + LET (2.5 mg/day); concomitant goserelin (3.6 mg every 28 days) or leuprolide (7.5 mg every 28 days) was used in men and premenopausal women. In this subgroup analysis of 50 pts with CNS metastases, we assessed the primary outcomes (safety and tolerability) and time to progression (TTP), overall response rate (ORR), and clinical benefit rate (CBR). Results In pts with CNS metastases, the median duration of follow-up was 10.35 months and median duration of exposure to RIB was 7.8 months. Adverse events (AEs) were reported in 48 (96%) pts; 46 pts had treatment-related AEs. Grade 3/4 AEs were reported in 34 (68%) pts; 4 severe AEs were reported. There was 1 treatment-related fatal AE (sepsis). The most common all-grade AEs were neutropenia (52%), nausea (36%), and fatigue (26%). The most common grade 3/4 AEs were neutropenia (40%), neutrophil count decreased (14%), leukopenia (6%), and increased AST (6%) and ALT (6%). No neurological AEs were recorded. Seventeen (34%) pts had ≥ 1 dose reduction of RIB, 12 due to AEs, and 18 (36%) pts permanently discontinued treatment, 5 due to AEs. Median TTP was 16 months (95% CI, 16.0-NE) in pts with CNS metastasis; treatment of 32 (64%) pts was ongoing by cut-off date. For pts with measurable disease, ORR was 41.2% (95% CI, 24.6-59.3%) and CBR was 61.8% (95% CI, 43.6-77.8%). Conclusions This subgroup analysis from CompLEEment-1 supports the safety and efficacy of RIB + LET in pts with CNS metastasis. Additional patient follow-up is ongoing. Clinical trial identification NCT02941926. Editorial acknowledgement Medical editorial assistance was provided by Heyuan Sun, PhD, of Healthcare Consultancy Group, LLC, and funded by Novartis Pharmaceuticals Corporation. Legal entity responsible for the study Novartis. Funding Novartis Pharmaceuticals. Disclosure M. De Laurentiis: Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy: Eli Lilly; Honoraria (self), Advisory / Consultancy: Amgen. P. Marchetti: Advisory / Consultancy: Novartis; Advisory / Consultancy: BMS; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Incyte; Advisory / Consultancy: Molteni; Advisory / Consultancy: Roche; Advisory / Consultancy: MSD. F.P. Duhoux: Research grant / Funding (institution): Novartis; Honoraria (institution): Roche; Honoraria (institution): Pfizer; Honoraria (institution): AstraZeneca. All other authors have declared no conflicts of interest.

Background In this study we aimed to examine the independent effect of baseline QoL and persistent CRT among pts with early BC. Methods We included data stage I-III BC pts treated with chemotherapy who were included in the CANTO prospective cohort study (NCT-01993498) from 03/2012 to 12/2014. The primary outcome was CRT defined as the presence at 3-6 months after the end of treatment, of any of the following toxicities (NCI-CTC-AE): infection, venous or arterial thrombosis, neurological G2-4, digestive G3-4 or pulmonary toxicities G3-4). Treatment deliver including chemotherapy dose reductions were also examined. The independent variable of this study was baseline Qol defined by the EORTC QLQ-C30 subscales of general global health status (GHS) ( Results Among 3079 BC pts included in this analysis, 33% received neoadjuvant and 77% adjuvant treatment. Median age at diagnosis was 53 years, median BMI= 25 kg/m2, 94% of patients had a PS = 0 and 83% stage I-II disease. Pts reported on average a good GHS = 68 (±19) and PF = 90 (±14). GHS and PF were higher in women with better performance status PS = 0 vs 1+, (68 vs 60 p Conclusions Global and physical QoL before BC treatments are independently associated with CRT. QoL should be assessed before any treatment to identify patients at risk CRT. Clinical trial identification NCT01993498. Legal entity responsible for the study UNICANCER/Villejuif, France, 94805 Principal Investigator: Fabrice Andre Gustave Roussy – Villejuif. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

