TLSB-19 CENTRAL NERVOUS SYSTEM DISSEMINATION IN METASTATIC LOBULAR BREAST CANCER: A HISTOLOGY-BASED ANALYSIS

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Abstract Background Invasive lobular carcinoma (ILC) exhibits distinct biological and metastatic behavior compared with invasive breast carcinoma of no special type (BC-NST), yet patterns of central nervous system (CNS) dissemination remain incompletely defined. We examined determinants of CNS metastases and LMD to assess whether histology confers independent CNS risk. Methods Retrospective analysis using data from EMBRACE, a prospectively maintained cohort of patients with metastatic BC (mBC). Patients with BC-NST or ILC were included. CNS mets was defined as parenchymal brain mets and/or leptomeningeal disease (LMD). Associations between histology and CNS mets or LMD were evaluated using logistic regression. Multivariable models were adjusted for age, tumor grade, hormone receptor status, HER2 status, and de novo versus recurrent presentation. Results 3835 patients with mBC (3247 BC-NST; 588 ILC) were included (median follow-up, 16.4 years). Overall, 78.2% had recurrent disease; subtype distribution was HR+/HER2 − (61.2%), HER2 + (19.7%), and TNBC (19.1%). CNS mets occurred in 26.4% of BC-NST and 17.5% of ILC cases. ILC was associated with lower odds of CNS mets in unadjusted analyses (OR 0.59; 95% CI, 0.47–0.74) but not after adjustment (OR 1.08; 0.83–1.41). No histology-based difference was observed in HER2+ disease. Among HER2− tumors, CNS mets were less frequent in ILC than BC-NST (OR 0.63; 0.49–0.81), driven by TNBC (OR 0.25; 0.06–0.74), with no difference in HR+/HER2−. In multivariable models, CNS mets were associated with younger age, higher grade, ER/PR-negative status, HER2+ disease, and recurrent presentation. LMD occurred in 5.7% of BC-NST and 11.1% of ILC cases and was more frequent in ILC in adjusted analyses (OR 3.52; 2.44–5.05). Conclusion Histology differentially influences CNS dissemination in mBC. Although the lower CNS metastasis risk in ILC can be explained by tumor and clinical factors, ILC remains independently associated with a markedly higher risk of LMD.

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