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Adjuvant therapy; Breast cancer; Olaparib Terapia adyuvante; Cáncer de mama; Olaparib Teràpia adjuvant; Càncer de mama; Olaparib Background The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. Patients and methods One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. Results With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Δ 3.4%, 95% CI −0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Δ 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Δ 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. Conclusion With 3.5 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDFS and DDFS with no new safety signals. Funding for this work, which was conducted as a collaborative partnership among the Breast International Group, NRG Oncology, Frontier Science, AstraZeneca, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, U.S.A. (MSD), was provided by the National Institutes of Health (grant numbers: U10CA 180868, UG1CA 189867, and U10CA 180822) and by AstraZeneca as part of an alliance between AstraZeneca and MSD. Provision of olaparib and placebo was from AstraZeneca.

Study question Do fertility preservation (FP) strategies using ovarian stimulation or not, impact long-term disease-free survival of breast cancer (BC) patients? Summary answer The disease-free survival of BC patients is not impacted by FP techniques whatever the timing of chemotherapy (neoadjuvant /adjuvant) and the use of ovarian stimulation. What is known already Fertility is often impaired in young women treated for BC. Therefore, FP has become a major issue in this population. Cryopreservation of oocytes or embryos after controlled ovarian hyperstimulation (COH) represents the most established method in this clinical situation. However, the hormonal consequences of COH protocols still raise safety concerns, often leading oncologists to contraindicate the use of this FP technique. Although alternative FP options without exogenous hormone administration may be considered, they remain suboptimal for treating the putative future infertility. Study design, size, duration Retrospective bicentric cohort study including including 740 BC women, 18-43 years of age, referred for FP between 2013 and 2019. Participants/materials, setting, methods Overall, 328 underwent at least one ovarian stimulation cycle (STIM group) and 412 had a technique without hormonal administration (No STIM group). Log Rank test was used to compare both groups and Cox proportional-hazard model was applied for multivariable analyses. Main results and the role of chance Women of the No STIM group were significantly younger and present with more severe disease. Follow-up data for recurrences were available for 80.9% of the cohort and the median time to follow-up was 4.2 [2.9-5.8] vs. 5.6 [4.1-6.7] years between STIM and No STIM group (p Limitations, reasons for caution The retrospective nature of the study represents the main limitation. The median follow-up of 4.2 to 5.6 years, might be considered short to assess the long-term safety of FP techniques. The heterogeneity between oncological centers regarding the use of COH and specific protocols may lalso be a reason for caution. Wider implications of the findings Our findings provide reassuring safety data on the use COH for FP in BC patients, whatever the timing of chemotherapy. However, further investigations with a longer follow-up are needed to definitely consider COH safe in particular in neoadjuvant situations. In addition, the benefit of letrozole supplementation during COH requires confirmation. Trial registration number Not applicable

BEROSE is a single-center observational study, which aimed to determine the proportion of women with breast cancer who received information on sexual health from health professionals throughout their whole care pathway. A total of 318 women with all stages of breast cancer (30% metastatic) and at different time interval from diagnosis (up to 7 years) participated to the survey. Sixty-five percent of women reported that they had not received any information about sexual health over the whole care. Increased awareness among the healthcare professionals and particularly the oncology community is needed to discuss sexual health in women with breast cancer.

Background: The incidence of breast cancer (BC) increases with age. However, there appears to be a trend that elderly patients with BC receive less than the standard treatment compared to younger ones and this leads to poorer outcomes. The aim of this work was to assess whether chemotherapy has a differential impact on the health related quality of life (HRQOL) of elderly patients with BC, compared to younger ones. 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. HRQOL at the end of acute treatments of patients aged 70 and over treated by chemotherapy was compared to that of the youngest ones. Multivariable mixed linear model was used to assess the determinants of HRQOL for the dimensions with minimal clinically important differences; defined as a mean difference of at least 5 points in HRQOL scores; between younger and older patients. Results: 3079 patients were included in the CANTO cohort from March 2012 to December 2014 and treated by chemotherapy. The mean age at diagnosis was 53 years and 7.3% of this population was ≥70 years old. Older and younger patients treated by chemotherapy were similar for the disease stage at diagnosis (p=0.7869), the tumor histology (p=0.07), the SBR grade (p=0.2350) and the HER2 status (p=0.4268). However, elderly patients treated by chemotherapy were more likely to be overweight (p Citation Format: Sandrine Dabakuyo Yonli, Oumar Billa, Olivia Dialla, Florence Joly, Sarah Dauchy, Charles Cecile, Cedric Lemogne, Patrick Soulie, Marie-Ange Mouret-Reynier, Carole Tarpin, Mario Campone, Sophie Guillermet, Jean-Marc Ferrero, Sylvie Giacchetti, Florence Lerebours, Suzette Delaloge, Anne-Laure Martin, Sibille Everhard, Charles Coutant, Fabrice Andre, Patrick Arveux. Impact of chemotherapy on the health related quality of life among elderly patients with localized breast cancer: Findings from the prospective CANTO cohort [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 P6-11-07.

KAMILLA is a single-arm safety study of trastuzumab emtansine (T-DM1) in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (BC; NCT01702571). We report the final analysis of cohort 2 (Asia) within the context of published cohort 1 (Global) findings.Patients had HER2-positive, locally advanced, or metastatic BC progressing after chemotherapy and anti-HER2 therapy or ≤6 months after adjuvant therapy. The primary objective was to further evaluate T-DM1 (3.6 mg/kg, administered intravenously every 3 weeks) safety/tolerability, including the following adverse events of primary interest (AEPIs): grade ≥3 AEPIs (hepatic events, allergic reactions, thrombocytopenia, hemorrhage events), all grade ≥3 treatment-related AEs, and all-grade pneumonitis.KAMILLA enrolled 2185 patients (cohort 1, n = 2003; cohort 2, n = 182) as of 31 July 2019. Of these, 2002 and 181 per cohort were treated and included in the safety population. Approximately 70% of patients had two or more previous treatment lines in the metastatic setting. Median T-DM1 exposure was 5.6 and 5.0 months per cohort; median follow-up was 20.6 and 15.1 months. The overall AEPI rate was higher in cohort 2 (93/181; 51.4%) versus cohort 1 (462/2002; 23.1%), mostly driven by a higher grade ≥3 thrombocytopenia rate in cohort 2. In cohort 2, grade ≥3 thrombocytopenia was not associated with grade ≥3 hemorrhagic events and most (128/138) fully resolved. Grade ≥3 treatment-related AEPI rates were 18.4% (cohort 1) and 48.6% (cohort 2), the latter mainly due to thrombocytopenia. Any-grade pneumonitis rates were 1.0% and 2.2%. No new safety signals were identified. Median (95% confidence interval) progression-free survival was 6.8 months (5.8-7.6 months) and 5.7 months (5.5-7.0 months) in cohorts 1 and 2, respectively; median overall survival was 27.2 months (25.5-28.7 months) and 29.5 months (21.1 months to non-estimable). In both cohorts, median progression-free survival and overall survival decreased with increasing prior therapy lines.Cohort 2 results aligned with previous findings in Asian patients, supporting the manageable safety profile and use of T-DM1 in advanced BC.

Background: Therapeutic options at diagnosis for metastatic breast cancers (MBC) differ largely according to cancer phenotype (namely, hormone receptor (HR) and HER2 status). Reported discordance rates between primary tumor and metastasis vary widely in literature, with a median of 18% for estrogen receptor, 31% for progesterone receptor and 10% for HER2. The present study aimed to compare phenotypic profiles between primary and MBC in the real-life setting. Patients (pts) and methods: Epidemio-Strategy and Medical Economics (ESME)MBC data platform (NCT03275311) is a French national, multicenter, observational cohort using clinical trials' methodology for data capture, monitoring and quality controls. At the time of analysis, it comprised data of 16703 consecutive newly diagnosed MBC pts (1/01/08-31/12/14) treated in 18 French comprehensive cancer centres. The primary endpoint was the discordance rate of HR and HER2 status between primary tumor and MBC (biopsy of metastatic site done within 6 months of MBC diagnosis). Only patients with both histological reports available were considered. Potential factors associated with phenotype discordance were assessed in a multivariate logistic regression. Results: 2933 out of 16703 (17.6%) had a biopsy in the first 6 months of metastatic disease. HR and/or HER2 status was available in 1677 pts. The discordance rate between primary and matched MBC was 14.2% (222/1566) for HR: loss of expression in 72.5%, gain in 27.5%. For HER2, the discordance rate was 7.8% (84/1076): 45.2% of losses and 54.8% of gains of expression. The primary HR+/HER2+ subgroup had the highest rate of changes: 53% (49/92) with either a loss of HR (43%), loss of HER2 (43%) or a loss of both (14%). 18% (33/181) of primary triple-negative breast cancer (TNBC) had a phenotypic change with a majority of HR gain (79%). In multivariate analysis, administration of adjuvant chemotherapy +/- targeted therapy was the sole independent predictor of HR status modification (OR: 1.73, 95%CI 1.27-2.36, p=0.001). The presence of a mixed histology was the only predictor of HER2 discordance (OR =2.57, 95%CI 1.19-5.55, p=0.016). Patient characteristics Total population (n=16703)Pts with primary and MBC phenotype available (n=1677)Age at metastatic diagnosis Median (range)61 (19-99)60 (24-93)De novo MBC4507 (27.1%)221 (13.2%)Number of metastatic sites Median (range)1 (1-9)2 (1-7)MBC sites Brain1200 (7.2%)138 (8.2%)Visceral7755 (46.4%)928 (55.3%)Non-visceral7748 (46.4%)611 (36.4%)Phenotypic profileN = 2933N=1677TNBC356 (18.5%)272 (19.3%)HR+/HER2-1251 (65.0%)917 (65.2%)HR-/HER2+150 (7.8%)105 (7.5%)HR+/HER2+168 (8.7%)112 (8%)Missing1008271Metastatic site samplingN=2933N=1677Bone692 (24.2%)419 (25.5%)Liver514 (18.0%)355 (21.6%)Skin379 (13.3%)203 (12.4%)Node306 (10.7%)169 (10.3%)Lung258 (9.0%)168 (10.2%)Pleura283 (9.9%)121 (7.4%)CNS/CSF*132 (4.6%)42 (2.6%)Other or multiple296 (10.3%)165 (10.0%)Missing7335* CNS= central nervous system, CSF=cerebro-spinal fluid Conclusion: Biopsy and phenotype re-evaluation of MBC early in the disease course has a confirmed potential significant therapeutic impact in this large scale real life setting and should be proposed as often as possible. Citation Format: Lefevre S, Lusque A, Joyon N, Arnould L, Penault-Llorca F, MacGrogan G, Treilleux I, Vincent-Salomon A, Haudebourg J, Maran-Gonzalez A, Charafe-Jauffret E, Courtinard C, Franchet C, Verriele V, Brain E, Tas P, Delaloge S, Filleron T, LaCroix-Triki M. Phenotypic discordance between primary and metastatic breast cancer (MBC) in a large scale real-life multicentre French cohort [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-12-05.

