98P - Heterogeneous responses of triple negative breast cancer cell lines to radiation and pharmacological treatments

Date 07 May 2015
Event IMPAKT 2015
Session Welcome reception and Poster Walk
Topics Anti-Cancer Agents & Biologic Therapy
Basic Science
Breast Cancer
Surgery and/or Radiotherapy of Cancer
Presenter Xiaoxi Xie
Citation Annals of Oncology (2015) 26 (suppl_3): 31-33. 10.1093/annonc/mdv121
Authors X. Xie1, B. Wieland2, B. Schröder-Heurich2, N. Bogdanova3, T. Dörk-Bousset2
  • 1Gynecology Research Unit/ Radiation Oncology Department, Hannover Medical School, 30625 - Hannover/DE
  • 2Gynecology Research Unit, Hannover Medical School, 30625 - Hannover/DE
  • 3Radiation Oncology Department, Hannover Medical School, 30625 - Hannover/DE

Abstract

Body

Purpose: The optimal treatment for triple negative breast cancer remains a therapeutic challenge. We aimed to conduct a comparative analysis of clinically relevant treatments to determine the extent of heterogeneity of triple negative breast cancer (TNBC) cell lines towards these agents in vitro.

Methods: Five different triple negative breast cancer cell lines were treated with either ionizing radiation (IR, 1.5 or 6 Gy) or inhibitors of ATM (KU55933), PARP1 (Olaparib) or PI3K (BKM120). Their biological responses were compared with the normal epithelial breast cell line MCF10A using colony formation assays and DNA double strand break foci analyses (ɣH2AX, 53BP1).

Results: In colony survival assays, the most sensitive cell line towards treatment with either IR, Olaparib or BKM120 was HCC1395, a line mutated in both the NBN and BRCA1 genes. HCC1937, also mutated in BRCA1, was particularly sensitive towards IR and ATM inhibition. By contrast, the HCC1806 cell line showed a similar behavior as the MCF10A wild-type control under these experimental conditions. BKM120 induced DNA breaks selectively in HCC1806 as evidenced by the repair foci but these disappeared within 24 hours indicating proficient damage repair.

Conclusion: TNBC cell lines are heterogeneous in their responses to treatment with radiation or chemical inhibition of DNA repair pathways. The mutational profile of TNBCs may be used to inform therapeutic decisions.

Supported by grants from the Chinese Scholarship Council and from Novartis AG.

Disclosure: All authors have declared no conflicts of interest.