Survival outcomes after neoadjuvant chemotherapy in hormone receptor-positive breast cancer patients with nodal metastases: A National Cancer Database analysis.

BACKGROUND: Neoadjuvant chemotherapy is commonly used in node-positive breast cancer to facilitate axillary downstaging. While benefit is established in triple-negative and human epidermal growth factor receptor 2-positive disease, its role in hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer remains controversial because of lower chemosensitivity. We evaluated survival outcomes associated with neoadjuvant chemotherapy versus upfront surgery in node-positive hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer.

METHODS: We performed a retrospective analysis of female patients diagnosed between 2010 and 2022 with node-positive hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer (cN1-3) in the National Cancer Database undergoing definitive surgery. Patients were classified as receiving neoadjuvant chemotherapy or non-neoadjuvant therapy. Overall survival was the primary outcome. Inverse probability of treatment weighting adjusted for baseline differences. Survival was compared using weighted Kaplan-Meier and Cox models. Predictors of nodal pathologic complete response (ypN0) were evaluated using multivariable logistic regression.

RESULTS: A total of 146,842 patients met the inclusion criteria: 44,046 (30.0%) received neoadjuvant chemotherapy, and 102,796 (70.0%) received non-neoadjuvant chemotherapy. Among neoadjuvant chemotherapy patients, 10.2% achieved ypN0. In adjusted analyses, neoadjuvant chemotherapy was associated with inferior overall survival compared with non-neoadjuvant chemotherapy (80% survival: 67.2 vs 71.2 months; P= .0006), most pronounced in N1 disease. Patients achieving ypN0 had the most favorable survival (80% survival: 93.1 months). Predictors of ypN0 included high grade, high Oncotype DX score, ductal histology, younger age, lower progesterone receptor expression, the absence of lymphovascular invasion, and smaller tumor size.

CONCLUSION: In node-positive hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer, neoadjuvant chemotherapy is associated with inferior overall survival compared with upfront surgery, particularly among patients with limited nodal burden. However, patients who achieve nodal complete response experience excellent long-term outcomes, supporting careful selection for neoadjuvant treatment.