1. Adjuvant capecitabine-containing chemotherapy benefit and homologous recombination deficiency in early-stage triple-negative breast cancer patients
- Author
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de Boo, Leonora W., Jozwiak, 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., de Boo, Leonora W., Jozwiak, 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, and Linn, Sabine C.
- Abstract
Background 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. Methods 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. Results 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). Conclusion 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.
- Published
- 2022
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