Search

TPS10125 Background: Corresponding with improved survival among breast cancer patients an awareness of the long term effects of cancer treatments has increased. There is now a call for better coordination of care and management of these patients to focus on their survivorship. This study will identify factors associated with the development and persistence of long term toxicities in patients treated for Stage I-III breast cancer. In addition, it will characterize their incidence as well as, psychological, social and economic impacts. Methods: This is a prospective cohort study enrolling newly diagnosed invasive cT0-cT3, cN0-3, M0 breast cancer patients of 26 French comprehensive cancer centers. All patients will be followed for a minimum of 5 years. Patients will be assessed at diagnosis, 3-6 (M0), 12 (M12), 36 (M36), 48 (M48), 60 (M60), months after treatment completion. Treatment completion is defined as completion of primary surgery, chemotherapy or radiotherapy, whichever comes last. Adjuvant trastuzumab, endocrine therapy or participation in clinical trials can be ongoing. CANTO collects an extensive list of clinical, treatment, and toxicity data including validated patient reported outcomes questionnaires ( Hospital Anxiety and Depression scale [HADS], Scheier et Carver’s Questionnaire, Life Orientation Test-Revised [LOT-R], Beck Depression Inventory [BDI-SF], European Organization for Research and Treatment-QOL questionnaire for breast cancer [EORTC QLQC30-BR23], EORTC-FA13, 12 Item Short Form Survey [SF12], Global physical activity questionnaire [GPAQ]6, impact of cancer questionnaire [IOCv2], economic and social questionnaires). Blood collection is available for all patients at diagnosis, M0, M12, M36 and M60. Genotyping will be performed in all samples. Biologic substudies are ongoing (e.g, microbiotic and cognitive substudy). CANTO aggregates a multidisciplinary team of French investigators and created a dedicated national network. Enrolment started in 2012 and by December 2016, 10030 patients were already enrolled, with a goal of 12.000 patients. Clinical trial information: NCT01993498.

1078 Background: Real-life data may help checking that public investments match closely medical needs. During the last decade, several drugs have been released on the market for MBC on the basis of a potential impact on overall survival (OS). Based on the large real-life ESME cohort, we aimed to describe the time evolution of MBC OS according to main phenotypes. Methods: ESME is a unique MBC national cohort including all consecutive patients (pts) who initiated treatment for MBC between 1/01/08 and 31/12/14 in the 18 French comprehensive cancer centres. ESME collects retrospective data using clinical trial-like methodology including quality assessments. Database lock was 8/12/2016. Primary objective was the impact of year of MBC diagnosis on OS. Multivariate Cox regressions were used with adjustment for main prognostic covariates. Results: 15170 out of 16703 pts in ESME had full IHC data allowing their classification as HR+HER2- (N=9922), HER2+ (N=2863), or HR-HER2- (N=2321) cases. Median FU and OS for the whole cohort are 4.05 yrs [95 CI: 3.98-4.12], and 3.1 yrs [95 CI: 3.03-3.18] respectively. In the adjusted multivariate analysis, year of MBC diagnosis, age at MBC, subtype (using HER2+ as reference), disease-free interval (DFI), visceral involvement, and number (nbr) of metastatic sites are significant OS predictors (table) although with low effect for the first item. Age at MBC, DFI, visceral involvement, and nbr of metastatic sites remained significant prognostic variables in subtypes. Year of diagnosis was no longer significant in HR+HER2- nor HR-HER2- cases (HR=0.997, p=0.71 and HR=0.997, p=0.84), while it was highly significant in HER2+ cases (HR=0.91, p

International audience; PURPOSE: Cognitive deficits (CD) are reported among cancer patients receiving chemotherapy, but may also be observed before treatment. Though elderly patients are expected to be more prone to present age-related CD, poor information is available regarding the impact of cancer and chemotherapy on this population. This study assessed baseline cognitive functions (before adjuvant treatment) in elderly early stage breast cancer (EBC) patients. METHODS: Women >65years-old with newly diagnosed EBC were included in this prospective study. Episodic memory, working memory, executive functions and information processing speed were assessed by neuropsychological tests. Questionnaires were used to assess subjective CD, anxiety, depression, fatigue, quality of life and geriatric profile. Objective CD were defined using International Cognition and Cancer Task Force criteria. A group of elderly women without cancer coupled with published data related to healthy women were used for comparison (respectively to subjective and objective CD). RESULTS: Among the 123 elderly EBC patients (70±4years) included, 41% presented objective CD, which is greater than expected in healthy population norms (binomial test P

The purpose of this multicenter prospective and descriptive study was to determine late toxicities and outcomes among patients with non-metastatic breast cancer receiving concurrent bevacizumab (BV) and radiation therapy (RT) in the clinical trials. Early and late toxicities were assessed and evaluation was available for 63 patients (pts) at 12 months. Acute radiation dermatitis was observed in 48 (76%): grade 1 for 27, grade 2 for 17 and grade 3 for 4 pts. Grade 2 acute oesophagitis was observed in one patient (2%). Little toxicity was described 1 year after the completion of RT: 7 pts (12%): grade 1–2 pain, 3 (5%) presented grade 1 fibrosis, and 2 pts (4%) – telangiectasia. One patient (2%) experienced grade 1 dyspnoea. Five grade 1–2 lymphoedema occurred. Only one patient experienced a LEVF value less than 50% one year after the end of RT. In conclusion , the concurrent BV with locoregional RT provides acceptable toxicities.

