The incidence of brain metastases in breast cancer according to molecular subtype and stage: a 10-year single institution analysis.

BACKGROUND: Breast cancer (BC) is the second most common etiology of brain metastases (BrM). We aimed to examine the incidence of BrM among all BC patients presenting to a large tertiary cancer centre over one decade. METHODS: We included all BC patients presenting consecutively between 2009 and 2019 and cross referenced that cohort to a radiotherapy database, identifying patients treated for BrM at any time following their initial presentation. Cumulative incidences (CI) of BrM diagnoses were calculated using death as a competing risk and compared using the Fine-Gray method. Overall survival was estimated using the Kaplan Meier method. RESULTS: We identified 12,995 unique patients. The CI of BrM in patients who initially presented with Stage 0-4 disease was 2.1%, 3.7%, 9.4%, 10.6%, and 28.7%, respectively at 10 years. For 8,951 patients with available molecular subtype data, 6,470 (72%), 961 (11%), 1,023 (11%), and 497 (6%) had hormone-receptor (HR)-positive/ERBB2-, HR-negative/ERBB2-, HR-positive/ERBB2 + , and HR-negative/ERBB2 + disease, respectively; the CI of BrM in each was 7.6%, 25.3%, 24.1%, and 26.6%, at 10 years following BC diagnosis, respectively. Median overall survival (OS) following BC diagnosis and BrM diagnosis was 28 years 95% CI [25, 32] and 10 months 95% CI [9, 12], respectively. CONCLUSIONS: From a large, registry-based study, we observed that patients with ERBB2 + and triple negative BC have the highest incidence of BrM. Our data supports prospective surveillance brain MRI studies. Given advancements in BrM treatment, clinicians should have a low threshold for brain imaging in BC patients with high risk subtypes.

Durability of CNS disease control in NSCLC patients with brain metastases treated with immune checkpoint inhibitors plus cranial radiotherapy.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have excellent systemic activity and are standard first line treatment in EGFR/ALK wild type metastatic non-small cell lung cancer (NSCLC). However, their role in patients with brain metastases, which affects over 20% of patients and cause significant morbidity, is less clear. METHODS: We reviewed patients with EGFR/ALK wild-type mNSCLC with CNS metastases. Serial MRIs were reviewed to determine the time to intracranial progression (iPFS). Multivariate regression was performed to adjust for the disease-specific graded prognostic score (ds-GPA). RESULTS: We identified 36 ICI- and 33 chemotherapy-treated patients with baseline CNS metastases and available serial MRIs (average frequency:3.5 months). Baseline radiation was given except for 2 chemotherapy-treated patients with asymptomatic solitary metastasis. The CNS burden of disease was higher in the ICI-treated group (ICI:22% vs. chemotherapy:0% had >10 lesions; p = 0.02), but the utilization of WBRT was not (ICI:31% vs. chemotherapy:45%; p = 0.09). At the time of progression, CNS involvement was identified in 30 % of ICI-treated patients compared to 64 % of chemotherapy controls (p = 0.02). ICI-treated patients had superior iPFS (13.5 vs 8.4 months) that remained significant in multivariate analysis (HR 1.9; 95%CI 1.1--3.4). Superior CNS outcomes in ICI-treated patients were driven by the PD-L1 high subgroup where the 12-month cumulative incidence rate of CNS progression was 19% in ICI-treated PD-L1 ≥ 50%, 50% in ICI-treated PD-L1 < 50% and 58% in chemotherapy-treated patients (p = 0.03). CONCLUSIONS: Remarkable CNS disease control is seen with baseline RT plus ICIs in patients with PD-L1 ≥ 50%. Strategies for delaying WBRT should be investigated in this subgroup of patients.