Insights from a Long-Term Follow-Up Evaluation of Early Breast Cancer Outcomes by Tumor Subtype.

INTRODUCTION: Our understanding of the granularity of breast cancer (BC) clinical outcomes by biologic subtype may be impaired by limited study follow-up times. OBJECTIVE: We evaluated the impact of modern immunohistochemistry (IHC)-based BC subtypes on long-term mortality. METHOD: We used a cohort of 200 women diagnosed with stage I-III BC in the period 1985-1990. Surgical samples underwent centralized pathology review. Multivariate models assessed associations of subtype with overall survival (OS) and BC-related survival (BCRS). RESULT: 42.0% women had luminal A-like, 32.5% luminal B-like/human epidermal growth factor receptor (HER)2-negative, 8.5% had HER2-positive, and 17.0% had triple-negative BC. 53.0% had tumor size (T) >2 cm and 47.5% had a positive nodal status (N). Over 18.7 years of median follow-up (range 0.3-32.0 years),140 deaths were recorded (75 BC-related). Median OS was longest for patients with luminal A-like tumors (21.2 years; 95% confidence interval [CI] 17.4-24.9]). The luminal B-like/HER2-negative subtype was significantly associated with worse BCRS (adjusted hazard ratio [HR] = 1.86; 95% CI 1.09-3.16). After multivariable analysis, T >2 cm (HR [vs. ≤2 cm] = 1.71 [95% CI 1.03-2.84]) and positive N (HR [vs. negative] = 2.19 [95% CI 1.03-4.65]) impacted BCRS. CONCLUSION: IHC-defined subtype will continue informing treatment algorithms for BC, until more precise tools like molecular profiling become widely available. Although confirmation in larger and adequately powered studies is warranted, modern surrogate subtype definitions produced a valid long-term prognostic stratification in this mature cohort.