METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
方法:使用HRD面板和同源重组相关(HRR)基因表达数据评估了来自225名连续TNBC患者的肿瘤组织。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。临床病理因素,新辅助治疗反应,并对这些TNBC患者的HRD状态进行了预后分析。
结果:在53.3%的患者中发现HRD阳性,并且与高Ki67水平显着相关(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)与更高的病理完全缓解(pCR)率显着相关,尤其是在接受含卡铂新辅助治疗方案的患者中(HRD阳性与消极:50.00%vs.17.65%,P=0.040)。HRD阳性与良好的无远处转移生存率(风险比HR0.49,95%置信区间CI0.26-0.90,P=0.022)和总生存率(HR0.45,95%CI0.20-0.99,P=0.049)相关,不管卡铂治疗。
结论:高HRDs的TNBC患者具有高Ki67水平和BRCA突变。用卡铂治疗的HRD阳性TNBC患者的pCR率较高。HRD阳性的患者预后较好,不管卡铂治疗,值得进一步评估。