同源重组缺陷在乳腺癌新辅助化疗疗效评估中的指导作用

Guiding role of homologous recombination deficiency in evaluating the efficacy of neoadjuvant chemotherapy for breast carcinoma

摘要

目的 本研究旨在分析不同同源重组修复缺陷(HRD)状态的乳腺癌患者新辅助治疗效果的区别,探索HRD状态在乳腺癌新辅助治疗分层决策中的作用。方法 纳入2021年10月至2024年8月期间在西安交通大学第一附属医院接受新辅助化疗(NAC)且行同源重组缺陷检测的50例乳腺癌患者。根据AmoyDx标准判读体系,使用基因组瘢痕评分(GSS)量化HRD水平,将研究对象分为HRD阴性与HRD阳性两组。Logistic多因素分析探索影响新辅助治疗效果的关键临床病理因素。结果 本研究共纳入50例接受新辅助治疗的乳腺癌患者,其中,HRD阳性组30例,HRD阴性组20例。HRD阳性患者中组织学3级的比例高于阴性患者,差异有统计学意义(60.00% vs. 20.00%,χ²=7.792,P<0.05);对比未达到获得病理完全缓解(pCR)的组别,pCR组别患者的中位基因组瘢痕评分(GSS)更高,差异有统计学意义(98.40 vs. 29.80,U=152.000,P=0.018);对比HRD阴性,HRD阳性组别pCR的比例更高,差异有统计学意义(43.33% vs. 10.00%,P_Fisher=0.014);是否使用含铂类方案其NAC疗效差异无统计学意义(pCR率,P>0.05);存在TP53突变(中位GSS,97.80 vs. 10.00,U=68.000,P=0.018)或BRCA突变(中位GSS,99.30 vs. 50.10,U=126.000,P=0.036)时GSS显著增加;多因素Logistic回归分析发现肿瘤为右侧的患者、肿瘤T分期为3~4期、N分期为1~3期的患者更不容易达到pCR,而HRD阳性的患者在接受新辅助治疗时更容易达到pCR(OR值分别为0.12、0.03、0.14、29.55,P<0.05)。结论 HRD阳性的乳腺癌患者组织学分级较高。HRD状态与乳腺癌新辅助治疗效果显著相关,或可作为预测pCR的独立生物标志物。另外,肿瘤位置、大小及是否存在腋窝淋巴结转移,共同构成评估新辅助治疗反应的预测体系。

Abstract

Objective To investigate the differences in the efficacy of neoadjuvant chemotherapy (NAC) among breast carcinoma patients with different homologous recombination deficiency (HRD) statuses,and to explore the role of HRD status in stratified decision-making for NAC in breast carcinoma. Methods A total of 50 breast carcinoma patients who underwent NAC and HRD testing at The First Affiliated Hospital of Xi'an Jiaotong University between October 2021 and August 2024 were retrospectively enrolled.According to the AmoyDx interpretation criteria,the genomic scar score (GSS) was used to quantify HRD levels,and patients were divided into HRD-negative and HRD-positive groups.Multivariate Logistic regression analysis was performed to identify key clinicopathological factors associated with NAC efficacy. Results Among the 50 breast carcinoma patients included in this study,30 were HRD-positive and 20 were HRD-negative.The proportion of histological grade 3 tumors was significantly higher in the HRD-positive group than in the HRD-negative group (60.00% vs. 20.00%,χ ²=7.792,P<0.05).Compared with patients who did not achieve pathological complete response (pCR),patients who achieved pCR had a significantly higher median GSS (98.40 vs. 29.80,U=152.000,P=0.018).The pCR rate was significantly higher in the HRD-positive group than in the HRD-negative group (43.33% vs. 10.00%,P_Fisher=0.014).No significant difference in NAC efficacy was observed between patients treated with platinum-containing regimens and those without platinum agents (pCR rate,P >0.05).Patients harboring TP53 mutations (median GSS:97.80 vs. 10.00,U =68.000,P =0.018) or BRCA mutations (median GSS:99.30 vs. 50.10,U =126.000,P =0.036) showed significantly increased GSS values.Multivariate Logistic regression analysis demonstrated that patients with right-sided tumors,T stage 3-4 tumors,and N stage 1-3 disease were less likely to achieve pCR,whereas HRD-positive patients were more likely to achieve pCR following NAC (OR =0.12,0.03,0.14,and 29.55,respectively,P <0.05). Conclusion Breast carcinoma patients with HRD positivity tend to exhibit higher histological grades.HRD status is significantly associated with the efficacy of NAC in breast carcinoma and may serve as an independent biomarker for predicting pCR.In addition,tumor location,tumor size,and axillary lymph node metastasis collectively constitute a predictive system for evaluating response to NAC.

关键词

同源重组缺陷 / 乳腺癌 / 新辅助化疗 / 病理完全缓解

Key words

homologous recombination deficiency / breast carcinoma / neoadjuvant chemotherapy / pathologic complete response

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基金资助

国家自然科学基金青年科学基金项目(82504145)

西安交通大学第一附属医院国自然培育青年项目(2024-QN-30)

西安交通大学第一附属医院横向课题(HX202428)