Abstract 4247: BRCAness by MLPA is clinically useful for tailored treatment in triple-negative breast cancer

Abstract

Abstract BACKGROUBD: Cytotoxic anticancer drugs are the only clinically available agents for treating triple-negative breast cancer (TNBC). Recent gene expression analysis revealed that TNBC shows considerable overlap with basal-like tumors characterized by a potential loss of BRCA1 function. Further subdivision of TNBC represents an important clinical topic for treatments. We therefore subdivided TNBC into basal-like (BL) and non-BL subtypes defined by EGFR and/or CK5/6 positive in our previous neoadjuvant chemotherapy (NAC) study (KBOG1101 study). We reported that BL subtype were resistant to taxane regimen at AACR2013. AIM: To examine impaired BRCA1 function “BRCAness” is beneficial for tailored chemotherapy in TNBC. METHODS: Sixty-six TNBC cases from a randomized phase II trial comparing Docetaxel and cyclophosphamide x 6 (TC6) with 5-fluorouracil, epirubucin and cyclophosphamide followed by docetaxel (FEC-D) as NAC for hormone receptor-negative breast cancer (Kanagawa Breast Oncology Group 1101 Study). TNBC was subdivided by 1) Immunohistochemistry (IHC) of CK 5/6 and EGFR into BL and non-BL subtypes, and 2) Multiplex Ligation-dependent Probe Amplification (MLPA) of BRCAness into BRCAness and non-BRCAness subtypes. The pCR rates were examined according to each regimen and subtype. 3) The association of grade 3 pCR was examined with Ki-67, p53, aldehyde dehydrogenase (ALDH) 1 and topoisomerase 2A (topoIIα) by IHC and TOP2A by FISH for each regimen. RESULTS: 1) The pCR rates of FEC-D and TC were 37% vs 18.5% in BL(n = 54), while 40.4% and 16.7% in non-BL (n = 11), respectively. FEC-D was superior in both subtypes without statistical significance. 2) In BRCAness (n = 34), FEC-D was significantly superior to TC6 (FEC-D vs TC: 56.3% vs 16.7%, p = 0.030), while not different in non-BRCAness (20.0% vs 16.7%). 3) No factors were associated with pCR. DISCUSSION: TC6 was less effective than FEC-D in TNBC with BRCAness, showing that taxane cannot exert their anticancer role in tumors with BRCA1 dysfunction. Although BL may contain more BRCA1-defective tumors than non-BL, MLPA of BRCAness was better to identify subtype resistant to taxane than BL defined by IHC. BRCAness by MLPA method is practically useful for treatment selection in TNBC. Citation Format: Takashi Ishikawa, Kazutaka Narui, Akimitsu Yamada, Sadatishi Sugae, Yasushi Ichikawa, Mari S. Oba, Saeko Teraoka, Kumiko Kida, Hidetaka Shima, Itaru Endo. BRCAness by MLPA is clinically useful for tailored treatment in triple-negative breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4247. doi:10.1158/1538-7445.AM2015-4247