Background: Palbociclib (Pal) combined with an aromatase inhibitor (AI) is a standard of care as first line therapy in ER+ HER2- metastatic breast cancer (MBC). While ESR1 mutations (ESR1mut) are a characterized mechanism of resistance to AI as single agent, it remains unknown how these mutations, when detected prior to treatment initiation, may affect the efficacy of Pal+AI. In a subsidiary analysis of the first line PADA-1 trial, we report the ESR1mut detection rate at baseline and, in patients with ESR1mut detected at baseline, how ESR1 circulating tumor DNA levels changed after the first cycle of AI-Pal therapy. Methods: PADA-1 (NCT03079011) is a randomized phase III trial testing the clinical utility of real time ESR1mut detection (baseline, at 1 month and then every 2 months) in the blood of patients treated with AI-Pal (first step). Patients with rising ESR1mut in circulating tumor DNA (i.e. increasing or appearing mutations during first line AI-Pal therapy) are randomized in a second step between keeping AI-Pal or switching to Fulvestrant-Pal. Main inclusion criteria are patients with ER+ HER2- MBC, who never received adjuvant AI or completed adjuvant AI for >12 months, with neither prior therapy for MBC nor visceral crisis. ESR1mut are tracked in circulating DNA from up to 4ml of plasma by a ddPCR-based assay targeting E380, L536, Y537 and D538 hotspots (i.e. #90% of known ESR1 activating mutations) with #0.1% sensitivity (Bidard et al, AACR 2018 #3867). Results: From 04/2017 to 05/2018, 803 MBC patients have been included in 80 centers. Among these patients, ESR1mut were detected at baseline, prior to any systemic therapy, in 17 patients (2.1%, 95%CI=[1.3;3.3%]). ESR1mut levels ranged from 6 to 3959 copies/ml of plasma (median: 30 copies/ml); allelic frequency ranged from 0.3% to 47% (median=3.5%). ESR1mut were not associated with any of the tumor pathological characteristics (including PR status, primary TNM stage, number and type of metastatic sites); a non-significant association was observed with primary tumor grade (1.7% vs 4.1% in grade I-II vs III, Fisher: p=0.15). Among patients who received a prior adjuvant endocrine therapy, ESR1mut detection rate was lower in patients treated with tamoxifen (0.9% with any tamoxifen exposure vs 5.7% with no tamoxifen exposure; Yates Chi2: p=0.01) and observed only in patients treated with AI (4.9% with any AI exposure vs 0% with no AI exposure, Yates Chi2: p=0.009). Among the 17 patients with ESR1mut detected at baseline, only 4 patients had residual detectable ESR1mut detected after 1 month of AI-Pal therapy (3 of these 4 had decreased levels of ESR1 mutation). Conclusion: ESR1mut is a rare event in untreated AI-sensitive, ER+ HER2- MBC patients. Such detection is primarily associated with prior use of AI in the adjuvant setting. Interestingly, in most MBC patients with ESR1mut detected at baseline, ESR1mut became undetectable after 1 month of AI-Pal therapy, suggesting that this combination may retain early antitumor efficacy. Funding: Pfizer Citation Format: Bidard F-C, Pistilli B, Dalenc F, De la Motte Rouge T, Sabatier R, Frenel J-S, Ladoire S, Dubot C, Ferrero J-M, Levy C, Lortholary A, Stefani L, Mouret-Reynier M-A, Hardy A-C, Jacquin J-P, Grenier J, Chakiba C, Teixeira L, Soulie P, Everhard S, Lemonnier J, Jeannot E, Bieche I, Berger F, Pierga J-Y, Bachelot T, Delaloge S. Circulating ESR1 mutation detection rate and early decrease under first line aromatase inhibitor and palbociclib in the PADA-1 trial (UCBG-GINECO) [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 PD2-06.

Background The role of chemotherapy in early luminal breast cancer remains challenged. The NEOPAL trial (NCT 02400567; Cottu et al, ESMO 2017 LBA09) compared sequential chemotherapy (CT) and letrozole-palbociclib (LP) as neoadjuvant treatment in PAM50 defined high-risk luminal breast cancer patients, showing that LP might be as efficient as CT with regard to breast conserving surgery and pathological response. We report here extended exploratory pathological results, focusing on tumor infiltrating lymphocytes (TILs), proliferative response and preoperative endocrine prognostic index (PEPI) scores. Material and Methods Tumor blocks from baseline biopsy and surgical specimens were available for centralized review from the 106 randomized patients (53 in each arm). TILs quantification, KI67 staining and counting, and ER quantification were performed according to standard methods. Residual proliferative cancer burden (RPCB) and PEPI scores were computed according to published algorithms. Wilcoxon rank sum test and Mann Whitney test were used to compare paired and unpaired data. The chi-square and Fisher exact tests were used for categorical variables. Results Overall, median TILs count did not differ between LP and CT patients, both at baseline (p=0.37) and at the end of treatment (p=0.42). Median TILs count climbed from 5% (0-60) to 10% (1-60) in the LP arm (p=0.0026) and from 2% (0-30) to 10% (0-60) in the CT arm (p=0.0023). Median Ki67 dropped sharply in both arms, from 30% (1-80) to 1% (0-30) in the LP arm (p=1.10e-8) and from 30% (2-80) to 5% (0-30) in the CT arm (p=3.10e-9). Decrease in the Ki67 geometric mean was as sharp. Of note, while baseline Ki67 was similar in both arms (p=0.315), decrease in the LP arm was significantly more profound than in the CT arm (p=0.00075). Pathological response according to RPCB were as follows, in the LP and CT arm, respectively: class 0: 9.6%/10.2%; class I: 84.6%/73.5%; class II: 5.8%/16.3%. The relapse free survival PEPI scores were as follow in the LP and CT arm, respectively: class I: 13.5%/16.3%; class II: 59.6%/46.9%; class III: 28.9%/36.8% (p=0.504). Breast cancer specific survival PEPI scores were as follow in the LP and CT arm, respectively: class I: 18.9%/8.2%; class II: 54.7%/40.8%; class III: 26.4%/51%. These results were significantly better in the LP arm (p=0.027). There was no correlation between final TILs quantification and the RPCB or PEPI scores. Conclusions In this prospective multicenter study with centralized pathological review, neoadjuvant letrozole-palbociclib combination generates impressive proliferative and endocrine specific response features. It compared well with chemotherapy. The LP combination also significantly increased lymphocytic infiltration. Its clinical significance and utility remain to be elucidated, but it potentially adds new prognostic and theranostic information. Citation Format: Vincent-Salomon A, Mathieu M-C, Bataillon G, Arnould L, Verrièle V, Ghnassia J-P, Haudebourg J, Penault-Llorca F, Lefebvre C, Maran-Gonzalez A, Guinebretière J-M, Duprez R, Berghian A, Blanc-Fournier C, Calès V, Galant C, Delrée P, Lemonnier J, Delaloge S, Cottu PH. TILs variations, proliferative response and PEPI scores in patients with luminal breast cancer receiving neoadjuvant letrozole-palbociclib or chemotherapy: An extended analysis of the NEOPAL 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 P4-15-02.

Background In the phase III IMpassion130 trial, combining atezolizumab with first-line nanoparticle albumin-bound-paclitaxel for advanced triple-negative breast cancer (aTNBC) showed a statistically significant progression-free survival (PFS) benefit in the intention-to-treat (ITT) and programmed death-ligand 1 (PD-L1)-positive populations, and a clinically meaningful overall survival (OS) effect in PD-L1-positive aTNBC. The phase III KEYNOTE-355 trial adding pembrolizumab to chemotherapy for aTNBC showed similar PFS effects. IMpassion131 evaluated first-line atezolizumab–paclitaxel in aTNBC. Patients and methods Eligible patients [no prior systemic therapy or ≥12 months since (neo)adjuvant chemotherapy] were randomised 2:1 to atezolizumab 840 mg or placebo (days 1, 15), both with paclitaxel 90 mg/m2 (days 1, 8, 15), every 28 days until disease progression or unacceptable toxicity. Stratification factors were tumour PD-L1 status, prior taxane, liver metastases and geographical region. The primary endpoint was investigator-assessed PFS, tested hierarchically first in the PD-L1-positive [immune cell expression ≥1%, VENTANA PD-L1 (SP142) assay] population, and then in the ITT population. OS was a secondary endpoint. Results Of 651 randomised patients, 45% had PD-L1-positive aTNBC. At the primary PFS analysis, adding atezolizumab to paclitaxel did not improve investigator-assessed PFS in the PD-L1-positive population [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.60-1.12; P = 0.20; median PFS 6.0 months with atezolizumab–paclitaxel versus 5.7 months with placebo–paclitaxel]. In the PD-L1-positive population, atezolizumab–paclitaxel was associated with more favourable unconfirmed best overall response rate (63% versus 55% with placebo–paclitaxel) and median duration of response (7.2 versus 5.5 months, respectively). Final OS results showed no difference between arms (HR 1.11, 95% CI 0.76-1.64; median 22.1 months with atezolizumab–paclitaxel versus 28.3 months with placebo–paclitaxel in the PD-L1-positive population). Results in the ITT population were consistent with the PD-L1-positive population. The safety profile was consistent with known effects of each study drug. Conclusion Combining atezolizumab with paclitaxel did not improve PFS or OS versus paclitaxel alone. ClinicalTrials.gov NCT03125902.

