BackgroundSOLAR-1 and BYLIEVE trials documented the e cacy of the PI3K-inhibitor alpelisib in pre-treated PIK3CAmutant, hormone receptor-positive, HER2-negative (HR+/HER2-) advanced breast cancer (ABC) patients.We report here real-life data of patients prospectively registered in the French alpelisib early access program (EAP). Patients and methods:The French EAP was opened to PIK3CA-mutant HR+/HER2-ABC patients treated with alpelisib and fulvestrant, managed per standard of care. Primary endpoint was PFS by local investigators using RECIST1.1. ResultsEleven centers provided individual data on 233 consecutive patients. Patients had received a median number of 4 (range: 1-16) prior systemic treatments for ABC, including CDK4/6 inhibitor, chemotherapy, fulvestrant and everolimus in 227 (97.4%), 180 (77.3%), 175 (75.1%) and 131 (56.2%) patients, respectively. After a median follow-up of 7.1 months and 168 events, median PFS was 5.3 months (95%CI, 4.7-6.0). Among 186 evaluable patients, CBR at 6 months was 45.3% (95%CI, 37.8-52.8). In multivariable analysis, characteristics signi cantly associated with a shorter PFS were age < 60 years (HR = 1.5, 95%CI = 1.1-2.1), > 5 lines of prior treatments (HR = 1.4, 95%CI = 1.0-2.0) and the C420R PI3KCA mutation (HR = 4.1, 95%CI = 1.3-13.6). Most frequent grade 3/4 adverse events (AEs) were hyperglycemia, rash, fatigue and diarrhea occurring in 11.6, 9.9, 4.3 and 3% of patients, respectively. N = 91 (39.1%) patients discontinued alpelisib due to AEs. DiscussionTo our knowledge, this is the largest real-life assessment of alpelisib e cacy. Despite heavy pretreatments, patients derived a clinically relevant bene t from alpelisib and fulvestrant. PFS was not overtly impaired by a prior use of either everolimus or fulvestrant. No new safety signal was found.

Prophylactic mastectomies are more and more frequent. As a result, breast reconstruction is also more frequent and mammary lipofilling often used to improve the aesthetic results. Contradictory cliniacal data have been published concerning the risk of breast cancer after using this technique. It is possible that Adipose-Derived Stem / Stromal Cells (ADSC or ASC), present in the lipofilling may interact with normal or tumoral epithelial mammary cells. In this context, we studied the effect of conditioned media of human ASC on different tumor breast lines (MCF7, T47D, ZR75-1, SKBR3, SUM159). The ASCs were extracted from non-cancer patients with identical body mass index (BRCA1 and BRCA2 mutated or wild-type). We observed that the conditioned media of ASC induced the proliferation of luminal, Her2 and basal-like tumor breast lines. This proliferative effect is more important when ASCs are differentiated and the BRCA mutation status has no impact on it. Finally, we have demonstrated an estrogen signaling within the ASCs which is set up during their differentiation. Differentiated ASCs express ERα and produce 17β-estradiol (E2). This estrogenic pathway seems to be established independently of the BRCA mutational status. The proliferative effect on luminal mammary lines induced by conditioned media of ASC could pass through this estrogenic signaling, but remains to be confirmed. These data highlight the fact that adipose-derived stem cells in mammary lipofilling should only be used after a cancer has been eliminated, as there are still some uncertainties concerning their implication on carcinogenesis. Citation Format: Benderra M-A, Zaoui M, Atlan M, Ferrand N, Denis JA, Leban M, Lamari F, Larsen AK, Sabbah M, Gligorov J. Interactions between adipocyte stem cells and normal or tumoral mammary epithelial cells. Potantial role of BRCA status and estrogen pathway [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-07-05.

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