Long-term outcomes of invasive lobular carcinoma compared with invasive ductal carcinoma in HR-positive/HER2-negative breast cancer: a focus on luminal subtypes.

backgroundInvasive lobular carcinoma (ILC) differs from invasive ductal carcinoma (IDC) in clinicopathological characteristics, treatment responsiveness, and recurrence patterns. However, its long-term prognostic significance, particularly in hormone receptor (HR)-positive/HER2-negative disease, remains incompletely understood.

methodsWe retrospectively analyzed 2,423 women with clinical stage I-III breast cancer who underwent partial mastectomy or total mastectomy between January 2013 and December 2017, including 2,262 patients with IDC and 161 with ILC. The primary endpoint was invasive breast cancer-free survival (iBCFS), and overall survival (OS) was evaluated as a secondary endpoint. Multivariable Cox proportional hazards models were used to compare outcomes between ILC and IDC. Subtype-specific analyses were restricted to HR-positive/HER2-negative luminal A-like and luminal B-like tumors defined according to the St. Gallen 2013 criteria. Exploratory analyses assessed the associations of neoadjuvant and adjuvant chemotherapy with outcomes.

resultsCompared with IDC, ILC was more frequently ER-positive/HER2-negative, had lower Ki-67, and presented with more advanced pathological tumor burden. Five-year iBCFS was 84.9% in ILC and 91.5% in IDC (log-rank p = 0.053). In the adjusted overall model, ILC tended to be associated with poorer iBCFS (hazard ratio [HR] 1.43, 95% confidence interval [CI] 0.94-2.19; p = 0.096). In subtype-specific analyses, ILC was not significantly associated with iBCFS in luminal A-like disease (HR 1.15, 95% CI 0.67-1.98; p = 0.619), whereas the adverse prognostic association of ILC was more apparent in luminal B-like disease (HR 1.47, 95% CI 1.03-2.09; p = 0.033). The histology-by-subtype interaction was not statistically significant. In luminal disease, neoadjuvant chemotherapy was not independently associated with improved outcomes after adjustment for pretreatment clinical stage, whereas adjuvant chemotherapy was associated with better iBCFS in the combined luminal ILC group.

conclusionsILC tended to be associated with poorer long-term invasive outcomes than IDC, particularly in HR-positive/HER2-negative disease. The adverse prognostic association of ILC was more apparent in luminal B-like tumors than in luminal A-like tumors. These findings support a risk-adapted approach to ILC that integrates histology, tumor burden, and proliferative activity. Further validation in larger prospective studies is warranted.