Abstract P6-01-08: BRCAness and prognosis in triple-negative breast cancer patients treated with neoadjuvant chemotherapy

Abstract

Abstract <Background> Microarrays have shown that triple-negative breast cancers (TNBCs) are a heterogeneous group of disorders that have differential responses to chemotherapy. On the other hand, BRCA genes play an important role in DNA damage repair. Gene mutations and methylation of BRCAs causes functional abnormalities, leading to defects in DNA repair capacity. This state is called "BRCAness." In this study, we addressed BRCAness, therapeutic effects, recurrence, and prognosis in patients with TNBCs who were treated with neoadjuvant chemotherapy. <Subjects and Methods> We enrolled 40 patients with TNBC who were treated with neoadjuvant chemotherapy (anthracyclines alone in 3 patients and anthracyclines plus taxanes in 37 patients) at our hospital between April 2006 and October 2012. BRCAness was determined by preoperative core needle biopsy (CNB) specimens and surgical specimens. Genes from those specimens were amplified by multiplex ligation-dependent probe amplification (MLPA), and the amplicons were scored after separation by electrophoresis. With a cutoff value of 0.5, values of 0.5 or more were determined as the BRCA1-like Type (BRCAness) and those of less than 0.5 as the Sporadic Type to analyze clinical effects, pathological complete response (pCR) rate, recurrence, and prognosis. <Results> With regard to therapeutic effects of neoadjuvant chemotherapy, pCR (ypT0/Tis/N0) was observed in 15 patients and non-pCR in 25 patients (pCR rate: 37.5%). Twelve patients had recurrence after surgery, and 8 of whom died of the original disease. (1) The BRCA1-like Type accounted for 22 patients while the Sporadic Type accounted for 18 patients in CNB specimens. No major differences were observed between the BRCA1-like Type and Sporadic Type with regards to the pCR rate (7/22 vs. 5/18). Those two types had equivalent results in recurrence rate and prognosis. (2) Among the 24 non-pCR patients whose BRCA status could be determined by surgical specimens, 9 were found to be of the BRCA1-like Type. Patients with a BRCA1-like tumor had more recurrences (7/9 vs. 5/15), and their relapse-free survival was also lower (p<0.05). No association with prognosis was found. Six patients whose BRCA status of CNB specimens was of the BRCA1-like Type and that of surgical specimens turned to be of the Sporadic Type were better in recurrence (p<0.01) and prognosis (p<0.05), compared with seven patients whose BRCA status of surgical specimens remained to be of the BRVA-1 like Type. <Discussion> Patients with TNBC who achieved a pCR by neoadjuvant chemotherapy had a better prognosis even if the type is BRCA1-like. In contrast, the recurrence rate was higher when residual tumor remained after neoadjuvant chemotherapy and when the BRCA status became BRCA1-like. New clinical trials assessing the true recurrence (TR) rate of BRCA are expected since neither platinum-containing drugs nor poly (ADP-ribose) polymerase (PARP) inhibitors are effective against tumors with nonfunctional BRCA genes. Citation Format: Hirokazu Tanino, Yoshimasa Kosaka, Norihiko Sengoku, Mina Waraya, Hiroshi Nishimiya, Hirozhi Katoh, Mariko Kikuchi, Naoko Minatani, Saeko Teraoka, Takumo Enomoto, Takeo Sato, Masahiko Masahiko. BRCAness and prognosis in triple-negative breast cancer patients treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-01-08.