Summary Background Breast cancer is characterised by genomic alterations. We did a multicentre molecular screening study to identify abnormalities in individual patients with the aim of providing targeted therapy matched to individuals' genomic alterations. Methods From June 16, 2011, to July 30, 2012, we recruited patients who had breast cancer with a metastasis accessible for biopsy in 18 centres in France. Comparative genomic hybridisation (CGH) array and Sanger sequencing on PIK3CA (exon 10 and 21) and AKT1 (exon 4) were used to assess metastatic biopsy samples in five centres. Therapeutic targets were decided on the basis of identified genomic alterations. The primary objective was to include 30% of patients in clinical trials testing a targeted therapy and, therefore, the primary outcome was the proportion of patients to whom a targeted therapy could be offered. For the primary endpoint, the analyses were done on the overall population registered for the trial. This trial is registered with ClinicalTrials.gov, number NCT01414933. Findings 423 patients were included, and biopsy samples were obtained from 407 (metastatic breast cancer was not found in four). CGH array and Sanger sequencing were feasible in 283 (67%) and 297 (70%) patients, respectively. A targetable genomic alteration was identified in 195 (46%) patients, most frequently in PIK3CA (74 [25%] of 297 identified genomic alterations), CCND1 (53 [19%]), and FGFR1 (36 [13%]). 117 (39%) of 297 patients with genomic tests available presented with rare genomic alterations (defined as occurring in less than 5% of the general population), including AKT1 mutations, and EGFR, MDM2, FGFR2, AKT2, IGF1R , and MET high-level amplifications. Therapy could be personalised in 55 (13%) of 423 patients. Of the 43 patients who were assessable and received targeted therapy, four (9%) had an objective response, and nine others (21%) had stable disease for more than 16 weeks. Serious (grade 3 or higher) adverse events related to biopsy were reported in four (1%) of enrolled patients, including pneumothorax (grade 3, one patient), pain (grade 3, one patient), haematoma (grade 3, one patient), and haemorrhagic shock (grade 3, one patient). Interpretation Personalisation of medicine for metastatic breast cancer is feasible, including for rare genomic alterations. Funding French National Cancer Institute, Breast Cancer Research Foundation, Odyssea, Operation Parrains Chercheurs.

Background The population of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) who develop central nervous system (CNS) metastases is growing. Treatment strategies in this population are highly diverse. The objective of the study was to assess health care costs for the management of HER2 positive BC with CNS metastases. Methods This multicentre, retrospective, observational study was conducted on HER2-positive BC patients diagnosed with CNS metastases between 2006 and 2008. Data were extracted from patient medical records to estimate health care resource use. A partitioned estimator was used to adjust censoring costs by use of the Kaplan-Meier survival estimate. Results 218 patients were included and costs were estimated for 200 patients. The median time to detection of CNS metastases was 37.6 months. The first metastatic event involved the CNS in 39 patients, and this was the unique first metastatic site in 31 of these patients. Two years following diagnosis of CNS metastases, 70.3% of patients had died. The mean per capita cost of HER2-positive BC with CNS metastases in the first year following diagnosis was €35,735 [95% CI: 31,716-39,898]. The proportion of costs attributed to expensive drugs and those arising from hospitalisation were in the same range. Conclusion A range of individualised disease management strategies are used in HER2-positive BC patients with CNS metastases and the treatments used in the first months following diagnosis are expensive. The understanding of cost drivers may help optimise healthcare expenditure and inform the development of appropriate prevention policies.

Le bevacizumab (BEV) en premiere ligne associe au paclitaxel hebdomadaire, au docetaxel ou a une autre chimiotherapie ameliore significativement la survie sans progression (SSP) dans le cancer du sein metastatique (CSM) HER2-negatif, comme l’ont montre les essais E2100 [1], AVADO [2] et RIBBON-1 [3]. Dans l’etude ATHENA [4], 21 % des patientes ont poursuivi le BEV pendant ⩾ 1 an, sans nouveau signal de tolerance et avec un temps jusqu’a progression de 19,9 mois (IC a 95 % 18,9–21,8 mois). Pour mieux comprendre l’efficacite et la tolerance du traitement chez les longs repondeurs au BEV en premiere ligne, nous avons conduit une etude descriptive de 2 cohortes differentes de patientes atteintes d’un CSM : hormonosensible (RH+) et triple negatif (TN), traitees dans la pratique oncologique courante par au moins 1 an de BEV en premiere ligne.

