Treatment patterns and health care resource use of patients with metastatic breast cancer with HER2-low expression: A cancer registry-linked insurance claims study.
Authors: Check Devon K , Jackson Bradford E. , Spees Lisa , Dinan Michaela Ann , Kwong Jackie , Mehta Sandhya , Wheeler Stephanie B. , Wilson Lauren E. , Faherty Eleanor , Reeder-Hayes Katherine Elizabeth , Lam Clara 
Published: September 2022

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Background: Metastatic breast cancer (mBC) expresses varied levels of HER2 protein. While HER2+ mBC patients are treated with anti-HER2 therapies, those with lower levels of HER2 expression [HER2-low; immunohistochemistry (IHC) 1+, IHC 2+ with In Situ Hybridization (ISH) -] are currently classified as HER2-negative and are not treated with anti-HER2 therapies. This study aims to estimate population-based prevalence of HER2-low expression among mBC patients and assess healthcare resource utilization and breast cancer specific mortality rates, comparing HER2-low and HER2 IHC 0 patients. Methods: This was a retrospective population-based cohort study of women diagnosed with de novo mBC in North Carolina from 2010-2016, using a multi-payer linkage of insurance claims to state cancer registry data. We examined demographic and clinical characteristics, inpatient, emergency department (ED), and outpatient infusion visits over 12 months and lines of systemic therapy over 24 months by HER2 status and hormone receptor (HR) status. We estimated rates of hospitalization, emergency department (ED) and outpatient infusion visits per 1000-person days as well as hazard ratios for 3-year breast cancer specific mortality. Results: The cohort included 635 mBC patients; 53% (n = 337) met HER2-low criteria and 23.1% (n = 147) were HER2 IHC 0. Compared to HER2 IHC 0 patients, more HER2-low patients had hormone receptor (HR)+ disease (82% vs. 71%, p = 0.008) and were Black (26% vs. 16%, p = 0.029). HER2-low patients also had slightly higher rates of hospitalization (21.4 vs. 18.9, p = 0.003) and ED visits (2.4 vs. 1.8, p = 0.015), but similar rates of outpatient infusion visits (15.7 vs. 16.0, p = 0.684) compared to HER2 IHC 0. There were no differences in mortality due to mBC, comparing HER2 IHC 0 and HER2-low patients (HR: 0.90, 95% CI: 0.68-1.20, p = 0.483). Among HER2-low/HR+ patients, the most common regimens in first line (1L) included endocrine monotherapy (46.6%), chemotherapy (combination or monotherapy) (32.9%), and endocrine therapy with CDK4/6 inhibitors (18.8%). Similar patterns were seen in the second line (2L) with endocrine monotherapy (63.5%), chemotherapy (combination or monotherapy) (25.9%), and endocrine therapy with CDK4/6 inhibitors (9.5%). Most HER2-low/HR- patients received chemotherapy in 1L (88.9%) and 2L (90.9%). Conclusions: About 1 in 2 mBC patients met criteria to be classified as HER2-low. Overall, HER2-low patients experienced slightly higher rates of healthcare utilization than HER2 IHC 0 patients but had similar outcomes. Among HER2-low patients, treatment patterns by HR status were consistent with the standard of care for HER2 IHC 0 patients. There may be potential to improve outcomes among HER-low patients with anti-HER2 therapies demonstrating efficacy across levels of HER2 expression.