512 Background: We recently witnessed a trend to de-escalate CT and escalate ET in adjuvant BC treatment (tx). However, there has been limited prior research investigating the differential impact on QoL of tx classes. We aimed to test the impact of CT and ET on QoL PROs 2 yrs after diagnosis (dx). Methods: CANTO (NCT01993498) is a multicenter prospective longitudinal study of stage I-III BC pts that characterizes long-term toxicities of BC tx. For this analysis we included 4262 pts recruited from 2012-14. QoL was extensively evaluated using the EORTC QLQ C30 and BR23. Linear regression modeling was performed, adjusting for demographic and clinical factors, with use of CT and/or ET as independent variables. Analyses were stratified by menopausal status due to different tx patterns and sequelae of CT. Results: Median age at dx was 56 yrs, 63% of pts were post (PostM) and 37% premenopausal (PreM), 80% had Charlson score 0, 91% stage I-II. 26% received mastectomy, 52% CT (preM 68%, postM 44%; 86% anthracycline+taxane) and 82% ET (preM 89% tamoxifen; postM 88% aromatase inhibitor). 32% preM pts had menses 1 year after ET initiation. Overall, QoL deteriorates 2 yrs after dx. ET negatively impacts more QoL domains than CT at 2 yrs. Also, young age, smoking, income, aggressive local tx and physiological distress are often associated with low QoL. In the stratified analyses, in postM pts, mostly ET (not CT) is associated with deteriorated QoL. In contrast, in preM pts, mostly CT (not ET) is associated with deteriorated QoL. Table shows eg of associations. Conclusions: In a large prospective cohort of BC survivors, detrimental QoL 2 yrs after dx is mostly associated with ET; however, negative effects of CT persist on preM. This differential effect on QOL should be considered when choosing optimal adjuvant therapy and appropriate selection of pts for ET escalation should be a research priority. [Table: see text]

Background: Ex vivo colospheres have been previously characterised as a colorectal cancer (CRC) well-rounded multicellular model, exclusively formed by carcinoma cells, and derived from fresh CRC tissue after mechanical dissociation. The ability to form colospheres was correlated with tumour aggressiveness. Their three-dimensional conformation prompted us to further investigate their potential interest as a preclinical cancer tool. Methods: Patient-derived CRC xenografts were used to produce numerous colospheres. Mechanism of formation was elucidated by confocal microscopy. Expression analysis of a panel of 64 selected cancer-related genes by real-time qRT–PCR and hierarchical clustering allowed comparison of colospheres with parent xenografts. In vitro and in vivo assays were performed for migration and chemosensitivity studies. Results: Colospheres, formed by tissue remodelling and compaction, remained viable several weeks in floating conditions, escaping anoikis through their strong cell–cell interactions. Colospheres matched the gene expression profile of the parent xenograft tissue. Colosphere-forming cells migrated in collagen I matrix and metastasised when subrenally implanted in nude mice. Besides, the colosphere responses to 5-fluorouracil and irinotecan, two standard drugs in CRC, reproduced those of the in vivo original xenografts. Conclusion: Colospheres closely mimic biological characteristics of in vivo CRC tumours. Consequently, they would be relevant ex vivo CRC models.

Aims: HER2 gene amplification is observed in up to 15% of breast carcinomas. In a rare subset of breast cancers classified as HER2-positive by immunohistochemistry and in situ hybridisation, HER2 overexpression and gene amplification are restricted to a subset of >30% but not all cancer cells. Here we sought to characterise the repertoire of gene copy number aberrations and somatic mutations in the HER2-positive and HER2-negative components of cases with heterogeneous HER2 overexpression and gene amplification. Material and methods: Cases diagnosed as HER2 positive but with >30% but Results: Twelve cases yielded sufficient DNA for aCGH analysis. Tumours were preferentially ER positive (83%) and of histological grade 3 (67%). The HER2-positive and HER2-negative components of all cases shared most of the copy number aberrations. A pairwise comparison of the genomic profiles of the two components from each case revealed that in ten of the twelve cases, copy number aberrations in addition to 17q12 amplification encompassing the HER2 gene locus were restricted to one of the two components. Exome sequencing of two cases suggested that the HER2-positive and HER2-negative components from each case harboured >30 somatic mutations in common, including identical TP53 somatic mutations in both components of each case. The HER2-negative component of one of the cases displayed a somatic mutation in NRG2, an ERBB receptor ligand, and the HER2-negative component of the other case harboured a mutation in PTTG1IP, a proto-oncogene with putative oestrogen receptor elements. Conclusions: Our results demonstrate that in HER2-positive breast cancers with heterogeneous HER2 gene amplification, the HER2-positive and HER2-negative components are clonally related. The distinct genomic profiles of HER2-positive and HER2-negative components, however, suggest that, at least in some of these cases, HER2 amplification may constitute a relatively late event in tumour evolution. Exome sequencing revealed mutations restricted to the HER2-negative components of HER2-positive tumours with heterogeneous HER2 overexpression/gene amplification, which may constitute potential drivers in the absence of HER2 overexpression/gene amplification. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD05-08.

