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

•Risk of BLMM was similar in HER2− patients compared to HER2-low mBC and higher in those with HER2+ compared to HER2-low.•The risk of BLMM was similar in HER2− compared to HER2-low and higher in the HER2+ group.•Median overall survival was 6.6 (5.8-7.4), 5.5 (5.0-5.9) and 24.4 (21.8-26.9) m in HER-low, HER2− and HER2+ mBC patients.•Prognosis of BLMM remains dismal in HER2-low mBC patients.•Development of new treatment is eagerly awaited for patients with HER2-low or HER2− mBC. BackgroundBreast 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 methodsThis 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.Results19 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).ConclusionsThe 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. 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. 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. 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). 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.