Bai Qianming, Lv Hong, Bao Longlong, Yang Yu, Zhang Xin, Chang Heng, Xue Tian, Ren Min, Zhu Xiaoli, Zhou Xiaoyan, Yang Wentao
Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, People's Republic of China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China.
Breast Cancer (Dove Med Press). 2023 Aug 3;15:563-575. doi: 10.2147/BCTT.S420738. eCollection 2023.
To investigate the HER2 status and clinicopathological features in invasive breast cancer with HER2 ≥4.0 and <6.0, which has always been controversial.
Forty breast cancer cases with HER2 ≥4.0 and <6.0 by fluorescence in situ hybridization (FISH) were collected and classified into two groups based on the HRE2/CEP17 ratio (Group A: ≥2.0, n=22; Group B: <2.0, n=18). Clinicopathological characteristics, HER2 status, risk classification, and molecular typing were further analyzed and compared by 21-Gene expression assay and MammaPrint plus BluePrint test.
The majority of cases in both groups were invasive carcinoma (NOS), with histological grade II, HR+, Ki-67 ≥20%, HER2 2+, and a high risk of recurrence, although younger patients and lymph node metastases were more common in Group A. Surprisingly, all HR+ breast cancers in both groups were classified as luminal-type, HR- cases were all basal-type or unknown, and the index of HER2 in all cases was <0.000 using the BluePrint test, which indicated that HER2 status should be negative. Furthermore, the level of HER2 mRNA expression in all cases of both groups was <10.7, which was defined as HER2 negative by the 21-Gene expression assay. In addition, 10 patients of Group A received anti-HER2 neoadjuvant therapy; only one patient with HR- achieved Grade 5 based on the Miller-Payne system, whereas none of the patients achieved pathological complete response (pCR) based on the Residual Cancer Burden system.
Group A breast cancer, which has always been unquestionably diagnosed as HER2 amplification, was more likely to be HER2 negative and derived less benefit from anti-HER2 neoadjuvant chemotherapy. Group A breast cancer should be distinguished from classical HER2-positive breast cancers when assessing HER2 FISH, and a larger cohort of Group A patients should be included in further studies.
探讨人表皮生长因子受体2（HER2）≥4.0且<6.0的浸润性乳腺癌的HER2状态及临床病理特征，这一情况一直存在争议。
收集40例荧光原位杂交（FISH）检测HER2≥4.0且<6.0的乳腺癌病例，并根据HRE2/CEP17比值分为两组（A组：≥2.0，n = 22；B组：<2.0，n = 18）。通过21基因表达分析和MammaPrint加BluePrint检测进一步分析和比较临床病理特征、HER2状态、风险分类及分子分型。
两组中的大多数病例为浸润性癌（非特殊型），组织学分级为II级，激素受体（HR）阳性，Ki-67≥20%，HER2 2+，复发风险高，不过A组中年轻患者和淋巴结转移更为常见。令人惊讶的是，两组中所有HR阳性乳腺癌均被分类为管腔型，HR阴性病例均为基底型或未知类型，并且使用BluePrint检测所有病例中HER2指数均<0.000，这表明HER2状态应为阴性。此外，两组所有病例中HER2 mRNA表达水平均<10.7，根据21基因表达分析定义为HER2阴性。此外，A组10例患者接受了抗HER2新辅助治疗；基于米勒-佩恩系统，只有1例HR阴性患者达到5级，而基于残余癌负荷系统，没有患者达到病理完全缓解（pCR）。
一直被明确诊断为HER2扩增的A组乳腺癌更可能为HER2阴性，且从抗HER2新辅助化疗中获益较少。在评估HER2 FISH时，A组乳腺癌应与经典HER2阳性乳腺癌相区分，并且应纳入更多A组患者进行进一步研究。
