Single-center retrospective cohort study of prevalence of HER2-low status and outcomes in early-stage HER2-negative breast cancer

HER2-low breast cancer (IHC 1+ or 2+ without HER2 gene amplification) is a distinct and understudied subtype. In a cohort of 14,593 early-stage breast cancer patients treated at MD Anderson Cancer Center (Houston, TX) from 2006 to 2019, 60.4% were HER2-low. In multivariable analysis, HER2-low status was independently associated with race, histologic subtype, higher nuclear grade and stage, and ER positivity. Among 2464 patients receiving neoadjuvant chemotherapy, HER2-low status was not linked to pathologic complete response (pCR), overall survival (OS), or disease-free survival (DFS), compared to HER2-0 tumors. Factors predicting pCR included nuclearg grade III, stage I, invasive ductal carcinoma, lower ER/PR expression, and absence of lymphovascular invasion (LVI). Patients with TNBC had significantly higher pCR rates than those with luminal type (31.9% versus 2.2%; p<0.0001). Longer OS and DFS were associated with non-White race, lower stage and grade, negative LVI, and higher ER/PR levels. The authors conclude that HER2-low status is common but not independently prognostic for response or survival.