This abstract was withdrawn by the authors.

Purpose:Incidence of LRs in patients (pts) treated for HR+ HER2- localized BC and distribution overtime have not been described in recent years after introduction of new generation of adjuvant therapies and more extensive use of radiotherapy. We evaluated the incidence and distribution overtime of LRs in pts with HR+ HER2- N+ BCs who entered PACS 01 and PACS04 trials. Patients and Methods: Data were analyzed from 2909 pts with HR+/HER2- BC out of 5008 included in both trials. Pts underwent mastectomy or lumpectomy plus axillary dissection for a localized N+ BC and, according to study design, were randomized to: 6 cycles of FE100C (standard arm) versus FE100C x 3 cycles followed by docetaxel 100 mg/m2 x 3 cycles (FEC-D) (PACS01) or 6 cycles of Epirubicin 75mg/m2 and Docetaxel 75 mg/m2 (ED75)(PACS04). Loco-regional radiotherapy was mandatory after lumpectomy and recommended in other cases. All pts received 5 years of hormone therapy (HT). A competing risk multivariate analysis was conduct using Fine and Gray model to identify risk factors associated to isolated LRs. Competing events were nodal recurrence, contralateral BC, distant metastasis and death. Cumulative incidence associated to each event was estimated by a Kablfleish-Prentice estimator. Results: Pts' median age was 50 (22-65); 67.2% underwent lumpectomy, 32.8% mastectomy; 67.6% had 1 to 3 N+, 32.4% more than 3 N+; 45.7% had lymphovascular invasion; 49.5% received FE100C, 35.8% ET75, 14.7% had FEC-D; while radiotherapy was given to 97.3% and HT to 92.2%, of whom 90.5% received tamoxifen. At a median follow-up of 9.1 years, 60 pts (2.1%) experienced LR as first event. The 5-year and 10-year cumulative incidence of LRs were 1.04% and 2.53%, respectively. The cumulative incidence of LRs increased from the 5th year, and the annual risk tended to remain constant over time. Multivariate analysis of competing risk showed that younger age, conservative surgery and omission of HT (not prescribed or non-adherence) were independently associated with risk of developing LRs. Table 1. Multivariate analysis on competing risk of predictors of LRsVariablesHR 95%CIP valueAge at entry ( 20mm, ≤20 mm0.68 [0.37; 1.24]0.203N+ >3, 1-31.73 [0.99; 3.02]0.055Grade II/III, I1.06 [0.50; 2.24]0.885PR+,PR-1.78 [0.70; 4.53]0.223Type of chemotherapy 3FEC-3D, 6FEC/6ET1.32 [0.65; 2.69]0.446Number of cycles 6, Conclusion: Our analysis showed that incidence of LRs in pts with HR+ N+ BCs treated within PACS trials were considerably lower as compared to earlier studies. These findings may reflect differences in treatment era, as the more extensive use of radiotherapy and new generation of adjuvant chemotherapy. Despite current adjuvant strategies, young age at diagnosis and omission of HT remain independent risk factors of LRs. Citation Format: Pistilli B, Filleron T, Mazouni C, Zingarello A, Lacroix-Triki M, Rivera S, Coudert B, Serin D, Canon J-L, Campone M, Bachelot T, Goncalves A, Levy C, Cottu P, Petit T, Eymard J-C, Tunon De Lara C, Roché H, Roca L, Lemonnier J, Delaloge S. Overtime distribution and predictors of local recurrences (LRs) in patients with hormone receptor positive (HR+) and node positive (N+) breast cancers (BCs): 10 -year follow-up analysis of UNICANCER-PACS 01 and PACS04 trials [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-07-07.

This abstract was withdrawn by the authors.

Purpose: There is a need to identify which patients present a high risk of relapse after optimal adjuvant therapies, in order to better define which population of early breast cancer patients is eligible to new drugs. Previous studies have shown that gene copy numbers drive breast cancer progression. In the BIG1-98 trial, FGFR1 (8p11) and ZNF217 (20q13) amplifications were associated with poor outcome in patients with HR+/Her2- early breast cancers. In the present study, we aim to validate these findings using retrospective analysis of samples prospectively collected in a randomized trial (PACS04). Patients and methods: Tumor DNA was extracted from FFPE samples obtained from patients included in PACS04 trial. This trial compared FEC to ED75 in patients with node positive, early breast cancer and included 3000 patients between 2001 and 2004. The biomarker study focuses on HR+/Her2- breast cancer. 500 samples were collected and hybridization was performed on 390. DNA copy numbers were assessed on 900 genes using Oncoscan FFPE assay kit. Prognostic value of FGFR1 (8p11) and ZNF217 (20q13) copy numbers was assessed in a Cox model that included prognostic parameters. Prognostic value was assessed using CNA as continuous variable, and with a predefined cut-off (CN>=3). Metastases-free survival (MFS) was chosen as endpoint for this biomarker study. Results: Tumor copy numbers alterations were obtained in 390 patients with HR+/Her2-, node positive, early breast cancer. 31% of the patients presented more than 3 lymph node involved, and 25% a poorly differenciated tumor. The median tumor size was 20 mm. 120 (30%) and 112 (28%) patients presented FGFR1 and/or ZNF217 gene gain with a cut-off for amplification predefined at 3 copies. When assessed as continuous variable, FGFR1 (HR: 1.02, 95%CI:1.007-1.04, p=0.0045) and ZNF217 (HR: 1.011, 95%CI:1.003-1.01, p=0.006) copy numbers were associated with MFS. The 10 years MFS rates were 68% (95%CI: 59-78%) and 85% (95%CI: 81-91%) in patients with FGFR1-gained and FGFR1-normal tumors respectively (HR: 2.51, 95%CI:1.56-4.01, p=0.0001). The 10 years MFS rates were 72% (95%CI:65%-83%) and 83% (95%CI: 77-87%) in patients with ZNF217-gained and ZNF217-normal tumors (HR: 1.79, 95%CI:1.12-2.86, p=0.013). In a multivariate analysis, FGFR1-gain (HR: 2.45, 95%CI:1.42-4.22, p=0.0012) and ZNF217-gain (HR:1.78, 95%CI:1.00-3.17, p=0.049) were associated with a higher likelihood of metastases and/or death. The 10 MFS rate was 88% (95%CI: 83-94%) for patients who presented FGFR1- and ZNF217-normal tumor (n=191), and 71% (95%CI: 66-76%) in patients presenting FGFR1 and/or ZNF217 gene gain. Conclusion: Using samples prospectively collected in a randomized trial, this study validates the prognostic value of FGFR1- and ZNF217- copy numbers in patients who present HR+/Her2- early breast cancer. Exploratory analyses on copy number alterations, together with targeted sequencing are ongoing and will be presented. Citation Format: Andre F, Penault Llorca F, Carene D, Roche H, Delaloge S, Lacroix L, Scott V, Richon C, Lacroix-Ticrit M, Lemonnier J, Michiels S. FGFR1 / ZNF217 copy numbers and outcome in patients with node positive, HR+/Her2- early breast cancer: A genomic analysis of PACS04 trial [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD4-10.

Background Anti-HER2 therapies are associated with a risk of cardiac toxicity, particularly as part of anthracycline-based regimens. BERENICE (NCT02132949), a nonrandomized, Phase 2 cardiac safety study showed neoadjuvant treatment with pertuzumab (P) + trastuzumab (H) and 2 common anthracycline–taxane-based regimens had a safety profile consistent with prior studies of P+H, and was associated with high pathologic complete response rates. Here we report safety data from the P+H adjuvant treatment period (AP). Methods Patients (pts) with centrally confirmed, localized HER2-positive breast cancer and normal cardiac function received 4 q2w dose-dense doxorubicin and cyclophosphamide cycles (60/600mg/m2) then 12 qw paclitaxel injections (80mg/m2; Cohort A), or 4 q3w fluorouracil/epirubicin/cyclophosphamide cycles (500/100/600 mg/m2) then 4 q3w docetaxel cycles (75mg/m2, up to 100mg/m2;Cohort B). In both cohorts, 4 q3w cycles of P (loading:840mg; maintenance:420mg) + H (loading:8mg/kg; maintenance:6mg/kg) were started with taxane therapy and continued in the adjuvant setting (for up to 13 cycles to complete 1 year of treatment). Surgery was scheduled after 8 cycles of preoperative therapy. Primary endpoints were incidence of New York Heart Association (NYHA) Class III/IV heart failure and incidence of left ventricular ejection fraction (LVEF) declines (≥10%-points from baseline to Results In total, 397 pts received ≥1 dose of study medication and were included in the overall treatment period (OTP) safety analysis. Of these, 371 (Cohort A:181; Cohort B:190) pts entered the AP and were included in the AP safety analysis. Mean (SD) number of AP treatment cycles of P and H were 12.3 (2.0) in Cohort A and 12.3 (2.2) in Cohort B. In the AP, incidence of heart failure was minimal (0.5%) and confirmed LVEF decline incidence was low (Table 1). Table 1: Cardiac AE Cohort ACohort B OTP n=199AP n=181OTP n=198OTP n=190NYHA Class III/IV heart failure Events, n4011Pts with event, n (%)3(1.5)01(0.5)1(0.5)LVEF decline Events, n36223429Pts with LVEF decline, n (%)21(10.6)14(7.7)22(11.1)20(10.5)Pts with confirmed LVEF decline, n (%)7(3.5)5(2.8)7(3.5)6(3.2) General adverse events (AEs) are shown in Table 2; 26 (14.4%) pts in Cohort A and 45 (23.7%) in Cohort B had diarrhea AEs (mostly grade 1). Table 2: General AE Cohort ACohort BPts, n (%)OTP n=199AP n=181OTP n=198AP n=190Any AE198(99.5)171(94.5)198(100.0)171(90.0)Grade ≥3 AE109(54.8)23(12.7)126(63.6)40(21.1)Serious AE54(27.1)15(8.3)61(30.8)17(8.9)AE leading to P or H discontinuation19(9.5)9(5.0)14(7.1)11(5.8) Conclusion P+H in the adjuvant setting, following P+H with anthracycline-based regimens in the neoadjuvant setting, are associated with low incidence of cardiac AEs. Cardiac safety results for P+H in the AP and OTP of BERENICE were consistent with results from prior studies evaluating adjuvant treatment with single-agent H, suggesting the addition of P to H in the adjuvant setting does not increase cardiac toxicity. Citation Format: Dang C, Ewer MS, Delaloge S, Ferrero J-M, Verrill M, Colomer R, Vieira C, de la Cruz Merino L, Lucas J, Werner TL, Douthwaite H, Bradley D, Waldron-Lynch M, Eng-Wong J, Swain SM. Safety of adjuvant treatment with pertuzumab plus trastuzumab after neoadjuvant anthracycline-based chemotherapy in patients with HER2-positive localized breast cancer: Updated results from the BERENICE study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-20-04.

