Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, 712 Eonjuro, Gangnam-gu, Seoul, 06273, Republic of Korea.
Institute for Breast Cancer Precision Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
Breast Cancer Res. 2024 Nov 6;26(1):154. doi: 10.1186/s13058-024-01911-9.
HER2-positivity is an essential marker for therapeutic decisions, while HER2 expression is heterogenous. In recent years, there has been increasing recognition of a subgroup of breast cancer patients who have low levels of HER2 expression, also known as HER2-low because trastuzumab deruxtecan offers clinical benefit for patients with HER2-low metastatic breast cancer. Despite the growing interest in HER2-low breast cancer, there is limited research on how multigene assays can help differentiate between HER2-low and HER2-negative breast cancer. Among HR + HER2- breast cancer, we compared genomic characteristics between HER2-low and HER2-zero using the 21-gene assay.
A retrospective review of clinical records was performed in 2,295 patients who underwent Oncotype DX test in two hospitals between 2013 and 2020. Patients were classified into two groups as the HER2-zero and HER2-low based on HER2 immunohistochemistry. In cases with HER2 2+, no amplification of HER2 gene was confirmed by silver in situ hybridization. High genomic risk was defined as cases with 21-gene recurrence score (RS) > 25. Multivariable binary logistic-regression analysis was performed.
Of these, 944 (41.1%) patients were assigned to the HER2-zero group, while 1351 (58.9%) patients were assigned to the HER2-low group. The average Recurrence Score (RS) was found to be 17.802 in the HER2-zero breast cancer group and 18.503 in the HER2-low group, respectively (p-value < 0.005). When comparing the proportion of high RS between the two groups, the HER2-zero group had a high RS rate of 12.4% (117 out of 944), while the HER2-low group had a high RS rate of 17.0% (230 out of 1351) (p = 0.002). The HER2 score identified by qRT-PCR was 8.912 in the HER2-zero group and 9.337 in the HER2-low group (p < 0.005). In multivariable analysis, HER2-low status was found to be an independent factor for high RS, with an odds ratio of 1.517 (1.172-1.964), independent of ER, PR, and Ki67. Within the subgroup of patients with invasive ductal carcinoma, the high RS rates were 19% in the HER2-low group and 14% in the HER2-zero group. However, when considering all patients, there were no significant differences observed in recurrence-free survival and overall survival between the HER2-low and HER2-zero groups.
Within HR + HER2- breast cancer, HER2-low tumors are associated with high RS, especially for histologically invasive ductal carcinoma. A prognostic influence of HER2-low expression among HR + HER2- breast cancer remains as an area that requires further study.
HER2 阳性是治疗决策的重要标志物，而 HER2 表达具有异质性。近年来，人们越来越认识到一小部分乳腺癌患者 HER2 表达水平较低，也称为 HER2-低，因为曲妥珠单抗 deruxtecan 为 HER2-低转移性乳腺癌患者提供了临床获益。尽管人们对 HER2-低乳腺癌越来越感兴趣，但关于多基因检测如何帮助区分 HER2-低和 HER2-阴性乳腺癌的研究有限。在 HR+HER2-乳腺癌中，我们使用 21 基因检测比较了 HER2-低和 HER2-零组的基因组特征。
对 2013 年至 2020 年期间在两家医院接受 Oncotype DX 检测的 2295 例患者的临床记录进行回顾性分析。根据 HER2 免疫组织化学，患者分为 HER2-零和 HER2-低两组。HER2 为 2+，且未通过银原位杂交确认 HER2 基因扩增。高基因组风险定义为 21 基因复发评分（RS）>25。进行多变量二项逻辑回归分析。
其中，944 例（41.1%）患者被分配到 HER2-零组，1351 例（58.9%）患者被分配到 HER2-低组。HER2-零乳腺癌组的平均复发评分（RS）为 17.802，HER2-低组为 18.503（p 值<0.005）。比较两组高 RS 的比例，HER2-零组高 RS 率为 12.4%（944 例中有 117 例），HER2-低组高 RS 率为 17.0%（1351 例中有 230 例）（p=0.002）。qRT-PCR 检测到的 HER2 评分在 HER2-零组为 8.912，在 HER2-低组为 9.337（p<0.005）。多变量分析显示，HER2-低状态是 RS 高的独立因素，优势比为 1.517（1.172-1.964），与 ER、PR 和 Ki67 无关。在浸润性导管癌亚组中，HER2-低组的高 RS 率为 19%，HER2-零组为 14%。然而，考虑到所有患者，HER2-低和 HER2-零组之间在无复发生存率和总生存率方面没有观察到显著差异。
在 HR+HER2-乳腺癌中，HER2-低肿瘤与高 RS 相关，尤其是组织学浸润性导管癌。HR+HER2-乳腺癌中 HER2 低表达的预后影响仍需进一步研究。
