230P HER2-low status in advanced breast cancer patients treated with CDK4/6 inhibitors: Is it predictive of outcome?

Current research has yet to definitively determine if a low status of Human Epidermal Growth Factor Receptor 2 (HER2) can serve as a predictive and prognostic biomarker for patients with advanced hormone receptor (HR)-positive, HER2-negative breast cancer (BC) who are undergoing treatment with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i). The advent of new anti-HER2 antibody-drug conjugates has broadened the horizon of potential treatments. The present study aimed to assess whether low expression of HER2 is a predictive biomarker for the clinical efficacy of CDK4/6i in this clinical setting. We analyzed patients with advanced HR-positive, HER2-negative BC treated with CDK4/6i at our institution between 2018-2023. We defined HER2-0 as an immunohistochemistry (IHC) score of 0, while HER2-low disease was classified as IHC 1+ or IHC 2+ with negative in situ hybridization. The primary objective was to evaluate the association between HER2-low status and PFS during CDK4/6i treatment, whereas the association with OS was a secondary objective. A total of 352 patients (pts) with advanced HR-positive HER2-negative BC were analyzed. The mean age was 61 years (range 23–87). The majority (271 pts) were treated in the first-line setting, and nearly half (171 pts) had de novo disease. Most pts had either bone-only disease (147 pts) or both bone and visceral involvement (144 pts). 203 pts received ribociclib, 96 palbociclib, and 53 abemaciclib. As for the endocrine compound, 240 pts were treated with letrozole, and 112 pts with fulvestrant. 151 pts were diagnosed with HER2-0 (43%), whereas 201 pts had HER2-low status (57%, including 128 pts with HER2 1+ and 73 pts with HER2 2+). The median PFS was 31.7 months and the median OS was 49.7 months. HER2-low status was not associated with PFS (HR 1.10, 95% CI 0.79 – 1.51; p = 0.58) nor OS (HR 1.23, 95% CI 0.80 – 1.89; p = 0.33). HER2-low status was not associated with age, line of treatment, de novo disease, bone or visceral involvement, progesterone receptor, histopathologic grade, and Ki67. HER2-low status, albeit being predictive for subsequent anti-HER2 treatment modalities, was not predictive for PFS nor OS in advanced breast cancer patients treated with CDK4/6 inhibitors.