Background: Neoadjuvant pertuzumab (P)+trastuzumab (H)+standard chemotherapy (CT) significantly increases pathologic complete response (pCR) rates v H+CT. However, anti-HER2 therapy following anthracyclines can cause heart failure, and data are limited or lacking on combining P+H after epirubicin or doxorubicin. We report cardiac and overall safety as well as total pCR (tpCR) rates with widely used but understudied anthracycline-containing regimens. Methods: BERENICE (NCT02132949), a non-randomized, open-label, phase II study, enrolled patients (pts) with centrally confirmed HER2-positive, locally advanced, inflammatory, or early-stage, unilateral, and invasive breast cancer, Eastern Cooperative Oncology Group performance status ≤1, and baseline left ventricular ejection fraction (LVEF) ≥55%. In the neoadjuvant period, Cohort A pts received four q2w dose-dense doxorubicin+cyclophosphamide cycles (60 mg/m2/600 mg/m2 with granulocyte-colony stimulating factor support as needed) followed by 12 qw paclitaxel doses (80 mg/m2) + four q3w P+H cycles (P 840 mg, then 420 mg; H 8mg/kg, then 6 mg/kg). Cohort B received four q3w fluorouracil/epirubicin/cyclophosphamide cycles (500 mg/m2/100 mg/m2/600 mg/m2) followed by four q3w docetaxel cycles (75 mg/m2 escalated to 100 mg/m2) + four q3w P+H cycles. Surgery was performed after cycle 8 for both cohorts. The primary objective was to evaluate cardiac safety during the neoadjuvant period, assessed by incidence of 1) New York Heart Association (NYHA) Class III/IV heart failure and 2) significant LVEF declines (≥10% from baseline with a value of Results: Four hundred one pts were enrolled between Jul 2014–Aug 2015. Clinical cutoff was Mar 3, 2016. Demographics and baseline characteristics were generally balanced between cohorts; 64.3% v 61.7% of pts had centrally confirmed hormone receptor (HR)-positive disease and 95.0% v 93.0% had T1–T3 primary tumors. Three pts in Cohort A and none in Cohort B experienced NYHA Class III/IV heart failure during neoadjuvant treatment (table). Thirteen pts in Cohort A v four in Cohort B had significant LVEF declines (table). One Cohort B pt's LVEF decline was prior to anti-HER2 treatment. AE and serious AE (SAE) rates were well balanced between cohorts. The most common AEs were nausea, diarrhea, and alopecia. The most common SAE was febrile neutropenia. tpCR rates were similar between cohorts (table). Neoadjuvant periodCohort ACohort BSafety: Pts, n (%)N=199N=198NYHA Class III/IV heart failure3 (1.5%)0Significant LVEF decline13 (6.5%)4 (2.0%)tpCR (ypT0/Tis ypN0): Pts, n/N (%) Intention-to-treat123/199 (61.8%)122/201 (60.7%)HR-positive66/128 (51.6%)71/124 (57.3%)HR-negative53/65 (81.5%)51/75 (68.0%) Conclusion: Cardiac and general safety of the two anthracycline-containing regimens in BERENICE were as expected and were consistent with the known P+H+CT profiles. Both regimens were active, and tpCR rates were high. Citation Format: Swain SM, Ewer MS, Viale G, Delaloge S, Ferrero JM, Verrill M, Colomer R, Vieira C, Werner TL, Douthwaite H, Bradley D, Waldron-Lynch M, Eng-Wong J, Dang C. Primary analysis of BERENICE: A phase II cardiac safety study of pertuzumab, trastuzumab, and neoadjuvant anthracycline-based chemotherapy in patients with locally advanced, inflammatory, or early-stage, unilateral, and invasive HER2-positive breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-41.

Background: Genomic tests can identify ER-positive Her2-negative localized breast cancer (BC) patients (pts) who may not drive any benefit from adjuvant chemotherapy (CT). Several genomic tests have reached a high level of analytical and clinical validity, as well as clinical utility in such situation. Recent results suggest that the safe de–escalation of adjuvant chemotherapy may be most beneficial in pts with clinical high or indetermediate risk, as assessed by classical variables or online tools, through the use of a genomic test. The clinical risk though remains quite uncertain with variable definition and grey zones. The present study aimed at determining if EPclin clinico-genomic test had a significant impact on treatment decision making among pts with predefined intermediate /borderline clinical risk. Patients and methods: Women were eligible for the present study if they had complete surgical removal of a localized ER+ Her2- pN0 or pN1mi BC, and were considered by the multidisciplinary team meeting (MTM) of the center as being in a "grey zone" of uncertain CT benefit based on classical clinic-pathological assessment. The MTM1 proposed a decision (chemo/no chemo). After informed consent, an EPclin signature classified the tumor as low risk (EPclin Score < 3.3, no chemo advised) or high risk (> 3.3, a theoretical indication for adjuvant chemo). Primary end point was the proportion of change between initial adjuvant CT decision at MTM1 and final administration of CT (yes/no). A 5 steps Fleming design was planned, considering that a change rate of 15% or less was not acceptable (low clinical utility). A one-step design was used (unilateral α = 2.5% and β = 1%). Results: 203 pts were included, of whom 198 are evaluable for the main end point. 74% of the tumors were grade 2, 72% T1 , 25% T2, 3% T3; 16% were pN1mi and 84% pN0. Median age was 57. EpClin® was low risk in 67% and high risk in 33% of the cases. The global rate of decision change between MTM1 and final administration of CT was 70/198 (35.4% IC-95% = [28.7-42.1]), with 55 (27.7%) decreases and 15 (7.6%) increases in CT indication. 27% instead of 47% of all pts finally received CT (43% decrease in CT prescription). In the multivariate analysis, the factors associated to decrease for less CT were EPclin score (OR 0.11 [0.03-0.35]), proliferation (OR 1.08 [1.03-1.13]) and higher grades (OR 5.22 [1.04-26.08]); while EPclin score was positively (OR 76.6 [7.11-824.8]), but higher grades inversely (OR 0.06 [0-0.86]) associated to an increase in CT administration. Of note, the change in final decision occurred after the MTM2 and after report of the results and discussion with the patient in 9 of the 70 cases (12% of changes; 4.5% of the whole population)(8 decreases and 1 increase in CT administration). Conclusion: Adendom met its primary objective, with 35% of intermediate clinico-pathological risk pts getting significant therapeutic changes upon the receipt of an EPclin gene expression profile. 43% of these "intermediate risk" pts planned for CT avoided it. 12% of the changes were discrepant with the test's results and occurred after discussion with the patient. Citation Format: Penault-Llorca F, Kwiatkovski F, Grenier J, Levy C, Leheurteur M, Uwer L, Derbel O, Le Rol A, Jacquin J-P, Jouannaud C, Quenel-Tueux N, Girre V, Foa C, Guardiola E, Lortholary A, Catala S, Lemonnier J, Delaloge S. UCBG 2-14: A prospective multicenter non-randomized trial evaluating the effect of EndoPredict® (EPclin®) clinico-genomic test on treatment decision making among patients with intermediate clinical risk [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-05-10.

