Impact of Low Hormone Receptor Expression on Neoadjuvant Chemotherapy Response and Patterns of Care in Non-Metastatic HER2-negative Breast Cancer: a US National Cancer Database Analysis

Background:Hormone receptor (HR)-low human epidermal growth factor receptor 2 (HER2)-negative breast cancers (BC) have similar outcomes to triple-negative BC; however, there is a lack of consensus on treatment recommendations for this subset. We present results from a US National Cancer Database (NCDB) analysis of patients with stage I-III HER2-negative BC categorized into groups by estrogen and progesterone receptor (PR) expression: HR-Neg, HR-Low, HR-Intermediate (HR-Int), and HR-High. Objectives:The primary objective was to assess the effect of HR expression on neoadjuvant chemotherapy (NAC) pathologic complete response (pCR) rates. Secondary objectives included assessment of clinico-pathologic characteristics and practice patterns. Design and methods:Patients with stage I-III HER2-negative BC diagnosed in 2018 were identified in the NCDB, a nationwide oncology outcomes database in the United States. Quantitative HR expression was unavailable prior to 2018. Data were categorized into four groups by estrogen receptor (ER) and PR expression: ER <1% and PR <1% (HR-Neg); ER 1%-10% and/or PR 1%-10% (HR-Low); ER >11%-30% and/or PR >11%-30% (HR-Int); and ER >30% and/or PR >30% (HR-High). Those with undocumented HR status (3%) or without curative intent surgery (5%) were excluded. Results:Significant differences were found between HR groups with higher grade, clinical stage, and Ki-67 in HR-Low versus HR-Int or HR-High groups. pCR rates in those receiving NAC were significantly different by HR status, with higher pCR rates in HR-Low versus HR-High groups (p < 0.001). NAC utilization significantly differed between groups, with a higher proportion of patients with HR-Low BC receiving NAC than other HR-positive groups (p < 0.001). Less than half of patients with HR-Low BC received endocrine therapy compared to higher rates in the HR-Int and HR-High groups (p < 0.001). Conclusion:This large real-world analysis shows variability in NAC utilization and endocrine therapy for HR-Low and HR-Int BC, with further work needed to enhance representation of these in trials.