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Central nervous system (CNS) is a frequent metastatic site in HER2+ breast cancer (BC). Despite the development of new targeted agents, survival rate remains poor. We investigated the clinical and pathological factors correlated to CNS development focusing on their management in daily clinical practice. A retrospective review of HER2-positive metastatic (M) BC patients diagnosed between 2007 and 2022 at the Modena Cancer Center was done. Descriptive statistical analyses were used to correlate disease characteristics and type/time of CNS recurrence. Time to treatment failure (TTF) and Overall Survival (OS) were estimated by log-rank test and Kaplan-Meier curves. All analyses were performed using R version 4.3.2 (The R Foundation for Statistical Computing, 2023). 171 patients with HER2+ MBC were identified, 43.1% developed CNS metastasis during disease history. The median age was 54, 6 years. Hormone negative BC was the only independent risk factor for CNS recurrence (p 0.003). Overall, 45% of cases had diagnosis of brain relapse due to clinical signs/symptoms. CNS recurrence was the early metastatic site in more than half of cases. The early onset as well as the number of brain lesions were negative independent prognostic factors for OS (p < 0.05). Indeed, 18% had de novo CNS metastatis, 37% developed brain disease during first-line treatment while only 45% had late onset. Independently from the treatment line, local regional therapy was the first physician treatment choice: 27% received whole brain radiation therapy, 18% stereotactic radiation and only 9% underwent surgery. Patients with CNS disease had a statistically significant worse 1st line TTF and OS compared to patients without brain relapse (mTTF 14 months vs 24 months, p 0.048 and mOS 48 months vs 74 months, p=0, 0084, respectively). Brain disease is an early metastatic site in most of HER2-positive patients, mainly in hormone negative disease. CNS relapse remain a negative prognostic factors in term of TTF and OS independently from other known clinical and pathological features. Studies investigating brain-penetrable HER2-targeted therapies are still an urgent needed.
Ponzoni et al. (Wed,) studied this question.