Background: Major advances have been achieved in the understanding of breast cancer biology using high throughput technologies at the DNA and RNA levels. Most of these advances were made in early breast cancers (eBC) which are cured in about 80% of the cases. Nevertheless, little is known about metastatic breast cancers (mBC) which remain lethal in most of the cases. Methods: Whole-exome sequencing was performed on 216 tumour-normal pairs from mBC patients who underwent a biopsy in the context of the SAFIR01/SAFIR02/SHIVA or MOSCATO prospective trials. TCGA dataset (n = 772) was used to assess frequency of mutations in eBC. Findings: Twelve genes (TP53, PIK3CA, GATA3, ESR1, MAP3K1, CDH1, AKT1, MAP2K4, RB1, PTEN, CBFB, CDKN2A) were identified as drivers using MutSig algorithm (FDR150 non-synonymous mutations). This subset was observed in 2% of early breast cancers (TCGA, p = 7.1e?06). The prevalence of this subset increased with the time from diagnosis of metastasis to biopsy. Highly mutated HR+/Her2- mBC (n = 17) presented higher rate of PIK3CA mutations (n = 12, 70%), high number of neoantigens, an APOBEC mutational signature and a poor outcome (multivariate analysis, HR = 4.68, 95%CI: 1.8-12.1, p = 0.001). Interpretation: Whole exome sequencing of metastatic breast cancers identifies a subset of HR+/Her2- mBC who present a high mutational load. RB1, PALB2 and TSC1/2 mutations were found enriched in either mBC or HR+ mBC. Fundings: Breast Cancer Research Foundation, Fondation ARC, Fondation Lombard-Odier “Philanthropia”, Odyssea, Operation Parrains Chercheurs, Dassault Foundation, French NCI: INCa-DGOS-INSERM 6043 Citation Format: Maud Kamal, Celine Lefebvre, Thomas Bachelot, Thomas Filleron, Marion Pedrero, Mario Campone, Jean-Charles Soria, Christophe Massard, Christelle Levy, Monica Arnedos, Julie Garrabey, Yannick Boursin, Marc Deloger, Yu Fu, Frederic Commo, Veronique Scott, Ludovic Lacroix, Emmanuel Martin, Veronique Dieras, Anthony Goncalves, Jean-Marc Ferrero, Gilles Romieu, Laurence Vanlemmens, Marie-Ange Mouret-Reynier, Jean-christophe Thery, Pierre Kerbrat, Severine Guiu, Florence Dalenc, Gilles Clapisson, Hervé Bonnefoi, Martha Jimenez, Christophe Le Tourneau, Fabrice Andre. Mutational profile of metastatic breast cancers using whole-exome sequencing: a retrospective analysis of 216 samples from SAFIR01 / 02 / SHIVA / MOSCATO trials. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-353.

1013Background: In 2014, UNICANCER (composed of 18 French Comprehensive Cancer Centers) launched the Epidemiological Strategy and Medical Economics (ESME) program to centralize real-world data in oncology. Metastatic breast cancer (mBC) was first selected to address the value of bevacizumab (B) added to paclitaxel (P) as first-line chemotherapy (CT) for HER2-negative tumours, while randomized trials have led to mixed results on outcome. Methods: The ESME-mBC database was built from information systems, treatment databases and patients’ electronic files including quality control processes. All patients who started a first-line anti-cancer treatment for mBC between 01-Jan-2008 and 31-Dec-2013 were selected. The primary objective of the present study was to assess overall survival (OS) in patients with HER2-mBC treated with a first-line P-based CT ± B. Cox regression with adjustment for the main prognostic covariates was used to estimate the hazard ratio (HR) for OS and progression-free survival (PFS). To ad...

Background: Third generation aromatase inhibitors are a more effective treatment option than tamoxifen for hormone receptor positive invasive breast cancer in postmenopausal women. However, it is not known whether anastrozole is more effective than tamoxifen in preventing the recurrence of breast cancer in women with hormone receptor (HR) positive ductal carcinoma in situ (DCIS). Here, we compare the efficacy of anastrozole versus tamoxifen in postmenopausal women with HR positive DCIS. Methods: A multi-centre randomised placebo-controlled trial of 1mg/day anastrozole (oral) vs. 20mg/day tamoxifen (oral) for five years was conducted in 2980 postmenopausal women with locally excised HR positive DCIS. The primary endpoint was to determine if anastrozole is at least as effective as tamoxifen in loco-regional control and prevention of contralateral disease. Secondary endpoints included breast cancer mortality, other cancers, cardiovascular disease, fractures, adverse events and non-breast cancer deaths. All analyses were done on an intention-to-treat basis and Cox proportional hazard were used to compute hazard ratios and corresponding confidence intervals for recurrence. Results: Between 2003 and 2012, a total of 2980 postmenopausal women were recruited into the IBIS-II DCIS trial. 1471 women were randomly assigned to receive anastrozole and 1509 women tamoxifen. Median follow-up for this first analysis is 6.8 years and 131 breast cancer recurrences have been recorded. Median age was 60.3 years (56.1-64.6), median BMI was 26.7 (23.6-30.7), and 45.6% of women had used hormone replacement therapy (HRT) before joining the trial. Of the 131 women with recurrent disease, 77 had a loco-regional recurrence and 51 reported contralateral disease. A total of 61 deaths were recorded. We will present a comprehensive analysis of the efficacy of anastrozole and tamoxifen for preventing loco-regional/contralateral breast cancer and major adverse events by intention to treat (ITT). Conclusions: To follow. Citation Format: Cuzick J, Forbes JF, Sestak I, Howell A, Bonanni B, Bundred N, Levy C, von Minckwitz G, Eiermann W, Neven P, Stierer M, Holcombe C, Coleman RE, Jones LJ, Ellis I. Anastrozole versus tamoxifen for the prevention of loco-regional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in-situ (IBIS-II DCIS). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr S6-03.

