Long-term outcomes and treatment response in early-stage invasive lobular carcinoma: insights from a nationwide population-based study

BACKGROUND: Invasive lobular carcinoma (ILC), the second most common breast cancer subtype, differs from invasive breast carcinoma of no special type (BC-NST) in biology, presentation, and treatment response. Evidence on its prognostic impact remains inconsistent. PATIENTS AND METHODS: Our nationwide, population-based study of stage I-III breast cancer diagnosed in Belgium (2008-2014) compared characteristics, treatment patterns, and overall survival (OS) between ILC and BC-NST. RESULTS: Of 51 815 eligible patients, 7593 (14.6%) had ILC. Compared with patients with BC-NST, patients with ILC were older (median 62 versus 59 years), more often T3-T4 (16.5% versus 7.4%) or N3 (5.4% versus 2.9%), and less frequently grade 3 (19.3% versus 40.7%; P < 0.0001). ILC was associated with worse unadjusted OS [hazard ratio (HR) 1.13, 95% confidence interval (CI) 1.08-1.18], with 15-year OS of 62.1% (versus 65.9% for BC-NST), but no difference after adjustment [adjusted HR (aHR) 0.97, 95% CI 0.92-1.02]. In subgroup analyses, inferior OS persisted in patients with N3 disease (aHR 1.29, 95% CI 1.07-1.55) and in those treated with neoadjuvant therapy (aHR 1.27, 95% CI 1.06-1.52). Flexible parametric models demonstrated a time-dependent effect, with lower early mortality but higher late mortality in ILC. Patients with ILC had lower odds of response to neoadjuvant therapy overall (odds ratio 0.34, 95% CI 0.27-0.43), consistent across hormone receptor-positive/human epidermal growth factor receptor 2-negative and triple-negative subtypes. CONCLUSIONS: The apparent survival disadvantage of ILC is largely explained by clinicopathologic features, with no independent association with OS. However, ILC demonstrates a time-dependent survival pattern, with lower early but higher late mortality, and worse outcomes in patients with extensive nodal involvement.