Summary Background In 2013, the interim analysis of the Protocol for Herceptin as Adjuvant therapy with Reduced Exposure (PHARE) trial could not show that 6 months of adjuvant trastuzumab was non-inferior to 12 months. Here, we report the planned final analysis based on the prespecified number of occurring events. Methods PHARE is an open-label, phase 3, non-inferiority randomised trial of patients with HER2-positive early breast cancer comparing 6 months versus 12 months of trastuzumab treatment concomitant with or following standard neoadjuvant or adjuvant chemotherapy. The study was undertaken in 156 centres in France. Eligible patients were women aged 18 years or older with non-metastatic, operable, histologically confirmed adenocarcinoma of the breast and either positive axillary nodes or negative axillary nodes but a tumour of at least 10 mm. Participants must have received at least four cycles of a chemotherapy for this breast cancer and have started receiving adjuvant trastuzumab-treatment. Eligible patients were randomly assigned to either 6 months or 12 months of trastuzumab therapy duration between the third and sixth months of adjuvant trastuzumab. The randomisation was stratified by concomitant or sequential treatment with chemotherapy, oestrogen receptor status, and centre. The primary objective was non-inferiority in the intention-to-treat population in the 6-month group in terms of disease-free survival with a prespecified hazard margin of 1·15. This trial is registered with ClinicalTrials.gov, number NCT00381901. Findings 3384 patients were enrolled and randomly assigned to either 12 months (n=1691) or 6 months (n=1693) of adjuvant trastuzumab. One patient in the 12-month group and three patients in the 6-month group were excluded, so 1690 patients in each group were included in the intention-to-treat analysis. At a median follow-up of 7·5 years (IQR 5·3–8·8), 704 events relevant to disease-free survival were observed (345 [20·4%] in the 12-month group and 359 [21·2%] in the 6-month group). The adjusted hazard ratio for disease-free survival in the 12-month group versus the 6-month group was 1·08 (95% CI 0·93–1·25; p=0·39). The non-inferiority margin was included in the 95% CI. No differences in effects pertaining to trastuzumab duration were found in any of the subgroups. After the completion of trastuzumab treatment, rare adverse events occurred over time and the safety analysis remained similar to the previously published report. In particular, we found no change in the cardiac safety comparison, and only three additional cases in which the left ventricular ejection fraction decreased to less than 50% have been reported in the 12-month group. Interpretation The PHARE study did not show the non-inferiority of 6 months versus 12 months of adjuvant trastuzumab. Hence, adjuvant trastuzumab standard duration should remain 12 months. Funding The French National Cancer Institute.

Background: Women's awareness about their personal breast cancer (BC) risk in the general population is generally low. Mass screening and mass prevention interventions have as yet been moderately efficient in breast oncology. "Personalized prevention" including risk communication, personalized screening and primary prevention recommendations is a promising. A personal history of BBL slightly increases subsequent BC risk. Objectives: the main objective was to evaluate the acceptability of a mathematical tool- based breast cancer risk assessment and subsequent proposal of a personalized BC prevention program in a BBL population. Secondary objectives were to evaluate information receipt, awareness, satisfaction, and anxiety. Methods: Women were eligible for the study if aged 40-74, were recently diagnosed with a benign breast lesion at the one stop breast Unit of the center, had no personal history of cancer or atypical lesions and were not BRCA carriers. Women were proposed a personalized risk assessment using a mathematical tool (BCSC score adapted to the French population-Ragusa et al) together with personalized information on risk, BC screening and prevention, release of a personalized program and evaluation of their receipt. The main end point was the proportion of women willing to have a risk assessment and personalized counseling. A cut-off point of 70% was considered critical to consider acceptability. Secondary end points were perceived BC risk, satisfaction, anxiety and distress levels at day 2 using standardized questionnaires, as well as adherence with the proposed programs. Results: Of 150 women proposed BC risk assessment and personalized prevention information between 02/2014 and 03/2015, 129 (86%) accepted. Median age: 53.6 years. 33% had a low BC risk (< 1.1% at 5 yrs [mean risk of 50 yrs-old women in France]), 53% a moderate risk (1.1-1.66% at 5 yrs), while 14% were high risk (> 1.66% at 5 yrs). 87% had never had any previous information on BC risk. 3 pts required a genetic assessment. Participants were globally very satisfied with physicians' and nurses' interpersonal skills, availability and provision of information (mean score > 4; range 2-5). The mean scores of clarity of the BC risk information (4.14±1;range 2-5) and screening program information (4.21±0.93; range 2-5) were high. The mean score of perceived risk level was estimated to 33.5% (SD=21.9). Mean scores of state anxiety (36.7±12.2; range 20-71), trait anxiety (39.5±8.9; range 23-59), depressive symptoms (3.4±3.3; range 0-12) and psychological distress indicated low levels of all. Higher level of state-anxiety was associated with lower scores of satisfaction with doctors and nurses human qualities (r = 0.26, p Conclusion: The receipt of breast cancer risk assessment and personalized prevention information among women diagnosed with BBL was high (86%). Information need is high given the low level of real risk awareness. Such population may benefit from personalized prevention. Anxiety and distress scores were low and satisfaction rates high. Citation Format: Tlemsani C, Boinon D, Yung MF, Ragusa S, Mazouni C, Balleyguier C, Saghatchian M, Ghouadni A, Rivera S, Michiels S, Delaloge S. Receipt of breast cancer risk assessment and personalized prevention information among women diagnosed with a benign breast lesion (BBL) in a one stop breast unit: A prospective assessment. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-10-03.

Background: Breast cancer (BC) during pregnancy (BCP) is a rare situation that requires collaboration between oncologists, surgeons and obstetricians. The main objectives of this study were to compare the overall survival (OS) and disease free survival (DFS) of a multicenter cohort of pregnant patients (pts) with those of matched control pts. Methods: Patients from 27 centers and diagnosed between 2000 and 2006 with histological confirmed M0 invasive BC were included in this retrospective study. For the cohort of BCP, pts whose pregnancy was interrupted were not eligible. Controls were matched to BCP pts on 5 criteria: clinical T (of TNM), hormonal receptor (HR) status, HER2 status, administration of neo-adjuvant chemotherapy and pathological nodal status in the absence of neo-adjuvant chemotherapy. Survival times were estimated from the date of diagnosis using Kaplan-Meier method. OS was calculated until death from every cause, DFS was calculated until relapse or death from every cause; patients alive were censored at the date of last news. Results: 100 BCP pts were identified. Their clinical and pathological characteristics were described on a previous presentation (SABCS 2013 P6-06-07). Matched controls could not be found for 12 BCP pts. 88 BCP pts were matched with 204 controls. The only differences between the 2 populations in terms of characteristics or treatment were more radical mastectomy (p=0.036) and fewer taxane administrations in the BCP group (p=0.06). The median duration of follow-up was 8.2 years for cases and 7.7 years for controls. There were no differences between BCP pts and controls in 5-year OS: 83.4%, IC 95% (73.5-89.8) vs 83.8%, IC 95% (77.9-88.3) nor 7-year OS: 76.5% (65.5-84.4) vs 78.1% (71.5-83.3) (p=0.52). The 5-year DFS was 58.6% IC 95% (47.3-68.3) vs 67.2% IC 95% (60.2-73.2) (p= 0.16). However, 5-year DFS was lower in HR+ BCP pts subgroup than in HR+ control group (56.7% IC 95% (40.7-69.8) vs 70.9% IC 95% (61.4-78.5) (p=0.023). Conclusion: This multicenter French large study confirmed that there are no differences on OS and DFS between pregnant and no pregnant pts, though this might not be true for HR subgroup. Citation Format: Vanlemmens L, Ploquin A, Delaloge S, Rouzier R, Lesur A, Frenel J-S, Loustalot C, Bachelot T, Provansal M, Ferrero J-M, Coussy F, Debled M, Kerbrat P, Vinceneux A, Djelila A, Baron M, Jebert S, Decoupigny E, Tresch E, Bonneterre J. 5-year overall survival of early breast cancer during pregnancy: A multicenter French case control study. [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 P1-07-02.

Backgound : The primary analysis of the REMAGUS-02 multicenter randomized phase II trial demonstrated that celecoxib did not improve pCR rates in pts with HER2-negative localized invasive breast cancer (BC), whereas trastuzumab increased pCR rates in HER2-positive ones [Pierga BCRT 2010]. We report here the long-term follow-up results of this trial for disease free survival (DFS) and overall survival (OS). Patients and methods: From May 2004 to October 2007, 340 stage II-III BC patients were randomly assigned to receive 4 cycles (c) of epirubicin–cyclophosphamide q 3 w followed by 4 c of docetaxel q 3 w +/- trastuzumab in HER2 positive pts (120 pts) or +/- celecoxib in HER2 negative pts (n=220). From September 2005, all pts with HER2 positive BC received adjuvant T for a total of 18 c (n=106). Patients with hormone receptors (HR) positive tumor received adjuvant endocrine treatment according to menopausal status Results: With a median follow up of nearly 8 years (94.4 months, 20-127m), 112 relapses and 75 deaths have been observed (median DFS and OS not reached). Eight years DFS and OS were respectively 63 % [57%-71%] and 75 % [70%-81%] in HER2 negative group; and 75% [67%-83%] and 82 % [74%-90%] in HER2 positive group. DFS was significantly higher in HER+ pts than in HER2-(HR: 0.64 [0.42-0.99], p=0.042), whereas OS did not differ significantly (HR: 0.67, [0.41-1.11], p=0.123). In the overall population, progesterone receptor (PgR) positivity was associated with a better DFS (p=0.012) and OS (p In the HER2- subgroup, no effect of neoadjuvant celocoxib was observed on survival, neither in intention to treat (ITT) nor in per protocol analyses. In the multivariate analysis clinical stage (T3/T4 versus T2, HR: 1.92 [1.209 - 3.05], p=0.006), PgR status (positive versus negative HR : 0.52, [0.32-0.84], p=0.007) and pCR (yes vs no, HR : 0.213 [0.066-0.687], p=0.01) were significant predictors of DFS. In the HER2+ subgroup, neoadjuvant versus adjuvant trastuzumab was not significantly associated with DFS, neither in the ITT, nor in the per protocol analysis. Conclusion: Celecoxib was not associated with pCR or survival benefit when added to conventional neoadjuvant CT in Her2-negative BC pts. Lack of PgR expression is a major prognostic factor for survival. Neoadjuvant versus adjuvant trastuzumab increased pCR rates but did not change significantly DFS and OS of HER2 positive BC pts. Citation Format: Giacchetti S, Hamy-Petit A-S, Delaloge S, Brain E, Berger F, Mathieu M-C, de Cremoux P, Bertheau P, Guinebretière J-M, Saghatchian M, Tembo O, Marty M, Pierga J-Y. Long term survival of locally advanced breast cancers (LABC) treated with neoadjuvant treatment, results of a multicenter randomised phase II study (Remagus 02 trial). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-14-09.

