不同HER-2表达水平乳腺癌患者新辅助化疗疗效与生存分析

Analysis of the efficacy and survival outcomes of neoadjuvant chemotherapy in breast cancer patients with different HER-2 expression levels

摘要:

背景与目的 新辅助化疗是早期高危或局部晚期乳腺癌降期保乳和提高整体治愈率重要的治疗策略，新辅助化疗人群的选择和方案的制订依赖于分子分型。然而目前尚缺乏不同人表皮生长因子受体2（HER-2）表达水平的乳腺癌新辅助化疗疗效及生存预后差异的研究。本研究通过比较不同HER-2表达水平的乳腺癌患者新辅助化疗疗效及生存预后的差异，旨在明确其新辅助化疗疗效及生存预后的影响因素，为临床新辅助化疗人群选择和方案制订提供参考。方法 回顾性分析2018年1月—2022年5月于中南大学湘雅医院乳腺外科接受新辅助化疗且行根治性手术的乳腺癌患者资料。比较不同HER-2表达水平（0表达、低表达、过表达）患者临床病理特征的差异，用Logistic回归分析筛选病理完全缓解（pCR）的独立影响因素，用Kaplan-Meier方法估计患者的生存曲线，用Log-rank检验比较生存率的差异，通过Cox回归分析筛选预后的独立影响因素。结果 共纳入601例患者，其中HER-2 0表达231例（38.4%）、HER-2低表达137例（22.8%）、HER-2过表达233例（38.8%）。与HER-2 0表达患者和HER-2过表达患者比较，HER-2低表达患者具有更高的BMI，合并肿瘤家族史更少见，组织学分级更低，激素受体（HR）阳性比例更高；HER-2过表达患者的肿瘤纤维化程度明显低于HER-2 0表达和HER-2低表达患者（均P<0.05）。HER-2低表达患者中，HR阴性亚组患者较HR阳性亚组患者肿块更大，组织学分级更高，Ki-67水平更高（均P<0.05）。全组患者中，HER-2表达水平、pCR、临床淋巴结分期（cN）是患者无病生存（DFS）的独立影响因素（均P<0.05）。HER-2过表达患者的新辅助化疗pCR率及DFS率明显高于HER-2低表达和HER-2 0表达患者（均P<0.05），但HER-2低表达和HER-2 0表达患者的新辅助化疗pCR率及DFS率无明显差异（均P>0.05）。肿瘤纤维化程度和雌激素受体（ER）状态是HER-2 0表达乳腺癌pCR的独立影响因素，间质肿瘤浸润淋巴细胞（sTILs）水平是HER-2低表达乳腺癌pCR的独立影响因素，肿瘤纤维化程度和ER状态是HER-2过表达乳腺癌pCR的独立影响因素（均P<0.05）。结论 新辅助化疗对HER-2过表达乳腺癌患者的疗效优于HER-2 0表达和HER-2低表达乳腺癌患者。ER状态和纤维化程度、sTILs水平分别是HER-2 0表达与低表达患者pCR的独立影响因素，而ER状态与纤维化程度是HER-2过表达患者pCR的独立影响因素。

Abstract:

Background and Aims Neoadjuvant chemotherapy is an important treatment strategy for breast preservation after downstaging and improving overall cure rates in early high-risk or locally advanced breast cancer. The selection of patients and the development of treatment plans for neoadjuvant chemotherapy depend on molecular subtypes. However, there is currently a lack of research on the efficacy of neoadjuvant chemotherapy and differences in survival prognosis based on the expression levels of human epidermal growth factor receptor 2 (HER-2) in breast cancer. Therefore, this study was performed to compare the efficacy of neoadjuvant chemotherapy and differences in survival prognosis among breast cancer patients with different levels of HER-2 expression, and identify the factors influencing the efficacy of neoadjuvant chemotherapy and survival prognosis, so as to provide valuable insights for the selection of patients and development of treatment plans for clinical neoadjuvant chemotherapy.Methods The data of breast cancer patients who underwent neoadjuvant chemotherapy and radiacal mastectomy in the Department of Breast Surgery, Xiangya Hospital, Central South University, from January 2018 to May 2022 were retrospectively analyzed. The differences in clinicopathologic characteristics among patients with different HER-2 expression levels (zero-expression, low-expression, overexpression) were compared. Logistic regression analysis was used to identify independent factors influencing pathological complete response (pCR). Kaplan-Meier method was employed to estimate survival curves, and the Log-rank test was used to compare differences in survival rates. Cox regression analysis was conducted to identify independent prognostic factors.Results A total of 601 patients were included, among whom 231 (38.4%) had HER-2 zero-expression, 137 (22.8%) had HER-2 low-expression, and 233 (38.8%) had HER-2 overexpression. Compared to patients with HER-2 zero-expression and HER-2 overexpression, patients with HER-2 low-expression had higher BMI value, fewer cases of family history of tumors, lower histological grades, and a higher proportion of hormone receptor (HR) positivity; the degree of tumor fibrosis was significantly lower in patients with HER-2 overexpression compared to those with HER-2 zero-expression and HER-2 low-expression (all P<0.05). Among patients with HER-2 low-expression, the HR-negative subgroup had larger tumor size, higher histological grades, and higher Ki-67 level compared to the HR-positive subgroup (all P<0.05). In the entire cohort, HER-2 expression level, pCR, and clinical lymph node stage (cN) were independent factors influencing disease-free survival (DFS) (all P<0.05). Patients with HER-2 overexpression had significantly higher pCR and DFS rates after neoadjuvant chemotherapy compared to those with HER-2 low-expression and HER-2 zero-expression (all P<0.05), but there was no significant difference in neoadjuvant chemotherapy pCR and DFS rates between patients with HER-2 low-expression and HER-2 zero-expression (all P>0.05). Tumor fibrosis and estrogen receptor (ER) status were independent factors influencing pCR in HER-2 zero-expression breast cancer, while stromal tumor-infiltrating lymphocytes (sTILs) were independent factors influencing pCR in HER-2 low-expression breast cancer, and tumor fibrosis and ER status were independent factors influencing pCR in HER-2 overexpression breast cancer (all P<0.05).Conclusion Neoadjuvant chemotherapy is more effective in breast cancer patients with HER-2 overexpression compared to those with HER-2 zero-expression and low-expression. ER status, fibrosis degree, and sTILs level are independent factors influencing pCR in patients with HER-2 zero-expression and low-expression, while ER status and fibrosis degree are independent factors influencing pCR in patients with HER-2 overexpression.