BRCA1-like profile is not significantly associated with survival benefit of non-myeloablative intensified chemotherapy in the GAIN randomized controlled trial

• Published in: Breast cancer research and treatment 2017-12, Vol.166 (3), p.775-785
• Main Authors: van Rossum, A. G. J., Schouten, P. C., Weber, K. E., Nekljudova, V., Denkert, C., Solbach, C., Köhne, C. H., Thomssen, C., Forstbauer, H., Hoffmann, G., Kohls, A., Schmatloch, S., Schem, C., von Minckwitz, G., Karn, T., Möbus, V. J., Linn, S. C., Loibl, S., Marmé, F.
• Format: Article
• Language: English
• Subjects: Adult; Analysis; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; BRCA1 protein; BRCA1 Protein - genetics; Breast cancer; Cancer patients; Cancer research; Cancer therapies; Capecitabine - administration & dosage; Care and treatment; Chemotherapy; Clinical Trial; Copy number; Cyclophosphamide; Cyclophosphamide - administration & dosage; Disease-Free Survival; DNA damage; Epirubicin; Epirubicin - administration & dosage; Female; Homologous recombination; Humans; Lymph nodes; Medical research; Medicine; Medicine & Public Health; Middle Aged; Myeloablative Agonists - administration & dosage; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - pathology; Oncology; Paclitaxel; Paclitaxel - administration & dosage; Population studies; Survival; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - genetics; Triple Negative Breast Neoplasms - pathology; Tumors
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-017-4444-9

Purpose The BRCA1 -like profile identifies tumors with a defect in homologous recombination due to inactivation of BRCA1. This profile has been shown to predict which stage III breast cancer patients benefit from myeloablative, DNA double-strand-break-inducing chemotherapy. We tested the predictive potential of the BRCA1 -like profile for adjuvant non-myeloablative, intensified dose-dense chemotherapy in the GAIN trial. Methods Lymph node positive breast cancer patients were randomized to 3 × 3 dose-dense cycles of intensified epirubicin, paclitaxel, and cyclophosphamide (ETC) or 4 cycles concurrent epirubicin and cyclophosphamide followed by 10 cycles of weekly paclitaxel combined with 4 cycles capecitabine (EC-TX). Only triple negative breast cancer patients (TNBC) for whom tissue was available were included in these planned analyses. BRCA1 -like or non- BRCA1 -like copy number profiles were derived from low coverage sequencing data. Results 119 out of 163 TNBC patients (73%) had a BRCA1 -like profile. After median follow-up of 83 months, disease free survival (DFS) was not significantly different between BRCA1 -like and non- BRCA1 -like patients [adjusted hazard ratio (adj.HR) 1.02; 95% confidence interval (CI) 0.55–1.86], neither was overall survival (OS; adj.HR 1.26; 95% CI 0.58–2.71). When split by BRCA1 -like status, DFS and OS were not significantly different between treatments. However, EC-TX seemed to result in a trend to an improvement in DFS in patients with a BRCA1 -like tumor, while the reverse accounted for ETC treatment in patients with a non- BRCA1 -like tumor ( p for interaction = 0.094). Conclusions The BRCA1 -like profile is not associated with survival benefit for a non-myeloablative, intensified regimen in this study population. Considering the limited cohort size, capecitabine might have additional benefit for TNBC patients.