Background: Trials have shown benefit of adjuvant trastuzumab (TZM) for node-positive (N+) or T1c+ HER2−positive breast carcinomas. Methods: Retrospective series in 6 french cancer centers from 2000 to 2010 of T1abN0M0 HER2 positive breast carcinomas. Multifocal tumors were excluded. Results: Two hundred five N- cases were retrieved. Median size was 8 mm (range, 2 to 10 mm), 51 were T1a (25%), 152 tumors were T1b; 120 tumors (59 %) exhibited significant hormonal receptors (HR) expression. All patients had surgery, 65 % (n= 133) had a local irradiation. Ninety percent of HR+ patients (108/120) received hormonotherapy: 77 received aromatase inhibitors (AI) upfront or sequential; 23 received tamoxifen (TAM) alone 13 received LHRH agonists alone or in combination with TAM or AI. Forty-nine percent (n= 101) had chemotherapy (CT) (Anthracycline alone for 41 cases, taxane alone for 31 cases, sequential A/T for 28 cases and concurrent for 1 case), associated with TZM in 90 cases. TZM was administered without chemotherapy in 3 cases. Decision of adjuvant CT and/or TZM was associated with (all p Conclusion: T1abN0M0 HER2 positive tumors have a significant risk of recurrence which could be avoided by adjuvant chemotherapy associated with TZM. Interestingly, there were no differences in the risk of recurrence between T1a and T1b. Adjuvant chemotherapy associated with TZM should not only be discussed in T1bN0 HER2−positive tumors but also in T1aN0 HER2−positive cases. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-18-03.

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.

Resistance to endocrine therapy is a major complication of luminal breast cancer and studies of the biological features of hormonal resistance are limited by the lack of adequate preclinical models. The aim of this study is to establish and characterize a panel of primary human luminal breast carcinoma xenografts, and to evaluate their response to endocrine therapies. Four hundred and twenty-three tumor fragments obtained directly from patients have been grafted in the interscapular fatpad of Swiss nude mice. After stable engraftment with estradiol supplementation, xenografted tumors have been validated by conventional pathology and immunohistochemistry examination, and additional molecular studies. In vivo tumor growth and response to different endocrine treatments were evaluated. We have engrafted 423 tumors including 314 ER+ tumors, and 8 new luminal breast cancer xenografts have been obtained (2.5%). Tumor take was much lower for luminal tumors than for non-luminal tumors (2.5 vs. 24.7%, P < 0.0001), and was associated with two independent criteria, i.e., ER status (P < 0.0001) and a high grade tumor (P = 0.05). Histological and immunohistochemical analyses performed on patient’s tumors and xenografts showed striking similarities in the tumor morphology as well as in the expression level of ER, PR, and HER2. Response to hormone therapy, evaluated in 6 luminal models, showed different sensitivities, thus exhibiting heterogeneity similar to what is observed in the clinic. We have established a panel of primary human luminal breast cancer xenografts, recapitulating the biological and clinical behaviors of patient tumors, and therefore suitable for further preclinical experiments.

Resume Le cancer du sein est la cause la plus frequente de meningite carcinomateuse (MC) parmi les tumeurs solides. Cette serie monocentrique rapporte les caracteristiques de 91 patientes presentant une meningite carcinomateuse d’un cancer du sein traite par methotrexate intrathecal (MTX) entre 2000 et 2007. Un traitement intrathecal par : MTX (15 mg/j ; j1 a j5), depomedrol (40 mg ; j1) et acide folinique (12 mg IV ou 25 mg PO ; j1 a j5) etait administre toutes les deux semaines. La survie des patientes a ete analysee en fonction des caracteristiques de leur tumeur et de la reponse clinique et biologique au traitement. La survie mediane etait de 4,5 mois (0-53). En analyse multivariee, les facteurs de mauvais pronostic lors du diagnostic sont : l’OMS > 2 ( p = 0,006, RR = 0,33 [0,15-0,71]), plus de trois lignes de chimiotherapie avant le diagnostic ( p = 0,03, RR = 0,40 [0,19-0,93]), l’absence de recepteurs hormonaux sur la tumeur initiale [ p = 0,02, RR = 0,4 [0,19-0,90]) et un dosage eleve du cyfra-21-1 dans le LCR ( p = 0,048, RR = 0,09-0,99). La progression clinique apres un cycle et la reponse biologique apres deux cycles etaient correles de maniere independante a la survie globale ( p p = 0,003, RR = 3,6 [1,5-8,5], respectivement). Un score ayant pour but de definir trois groupes de patientes est propose. Conclusion Le pronostic des patientes atteint de MC est mauvais mais 25 % des malades sont encore en vie a un an. Ce score pronostique pourrait aider a la decision therapeutique apres avoir ete valide dans d’autres etudes cliniques.

