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 from 2006 to 2019, 60.4% were HER2-low. Multivariable analysis showed HER2-low status was independently associated with race, histologic subtype, higher nuclear grade and stage, and estrogen receptor (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 nuclear 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 (31.9%) than those with luminal type (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. These findings confirm HER2-low status is common but not independently prognostic for response or survival.
Raghavendra et al. (Mon,) studied this question.