Pathologic Complete Response to Neoadjuvant Chemotherapy in HER2-Low Versus HER2-Zero Breast Cancer: A Retrospective Cohort Study
Year: 2026
Type: article
Study design: Observational Study
Abstract: Purpose: Breast cancers with low human epidermal growth factor receptor 2 expression (HER2-low), defined as immunohistochemistry IHC 1+ or IHC 2+ with negative in situ hybridization, represent a distinct subset of HER2-negative disease.While this status is significant in metastatic breast cancer, its effect on neoadjuvant chemotherapy response and survival in early-stage disease is uncertain.This study investigates the relationship between HER2-low expression, pathological complete response (pCR), and survival outcomes in early-stage HER2-negative breast cancer.Patients and Methods: We conducted a retrospective analysis of 934 women with stage II-III HER2-negative breast cancer who received neoadjuvant chemotherapy from 2016 to 2021.Tumors were categorized as HER2-zero (IHC 0) or HER2-low (IHC 1+ or IHC 2+ with negative in situ hybridization).The primary endpoint was pathological complete response (pCR), defined as absence of residual invasive disease in both the breast and axillary lymph nodes (ypT0/Tis ypN0).Secondary endpoints included 5-year disease-free survival (DFS) and overall survival (OS).Data on hormone receptor status (estrogen receptor [ER] and progesterone receptor [PR]) and menopausal status were collected.We used multivariable logistic regression to identify pCR predictors, while survival outcomes were analyzed with Kaplan-Meier estimates; differences between groups were tested with the log-rank test.Results: About half of the tumors were HER2-low, with most patients presenting hormone receptor-positive disease.HER2-low tumors showed notably lower pCR rates compared to HER2-zero tumors.ER and PR positivity independently correlated with a decreased chance of achieving pCR in both HER2 subgroups.After a median follow-up of five years, there were no significant differences in DFS or OS between the groups.Conclusion: HER2-low breast cancer shows lower response rates to neoadjuvant chemotherapy, especially in hormone receptor-positive cases, yet there is no negative impact on 5-year survival..
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W7213670899