Most patients with localized breast cancer (LBC) who take adjuvant chemotherapy (CT) complain of fatigue and a decrease in quality of life during or after radiotherapy (RT). The aim of this longitudinal study was to compare the impact of RT alone with that occurring after previous CT on quality of life.Fatigue (the main endpoint) and cognitive impairment were assessed in 161 CT-RT and 141 RT patients during RT and 1 year later. Fatigue was assessed with Functional Assessment of Cancer Therapy-General questionnaires, including breast and fatigue modules.At baseline, 60% of the CT-RT patients expressed fatigue vs. 33% of the RT patients (p0.001). Corresponding values at the end of RT were statistically similar (61% and 53%), and fatigue was still reported at 1 year by more than 40% of patients in both groups. Risk factors for long-term fatigue included depression (odds ratio [OR] = 6), which was less frequent in the RT group at baseline (16% vs. 28 %, respectively, p = 0.01) but reached a similar value at the end of RT (25% in both groups). Initial mild cognitive impairments were reported by RT (34 %) patients and CT-RT (24 %) patients and were persistent at 1 year for half of them. No biological disorders were associated with fatigue or cognitive impairment.Fatigue was the main symptom in LBC patients treated with RT, whether they received CT previously or not. The correlation of persistent fatigue with initial depressive status favors administering medical and psychological programs for LBC patients treated with CT and/or RT, to identify and manage this main quality-of-life-related symptom.

1031 Background: There is currently no consensus on the efficacy of chemotherapy (CT) beyond 3rd line in MBC and only eribulin (which has been recently approved) has shown to improve survival. No p...

108 Background: We have reported that CTC detection is an independent prognostic factor in 52 primary HER2+ IBC (Pierga, CCR 2014). We present a pooled analysis of two prospective trials including ...

Background: increased levels of circulating tumor cells (CTC) are associated with worse progression-free survival (PFS) and overall survival (OS) in patients (pts) with MBC (Bidard FC et al, Lancet Oncol 2014). The failure of chemotherapy to reduce CTCs to levels below five CTCs per 7.5 mL whole blood at first follow-up after initiating a new systemic therapy for MBC predicts shorter time to progression and OS. It has been hypothesized that bevacizumab could modify CTC prognostic value due to extravasation or epithelio-mesenchymal transition induction. CEC variations to predict benefit of anti-angiogenic treatment is still controversial. Patients & methods: the French cohort COMET is a prospective study including first line HER2 negative pts receiving weekly paclitaxel and bevacizumab according to EMEA approved combination. The aim of this cohort is to evaluate clinical, biological and radiological parameters associated with pts outcome (CTC, CEC, VEGFA levels, ctDNA, pharmacogenomic polymorphisms, metabolomic parameters, visceral fat assessed by initial CTscan, serum estradiol level, and quality of life). We present here the first planned analysis on 206 patients evaluated for CTC and CEC using the FDA cleared CellSearch method. Results: inclusions started in 09/2012. At time of analysis, 219 patients were included, 211 were evaluable for CTC at baseline (failure rate 4%) and 207 for CEC at baseline (failure rate 5%). Due to short follow-up, 173 pts and 166 pts were evaluable for both CTC and CEC at baseline and first day of second cycle of CT (D1C2) respectively. At baseline, 100/211 (47%) pts had ≥ 5 CTC (median 4 (range 0-30,000) and 30% had no detectable CTC (0 CTC). After one cycle of chemotherapy (D28) 38 pts (22%) had still ≥ 5 CTC: 37 pts with initial high level and only one patient with low CTC at baseline had increased CTC above 5. Median number CEC was 21 (0)-2231) at baseline and 22 (1-881) at D1C2. CEC increased in 16% and decreased in 15% of the cases. CTC & CEC changes after one cycleCTC BaselineCTC at D1C2CEC BaselineCEC at D1C2≥ 5≥ 537 (21%)>20>2065 (39%)≥ 520≤ 2025 (15%)2027 (16%) CTC number at baseline line and CTC D1C2 were correlated (p Conclusion: this 22% rate of failure to reduce CTC < 5 after one cycle of first line CT in a homogeneously bevacizumab-treated cohort of MBC patients did not differ from previous series. As second lines of chemotherapy do not improve the poor prognosis of this group of patients according to the SWOG 500 study results (Smerage et al, JCO 2014), trials of novel therapeutic agents should be considered at the time of progression. Citation Format: Jean-Yves Pierga, Isabelle Vaucher, Maya Gutierrez, Olivier Tredan, Séverine Guiu, Gilles Romieu, Anthony Goncalves, Marc Debled, Christelle Levy, Jean-Marc Ferrero, Christelle Jouannaud, Elisabeth Luporsi, Marie-Ange Mouret-Reynier, Florence Dalenc, Bernard Asselain, Jerome Lemonnier, Francois-Clement Bidard. Circulating tumor cells (CTC) and endothelial cells (CEC) changes in HER2 negative metastatic breast cancer (MBC) patients treated with first line weekly paclitaxel and bevacizumab: Preliminary results of a prospective cohort from the French Breast Cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-01-12.

