Distribution and outcomes of HER2-low and HER2-zero metastatic breast cancer in Black and younger women.

Abstract

1109 Background: Black and younger patients with breast cancer (BC) have higher mortality. This racial disparity has been attributed to different BC biology, access to care, and treatment. With the advent of new antibody-drug conjugates (ADC) for metastatic BC (MBC), “HER2-negative” has been subdivided into HER2-low (IHC 1+ or 2+/ISH-negative) and HER2-0 (IHC 0). Little is known about these subcategories among Black and younger women with MBC. Methods: Clinical characteristics, treatment, and outcomes of patients diagnosed with HER2-negative MBC between 2011-2022 and with follow-up through a progression-free survival event on first-line therapy (PFS1) were retrieved from the UNC Metastatic Breast Cancer Database; hormone receptor (HR) and HER2 categories were by clinical criteria from the pathology report. Analyses were limited to HER2-negative BC and stratified/controlled by HR status. Fisher’s exact tests were used to compare HER2 status across race and age. The Kaplan Meier method and log-rank tests, as well as Cox proportional hazards models estimated PFS1. Results: The cohort included 772 MBC patients (56% HER2-low and 44% HER2-0), 22% Black women and 30% < 50 years old at MBC diagnosis. There were no differences in proportion with HER2-low by race or age (p>0.5). Patients with HER2-low had better observed median PFS1 compared to HER2-0, however, most of these differences were non-significant: overall (HR+ 12.2 vs 9.8m, p=0.11, HR- 4.3 v 3.3m, p=0.29) and within race and age categories (see table). In Cox modeling, Black women had worse PFS1 (p=0.03), that was no longer apparent after adjusting for HR status (p=0.1), there was no difference by age. Patients with HER2-0 had worse PFS1 (p=0.0005), which remained after adjusting for HR status (p=0.05). In a multivariable model comparing HER2-0 to HER2-low, adjusting for race and HR status, PFS1 remained shorter in the HER2-0 group (hazard ratio: 0.84, CI 0.692 – 1.015, p=0.07). Among those treated with uniform first-line therapy, better PFS1 was observed in HER2-low disease. This included 137 HR+ MBC treated with ET + CDK4/6i (mPFS1 14.3 v 10.3m, p=0.33) and 170 HR- MBC treated with chemotherapy (mPFS1 4.0 v 3.1m, p=0.22) with no variation by race or age. Conclusions: Within HER2-negative MBC, distribution of HER2-low and HER2-0 cancers does not differ by race and age. The clinical benefit of first-line therapy is strongly driven by HR status regardless of race and age, and is greater in HER2-low cancers although this cohort did not include HER2-directed ADCs. [Table: see text]