Background: The COVID-19 pandemic has dramatically changed the Health Care System organization in many European countries Many Oncology departments have rapidly implemented telehealth in their clinical practice For breast cancer (BC) patients (pts), up to 80% of all in-person visits have been transformed in TV Methods: 18 centers from France and Italy invited all BC pts who have had at least one TV (Visio conference or telephone) during the COVID-19 pandemic to answer an online, anonym questionnaire (Q) ontheir experience with TV Q included 42 questions: demographic data, BC medical situation, TSQ scale (telehealth specific Q), physician’s module of EORTC OUTPATSAT35 (11 SAT35), and HADS anxiety scale The primary objective was to evaluate satisfaction with TV Secondary objectives: anxiety, factors associated with satisfaction and description of satisfaction in pts’ subgroups Results: Between 6/4/2020 and 15/05/2020, 1244 pts (out of 3762 invited) filled in the Q and were included in the analysis Main characteristics and results are shown in the Table Mean 11 SAT35: 85 21 and 77 41 for pts who had visio versus telephone TVs respectively 11 SAT35 was highly correlated to HADS score (p < 0 001) Multivariate analyses will be presented [Formula presented] Conclusions: TV during the COVID-pandemic appeared feasible and well accepted by BC pts regardless of their medical situation and mode of TV Anxiety was high during this period, and correlated with satisfaction These findings help identifying BC pts who may be proposed TV beyond the pandemic crisis Legal entity responsible for the study: The authors Funding: Has not received any funding Disclosure: C Levy: Honoraria (self): Pfizer;Honoraria (self), Travel/Accommodation/Expenses: Roche;Honoraria (self): MSD;Honoraria (self), Travel/Accommodation/Expenses: Lilly;Travel/Accommodation/Expenses: Daiichi C Uzan: Honoraria (self), Advisory/Consultancy: Roche D Genet: Advisory/Consultancy: AstraZeneca;Travel/Accommodation/Expenses: Roche;Amgen;Pfizer;Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis A Patsouris: Travel/Accommodation/Expenses: Roche;Travel/Accommodation/Expenses: ESAI;Travel/Accommodation/Expenses: Pfizer;Honoraria (institution): Lily;Research grant/Funding (institution): ESAI V C Dieras: Advisory/Consultancy, Travel/Accommodation/Expenses, and travel expenses and speaker: Roche;Novartis;Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses, and travel expenses and speaker: Pfizer;Advisory/Consultancy, Travel/Accommodation/Expenses, and travel expenses and speaker: Lilly;AstraZeneca;Daiichi Sankyo;Advisory/Consultancy: Abbvie;MSD;Eisai Speaker Bureau/Expert testimony: Seattle Genetics J-Y Pierga:Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Roche;Honoraria (self), Speaker Bureau/Expert testimony: Ipsen;Novartis;AstraZeneca;Amgen S Ladoire: Speaker Bureau/Expert testimony: Lilly;Speaker Bureau/Expert testimony, and Travel/Accommodation expense: Pfizer;BMS;Ipsen;Janssen Oncology;Sanofi;Speaker Bureau/Expert testimony: Roche;Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis;Travel/Accommodation/Expenses: AstraZeneca;Travel/Accommodation/Expenses: Astellas Pharma W Jacot: Honoraria (self), Honoraria (institution), Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca;Honoraria (self), Travel/Accommodation/Expenses: Eisai;Lilly France;Pfizer;Roche;Honoraria (self): MSD;Travel/Accommodation/Expenses: Novartis;Sanofi Aventis;GSK;Fabre;Chugai Pharma S Delaloge: Honoraria (institution), Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca;Roche;Pfizer;Honoraria (institution), Research grant/Funding (institution): Sanofi;BMS;Honoraria (institution): Pierre Fabre;Puma;Lilly;Servier;Research grant/Funding (institution): Orion;MSD;Daichy M Lambertini: Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche;Spe ker Bureau/Expert testimony: Takeda;Lilly;Theramex B Pistilli: Advisory/Consultancy: PUMA biotechnologies;Speaker Bureau/Expert testimony: Fabre;Novartis;Myriad genetics;Travel/Accommodation/Expenses: MSD oncology;Astra Zeneca;Novartis;Pfizer All other authors have declared no conflicts of interest

Background To define a core set of geriatric data to be methodically collected in clinical cancer trials of older adults, enabling comparison across trials. Patients and methods Following a consensus approach, a panel of 14 geriatricians from oncology clinics identified seven domains of importance in geriatric assessment. Based on the international recommendations, geriatricians selected the mostly commonly used tools/items for geriatric assessment by domain (January–October 2015). The Geriatric Core Dataset (G-CODE) was progressively developed according to RAND appropriateness ratings and feedback during three successive Delphi rounds (July–September 2016). The face validity of the G-CODE was assessed with two large panels of health professionals (55 national and 42 international experts) involved both in clinical practice and cancer trials (March–September 2017). Results and discussion After the last Delphi round, the tools/items proposed for the G-CODE were the following: (1) social assessment: living alone or support requested to stay at home; (2) functional autonomy: Activities of Daily Living (ADL) questionnaire and short instrumental ADL questionnaire; (3) mobility: Timed Up and Go test; (4) nutrition: weight loss during the past 6 months and body mass index; (5) cognition: Mini-Cog test; (6) mood: mini-Geriatric Depression Scale and (7) comorbidity: updated Charlson Comorbidity Index. More than 70% of national experts (42 from 20 cities) and international experts (31 from 13 countries) participated. National and international surveys showed good acceptability of the G-CODE. Specific points discussed included age-year cut-off, threshold of each tool/item and information about social support, but no additional item was proposed. Conclusion We achieved formal consensus on a set of geriatric data to be collected in cancer trials of older patients. The dissemination and prospective use of the G-CODE is needed to assess its utility.

Background: Trastuzumab is indicated in neoadjuvant setting in locally advanced HER2 positive breast cancer patients (Gianni L. Lancet 2010). There is no data on the impact of the use of neoadjuvant Trastuzumab (T) compared to adjuvant T on survival. Patients and methods: From May 2004 to October 2007, 341 stage II-III breast cancer patients were included in a phase II randomized trial and received 4 cycles (c) of epirubicin (75 mg/m2 d1)–cyclophosphamide (750 mg/m2 d1) q 3 w followed by 4 (c) of docetaxel (100 mg/m2 d1) q 3 w. Pts with HER2+++ tumor (120 pts) were randomized to receive or not neoadjuvant T combined with docetaxel. From September 2005, all pts with HER2+cancer received adjuvant T for a total of 18 c (106 pts). All pts with hormone receptors positive tumor received hormonal treatment according to menopausal status (Pierga et al BCRT 2010). We report here overall survival (OS) and disease free survival (DFS) data at 5 year and associated prognostic factors. Results: At a median follow up of 49 months, the median DFS was not reached for the whole population and was statistically superior for the HER2 positive cancer patients treated with chemotherapy plus neoadjuvant T compared to the other groups, p = 0.018. The median OS is not reached for the whole population and is statistically higher in HER2 positive tumor group compared to HER2 negative group (p = 0.00077). For 106 HER2 positive breast cancer patients who had received one year of complete trastuzumab treatment, there was no significant difference in OS and DFS between pts who started T in neoadjuvant setting versus in adjuvant setting. DFS and OS were not significantly influenced by pathological Complete Response rate (pCR) (respectively, p = 0.22 and p = 0.56). At multivariate analysis including 6 factors (age, tumor size, clinical lymph node, ER, PgR), factors which influenced OS were tumor size (p = 0.03) and ER expression (p = 0.06) and for DFS, clinical lymph node status (p = 0.049) and PgR expression (p = 0.046). Conclusion: pCR is not a surrogate of survival in the HER2+subgroup. HER2 positive breast cancer pts receiving trastuzumab have a significant higher OS than those with HER2 negative tumors. OS and DFS do not seem to differ between the neoadjuvant T group and the T adjuvant group. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-14-03.

Background: However hormone receptor–positive, early-stage breast cancer is a disease with a long natural history and improved survival with 5-year adjuvant endocrine treatments. Yet late recurrence remains an important issue in adjuvant therapy. Predictors of late recurrence are not yet well characterized. Method: A total of 252 breast primary tumors were selected at the Netherlands Cancer Institute from retrospective series of ER+, HER2− breast cancer patients with a follow-up of at least 10 years. Gene expression analysis was performed using Agilent 4×44K microarrays. In order to identify genes associated to late survival differences, we used the survdiff function implemented in the R package survival and we set the parameter rho to −1 to give weight to the later part of the survival curve. The survdiff function was applied to each probe individually for DMFS time considering the probe as a covariate dichotomized into 2 groups (above and below the median expression across all samples). The parameter “strata” was used to stratify the 140 patients based on additional clinico-pathological parameters (Grade, Diameter, Lymph node status and MammaPrint), in order to find genes that add prognostic value to those parameters already known. This approach uses the distant-metastasis free survival (DMFS) time as a continuous variable. Results: After univariate analysis, MammaPrint, diameter, lymph node status and grade were significantly associated to late DMFS differences (Chi-square test p-values equal to 0.016, 0.004, In order to independently validate the prognostic power of these two genes, we tested their performance in the validation set of treated patients (n = 112) and in three publicly available datasets. In all datasets, the CH25H gene confirmed to be significantly associated to metastasis-free survival time in all tested series. Conclusions: These results might indicate that CH25H is an independent marker of late metastatic relapses. CH25H catalyzes the formation of 25-hydroxycholesterol from cholesterol, leading to repress cholesterol biosynthetic enzymes. In the last years, it is emerging that lipid metabolism plays an important role in breast cancer development and progression. Taken together, these findings make the CH25H gene a potential target for late metastasis control in breast cancer. These results warrant further prospective investigation and functional characterization of CH25H in this setting. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-09-05.

