Adjuvant capecitabine-containing chemotherapy benefit and homologous recombination deficiency in early-stage triple-negative breast cancer patients.

Autor: de Boo LW; Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Jóźwiak K; Institute of Biostatistics and Registry Research, Brandenburg Medical School Theodor Fontane, Neuruppin, Germany.; Department of Epidemiology and Biostatistics, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Joensuu H; Department of Oncology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland., Lindman H; Department of Immunology, Genetics and Pathology, Uppsala University Hospital, Uppsala, Sweden., Lauttia S; Laboratory of Molecular Oncology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland., Opdam M; Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., van Steenis C; Genomics Core Facility, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Brugman W; Genomics Core Facility, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Kluin RJC; Genomics Core Facility, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Schouten PC; Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Kok M; Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.; Division of Tumor Biology & Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Nederlof PM; Department of Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands., Hauptmann M; Institute of Biostatistics and Registry Research, Brandenburg Medical School Theodor Fontane, Neuruppin, Germany.; Department of Epidemiology and Biostatistics, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Linn SC; Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. s.linn@nki.nl.; Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. s.linn@nki.nl.; Department of Pathology, University Medical Centre, Utrecht, The Netherlands. s.linn@nki.nl.
Jazyk: angličtina
Zdroj: British journal of cancer [Br J Cancer] 2022 Jun; Vol. 126 (10), pp. 1401-1409. Date of Electronic Publication: 2022 Feb 05.
DOI: 10.1038/s41416-022-01711-y
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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