The aim of this phase II study was to evaluate safety and efficacy of an oxaliplatin/vinorelbine/5-fluorouracil (FON) combination in anthracycline and taxane-pretreated metastatic breast cancer patients. The following treatment was given: on day 1 of a 21-day cycle, oxaliplatin 130 mg/m (2-h intravenous infusion); on days 1 and 5, vinorelbine [dose level (DL) 1: 17.5 mg/m; DL2: 22 mg/m]; on days 1-5, continuous infusion 5-fluorouracil (DL1: 600 mg/m/day; DL2: 750 mg/m/day). Forty-seven patients were treated (DL1: 43; DL2: 4). Median age was 54 years; 68% had liver metastases, 53% were taxane refractory/resistant and 38% were anthracycline refractory/resistant. Patients received a median of six treatment cycles. Of 46 eligible patients, 16 had partial response; the overall response rate was 34.8% (95% confidence interval 21.3-50.3%), 11 had stable disease lasting more than 4 months. Median follow-up was 13.0 months, median time to progression 5.7 months and estimated overall survival 18.8 months. DL2 was too toxic with three patients having grade 3-4 toxicity, including one death. At DL1, 26 patients (60%) experienced grade 3-4 neutropenia (six febrile neutropenia) and eight had grade 3 oxaliplatin-specific peripheral neuropathy after a median of 646.4 mg/m oxaliplatin (range 124-1619 mg/m). Oxaliplatin (130 mg/m, day 1)/vinorelbine (17.5 mg/m, days 1,5)/5-fluorouracil (600 mg/m/day, days 1-5) demonstrate encouraging activity and a manageable safety profile in anthracycline- and taxane-pretreated metastatic breast cancer patients.

Aim: To assess the rate of breast carcinoma associated with Radial Scar (RS) and to identify risk factors of this association. The secondary objective was to build a carcinoma prediction score associated with RS. Methods: This is a retrospective study including 202 patients with histologically confirmed RS. The study was performed on electronic medical records from 1986 to 2012, in the anti-cancer center Francois Baclesse in Caen, France. Two subgroups of lesions were studied as a function of the final histological results: RS associated with or without carcinoma. Clinical, histological and radiological data were studied as possible risk factors. Results: Two hundred patients were operated. In total, 126 (63%) were pure RS, 26 (13%) were associated with atypical hyperplasia, 26 (13%) with in situ carcinoma, and 22 (11%) with invasive carcinoma. The mean age of patients with RS + carcinoma was significantly higher than patients without carcinoma (57 versus 51.1 years, p = 0.001). The median size of RS with carcinoma tended to be higher than without carcinoma (10 versus 8mm, p = 0.07). We built a score, considering age, RS size and mammographic criteria to classify patients at low (score= 0), medium (score from 1 to 5) or high risk (score > 5) of in situ or invasive carcinoma, with risk of carcinomas respectively 0%, 20% and 64%, p = 0.0005. Conclusions: RS is rare but may be associated with carcinoma. This lesion should undergo a preoperative biopsy. The advanced age of the patient and the large size of the lesion appear to be correlated with a higher risk of association between RS and carcinoma. The development of our carcinoma prediction score could help us to optimize patients' care. This score must be validated in a prospective study. Disclosure: All authors have declared no conflicts of interest.

Background: Chemotherapy (CT) is widely used in the management of estrogen receptor (ER) positive breast cancer patients (pts) pre-treated by hormone therapy (HT) . Single-agent CT in this setting has been validated in guidelines of management of the disease. Both paclitaxel and vinorelbine are recommended among the standard available CT agents for advanced breast cancer (ABC). Weekly paclitaxel (P) and oral vinorelbine (OV) as single agents are active with a good tolerance profile for these pts. Oral CT offers significant advantages over intravenous CT because of its greatest convenience, its ease of administration and reduced need for hospitalisation. Since the benefits and safety profile of OV and weekly P have never been compared in a face to face trial, this study will provide key clinical data regarding the optimal management of this patient population: ER positive and HER2-negative disease previously treated by a HT. Trial design: In this open-label study, pts are randomized to receive: OV 60 mg/m2/week (day 1, 8, 15) for the first cycle, then increased to 80 mg/m2/week from the second cycle in the absence of grade 3 or 4 toxicity or weekly P 80 mg/m2/week (day 1, 8, 15) intravenously. Treatments are continued until disease progression, unacceptable toxicity or pt's refusal. Main eligibility criteria include: age ≥18 years, documented locally recurrent or metastatic disease previously untreated by CT, ER positive disease previously treated by at least one HT, HER2-negative disease, Karnofsky PS ≥70. Primary objective: disease-control rate (defined as objective response or stable disease for a minimum of 6 weeks). Secondary objectives: other efficacy parameters, evaluation of safety profiles of both arms and quality of life assessment. Statistical methods: the one-sample multiple testing procedure for phase II clinical trials described by Fleming is used. This procedure employs the standard single stage test procedure at the last one of 2 pre-specified testings, while both allowing for early termination (should extreme results be seen) and essentially preserving the size and power of the single stage procedure. 124 pts will be enrolled in this randomized phase II study (62 per treatment arm). Randomisation is stratified according to prior taxane (yes or no) and presence of visceral metastases (yes or no). Disclosure: M. Aapro: Advisory Board Member, Pierre Fabre; M. Morand: Employee of Pierre Fabre Medicament; G.R. Villanova: Employee of Pierre Fabre Medicament. All other authors have declared no conflicts of interest.

