# Incidence of treated brain metastases among patients with stage I-III breast cancer: A population-based study

## TL;DR

This study found that up to 13% of patients with high-risk early-stage breast cancer may develop brain metastases within five years, suggesting the need for targeted screening.

## Contribution

The study provides population-based evidence on the incidence and timing of brain metastases in early-stage breast cancer subtypes.

## Key findings

- The 12-year cumulative incidence of treated brain metastases was 2.8% in the overall cohort.
- Stage III HER2+/HR- and TNBC patients had the highest 12-year incidence of 14.3% and 13.4%, respectively.
- Median time to brain metastasis treatment was shortest in stage III TNBC at 18.0 months.

## Abstract

The incidence and risk factors for brain metastases among patients with stage I-III breast cancer remain poorly defined.

We conducted a population-based cohort study using Ontario health administrative databases to identify patients diagnosed with stage I–III breast cancer between 2009 and 2021. Treatment of brain metastases with surgery or radiation was extracted from the same databases. Patients were stratified by breast cancer subtype: human epidermal growth factor receptor 2 positive/hormone receptor positive (HER2+/HR+), HER2+/hormone receptor negative (HER2+/HR-), HR+/HER2-, and triple-negative breast cancer (TNBC). Primary outcomes were the cumulative incidence of treated brain metastases and time to brain metastasis (TTBM) as defined by the time from primary breast cancer diagnosis to brain metastases treatment.

Among 92,973 patients, 7.9% had HER2+/HR+, 3.5% HER2+/HR−, 54.1% HR+/HER2−, 7.3% TNBC, and 27.2% unknown subtype. Median (IQR) follow-up was 84.2 (50.8–125.2) months. The 12-year cumulative incidence of treated brain metastases was 2.8% in the overall cohort. Among patients with stage III disease, 12-year incidence was 11.8% (HER2+/HR+), 14.3% (HER2+/HR−), 5.9% (HR+/HER2−), and 13.4% (TNBC); corresponding 5-year incidences were 7.5%, 11.2%, and 13.1% for stage III HER2+/HR+, HER2+/HR−, and TNBC, respectively. Among patients with stage III HER2+/HR− and TNBC, median TTBM was 23.3 and 18.0 months, respectively.

Up to 13% of patients with stage III HER2+ or TNBC received treatment for brain metastases within 5 years of diagnosis with early-stage breast cancer. These findings support prospective studies of risk-stratified screening for asymptomatic brain metastases in patients with early-stage breast cancer.

•Incidence of treated brain metastases (BrM) was assessed in a cohort of 92,973 patients with stage I-III breast cancer (BC).•The incidence of treated BrM was 2.8% in the overall cohort at 12 years.•In those with stage III triple negative (TN) or HER2+/hormone receptor (HR)- BC this risk was 13.4% and 14.3% at 12 years.•The shortest median time-to-treatment for BrM was 18.0 months in stage III TNBC and 23.3 months in stage III HER2+/HR- BC.•These findings support prospective, risk-stratified BrM screening studies for patients with high-risk HER2+ and TN early BC.

Incidence of treated brain metastases (BrM) was assessed in a cohort of 92,973 patients with stage I-III breast cancer (BC).

The incidence of treated BrM was 2.8% in the overall cohort at 12 years.

In those with stage III triple negative (TN) or HER2+/hormone receptor (HR)- BC this risk was 13.4% and 14.3% at 12 years.

The shortest median time-to-treatment for BrM was 18.0 months in stage III TNBC and 23.3 months in stage III HER2+/HR- BC.

These findings support prospective, risk-stratified BrM screening studies for patients with high-risk HER2+ and TN early BC.