Determinants of the interval to brain metastasis from initial breast cancer diagnosis and its relation to survival: a single-center retrospective cohort

Abstract Background: Brain metastasis (BM) carry short-term survival and a poor prognosis. Short-onset time to BM can lead to better survival than patients with delayed diagnosis. We intend to assess clinical factors associated with mortality and time to brain metastasis. Methods: We retrospectively reviewed the charts of 113 patients in our institution who developed BM from primary breast cancer from 2000-2020. Demographic and clinical characteristics were reviewed. One-hundred-thirteen patients were eligible for survival analysis by univariate and multivariate COX regression. In addition, we performed statistical analysis to determine factors associated with undergoing surgery. Results: Post-menopausal state at initial breast cancer (HR=1.66; CI 1.11-2.47, P=0.01), other ethnicities (HR=2.18; CI 1.17-4.04, P=0.01), and the subtype ER+/HER2+ (HR=2.13; CI 1.21-3.73, P=<0.05) were found on multivariate analysis to have a shorter interval to BM. Subgroup analysis of patients with ER+ tumors found that initial Stage IV at diagnosis (HR=1.83; CI 1.1-3.18, P=0.03) and HER2+ status (HR=1.81; CI 1.09-2.96, P=0.02) had shorter intervals to brain metastasis. Patients that underwent initial adjuvant endocrine therapy (HR=0.61; CI 0.39-0.95, P=0.03) and palbociclib therapy (HR=0.51; CI 0.28-0.96, P=0.04) had longer intervals to BM. In multivariate survival analysis, a BM onset shorter than 2 years (HR=0.24; CI 0.074-0.83, P =0.025, Figure 2C) was a protective factor. Conclusions: Patients with early development of breast BM have better survival than patients with longer time onsets. The subtype of tumor, receptor status, systemic therapy, and high initial stage are factors related to interval from breast cancer to brain metastasis.