Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.
Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.
Breast Cancer Res Treat. 2024 Nov;208(2):429-440. doi: 10.1007/s10549-024-07436-1. Epub 2024 Jul 24.
The aim of this study was to assess homologous recombination deficiency (HRD) status and its correlation with carboplatin treatment response in early triple-negative breast cancer (TNBC) patients.
Tumor tissues from 225 consecutive TNBC patients were evaluated with an HRD panel and homologous recombination-related (HRR) gene expression data. HRD positivity was defined as a high HRD score and/or BRCA1/2 pathogenic or likely pathogenic mutation. Clinicopathological factors, neoadjuvant treatment response, and prognosis were analyzed with respect to HRD status in these TNBC patients.
HRD positivity was found in 53.3% of patients and was significantly related to high Ki67 levels (P = 0.001). In patients who received neoadjuvant chemotherapy, HRD positivity (P = 0.005) or a high HRD score (P = 0.003) was significantly associated with a greater pathological complete response (pCR) rate, especially in those treated with carboplatin-containing neoadjuvant regimens (HRD positivity vs. negativity: 50.00% vs. 17.65%, P = 0.040). HRD positivity was associated with favorable distant metastasis-free survival (hazard ratio HR 0.49, 95% confidence interval CI 0.26-0.90, P = 0.022) and overall survival (HR 0.45, 95% CI 0.20-0.99, P = 0.049), irrespective of carboplatin treatment.
TNBC patients with high HRDs had high Ki67 levels and BRCA mutations. HRD-positive TNBC patients treated with carboplatin had a higher pCR rate. Patients with HRD positivity had a better prognosis, irrespective of carboplatin treatment, warranting further evaluation.
本研究旨在评估同源重组缺陷(HRD)状态及其与早期三阴性乳腺癌(TNBC)患者卡铂治疗反应的相关性。
对 225 例连续 TNBC 患者的肿瘤组织进行 HRD 面板和同源重组相关(HRR)基因表达数据评估。HRD 阳性定义为高 HRD 评分和/或 BRCA1/2 致病性或可能致病性突变。分析这些 TNBC 患者的 HRD 状态与临床病理因素、新辅助治疗反应和预后的关系。
发现 53.3%的患者 HRD 阳性,且与高 Ki67 水平显著相关(P=0.001)。在接受新辅助化疗的患者中,HRD 阳性(P=0.005)或高 HRD 评分(P=0.003)与更大的病理完全缓解(pCR)率显著相关,特别是在接受含卡铂新辅助方案治疗的患者中(HRD 阳性与阴性:50.00%比 17.65%,P=0.040)。HRD 阳性与无远处转移生存(HR 0.49,95%CI 0.26-0.90,P=0.022)和总生存(HR 0.45,95%CI 0.20-0.99,P=0.049)相关,而与卡铂治疗无关。
高 HRD 的 TNBC 患者具有高 Ki67 水平和 BRCA 突变。接受卡铂治疗的 HRD 阳性 TNBC 患者的 pCR 率更高。HRD 阳性患者的预后更好,而与卡铂治疗无关,值得进一步评估。