Background: Predicting a benefit from trastuzumab in patients with HER2+ breast cancer remains an important goal. Possible mechanisms of resistance include altered receptor antibody interaction, Akt and MAPK pathways, and loss of p27. The objective of this study was to determine the correlation between pMAPkinase (pMAPK), pAKT, p27, IGF-IR protein expression and the benefit of trastuzumab for patients randomized to chemotherapy (CT) alone and CT with trastuzumab. Patients and methods: From May 2004 to October 2007, 120 patients with stage II and III HER2+ breast carcinomas were enrolled in a phase II trial of neoadjuvant chemotherapy (CT) with epirubicin-cyclophosphamide (4 courses) followed by docetaxel ± trastuzumab (T) (4 courses). A complete pathological response (pCR) was defined by the absence of residual invasive carcinoma in the breast and axillary lymph nodes. A tissue microarray was constructed from paraffin-embedded tumor samples collected prior to neoadjuvant chemotherapy. Patients' tumours were scored HER2 3+ immunohistochemically (IHC) or 2+ IHC with HER2 amplification by FISH. Immunohistochemical analysis of pMAPK, pAKT, p27 and IGF-IR was performed on tumor tissue microarrays before CT. The H-score (intensity × %) was evaluated. Specimens were classified as exhibiting high or low expression based on a median value as the cut-off point for each marker. A logistic regression model, including the marker and its interaction with treatment, was used to analyse the markers predictive of a treatment effect on the pCR. The independent predictive value was analysed in a multivariate logistic regression adjusting on the lymph node and ER status. Results: 117/120 (97.5%) patients had sufficient tumor for the analysis. The pCR rate was 19% in the CT arm and 25% in the CT+T arm. The median H-score was: pMAPK = 28, pAKT= 25, p27= 50 and IGF-IR = 15. No significant difference was observed in the pCR rate between the two arms according to pAKT, p27, IGF-IR expression. The pCR rate was higher in CT+T compared to CT alone in patients with high pMAPK expression (OR = 4.7 (0.9–24.2); interaction p = 0.03). No difference was observed in the pCR rate in patients with low pMAPK expression (OR = 0.5 (0.1–1.8). Conclusions: In HER2-positive breast cancers, pMAPK expression evaluated by IHC was significantly associated with a pathological response in the arm with neoadjuvant trastuzumab. High pMAPK expression could be a predictive marker of response to trastuzumab in a CT +T regimen. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-06-04.

Background: Cox 2 is frequently over expressed in breast cancers. Celecoxib is a COX-2 inhibitor with anti angiogenic and pro-apoptotic activities. There are few data of anti-COX2 treatment in breast cancers. and no data on the impact of neoadjuvant anti COX 2 agent on survival. Patients and methods/: From May 2004 to October 2007, 340 stage II-III breast cancer patients were included in a phase II randomized trial and received 4 cycles (c) of epirubicin (75 mg/m2)–cyclophosphamide (750 mg/m2) q 3 w followed by 4 (c) of docetaxel (100 mg/m2) q 3 w. Pts with HER2 negative tumors (220 pts) were randomized to receive or not neoadjuvant celecoxib (200 mg bid) combined with docetaxel. All pts with hormone receptors positive tumor received hormonal treatment according to menopausal status (Pierga et al BCRT 2010). We report here overall survival (OS) and disease free survival (DFS) data and prognostic factors analyses at 5 years. Results/: At a median follow up of 49 months, the median DFS and OS are not reached for the whole population and none of them is significantly different between pts who received celecoxib or who did not (p = respectively 0.62 and 0.36). Celecoxib had no impact either on clinical and pathological complete response rate (pCR). DFS is significantly higher in patients who achieved pCR as compared to those who did not (p = 0.017; RR = 0.21 [0.051–0.88], whereas OS is borderline significant [p = 0.07; RR = 0.19 (0.026–1.4)]. Patients with triple negative (TN) tumors (78 pts) achieved worst DFS (p = 0.02) and OS (p Conclusion/: Celecoxib had no influence on pCR, DFS or OS. Despite higher pCR rate triple negative breast cancer patients' subgroup remains with the poorest outcome. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-14-18.

Introduction: Neoadjuvant chemotherapy increases the likelihood that breast conservation therapy for breast cancer patients will be successful. Breast Cancer Index (BCI), a gene expression assay combining HoxB13/IL17BR ratio and Molecular Grade Index (MGI), is prognostic for the risk of distant recurrence and overall survival in tamoxifen-treated and untreated breast cancer patients. It was previously reported that high risk patients, as determined by BCI, had a 10-fold greater probability of pathologic complete response (pCR) with neoadjuvant chemotherapy than low risk patients. The aim of the current study was to examine the relationship between BCI score and the use of breast conservation surgery (BCS) following treatment with neoadjuvant chemotherapy. Material and Methods: A total of 145 women (tumor size T1, T2 and T3) were treated with neoadjuvant cheomtherapy for stage I-III breast cancer. RNA was extracted from FFPE tumor samples and a real-time RT-PCR assay was completed to generate a BCI score and risk group categorization as previously described (Jerevall et al. Br J Cancer 2011). The relationship between BCS, BCI and clinicopathological factors was examined using univariate and multivariate logistic regression. Results: Of the 145 patients (67% ER+, 54% PR+, 57% >50 y old), 48 (33.1%) underwent BCS. BCI categorized 62 (43%) of patients as low, 50 (34%) as intermediate and 33 (23%) as high risk. The rate of BCS for the three BCI risk categories was 15% (low risk), 48% (intermediate risk) and 45% (high risk). In the low risk group, the rate of BCS was 15% corresponding to a NPV of 85%. This is consistent with previous data from the same cohort, where the NPV of BCI for pCR was 98.4% with only one patient in the low risk group achieving pCR. In univariate analysis, pathological tumor size (pT), ER, PR, grade and BCI were predictors of BCS. A higher BCI score was associated with higher likelihood of BCS (odds ratio of 3.90; CI: 1.45−10.49; p=0.0069). In multivariate analysis, pT and BCI remained significantly associated with BCS, while ER status was not (p=0.23). Results were similar in the subset of patients with T1 and T2 tumors (N=97). In this subset, BCI categorized 42% of patients as low, 37% as intermediate and 21% as high risk and the rate of BCS was 22%, 64% and 60%, respectively. In multivariate analysis of this subset, only BCI was significantly associated with BCS. In all patients, the concordance index based on a model with pT alone was 0.695. When BCI was incorporated into the model with pT, the concordance index increased to 0.801 (p= 0.0002). Conclusion: In this study, we have shown that patients with higher BCI scores were associated with a higher likelihood of receiving BCS after neoadjuvant chemotherapy. Addition of BCI to tumor size increased accuracy in predicting likelihood of BCS. BCI along with standard pathological factors may improve estimation of individual probability of BCS after neoadjuvant chemotherapy. This study gives rise to the hypothesis that patients with low BCI should not be eligible for neoadjuvant chemotherapy since the likelihood of breast conservation is low. Further large confirmatory studies are necessary. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-13-08.

Background Previous reports have described the use of microarrays to assess the molecular classification of human breast cancers and defined new subgroups based on gene expression that are relevant to patient management through their ability to predict metastatic relapse and survival relapse. However, different mechanisms may be associated with the development of early and late distant metastases. With the hypothesis that tumors may lead to early or distant metastases based on their intrinsic biological initial features, we aimed at defining molecular profiles for several subgroups of patients based on their outcome over time. Material and methods Breast primary tumors were selected from retrospective series of patients with frozen material available. These series include patients of all ages, LN- and LN+; Estrogen or Progesteron-receptor positive, Her2-negative, no adjuvant treatment, with a follow-up of more than 10 years (y) for the control group or distant metastatic relapse as first event (DM) for the study group (n=144). Patients tumors were classified in 4 groups: no relapse at 10 y (M0), DM before 3 y (M0-3, n=30), DM between 3 and 7 y (M3-7), DM after 7 y (M7+). Samples were collected in 2 different institutions (NKI series for identifying the signature and IGR series for validation). Gene expression analysis of breast tumor samples was performed using custom-made Agilent 44K high-density microarrays and hybridized against the Mammaprint® reference pool (MRP). Tumors were also assessed for their Mammaprint® status, wound-healing signature status and their intrinsic subtypes based on the Blueprint® signature. Moreover, we identified the pathway-level activities of the patient groups using PARADIGM. Results and Discussion For the NKI series, A subset of 144 samples was included based on the selection criteria: 57 M0, 31 M0-3, 25 M3-7, 31 M7+. None of the 3 previously mentioned signatures correctly identified M0 vs. M7+ patients. In order to identify a predictive signature of late relapse (after 7y) we considered M0 and M7+ MammaPrint-Low Risk patients and we split them in a training (n=41) and in a test (n=23) sets. A 73-gene signature was able to classify M7+ patients with 75% of sensitivity and 66% of specificity on the test set. DM after 7yr showed significant activation of pathway related to inflammatory response and angiogenesis. Detailed results and validation results on the independent IGR series will be presented at the meeting. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr S1-6.

