AUTHOR=Shao Yingbo , Luo Zhifen , Yu Yang , Chen Qi , He Yaning , Liu Chaojun , Nie Bing , Zhu Fangyuan , Liu Hui 

TITLE=HER2-low expression does not affect the clinical outcomes of metastatic breast cancer treated with CDK4/6 inhibitor: A real-world study

JOURNAL=Frontiers in Endocrinology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.1000704

DOI=10.3389/fendo.2022.1000704

ISSN=1664-2392

ABSTRACT=<sec><title>Background</title><p>There is accumulating evidence support human epidermal growth factor receptor 2 (<italic>HER2</italic>)-low as a biologically distinct subtype of breast cancer. The present study was conducted to explore whether <italic>HER2</italic>-low expression will affect the clinical efficacy of cyclin-dependent kinase (<italic>CDK</italic>) 4/6 inhibitor for patients with hormone receptor (HR)-positive, <italic>HER-2</italic> negative metastatic breast cancer.</p></sec><sec><title>Methods</title><p>Patients with HR+/<italic>HER2</italic>- metastatic breast cancer who were treated with palbociclib from January 2019 to June 2021 were retrospectively analyzed based on real-world clinical practice. <italic>HER2</italic>-zero was defined as immunohistochemistry (IHC) 0, and <italic>HER2</italic>-low was defined as IHC 1+ or IHC 2+/fluorescence <italic>in situ</italic> hybridization (FISH) negative. The primary end point was progression free survival (PFS), and the secondary end points were objective response rate (ORR), disease control rate (DCR), overall survival(OS) and safety.</p></sec><sec><title>Results</title><p>45 patients received palbociclib plus aromatase inhibitor (AI) or fulvestrant therapy, including 24 <italic>HER-2</italic>-zero and 21 <italic>HER-2</italic>-low patients. There were no statistically significant differences in clinicopathological characteristics between the two groups. No significant differences were observed in ORR (41.7% vs. 28.6%, P=0.360) and DCR (79.2% vs. 76.2%, P=0.811) between <italic>HER-2</italic>-zero and <italic>HER-2</italic>-low patients. And simultaneously, <italic>HER2</italic>-zero and <italic>HER2</italic>-low patients obtained similar median PFS (16.2m vs. 14.1m, P=0.263). The median OS was not reached. Neutropenia and leukopenia were the most common adverse events. Grade 3-4 adverse events(AEs) occurred in 58.3% and 57.1% of patients, respectively.</p></sec><sec><title>Conclusions</title><p><italic>HER2</italic>-low expression does not affect the clinical efficacy of palbociclib and our present study did not support incorporating <italic>HER2</italic>-low into systemic therapy decisions for patients with HR+/<italic>HER2</italic>- metastatic breast cancer treated with <italic>CDK4/6</italic> inhibitor.</p></sec>