2054 Background: BM, the most frequent malignancy in the central nervous system, remains of poor prognosis. Standard treatment is WBRT. Neo-angiogenesis plays an important role in BM growth. Angiog...

510 Background: Hormone resistance is linked in part to cross-talk between ER signalling and PI3K/Akt/mTOR pathway. Following results of the BOLERO-2 trial, everolimus (E), a potent mTOR inhibitor, has recently been approved in combination with exemestane in women with HR+ MBC refractory to aromatase inhibitor (AI). However, E is frequently associated with specific toxicities, and predictive markers of efficacy are needed. We report here the final results of translational studies within the TAMRAD randomized Phase II trial, comparing tamoxifen (TAM) to TAM+E in AI pre-treated MBC. Methods: Tumor samples from 51 patients among the 111 treated in the TAMRAD trial were retrieved. Hot spot mutations of PI3K (exon 9-20), and KRAS (exon 2) were described. TMA analysis evaluated IHC expression of PTEN, pAkt, PI3K, LKB1, S6K, pS6K, 4EBP1, p4EBP1, and eIF4E. Exploratory analysis of E efficacy in each biomarker subgroup (high vs low expression defined by median percentage of marked cells) was done. Results: Patients characteristics and treatment efficacy among this sub-population were similar to the results from the whole population: Time to progression was 10 months for the TAM+E treated patients vs. 5.5 months for the TAM treated patients, HR: 0.59 (95% CI 0.33-1.07). PI3K-Akt pathway: All patients derived benefit from E regardless of PI3K mutational status, PTEN or pAkt expression. Surprisingly, E efficacy was greater in patients with low PI3K expression (n=12, HR=0.11, 95%CI 0.01-0.96) than in patients with high PI3K expression (n= 28, HR=0.9; 95%CI 0.49-2.41) PI3K independent pathway: Patients with low expression of the anti-oncogene LKB1 derived greater benefit from E (n=22, HR=0.33; 95%CI 0.13-0.89) than patients with high LKB1 expression (n=25, HR=0.75; 95%CI 0.32-1.74) mTOR downstream effectors: Patients with high p4EBP1 (n=27, HR=0.37; 95%CI 0.15-0.90) or low 4EBP1 (n=21, HR=0.39; 95%CI 0.14-1.08) were the subgroups most likely to benefit from E. Conclusions: Those results are in favor of a better efficacy of E for patients with PI3K independent activation of mTOR. If confirmed, they could have important implications for future patient selection. Clinical trial information: NCT01298713.

Background First-line BEV combined with weekly paclitaxel, docetaxel or other chemotherapy significantly improves progression-free survival (PFS) in HER2-negative metastatic breast cancer (mBC), as shown in E2100, AVADO and RIBBON-1 trials. In the ATHENA study, 21% of pts continued BEV for ≥1 year with no new safety outcome and a time to progression of 19.9 months (95% CI 18.9-21.8 months). To further understand and provide insight into the efficacy and safety of long-term responders to first-line BEV, we conducted a descriptive study of 2 different cohorts of pts with mBC: HR+ and TN, treated in routine oncology practice with at least 1 year of first-line BEV. Methods Pts who had received first-line BEV(≥1 year) associated to chemotherapy were retrospectively included in the 2 independent cohorts and followed up, if they were alive at inclusion, for 18 months. Clinico-pathological characteristics, treatment received, efficacy and safety data were collected. Results The recruitment of the TNBC cohort was just completed (n = 80) and results will be presented at the meeting. In the HR+ cohort (n = 132), 28.1% of the pts had a disease-free interval 3 metastatic sites at diagnosis, and more than 1/3 of the patient had lung and/or liver involvement. In association to 1st line BEV, 93,2% had received a taxane as initial 1st line chemotherapy, 76.2% had received maintenance endocrine therapy and 4.2% had received maintenance chemotherapy (capecitabine). Best response obtained in 1st line was a complete response or partial response for 84,6%. With a median follow-up of 33 months, median PFS was 27.4 months (95% CI [23.2-33.8]). Overall survival data were immature as 84.8% of the pts were alive at inclusion. The most common BEV related grade 3/4 adverse events were hypertension (7.5%), bleeding (1.9%), proteinuria (1.3%) and congestive heart failure (1.3%). Conclusion Prolonged BEV-containing therapy in this HR+ cohort is of interest and suggests that some pts achieve sustained disease control with limited side effects. Disclosure V. Dieras: Advisory boards and Symposium participation. H. Simon: Member of an advisory board: Roche Mastology Group. N. Mesnard: Roche employee. E. Antoine: Membership of an advisory board. All other authors have declared no conflicts of interest.

