Breast Cancer Subtype as a Predictor of Lymph Node Metastasis according to the SEER Registry

PURPOSE Breast cancer subtype correlates with response to systemic therapy and overall survival (OS), but its impact on lymphatic spread is incompletely understood. In this study, we used the Surveillance, Epidemiology, and End Results registry to assess whether the subtype can predict the presence of nodal metastasis or advanced nodal stage in breast cancer. METHODS A total of 7,274 eligible patients diagnosed with T1-3 infiltrating ductal carcinoma with known estrogen or progesterone hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status, who underwent surgical excision of the primary tumor and pathologic lymph node evaluation, were included in this analysis. Patients were categorized into four breast cancer subtypes: HR+/HER2-; HR+/HER2+; HR-/HER2+; and HR-/HER2-. Binary logistic regression analysis was used to determine whether breast cancer subtype, tumor size, tumor grade, patient race, and patient age at diagnosis are independently predictive of lymph node positivity or advanced nodal stage. The Pearson chi-square test was used to determine whether progesterone receptor (PR) status had an impact on the incidence of lymph node positivity in estrogen receptor (ER) positive patients. RESULTS Independent predictors of nodal positivity included breast cancer subtype (p=0.040), tumor size (p<0.001), tumor grade (p<0.001), and patient age (p<0.001), whereas only tumor size (p<0.001), grade (p=0.001), and patient age (p=0.005) predicted advanced nodal stage. Triple-negative cancers had a significantly lower risk of nodal positivity than the HR+/HER2- subtype (odds ratio, 0.686; p=0.004), but no other significant differences between subtypes were observed. There was also no difference in lymph node positivity between PR+ and PR- tumors amongst ER+/HER2- (p=0.228) or ER+/HER2+ tumors (p=0.713). CONCLUSION The HR+/HER2-breast cancer subtype has a higher rate of lymph node involvement at diagnosis than the triple-negative subtype. These findings may play a role in guiding regional management considerations if confirmed in further studies.