Long-term Outcomes of Slowly Proliferating Luminal A-like Invasive Lobular Carcinoma Versus Invasive Carcinoma of No Special Type.

PURPOSE: Long-term outcome comparisons between invasive lobular carcinoma (ILC) and invasive carcinoma of no special type (NST, historically referred to as invasive ductal carcinoma) remain inconsistent, particularly in patients with low-proliferative hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2-) disease. This study evaluated the long-term outcomes of ILC and NST in a pathologically defined, low-proliferative, HR+/HER2- (luminal A-like) cohort. METHODS: This retrospective, single-institution study included patients with HR+/HER2- breast cancer and Ki-67 ≤ 20% who underwent surgery between 2008 and 2015. Patients with mixed histopathology, those who underwent palliative surgery, or those who received neoadjuvant chemotherapy were excluded. Survival was analyzed using the Kaplan-Meier method and multivariable Cox regression. A secondary 24-month landmark analysis included patients who were alive, disease-free, under observation, and receiving endocrine therapy 24 months after surgery. RESULTS: Among 3,439 patients, 3,156 had NST and 283 had ILC. Compared with NST, ILC was associated with a higher rate of synchronous bilateral breast cancer, a more advanced pathological stage, and a lower nuclear grade. In the comprehensive cohort, breast cancer-specific survival did not differ significantly (log-rank p = 0.081), whereas disease-free survival (DFS) and distant metastasis-free survival (DMFS) were worse in patients with ILC (log-rank p < 0.001 and p = 0.005, respectively). After adjustment for measured clinicopathological factors, these differences were no longer statistically significant (DFS: adjusted hazard ratio [HR], 1.27; 95% confidence interval [CI], 0.91-1.79; p = 0.164; DMFS: adjusted HR, 1.38; 95% CI, 0.83-2.30; p = 0.210). Detailed biomarker analyses showed similarly high estrogen receptor expression in both groups and lower exact Ki-67 values in ILC. The 24-month landmark analysis revealed the same overall pattern. CONCLUSION: In this low-proliferative HR+/HER2- cohort, ILC showed less favorable unadjusted long-term DFS and DMFS than NST, but these differences were attenuated and were no longer statistically significant after adjustment for measured clinicopathological characteristics.