# Temporal Dynamics and Clinical Predictors of Brain Metastasis in Breast Cancer: A Two-Decade Cohort Analysis Toward Tailored CNS Screening

## TL;DR

This study identifies clinical factors that predict brain metastasis development in breast cancer patients, aiming to improve screening and survival.

## Contribution

The study provides a 20-year cohort analysis to identify predictors for brain metastasis timing and survival in breast cancer patients.

## Key findings

- Early detection of brain metastases within 2 years of diagnosis is linked to better prognosis.
- Post-menopausal status, Asian ethnicity, and HER2+ tumor subtype are associated with faster brain metastasis development.
- Adjuvant endocrine therapy and Palbociclib delay the onset of brain metastases.

## Abstract

Breast cancer constitutes a prominent source of brain metastases (BMs), which significantly contribute to mortality among women. However, there are no established guidelines on when or how frequently brain imaging should be conducted in these patients. This retrospective study aimed to identify clinical factors that could predict overall survival and the time to the development of BMs over a 20-year period. We found that early detection of BMs (within 2 years after breast cancer diagnosis) was linked to better prognosis. Baseline factors such as post-menopausal status, ethnicity, and HER2+ tumor subtype were associated with a faster development of BMs, while treatments like adjuvant endocrine therapy and Palbociclib were found to delay BM onset. Our findings suggest that incorporating these clinical predictors into an algorithm could help improve survival and quality of life for breast cancer patients at risk of developing brain metastases.

Background/Objectives: Breast cancer is the most common malignancy in women and the second leading cause of cancer-related deaths globally. It is also the second most frequent source of brain metastases (BMs), contributing to 5–20% of cases. Despite this, routine brain imaging for screening is not recommended and is only conducted when clinical symptoms or physical findings suggest metastasis. This study aims to identify clinical predictors associated with overall survival (OS) and the timing of BM development in breast cancer patients. Methods: We performed a retrospective review of medical records for 113 patients diagnosed with BMs secondary to breast cancer at our institution between 2000 and 2020. Baseline demographic data and clinical characteristics related to BMs were collected. To identify factors associated with OS and time to BM development after breast cancer diagnosis, we conducted univariate analysis using Kaplan–Meier curves, bivariate analysis with the log-rank test, and multivariate analysis via the Cox Proportional Hazard model. Results: An early diagnosis of BMs was identified as a significant predictor of prolonged OS (aHR = 0.22; 95% CI: 0.049–0.98, p = 0.05). Post-menopausal status at breast cancer diagnosis (aHR = 1.69; 95% CI: 1.13–2.53, p = 0.01), Asian ethnicity (aHR = 2.30; 95% CI: 1.03–5.16, p = 0.04), and the ER+/HER2+ subtype (aHR = 2.06; 95% CI: 1.14–3.71, p = 0.02) were significantly associated with a shorter time to BM diagnosis. A subgroup analysis of patients with ER+ breast tumors revealed that Hispanic or Arabic ethnicity (aHR = 3.63; 95% CI: 1.34–9.81, p = 0.01) and stage IV diagnosis (aHR = 2.09; 95% CI: 1.16–3.76, p = 0.01) were significantly associated with shorter intervals to BM diagnosis. Conclusions: Breast cancer remains a significant global health burden for women, yet clear guidelines for routine BMs screening are still lacking. Early detection of BMs has been shown to notably improve long-term survival outcomes. Additionally, post-menopausal status, Hispanic or Arabic ethnicity, and the HER2+ tumor subtype are associated with shorter time to BM development, highlighting these factors as potential indicators for central nervous system screening.