AUTHOR=Hu Shihui , Zhao Yannan , Xie Yizhao , You Shuhui , Hu Xichun , Zhang Jian , Wang Leiping , Cao Jun , Gong Chengcheng , Wang Biyun 

TITLE=Clinicopathological characteristics, evolution, and treatment outcomes of hormone receptor-negative/HER2-low metastatic breast cancer: a pooled analysis of individual patient data from three prospective clinical trials

JOURNAL=Frontiers in Endocrinology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1449278

DOI=10.3389/fendo.2024.1449278

ISSN=1664-2392

ABSTRACT=<sec><title>Objective</title><p>With the approval of trastuzumab deruxtecan for the treatment of unresectable/metastatic HER2-low breast cancer, human epidermal growth factor receptor 2 (HER2)-low has emerged as a clinically actionable biomarker. There is an urgent need for a deeper understanding of HER2-low breast cancer patients. Therefore, this study was conducted to explore the clinicopathological characteristics, the evolution of HER2-low status, and its impact on the prognosis of hormone receptor (HoR)-negative/HER2-low metastatic breast cancer (MBC) patients.</p></sec><sec><title>Methods</title><p>This pooled analysis included 350 metastatic triple-negative breast cancer (mTNBC) patients who received first-line platinum-based chemotherapy at Fudan University Shanghai Cancer Center from November 2007 to July 2022. Patients were categorized into HER2-0 and HER2-low groups based on their HER2 status. Baseline clinicopathological characteristics, evolution of HER2 status between primary and metastatic lesions, and treatment efficacy were compared between the two groups.</p></sec><sec><title>Results</title><p>Among the 350 mTNBC patients, 34.9% (122/350) were HER2-low and 65.1% (228/350) were HER2-0. Significant differences were observed between HER2-low and HER2-0 patients in terms of age and menopausal status. HER2-low patients were older (54 <italic>vs.</italic> 49 years, <italic>p</italic>=0.002) and had a lower proportion of premenopausal patients (32.8% <italic>vs.</italic> 52.6%, <italic>p</italic>&lt;0.001) compared to HER2-0 patients. No significant differences were observed in progression-free survival (PFS) and overall survival (OS) between HER2-low and HER2-0 patients receiving first-line platinum-based chemotherapy (mPFS: 7.43 <italic>vs.</italic> 8.30 months, <italic>p</italic>=0.389, HR=1.11, 95% CI 0.88-1.40; mOS: 25.37 <italic>vs.</italic> 26.63 months, <italic>p</italic>=0.907, HR=1.02, 95% CI 0.76-1.37). Additionally, 32.3% (41/127) of patients exhibited discordant HER2 status between primary and metastatic lesions, primarily evolving from HER2-0 to HER2-low. Notably, patients with discordant HER2 status had significantly longer PFS compared to those with concordant status (mPFS: 11.07 <italic>vs.</italic> 7.53 months, <italic>p</italic>=0.020). The Cox multivariate analysis showed that HER2 status consistency (<italic>p</italic>=0.026) was an independent predictor of PFS.</p></sec><sec><title>Conclusion</title><p>In mTNBC patients, those with HER2-low status had similar responses to platinum-based chemotherapy as HER2-0 patients. There was significant discordance in HER2 status between primary and metastatic lesions. Patients with discordant HER2 status had better responses to platinum-based chemotherapy. Therefore, for patients with HER2-0 primary lesions, re-evaluation of HER2 status in metastatic lesions through biopsy may offer new treatment opportunities.</p></sec>