TPS108 Background: The EGFR pathways are important therapeutic targets in HER2/neu+ BC. Lapatinib (L) a dual, inhibitor of EGFR and HER2/neu tyrosine kinase activity improves overall survival (OS) ...

1026 Background: Predictive markers of response to chemotherapy are lacking in breast cancer patients. Preclinical data suggest that breast cancer cells that loose expression of Foxp3 gene develop ...

TPS131 Background: Ductal carcinoma in situ is defined as breast cancer confined to the ducts of the breast without evidence of penetration of the basement membrane. Local treatment quality represents one of the most prognostic factors as half of recurrences are invasive diseases. The main goal of adjuvant radiotherapy after conservative surgery is to decrease local recurrences and to permit breast conservation with low treatment-induced sequelae. Several randomized trials have established the impact of 50 Gy to the whole breast (WB) in terms of local control. Nevertheless, no randomized trial is still available concerning the role of the boost in this disease. The phase III randomized trial “BONBIS” is elaborated to evaluate the impact of a 16-Gy boost after 50 Gy delivered to the whole breast in 25 fractions and 33 days. Methods: A total of 1,950 DCIS breast cancer patients are planned to be enrolled in this trial. Patients will receive the following treatment: (A) WB radiotherapy of 50 Gy in 25 fractio...

515 Background: Our aim was to define the role of complete excision and the value of minimal margin on the local control in breast conserving surgery (BCT). Methods: Between 1973 and 2002, 4,832 pa...

Background: after a localized breast cancer, none study demonstrates any benefit on survival from extensive follow-up, so international guidelines recommend only annual mammography combined with clinical examination, without any radiological or biological investigation. But nowadays in the era of new drugs (targeted therapies, new cytotoxics) an anticipation of diagnosis of metastatic disease could impact the patient's outcome. However we first need to assess the efficacy of a planned follow-up for the detection of distant recurrences and its potential impact on survival.Method: we conducted a retrospective study in a large cohort of patients (n= 484) included in our center in 4 randomized phase III trials of the breast cancer adjuvant trials program (PACS) of the French cancer centers (FNCLCC). In these trials, a systematic and homogenous follow-up was planned: clinical examination every 6 months combined with an additional radiological (mammogram, chest radiography, liver ultrasonography, bone scan) and biological evaluation, once a year during 5 years. Two adjuvant chemotherapy trials were developed for node-positive pts (PACS 01: 6 FEC 100 (5FU-epirubicine-cyclophosphamide) vs 3 FEC 100 + 3 docetaxel and PACS 04: 6 FEC 100 vs 6 docetaxel-epirubicine +/- trastuzumab for HER2 + pts). For node-negative pts, PACS 05 explored 6 vs 4 FEC100. In PACS 02 (French population of IES trial) hormonal adjuvant therapy was explored, with a comparison of 5 years of Tamoxifen vs a switch of 2-3 years of exemestane after 2-3 years of tamoxifen. Respectively 108 pts were included in PACS 01, 161 in PACS 04, 118 in PACS 05 and 97 in PACS 02.Overall 109 relapses were observed (87 metastasis, 5 local breast recurrence, 7 regional nodal failure, 7 controlateral breast cancers, 3 second malignancies). Fifty-four relapses were diagnosed by the planned follow-up in the absence of clinical symptom and 55 were revealed by clinical symptoms occurring during the interval between two planned investigations. For distant metastasis, 40 were detected by investigations and 47 due to clinical symptoms. For local failure or contro-lateral breast cancer, most relapses were pointed out by annual planned mammography rather than symptomatic disease, respectively 4 and 7. All 3 second malignancies were diagnosed independently of radiographic follow-up.Conclusion: in a homogenous population from adjuvant clinical trials, assigned to a strictly defined extensive follow-up, more than 50% of distant relapses occurred outside this planned program, in favor of a low benefit of extensive follow-up on overall survival for the global population. The final presentation will provide survival data according to the modalities of the recurrences discovery and additional results according to some specific features of primary tumor (node positive/node negative, HER2 positive or triple negative patients) which can eventually impact the benefit of an earlier detection of metastatic disease. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5117.

Abstract #3129 Introduction: During the last three decades we observed a dramatic improvement in disease free and overall survival in early breast cancer. The improvement of survival of patients who underwent distant metastases is not obvious. The objective of the study was to determine whether the survival of women with distant recurrent breast cancer has improved from 1973 to 2002. Method: We analyzed survival of 4071 women who developed distant metastasis from breast cancer between January 1973 and December 2002 whatever the primary tumor status and initial treatment were. Patients were divided into five groups based on year of breast cancer distant recurrence. Results: In the unadjusted analysis there was a slight but significant improvement in survival across the five groups (p Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3129.

