Abstract 193P
Background
Escalating adjuvant treatment with capecitabine has substantially improved outcome for early-stage triple negative breast cancer (TNBC) patients. Over half of all TNBCs have a DNA copy number profile that resembles the profile found in gBRCA1m breast cancers. It is currently unknown whether BRCA1-like status leads to differential benefit from the use of adjuvant capecitabine-containing chemotherapy compared to conventional chemotherapy.
Methods
Early-stage TNBC patients participated in the FinXX trial and were randomized to either adjuvant capecitabine-containing chemotherapy (TX+CEX: capecitabine plus docetaxel, followed by cyclophosphamide, epirubicin and capecitabine) or adjuvant conventional chemotherapy (T+CEF: docetaxel, followed by cyclophosphamide, epirubicin, and fluorouracil). We used an established DNA comparative genomic hybridization algorithm on low coverage, whole genome next-generation sequencing data to classify tumors as BRCA1-like or non-BRCA1-like.
Results
BRCA1-like status could successfully be determined for 129/202 (63.9%) TNBC patients. During a median follow-up of 10.7 years, 35 recurrences and 32 deaths were observed. Among the 129 TNBC tumors, 68 tumors (52.7%) had a BRCA1-like profile. The beneficial effect of the adjuvant capecitabine-containing regime compared with conventional chemotherapy did not significantly differ between patients with BRCA1-like tumors (HR 0.66, 95% CI 0.24-1.83) and those with non-BRCA1-like tumors (HR 0.23, 95% CI 0.08-0.69) (recurrence-free survival, unadjusted test for interaction P = 0.17). No substantial differences were observed upon adjustment for standard clinico-pathological variables.
Conclusions
BRCA1-like status was not associated with a preferential benefit from capecitabine-containing adjuvant chemotherapy compared to conventional chemotherapy in the TNBC subgroup of the FinXX trial. Hence, the addition of capecitabine to adjuvant treatment should be considered for both non-BRCA1-like as well as BRCA1-like early-stage TNBC patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Dutch Cancer Society.
Disclosure
H. Joensuu: Shareholder/Stockholder/Stock options, Officer/Board of Directors, Outside the submitted work: Sartar Therapeutics; Full/Part-time employment: Orion Pharma; Honoraria (self), Outside the submitted work: Neutron Therapeutics. M. Kok: Research grant/Funding (institution), outside the submitted work: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution), outside the submitted work: BMS; Research grant/Funding (institution), outside the submitted work: Roche; Advisory/Consultancy outside the submitted work: Daiichi. S. Linn: Advisory/Consultancy, Research grant/Funding (institution), Outside the submitted work: AstraZeneca; Research grant/Funding (self), Outside the submitted work: ZonMw; Research grant/Funding (self), Outside the submitted work: A Sister's Hope; Research grant/Funding (institution), Outside the submitted work: Cergentis; Advisory/Consultancy, Research grant/Funding (institution), Outside the submitted work: IBM; Advisory/Consultancy, Research grant/Funding (institution), Outside the submitted work: Pfizer; Advisory/Consultancy, Research grant/Funding (institution), Outside the submitted work: Roche; Research grant/Funding (institution), Outside the submitted work: Agendia; Research grant/Funding (institution), Outside the submitted work: Eurocept-pharmaceuticals; Research grant/Funding (institution), Outside the submitted work: Genentech; Research grant/Funding (institution), Outside the submitted work: Novartis; Research grant/Funding (institution), Outside the submitted work: Tesaro; Research grant/Funding (institution), Outside the submitted work: Immunomedics. All other authors have declared no conflicts of interest.