Cardiovascular risk factors and breast cancer incidence in a large middle-aged cohort study

Abstract

Background: Several studies have demonstrated that cardiovascular risk factors play a role in the etiology of breast cancer. However, the combined effect of cardiovascular risk factors on the risk of breast cancer is still uncertain.

Methods: Data from the Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort of middle-aged women, were used to investigate the association of individual and combined cardiovascular risk factors with breast cancer. Cox proportional hazards models were applied to calculate the hazard ratio (HR) and 95% confidence intervals (CI).

Results: A total of 7501 women were included. During a mean follow-up of 19.7 years, 576 women were diagnosed with breast cancer. White women and premenopausal status were independently associated with increased risk of breast cancer. Of the individual cardiovascular risk factors, only obesity was independently associated with an increased risk of breast cancer (HR 1.29, 95% CI 1.04-1.61). Compared with women without cardiovascular risk factors, women having three or greater, but not those with fewer than three cardiovascular risk factors, had a significantly higher risk of developing breast cancer (HR 1.27, 95% CI 1.06-1.53). Subgroup analyses indicated that women with three or greater cardiovascular risk factors had higher risk of breast cancer among postmenopausal Black women, but not among premenopausal Black and White women.

Conclusions: Combinations of cardiovascular risk factors are associated with increased risk of breast cancer in middle-aged women, especially in postmenopausal Black women. Joint interventions to modify cardiovascular risk factors could be used to prevent breast cancer in these higher-risk individuals.

Keywords: Atherosclerosis risk in communities; Breast cancer; Cardiovascular disease; Cohort; Incidence; Menopause; Risk factors.

Fig. 1

Study flow chart. The Atherosclerosis Risk in Communities (ARIC) Study is a prospective cohort study designed to investigate risk factors for atherosclerosis. A total of 15,792 individuals aged 45–64 years were recruited from 1987 to 1989 (Visit 1). We ultimately included 7501 women in this analysis and collected related data from Visit 1 to achieve a long-term follow-up

Fig. 2

Kaplan-Meier curves for cumulative breast cancer incidence in subjects with a combination of cardiovascular risk factors. Shown is the association between a combination of cardiovascular risk factors and the incidence of breast cancer during the 23-year study period. Red lines indicate individuals having ≥3 cardiovascular risk factors. Compared with women without cardiovascular risk factors, women having ≥3 cardiovascular risk factors had a 27% higher cumulative breast cancer incidence (HR 1.27, 95% CI: 1.06–1.53, adjusted for race/ethnicity, menopausal status, education level, and income). However, no significant association was observed for women having < 3 cardiovascular risk factors

Fig. 3

Restricted cubic spline for breast cancer incidence in subjects with a combination of cardiovascular risk factors. Shown is the dose-response relationship between a combination of cardiovascular risk factors and the incidence of breast cancer. Red lines indicate hazard ratios and green lines indicate 95% confidence intervals. Adjusted HRs are from the Cox proportional hazards model with adjustment for race/ethnicity, menopausal status, education level, and income