Abstract #6122 Background : wPC and E are effective in the treatment of MBC. The main objective was to determine the efficacy of combined induction with wPC and E followed by consolidation with wPC. Secondary objective were to determine tolerance survivals and characterize antiangiogenic PC activity and predictive values of plasmatic neurotrophic and endothelial factors, in terms of neurotoxicity and efficacy. Methods : patients (pts) with RECIST measurable metastasis were recruited from april 2004 to may 2006 : ages (18-75 y) PS≤2, prior neoadjuvant adjuvant chemotherapy (NA-A CT) was permited if >6 month. 3 cycles [wPC 80 mg/m² (D1, D8, D15, reinduction D28) and epirubicine 100 mg/m² D15], were followed by wPC (no week rest). VEGF, IL6, IL6SR, BDNF were measured in plasma at baseline and C2. Evaluation was performed after 3 induction cycles and every 3 month. A Simon optimal two-stage design was performed with 13 objective responses, allowing to accrue 25 more patients (28 responses expected). Results : 54 patients: median age 58.5 (30-75); 81% had surgery, 53.7% radiotherapy and 40.7% had NA-A CT, 46.3% hormonotherapy. Metastatic sites were nodes (36) lung (36) liver (28) bone (23). 100% PC and 90% E dose were administered at C2 and C3. 49 patients were evaluable for response; 3 patients withdrawn for taxol hypersensitivity, 1 early death (GIII asthenia and dyspnea), 1 investigator's decision. ITT analysis was performed: 33 responses (ORR: 61 %) Median OS was 30 months. During induction, 16 grade III, 27 grade IV and 3 febrile neutropenia were reported. There were 13 serious adverse events. Consolidation was mainly associated with neurotoxicity n=28 (20pts), GIII (n=1; 3.6%) GIV (n=1; 3.6%), astenia n=26 (18pts) ), GIII n=1; 3.8% GIV n=1; 3.8%and onycholysis n=15 (13pts) ), GIII n=2 ; 13.4% GIV n=1; 6.7%. High initial VEGF plasma levels were correlated with poor survival s (PFS, OS) with an univariate cox model (OR=1.954, 95%CI 0.944-4.043, p=0.071 ; HR 4.437, 95%CI 1.731-11.371, p=0.0019). Thresholds were determined. No correlation were observed between neurotoxicity and IL6, IL6SR and BDNF plasma levels. Conclusion : Despite the significant but manageable haematologic toxicity, PC + E showed a high efficacy. VEGF plasma levels are predictive of the outcome and should be tested as antiangiogenic drugs targeting factors.This work was supported in part by BMS. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6122.

Abstract #6153 Background Breast cancer (BC) is the most frequent second malignancy in women treated for Hodgkin's disease (HD), but there are few specific data on these tumors. This study assesses histopathological features, locoregional and systemic treatments as well as prognostic factors of these secondary BC. Material and methods: 127 women treated for HD in 9 centers subsequently developed 143 BC. Median age at HD diagnosis was 25 years. HD stages were I, II, III and IV in 28%, 49%, 16% and 7%. Radiotherapy (RT) alone was used in 44 cases and chemotherapy (CT) + RT in 83 cases. Twelve patients relapsed and had a new treatment by RT (3), CT (5) or both (4). Results: First BC occurred after 18-year median interval (20 years: 40%). TNM classification (126/143) showed 23 mammographically detected T0 (18%), 54 T1 (43%, 40 T2 (32%) and 9 T3T4 (7%). 129 tumors were infiltrating carcinoma (IC) and 14 (10%) DCIS. Twenty-four (17%) tumors were multifocal. Five patients had metastasis at diagnosis; 135 tumors were operated (121 IC and 14 DCIS): 57 (42%) by conservative surgery (40 with RT) and 78 (58%) by mastectomy (5 with RT). Axillary dissection (AD) and SNB were performed in 74% and 23% of the cases. Median tumor size for IC was 19 mm. Axillary nodal involvement (ANI) was found in 28% of IC (pN1-3 : 22%; pN>3 : 6%). ER and PgR were positive in 57% and 49%. 43 (39%) tumors were SBR III (high grade). Chemotherapy (CT) and hormonotherapy (HT) were performed in 47% and 42% of IC. With a 5-year median FU, 17 patients (12%) developed local recurrences (LR) and 35 (30%) had metastases. Significant metastasis predictive factors were ANI and SBR III; 12 (10%) women developed a third cancer. 5 and 10-year overall survival (OS) rates were 69% and 53%, and disease-specific survival (DSS) rates 72% and 62%. 5-year DSS rates were 79% for T0T1 versus 44% for pT2T3T4 (p=0.0068) and 81% for pN0 versus 65% for pN+ (p=0.0012). Conclusion Young women (especially 15-25 years) treated for HD should be carefully monitored by mammography, ultrasound and maybe MRI in order to detect early occurrence of BC. The prognosis of small lesions (pTis/pT1) is excellent and conservative treatment often feasible. This study is still ongoing, with 200 planned cases. Optimal adjuvant treatment options will be discussed and compared with a former series including 133 cases (Radiotherapy and Oncology, 2001, 59: 247-255). Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6153.

1102 Background: MBC remains an incurable disease, with a median survival of two years. However, some patients experience a substantial longer survival. The aim of this study is to determine the pr...

9509 Background: Cognitive deficits (CD) have been reported among patients receiving chemotherapy (CT) for cancer.Despite their increased propensity for age-related CD that may worsen during CT, el...

600 Background: Addition of BEV to TRA-based NAC in HER2-positive IBC has been associated with high pathological complete response (pCR) rate and favorable outcome in the BEVERLY 2 phase II trial (...