Association between age and the presence and mortality of breast cancer synchronous brain metastases in the United States: A neglected SEER analysis

Abstract

Background: The extent of the relationship between age and the presence of breast cancer synchronous brain metastases (BCSBMs) and mortality has not yet been well-identified or sufficiently quantified. We aimed to examine the association of age with the presence of BCSBMs and all-cause and cancer-specific mortality outcomes using the SEER database.

Methods: Age-associated risk of the presence and survival of BCSBMs were evaluated on a continuous scale (restricted cubic spline, RCS) with logistic or Cox regression models. The main endpoints were the presence of BCSBMs and all-cause mortality or cancer-specific mortality. Cox proportional hazards regression and competing risk models were used in survival analysis.

Results: Among 374,132 adult breast cancer patients, 1,441 (0.38%) had BMs. The presence of BCSBMs displayed a U-shaped relationship with age, with the highest point of the curve occurring at the age of 62. In both the younger (age ≤ 61) and older (age ≥ 62) groups, the observed curve showed a nearly linear relationship between age and the presence of BCSBMs. The relationship between age and all-cause mortality (ASM) and cancer-specific mortality (CSM) was linear. Older age at diagnosis was associated with a higher risk of ASM (HR 1.019, 95% CI: 1.013-1.024, p < 0.001) and CSM (HR 1.016, 95% CI: 1.010-1.023, p < 0.001) in multivariable Cox models. Age (sHR 1.007, 95% CI 1-1.013, p = 0.049) was substantially related to a significantly increased risk of CSM in competing risk models.

Conclusion: Age had a non-linear U-shaped relationship with the presence of BCSBMs and a linear relationship with BCSBMs mortality.

Keywords: SEER; brain metastases (BMs); breast cancer; linearity; non-linearity; prognosis; restricted cubic spline (RCS).