Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Institute of Biostatistics and Registry Research, Brandenburg Medical School Theodor Fontane, Neuruppin, Germany.
Br J Cancer. 2022 Jun;126(10):1401-1409. doi: 10.1038/s41416-022-01711-y. Epub 2022 Feb 5.
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.
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.
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).
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.
在几项随机试验和荟萃分析中，添加辅助卡培他滨可提高早期三阴性乳腺癌（TNBC）患者的生存率。然而，许多患者并未从中受益。我们评估了 BRCA1 样 DNA 拷贝数特征，该特征表明同源重组缺陷，作为 FinXX 试验 TNBC 亚组中卡培他滨获益的预测生物标志物。
早期 TNBC 患者随机分为辅助卡培他滨（TX+CEX：卡培他滨-多西他赛，随后为环磷酰胺-表柔比星-卡培他滨）和常规化疗（T+CEF：多西他赛，随后为环磷酰胺-表柔比星-氟尿嘧啶）组。使用既定的 DNA 比较基因组杂交算法，在低覆盖率全基因组下一代测序数据上确定肿瘤的 BRCA1 样状态。
129/202（63.9%）例患者可确定 BRCA1 样状态，主要是由于缺乏组织。在中位随访 10.7 年期间，35 例复发，32 例死亡。与 BRCA1 样肿瘤（HR 0.66，95%CI 0.24-1.81）相比，卡培他滨的添加似乎更能改善 61 例（47.3%）非 BRCA1 样肿瘤患者的无复发生存率（HR 0.23，95%CI 0.08-0.70）（P 交互=0.17）。
根据我们的数据，非 BRCA1 样 TNBC 患者似乎受益于辅助化疗中添加卡培他滨。BRCA1 样 TNBC 患者也可能受益。需要进一步研究来确定 BRCA1 样 TNBC 患者亚组中哪些患者可能不能从辅助卡培他滨中获益。
