BRCA-mutation status combined with BCL2 protein in prediction of relapse in triple-negative breast cancer (TNBC) treated with adjuvant anthracycline-based chemotherapy.

Konference: 2014 50th ASCO Annual Meeting - účast ČR

Kategorie: Zhoubné nádory prsu

Téma: Breast Cancer - Triple-Negative/Cytotoxics/Local Therapy

Číslo abstraktu: 1132

Autoři: MUDr. Kateřina Bouchalová (Špačková), Ph.D.; prof. MUDr. Marek Svoboda, Ph.D.; MUDr. Gvantsa Kharaishvili, Ph.D.; Mgr. Jana Vrbková, Ph.D.; Mgr. Lenka Radová, Ph.D.; doc. Mgr. Jan Bouchal, Ph.D.; RNDr. Radek Trojanec, Ph.D.; MUDr. Vladimíra Koudeláková (Palková); MUDr. Karel Cwiertka, Ph.D.; doc. MUDr. Marián Hajdúch, Ph.D.; prof. MUDr. Zdeněk Kolář, CSc.

Background: 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. ASCO 2012). 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 whom were treated with adjuvant chemotherapy (164 had anthracyclines). BCL2 analysis was performed using IHC. BRCA1 was obtained from patients records: mutation (mut), wildtype (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 (logrank p<0.05). BCL2high protein expression predicts poor relapse free survival (RFS) in BRCA1wt TNBC patients treated with adjuvant anthracycline-based regimens (logrank 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 (logrank 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 (logrank p=0.065).

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 BCL2high/BRCA1wt other types of adjuvant therapy should be considered.

J Clin Oncol 32:5s, 2014 (suppl; abstr 1132)

Datum přednesení příspěvku: 2. 6. 2014