Miglietta Federica, Griguolo Gaia, Bottosso Michele, Giarratano Tommaso, Lo Mele Marcello, Fassan Matteo, Cacciatore Matilde, Genovesi Elisa, De Bartolo Debora, Vernaci Grazia, Amato Ottavia, Porra Francesca, Conte PierFranco, Guarneri Valentina, Dieci Maria Vittoria
Department of Surgery, Oncology and Gastroenterology (DISCOG), University of Padova, 35128, Padova, Italy.
Medical Oncology 2, Istituto Oncologico Veneto IOV-IRCCS, 35128, Padova, Italy.
NPJ Breast Cancer. 2022 May 20;8(1):66. doi: 10.1038/s41523-022-00434-w.
Approximately a half of breast tumors classified as HER2-negative exhibit HER2-low-positive expression. We recently described a high instability of HER2-low-positive expression from primary breast cancer (BC) to relapse. Previous studies reporting discordance in HER2 status between baseline biopsy and residual disease (RD) in patients undergoing neoadjuvant treatment did not include the HER2-low-positive category. The aim of this study is to track the evolution of HER2-low-positive expression from primary BC to RD after neoadjuvant treatment. Patients undergoing neoadjuvant treatment with available baseline tumor tissue and matched samples of RD (in case of no pCR) were included. HER2-negative cases were sub-classified as HER2-0 or HER2-low-positive (IHC 1+ or 2+ and ISH negative). Four-hundred forty-six patients were included. Primary BC phenotype was: HR-positive/HER2-negative 23.5%, triple-negative (TN) 35%, HER2-positive 41.5%. HER2-low-positive cases were 55.6% of the HER2-negative cohort and were significantly enriched in the HR-positive/HER2-negative vs. TN subgroup (68.6% vs. 46.8%, p = 0.001 χ test). In all, 35.3% of non-pCR patients (n = 291) had a HER2-low-positive expression on RD. The overall rate of HER2 expression discordance was 26.4%, mostly driven by HER2-negative cases converting either from (14.8%) or to (8.9%) HER2-low-positive phenotype. Among HR-positive/HER2-negative patients with HER2-low-positive expression on RD, 32.0% and 57.1% had an estimated high risk of relapse according to the residual proliferative cancer burden and CPS-EG score, respectively. In conclusion, HER2-low-positive expression showed high instability from primary BC to RD after neoadjuvant treatment. HER2-low-positive expression on RD may guide personalized adjuvant treatment for high-risk patients in the context of clinical trials with novel anti-HER2 antibody-drug conjugates.
大约一半被归类为HER2阴性的乳腺肿瘤表现出HER2低阳性表达。我们最近描述了从原发性乳腺癌（BC）到复发时HER2低阳性表达的高度不稳定性。先前关于接受新辅助治疗的患者基线活检和残留疾病（RD）之间HER2状态不一致的研究未包括HER2低阳性类别。本研究的目的是追踪新辅助治疗后从原发性BC到RD的HER2低阳性表达的演变。纳入了有可用基线肿瘤组织和匹配的RD样本（无pCR的情况）的接受新辅助治疗的患者。HER2阴性病例被分为HER2-0或HER2低阳性（免疫组化1+或2+且原位杂交阴性）。共纳入446例患者。原发性BC表型为：HR阳性/HER2阴性23.5%，三阴性（TN）35%，HER2阳性41.5%。HER2低阳性病例占HER2阴性队列的55.6%，在HR阳性/HER2阴性与TN亚组中显著富集（68.6%对46.8%，p = 0.001，χ检验）。总体而言，35.3%的非pCR患者（n = 291）在RD上有HER2低阳性表达。HER2表达不一致的总体发生率为26.4%，主要由HER2阴性病例转变为（14.8%）或从（8.9%）HER2低阳性表型驱动。在RD上有HER2低阳性表达的HR阳性/HER2阴性患者中，根据残留增殖性癌负担和CPS-EG评分，分别有32.0%和57.1%的患者估计有高复发风险。总之，新辅助治疗后HER2低阳性表达从原发性BC到RD表现出高度不稳定性。RD上的HER2低阳性表达可能在使用新型抗HER2抗体药物偶联物的临床试验背景下指导高危患者的个性化辅助治疗。
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