BRCA-MUTATION STATUS COMBINED WITH BCL2 PROTEIN IN PREDICTION OF RELAPSE IN TRIPLE-NEGATIVE BREAST CANCER (TNBC) TREATED WITH ADJUVANT ANTHRACYCLINE-BASED CHEMOTHERAPY

Background:

TNBC is aggressive and the prognosis is poor. Patients cannot benefit from targeted treatment. For this reason, there is an urgent need for markers that will predict the outcome of chemotherapy (Bouchalova et al., Current Drug Targets 2014). The role of BRCA mutation status as a predictor in TNBC is unclear. Data show an association of high BCL2 expression and resistance to anthracyclines. BCL2, size and nodal status are independent predictors for both relaps and death in TNBC treated with adjuvant anthracyclines (Bouchalova et al., Tumor Biology 2015). The objective of this study was to determine whether combination of BCL2 and BRCA1 status predicts outcome in TNBC patients treated with adjuvant anthracycline-based therapy.

Methods:

The study included 187 patients with TNBC, 178 of who were treated with adjuvant chemotherapy (164 had anthracyclines). BCL2 analysis was performed using IHC. BRCA1 status was obtained from patients records: mutation (mut), wild-type (wt) and unknown status were present in 21.39, 19.25, and 59.36%, respectively. The data were analysed with software Statistica and R.

Results:

Among six BCL2/ BRCA1 TNBC subtypes, BCL2high/ BRCA1wt predicts the worst, while BCL2low/ BRCA1mut the best RFS (log-rank p < 0.05). BCL2high protein expression predicts poor relapse free survival (RFS) in BRCA1wt TNBC patients treated with adjuvant anthracycline-based regimens (log-rank p = 0.007, hazard ratio, HR 13.24, 95%CI 1.19–147.93). Interestingly, there was no significant difference in RFS between BCL2low/ BRCA1mut and BCL2high/ BRCA1mut, but between BCL2low/ BRCA1mut and BCL2high/ BRCA1wt (log-rank p = 0.009) TNBC patients treated with adjuvant anthracycline-based therapy. BCL2high/ BRCA1wt predicts trend to the worst overall survival (OS) analyzed together with other subtypes treated with adjuvant anthracycline-based regimens (log-rank p = 0.081).

Conclusions:

Dividing TNBC into subtypes according BCL2 protein expression and BRCA1 mutation status predicts good, vs. poor outcome in patients treated with adjuvant anthracycline-based chemotherapy. BCL2 expression together with BRCA1 status could facilitate decision making on adjuvant therapy. Underlying mechanisms could be revealed by further research. In patients with BCL2 high/ BRCA1wt other types of adjuvant therapy should be considered.

The study was presented at ASCO Annual Meeting 2014 (Bouchalova et al., J Clin Oncol 2014; 32 (suppl): Abstr. 1132). Grants: IGA NT14599-32013, IGA NS10286-3, National Sustainability Programme (LO1304), and Czech Technology Agency (TE02000058), MZ ČR – RVO (MOÚ, 00209805).