Background Post-operative chemotherapy in poor responders after NAC is questionable. We evaluated the use of adjuvant Vinorelbin (NVB) + continuous infusion 5FU or Capecitabine (Cap) in women with poor pathological response to preoperative sequential Epirubicin Cyclophosphamide- Docetaxel.(ECT) Materials and methods: From May 2004 till October 2007, 340 patients (pts) with stage II or III breast adenocarcinoma received neoadjuvant ECT +/− Traztuzumab (HER2+), +/− Celecoxib (HER2 negative) in a randomized phase II trial (Pierga, 2010). 53 patients (15.5 %) had pathological complete response (no infiltrative or in situ carcinoma in the breast and lymph nodes). Eleven pts were not operated. 276 pts had grade 3–4 Chevallier residual disease. These poor responders could be optionally offered post surgery chemotherapy (NVB+5-FU or Cap)+/− Traztuzumab.This regimen started concomitantly with post-operative RT. All positive hormonal receptors received hormonotherapy. We attempted to evaluate DFS according to post operative CT in the 276 pts. To take into account the differences between populations, treated and untreated patients were matched (1:1) according to variables with a significant difference between the two groups, analyses were adjusted with all other prognostic factors. Results: Out of 276 pts with 3–4 chevallier's grade after NAC, 198 pts did not receive any CT (group A), 78 received adjuvant CT (group B): NVB + 5-FU (FUN: N=41) or Cap (N=17) + Traztuzumab (21pts, 11 FUN and 10 CapNVB), 28 pts HER2+ in the group A receive Traztuzumab alone after surgery. The main characteristics of these patients differed for the initial lymph nodes status (N0: 15 (19 %) in group A vs 88 (44 %) in group B, p = With a median follow up of 38.9 months, 63/276 pts (22.8 %) recurred, 44 (22 %) in the group A and 19 (24.3 %) in the group B. DFS for the 276 pts is 95% at 12 months (m) and 86% at 24 m, 95% and 87% in group A and 96% and 83% in group B. (logrank test: p= 0.63). We matched the 2 groups (124 pts; 62/group) according to initial lymph nodes status, local response (Chevallier grade 3 or 4) and pN status after NAC. Characteristics of this matched population were similar except for more ER negative in chemo group, 19 pts (30.6 %) and 9 pts (14.5 %) in non chemo arm. In this population, 27 events occurred, with 13 in the chemo group and 14 in the non chemo'one. Treatment effect was non significant in univariate analysis (p = 0.93). In multivariate analysis adjusted for initial tumor size (TNM), age, molecular status (hormonal receptor and HER2 status), histological grade, initial lymph node status, histological response after NAC, treatment effect was non significant (Hazard Ratio = 1 IC95% [0.38; 2.67], p = 0.99). There was no difference in treatment effect according to molecular status (test for interaction p = 0.30).This multivariate analysis was also completed in the 276 pts with similar results. Conclusion: In poor responders patients after Anthracyclins-Taxanes NAC, adjuvant chemotherapy with Vinorelbine- 5-FU or Capecitabine- did not appear to prolong DFS. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-18-13.

Background CTC count before a new line of treatment and CTC count early changes under chemotherapy have been reported as an independent prognostic marker in metastatic breast cancer in a recent pooled analysis in 841 pts (Liu M. ASCO 2011). The aim of this study was to build a prognostic tool including CTC and other parameters to assesse its predictive value for progression-free survival (PFS) and overall survival (OS). Methods: Data from the IC 2006–04 study were used. This prospective multicentre study included 267 metastatic breast cancer patients treated by first line chemotherapy with or without targeted therapy, in whom appropriate pre-treatment prognostic variables (age, performance status, number of metastatic sites, disease-free interval, ER, PR and HER2 status, tumor grade, LDH, serum markers, CTC count by CellSearch technique before treatment and before cycle 2) were available for statistical analysis. We constructed a multivariate Cox regression model for PFS and OS prediction. A stepwise selection process was applied to achieve the most informative and parsimonious models. Performance was measured with the C-index statistic. Internal validation was performed using leave-two-out technique. Results: Four nomograms have been obtained, in two clinical settings: at inclusion (before the start of any treatment) taking into account the initial CTC count, and during treatment (before cycle 2) taking into account CTC changes under treatment. Their accuracy was good for PFS and OS prediction, with C-index ranging from 0.72 to 0.88. Internal validations allow considering a good accuracy of the models in an external population. Conclusion: These clinically relevant nomograms are a simple tool for a personalized prognostic assessment including CTC assessment. Validation on independent series of patients are ongoing. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-07-04.

Background Patients with BRCA1-BRCA2 germline mutation who developed a first breast cancer (BC) have a high risk to develop a second BC, especially if aged less than 40 at first diagnosis. Thus, a positive BRCA test may influence the therapeutic management and orients towards non conservative surgery to reduce new BC occurrence. We set up a fast-track process to get BRCA1/2 and sometimes p53 mutation results within the shortest possible interval, in recently diagnosed BC patients whose probability to be mutation carriers was high (> 20%). Methods: Between 05/02/2009 and 03/01/2011, 61 patients diagnosed with localized BC requesting neo-adjuvant or adjuvant chemotherapy and whose personal or familial history fulfilled BRCA1/2 or P53 genetic testing criteria, were proposed genetic counselling. After a first multisciplinary team meeting (MT), genetic testing was proposed and performed according to usual genetic counselling rules. Psychological support was offered at every step of the process. Patients were informed that their test would be analysed as part of a fast-track process and were aware of the potential consequences of a positive test. Results were communicated and discussed during a second MT, when initial therapeutic plan was eventually changed. Results: All women who were referred to the genetic clinic for fasttrack testing accepted the analysis. The mean age at diagnosis was 38 (range 26–55). The whole process (from 1st genetic consultation till disclosure consultation) was completed in a median interval of 99 days (range 19–245). All pts received appointment within 5 days, when results were available. 50% pts postponed for more than 15 days their disclosure appointment (range 0–113 days). One patient (pt) declined result disclosure. 18 pts (30%) were found to be carrier of a deleterious mutation (13 BRCA1, 4 BRCA2, 1 p53). Variants of unknown significance (UV) in BRCA1 or BRCA2 genes were identified in another 4 patients. In 18 cases, surgery type initially proposed was changed because of the presence of the germline mutation: all pts were proposed ipsilateral mastectomy eventually associated to immediate reconstruction as often possible, as well as controlateral mastectomy. Final surgery turned to bilateral mastectomy in 3 patients with deleterious BRCA mutation and in one suspect UV 14 patients with mutation accepted the change, but four BRCA2 and one BRCA1 mutation carriers refused mastectomy or bilateral mastectomy. Radiotherapy was cancelled in a p53 mutation carrier. Conclusion: This data show that genetic testing might be considered as a part of therapeutic decision. Moreover, 22% (4/18) opted for a simultaneous controlateral prophylactic mastectomy. On the other hand, some women did not change their mind with mutation knowledge (4/18, 22%). Psychological impact of this procedure is currently retrospectively assessed by a self-questionnaire, fulfilled by mail. Analyses will be available for the meeting. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-13-06.

Background: A 1228-probeset molecular classifier (EHT Dx14) able to discriminate benign breast lesions from breast adenocarcinoma with a 96% performance was previously identified in a panel of 71 fine-needle aspirate (FNA) samples of nodular breast lesions collected at Institut Gustave Roussy (IGR). The microarray which enabled the signature identification was based on the genomewide RNA analysis using the ExonHit's SpliceArray™ technology. The objective of the current study was to validate the performance of the EHT Dx14 molecular classifier on an independent cohort of FNA samples stored at the Centre de Ressources Biologiques at IGR. Patients and methods: The samples were collected from women undergoing investigations for suspicious nodular breast lesions classified BIRAD ACR 4 or 5 on mammogram and/or ultrasonography. The morphological cytological analysis of FNA samples classified the lesions as either benign, malignant or indeterminate. All samples were associated with a definite clinico-pathological diagnosis of the breast lesions. The first part of the study aims at confirming the sensitivity, specificity and overall performance of EHT Dx14 among lesions clearly classified by morphological cytology. The second part aims at establishing its performance among lesions with indeterminate cytological results. Results: In the first part of the study, the EHT Dx14 transcriptomic signature was applied on a set of 94 FNA consecutive samples categorized as benign (n=47) or adenocarcinoma (n=47) on cytology. The benign/malignant status of the lesions was confirmed by subsequent investigations or follow-up. Results of EHT DX-14 assessment of the samples were respectively 97.9% (95%CI: [88.7%-99.9%]) for sensitivity and 91.5% (95%CI: [79.6%-97.6%]) for specificity. Results on indeterminate FNA samples are being investigated in the second part of the study. Conclusion: This study did confirm the high performance of EHT Dx14 signature in identifying malignant from benign breast lesions in clinically suspect lesions. EHT Dx14 may provide adequate biological diagnosis in the absence of capability of morphological evaluation. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-07-10.

Purpose: Circulating tumors cells (CTC) have been recently proposed as a new dynamic blood marker whose positivity at baseline is a prognostic factor and whose changes under treatment are correlated with progression-free survival (PFS) in metastatic breast cancer patients. However, serum markers levels are also used for the same purpose, and no clear comparison as been reported to date. Patients and methods: The IC 2006–04 enrolled prospectively 267 metastatic breast cancer patients treated by first line chemotherapy and confirmed that CTC levels are an independent prognostic factor for PFS and Overall survival (OS). A pre-planned endpoint was to compare prospectively the positivity rates and the value of CTC (CellSearch®), of serum tumor markers (CEA, CA 15–3, CYFRA 21.1), and of serum non-tumor markers (LDH, ALP) at baseline and under treatment for PFS prediction, independently from the other known prognostic factors, using univariate analyses and concordance indexes. Results: Table 1 shows the incidence of each of the 6 blood markers. Assessing all the 6 markers retrieved 90% of patients with at least one elevated marker at baseline. Interestingly, a combination of two markers (CA 15–3 and CYFRA 21.1, often used in lung cancer) retrieved 86% of patients with at least one marker elevated at baseline. All 6 markers were correlated with poor performance status, high number of metastatic sites and with each other. Each marker was associated, when elevated at baseline, with a significantly shorter PFS in univariate anlaysis. Serum marker changes during treatment, assessed either between baseline and week 3 or between baseline and week 6–9, were significantly associated with PFS, as reported for CTC. Concordance indexes comparison showed no clear superiority of any of the serum marker or CTC for PFS prediction. Conclusion: In the largest prospective CTC study in metastatic breast breast cancer, we previously reported that CTC count, but not serum markers, is an independent prognostic factor for PFS and overall survival. However, for the purpose of PFS prediction by measuring blood marker changes during treatment, currently available blood-derived markers (CTC and serum markers) had globally similar performances. Besides CEA and CA 15–3, CYFRA 21.1 is commonly elevated in metastatic breast cancer and has a strong prognostic value. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-07-18.