HER2-low breast cancer could be associated with an increased risk of brain metastasis

The HER2-low breast cancer is a newly recognized entity with the clinical characteristics is yet to be defined. We hypothesized that HER2-low breast cancer could lead to an increased rate of brain metastases in patients with localized breast cancer. We tested this hypothesis in a large cohort of breast cancer patients with long follow-up.

We included 2686 adult breast cancer patients followed up in Hacettepe University Cancer Center. Patients with 1 + positive HER2 expression and 2 + HER2 expression with a negative FISH were categorized as HER2-low disease. We evaluated the brain metastasis risk with binary logistic regression analyses and reported odds ratios (OR) with 95% confidence intervals (CI).

During a median 95.4 (IQR 72.6-123.1) month follow-up, 184 patients developed brain metastasis (6.9%). The brain metastases were developed in 5.1% of the patients with HER2-negative disease, 8.5% of the patients with HER2-low disease, and 10.1% of the patients with HER2-positive disease. A multivariable binary logistic regression model demonstrated an increased risk of brain metastasis in patients with HER2-low disease (OR: 1.611, 95% CI 1.055-2.460, p = 0.027) and in HER2-positive patients (OR: 1.837, 95% CI 1.308-2.580, p < 0.001). Additionally, HR + -HER2-low disease was associated with a decreased DFS compared to HR + -HER2-negative disease (p = 0.008).

In this study, we observed an increased risk of brain metastasis in localized breast cancer patients with HER2-low disease. We think that a high level of vigilance and a low threshold for brain imaging could benefit HER2-low breast cancer patients similar to the patients with HER-positive disease.