Senior Consultant Epidemiologist IQVIA, United States
Background: Of patients diagnosed with human epidermal growth factor receptor 2 protein-negative (HER2-neg) breast cancer (BC), an estimated 50-60% have low levels of HER2 expression (HER2-low), which may be beneficial for patients previously diagnosed with triple negative BC (TNBC), a diagnosis indicating absence of cell-surface targets for BC therapies. A better understanding of the characteristics and survival outcomes of patients diagnosed with HER2-low and HER2-zero BC, the components of HER2-neg, in real-world settings is needed.
Objectives: Review published real-world studies (RWS) and synthesize characteristics and survival outcomes for patients diagnosed with HER2-low BC.
Methods: A systematic literature review conducted of studies in PubMed published up to January 2023. Inclusion criteria were real-world observational studies focused on characteristics and/or survival outcomes among patients previously diagnosed with HER2-neg BC. Post-menopausal age was defined as >=50 years. Random effects meta-analyses with inverse variance were used to calculate pooled proportions for patient characteristics and pooled hazard ratios (HR) with 95% confidence intervals (CIs) to compare overall survival (OS) between HER2-low and HER2-zero BC.
Results: The search identified 41 retrospective RWS representing 66,551 patients with HER2-low BC eligible for inclusion. The HER2-low study populations varied with respect to disease stage, treatment history, and follow-up periods. Among the 40 studies with a HER2-neg BC study population, the pooled proportion of patients classified as HER-2 low BC was 0.56 (95% CI: 0.49-0.62, I2: 99.7%); and from study populations with TNBC, the pooled proportion of HER2-low BC was 0.40 (95% CI: 0.33-0.47, I2: 98.7%; reported in 26 studies). The pooled proportion of post-menopausal patients with HER2-low BC was 0.57 (95% CI: 0.47-0.67, I2: 99.5%; reported in 27 studies). Of the 13 studies reporting OS, patients with HER2-low BC had statistically significantly better OS (HR: 0.89, 95% CI: 0.84-0.95, I2: 53%, p: 0.01), relative to HER2-zero BC. When OS results were stratified by metastatic BC status, this finding remained statistically significant among early-stage HER2-low BC (HR: 0.73, 95% CI: 0.57-0.93, I2: 62%, p: 0.03, reported in 5 studies), but not for metastatic or mixed HER2-low BC.
Conclusions: This systematic review and meta-analysis examining HER2-low BC in real-world settings highlighted alignment with previous literature regarding the proportion of HER2-neg and TNBC populations redefined as HER2-low. Our review and analysis found that OS was better for HER2-low BC, relative to HER2-zero BC, which is promising for HER2-neg patients who were previously thought to have no HER2 cell-surface targets for treatment.
