Incidence and outcome of brain and/or leptomeningeal metastases in HER2-low metastatic breast cancer in the French ESME cohort

Background: Breast cancer (BC) is the second most common cancer that metastasizes to the brain. Particularly up to half of patients with human epidermal growth factor receptor 2 (HER2)-positive (HER2+) metastatic breast cancer (mBC) may develop brain metastases over the course of the disease. Nevertheless, little is known about the prevalence and the outcome of brain and leptomeningeal metastases (BLMM) in HER2-low BC. We compared the cumulative incidence of BLMM and associated outcomes among patients with HER2-low, HER2-negative (HER2-) and HER2+ mBC.

Patients and methods: This cohort study was conducted from the Epidemiological Strategy and Medical Economics (ESME) mBC database and included patients treated for mBC between 2012 and 2020 across 18 French comprehensive cancer centers and with known HER2 and hormone receptor (HR) status. The cumulative incidence of BLMM after metastatic diagnosis was estimated using a competing risk methodology with death defined as a competing event.

Results: 19 585 patients were included with 6118 (31.2%), 9943 (50.8%) and 3524 (18.0%) being HER2-low, HER2- and HER2+ mBC, respectively. After a median follow-up of 48.6 months [95% confidence interval (CI) 47.7-49.3 months], BLMM were reported in 4727 patients: 1192 (25.2%) were diagnosed with BLMM at first metastatic diagnosis and 3535 (74.8%) after metastatic diagnosis. Multivariable analysis adjusted for age, histological grade, metastases-free interval and HR status showed that the risk of BLMM at metastatic diagnosis was similar in patients with HER2- compared to HER2-low mBC [odds ratio (OR) (95% CI) 1.00 (0.86-1.17)] and higher in those with HER2+ compared to HER2-low [OR (95% CI) 2.23 (1.87-2.66)]. Similar results were found after metastatic diagnosis; the risk of BLMM was similar in HER2- compared to HER2-low [subdistribution hazard ratio (sHR) (95% CI) 1.07 (0.98-1.16)] and higher in the HER2+ group [sHR (95% CI) 1.56 (1.41-1.73)].

Conclusions: The prevalence and evolution of BLMM in HER2-low mBC are similar to those in patients with HER2- tumors. In contrast to patients with HER2+ mBC, the prognosis of BLMM remains dismal in this population.