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18.08.2017 | Clinical trial | Ausgabe 3/2017

Breast Cancer Research and Treatment 3/2017

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

Zeitschrift:
Breast Cancer Research and Treatment > Ausgabe 3/2017
Autoren:
A. G. J. van Rossum, P. C. Schouten, K. E. Weber, V. Nekljudova, C. Denkert, C. Solbach, C. H. Köhne, C. Thomssen, H. Forstbauer, G. Hoffmann, A. Kohls, S. Schmatloch, C. Schem, G. von Minckwitz, T. Karn, V. J. Möbus, S. C. Linn, S. Loibl, F. Marmé
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1007/​s10549-017-4444-9) contains supplementary material, which is available to authorized users.

Abstract

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.

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Zusatzmaterial
Supplementary material 1 (DOCX 421 kb)
10549_2017_4444_MOESM1_ESM.docx
Literatur
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