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- Title
Adjuvant capecitabine-containing chemotherapy benefit and homologous recombination deficiency in early-stage triple-negative breast cancer patients.
- Authors
de Boo, Leonora W.; Jóźwiak, Katarzyna; Joensuu, Heikki; Lindman, Henrik; Lauttia, Susanna; Opdam, Mark; van Steenis, Charlaine; Brugman, Wim; Kluin, Roelof J. C.; Schouten, Philip C.; Kok, Marleen; Nederlof, Petra M.; Hauptmann, Michael; Linn, Sabine C.
- Abstract
<bold>Background: </bold>The addition of adjuvant capecitabine to standard chemotherapy of early-stage triple-negative breast cancer (TNBC) patients has improved survival in a few randomised trials and in meta-analyses. However, many patients did not benefit. We evaluated the BRCA1-like DNA copy number signature, indicative of homologous recombination deficiency, as a predictive biomarker for capecitabine benefit in the TNBC subgroup of the FinXX trial.<bold>Methods: </bold>Early-stage TNBC patients were randomised between adjuvant capecitabine-containing (TX + CEX: capecitabine-docetaxel, followed by cyclophosphamide-epirubicin-capecitabine) and conventional chemotherapy (T + CEF: docetaxel, followed by cyclophosphamide-epirubicin-fluorouracil). Tumour BRCA1-like status was determined on low-coverage, whole genome next-generation sequencing data using an established DNA comparative genomic hybridisation algorithm.<bold>Results: </bold>For 129/202 (63.9%) patients the BRCA1-like status could be determined, mostly due to lack of tissue. During a median follow-up of 10.7 years, 35 recurrences and 32 deaths occurred. Addition of capecitabine appears to improve recurrence-free survival more among 61 (47.3%) patients with non-BRCA1-like tumours (HR 0.23, 95% CI 0.08-0.70) compared to 68 (52.7%) patients with BRCA1-like tumours (HR 0.66, 95% CI 0.24-1.81) (P-interaction = 0.17).<bold>Conclusion: </bold>Based on our data, patients with non-BRCA1-like TNBC appear to benefit from the addition of capecitabine to adjuvant chemotherapy. Patients with BRCA1-like TNBC may also benefit. Additional research is needed to define the subgroup within BRCA1-like TNBC patients who may not benefit from adjuvant capecitabine.
- Publication
British Journal of Cancer, 2022, Vol 126, Issue 10, p1401
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/s41416-022-01711-y