OBJECTIVES: To determine in a population of metastatic breast cancer the incidence of wound dehiscence after placement of an implantable venous access device (VAD) in patients treated with bevacizumab, observe the optimum interval between placement and initiation of treatment and study the risk of catheter thrombosis. PATIENTS AND METHODS: Between 1/1/2007 and 31/12/2009, this study enrolled all VADs placed by 14 anesthetists: 273 VADs in patients treated by bevacizumab for metastatic breast cancer and 4196 VADs in patients not treated by bevacizumab. The medical charts of the 266 metastatic breast cancer patients treated with bevacizumab between 1/1/2007 and 31/12/2009 were reviewed up until 1/3/2010. A VAD was placed in all patients (goal standard in our institution). 7 patients in whom the VAD was inserted in another institution were excluded from this study. The VAD was removed and replaced in 14 patients with continuation of bevacizumab after replacement of the VAD RESULTS: 1 patient was lost to follow-up. Thirteen cases of wound dehiscence occurred in 12 patients requiring removal of the VAD (5,1 %). All cases of dehiscence occurred when bevacizumab was administered during the first 7 days after VAD placement. Bevacizumab therapy was initiated less than 7 days after VAD placement in 150 cases, requiring removal of the device in 12 patients (8.6%). The risk of dehiscence was the same from 0 to 7 days. In parallel, the VAD wound dehiscence rate in patients not receiving bevacizumab was 8/4,197 (0.19%) (Fisher's test significant, P The other indications for VAD removal were end of treatment: 3 (0,91 %), mechanical problem other than thrombosis: 6 (1,8 %), local infection without wound dehiscence: 1 (0,31%). Bevacizumab was permanently discontinued in 5 patients related to wound dehiscence and in 1 patient due to extensive skin necrosis. Bevacizumab was continued in the other 7 patients. CONCLUSION: The risk of VAD thrombosis does not require any particular primary prevention. These data suggest the need to observe an interval of at least 7 days between VAD placement and initiation of bevacizumab therapy. Poor healing is a major complication of VAD, interfering with continuation of chemotherapy and the patient's subsequent management, resulting in a real risk of loss of chance. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-16-09.

During the past decade, molecular signatures allowed a better classification of breast carcinoma and a better evaluation of their prognosis. However, we still need predictive factors of treatment and /or prognosis factors specific of each patient. Regarding hormonal therapy, expression of hormone receptors is essential, but not sufficient to accurately predict response to treatment for all patients. To date, numerous data have identified different pathways of resistance to hormonal treatment, associated with heterogeneity in response to long term treatment. The challenge remains to identify and to anticipate these changes for each patient.

Resume Objectif de l’etude Evaluer retrospectivement les resultats therapeutiques obtenus chez des patientes atteintes d’un carcinome du col uterin classe selon les recommandations de la Federation de gynecologie obstetrique (Figo) IB2, IIA ou IIB apres chimioradiotherapie avec du cisplatine puis une curietherapie et enfin une hysterectomie radicale elargie. Patientes et methodes Les 70 patientes, d’âge median 46 ans, ont ete traitees a l’institut Curie entre aout 1995 et aout 2005. La probabilite de survie a ete estimee selon la methode de Kaplan-Meier. Les comparaisons de survie ont ete evaluees par le test de log-rank. Resultats L’examen anatomopathologique a montre que la reponse locoregionale etait complete dans 56 % des cas (n = 39). Une tumeur residuelle microscopique centropelvienne a ete retrouvee chez 28 patientes (40 %), sous la forme d’un carcinome in situ dans tous les cas, a l’exception d’un. Chez neuf patientes, il y avait aussi un residu parametrial. Le curage ganglionnaire a montre que les ganglions etaient atteints dans 20 % des cas (14/70), soit 11 % (8/55) si le cancer avait ete classe N0, 40 % (6/15) si N1 (p = 0,03). Chez 11 patientes sur 14, l’atteinte ganglionnaire etait associee a un residu tumoral centro- et lateropelvien. Le suivi median etait de 40 mois (8–141). La probabilite de survie etait a trois ans est de 77 % (intervalle de confiance a 95 % : 66–89 %), celles d’echec locoregional et de dissemination metastatique, respectivement, de 9,5 % (2–16 %) et 24 % (13–34 %). Conclusion Le traitement du carcinome du col uterin localement evolue necessite de nouvelles approches multidisciplinaires diagnostiques et therapeutiques utilisant de nouvelles armes therapeutiques afin d’ameliorer la probabilite de survie et la tolerance au traitement.

Anal epidermoid carcinoma is a rare malignant tumor, comprising less than 5% of all carcinomas of the colon, rectum, and anus. The primary therapy now includes radiotherapy, often in combination with chemotherapy. Radical surgery is now rarely indicated. Therapeutic indications are based on locoregional staging, the presence of visceral metastases and an evaluation of the medical history. Anorectal endosonography is helpful in evaluating locoregional extension. In addition, magnetic resonance imaging, positron emission tomography scanning and inguinal sentinel lymph node procedure should play a role in a more selective approach in patients with anal carcinoma.