Is the risk of brain metastasis and prognosis different in HER2-low breast cancer?

Abstract

Purpose We aimed to evaluate whether brain metastases, which are one of the most critical factors that have a poor prognostic value and make treatment difficult in breast cancer cases, differ in HER2-low breast cancer and to evaluate the prognosis of HER2-low breast cancer. Method This retrospective study included 1134 female patients diagnosed with breast cancer between June 2012 and June 2023 from two tertiary healthcare centers in T & uuml;rkiye. Molecular groups were examined in six categories according to hormone receptor (HR) and human epidermal growth factor receptor (HER2) status (HR(+) HER2(-), HR(+) HER2-low, HR(+) HER2(+), HR(-) HER2(-), HR(-) HER2-low, and HR(-) HER2(+)). Results The median follow-up period was 56.6 months (IQR 29.9-90.5). We detected HER2-low disease in 155 (13.7%) cases. Among the six molecular groups, the highest brain metastasis rate was observed in the HR(-) HER2-low group (22.2%) (p = 0.001). In the HR(+) HER2-low group, the brain metastasis rate was 3.8%, with no statistically significant difference (p = 0.13). In the multivariate binary logistic regression model, there was a 32.4-fold increase in the risk of brain metastasis for the HR(-) HER2-low group compared to the HR(+) HER2(-) group (OR: 12.4, 95% CI 6.70-156.2, p < 0.001). The analysis reveals no significant increase in risk for the HR(+) HER2-low group (OR: 1.68, CI: 0.42-6.67, p = 0.46). In the Cox's regression model, the highest risk for poor BMFS was found in the HR(-) HER2-low group compared to the HR(+) HER2(-) group, with a 32.8-fold increased risk (HR: 32.82, CI: 7.80-138.3, p < 0.001). In the Cox's regression model, the highest risk for poor DFS was detected in the HR(-) HER2-low group compared to the HR(+) HER2(-) group, with a fourfold increase in risk (HR: 4.05, CI 1.34-12.30, p = 0.013). Shorter BMSS times were observed in the triple-negative and HR(-) HER2-low groups (1.33 and 3.9 months, respectively; p = 0.001). Conclusion Our study found that the risk of brain metastasis and disease recurrence increased significantly in the HR(-) HER2-low group, and contrary to some literature data, the risk of brain metastasis in the HR(+) HER2-low group did not differ from the HR(+) HER2(-) group. Both in our study and in many existing studies in the literature, it seems that the HR(+) HER2-low group has a similar prognosis with the HR(+) HER2(-) group, and the HR(-) HER2-low group is in an intermediate form between the HR(-) HER2(+) and HR(-) HER2(-) groups. Recurrence with brain metastasis and general disease recurrence were more common in the HR(-) HER2-low group. The study's retrospective design and the limited number of patients, especially in the HR(-) HER2-low group, along with potential underreporting in 1 + HER2 cases, are notable limitations.