Bai Kyungah, Woo Ji Won, Kwon Hyun Jung, Chung Yul Ri, Suh Koung Jin, Kim Se Hyun, Kim Jee Hyun, Park So Yeon
Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Gyeonggi, Republic of Korea.
Pathology Center, Seegene Medical Foundation, Seoul, Republic of Korea.
Lab Invest. 2024 Aug;104(8):102092. doi: 10.1016/j.labinv.2024.102092. Epub 2024 Jun 8.
Recent studies have shown that novel antibody-drug conjugates (ADCs) can improve clinical outcomes in patients with HER2-low breast cancers. This study aimed to investigate alteration of HER2 status during breast cancer progression with an emphasis on HER2-low status. Using 386 paired samples of primary and recurrent breast cancers, HER2 discordance rate between primary and matched recurrent samples, the relationships between HER2 discordance and clinicopathological characteristics and clinical outcomes of the patients were analyzed. HER2 discordance rate between primary breast cancer and first recurrence was 25.9% (κ = 0.586) with mostly zero-to-low (10.6%) or low-to-zero (9.3%) conversion. There was no significant difference in the discordant rates according to type or location of the recurrence. Of 70 cases with a second recurrence, HER2 discordance rate between the primary tumor and the second recurrence was 27.1% (κ = 0.554). HER2 discordance was associated with lower HER2 level, lymphovascular invasion, and progesterone receptor positivity of the primary tumor. In further analyses, HER2-zero-to-low conversion was associated with lymph node metastasis and hormone receptor (HR) positivity, whereas HER2-low-to-zero conversion was associated with HR negativity and triple-negative subtype. In survival analyses, HER2 discordance was associated with decreased overall survival of patients in the HR-positive group but not in the HR-negative group. Furthermore, patients with HER2-low-to-zero converted tumors showed worse overall survival compared with those with HER2-low concordant tumors. In conclusion, HER2 status changes during breast cancer progression in significant proportions, mostly between zero and low status. As HER2 instability increases during progression and affects clinical outcome, HER2 status needs to be reevaluated in recurrent settings.
最近的研究表明，新型抗体药物偶联物（ADC）可改善HER2低表达乳腺癌患者的临床结局。本研究旨在调查乳腺癌进展过程中HER2状态的改变，重点关注HER2低表达状态。使用386对原发性和复发性乳腺癌样本，分析了原发性和配对复发性样本之间的HER2不一致率、HER2不一致与临床病理特征的关系以及患者的临床结局。原发性乳腺癌与首次复发之间的HER2不一致率为25.9%（κ = 0.586），主要是从无到低（10.6%）或从低到无（9.3%）的转变。根据复发类型或部位，不一致率无显著差异。在70例二次复发的病例中，原发性肿瘤与二次复发之间的HER2不一致率为27.1%（κ = 0.554）。HER2不一致与原发性肿瘤较低的HER2水平、淋巴管浸润和孕激素受体阳性相关。在进一步分析中，HER2从无到低的转变与淋巴结转移和激素受体（HR）阳性相关，而HER2从低到无的转变与HR阴性和三阴性亚型相关。在生存分析中，HER2不一致与HR阳性组患者的总生存期降低相关，但与HR阴性组无关。此外，HER2从低到无转变的肿瘤患者的总生存期比HER2低表达一致的肿瘤患者更差。总之，在乳腺癌进展过程中，相当比例的患者HER2状态会发生变化，主要是在无和低表达状态之间。由于HER2不稳定性在进展过程中增加并影响临床结局，因此在复发情况下需要重新评估HER2状态。
