Abstract：
BACKGROUND: 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.
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.
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.
摘要：
背景：本研究的目的是评估早期三阴性乳腺癌（TNBC）患者的同源重组缺陷（HRD）状态及其与卡铂治疗反应的相关性。
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。
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。
