Patient characteristics and treatment patterns of patients with locally advanced or metastatic HER2-low breast cancer, a single site descriptive study

Purpose: To evaluate the prevalence and characteristics of different HER2 categories among patients with advanced breast cancer (aBC) and describe treatment patterns and outcomes of those with HER2-low disease.

Methods: A retrospective cohort study was conducted via chart review at the Huntsman Cancer Institute, including patients diagnosed with aBC (stages IIIB, IIIC and IV) between 2010 and 2019. All patients with IHC1+ were considered HER2-low unless FISH was positive. Patients with IHC2+ were only classified as HER2-low if a negative FISH was documented. The prevalence and characteristics of each HER2 category were reported. Treatment patterns and survival outcomes of HER2-low patients who received first line treatment in 2017 or later were presented.

Results: A total of 240 of 414 patients (58%) with aBC were HER2-low, with the majority of patients (83%) classified as hormone receptor (HR)-positive. In first line, most HR-positive patients received endocrine therapy with chemotherapy for stage IIIB/IIIC (47%) and with CDK4/6 inhibitors for stage IV breast cancer (50%) Most HR-negative patients received chemotherapy alone (92% for stage IIIB/IIIC, 60% for stage IV). In second line, chemotherapy alone was the most common modality (21.4% for HR-positive; 45.5% for HR-negative). Median overall survival was 37.7 months while median progression-free survival from first line was 18.0 months, decreasing to 8.0 months in second line.

Conclusion: A substantial proportion of patients previously classified as HER2-negative have low but detectable HER2 expression and may benefit from novel HER2-directed agents, which have demonstrated clinical benefit in this population post-chemotherapy.