Association of Breast Density With Breast Cancer Risk Among Women Aged 65 Years or Older by Age Group and Body Mass Index

Importance: Breast density is associated with breast cancer risk in women aged 40 to 65 years, but there is limited evidence of its association with risk of breast cancer among women aged 65 years or older. Objective: To compare the association between breast density and risk of invasive breast cancer among women aged 65 to 74 years vs women aged 75 years or older and to evaluate whether the association is modified by body mass index (BMI). Design, Setting, and Participants: This prospective cohort study used data from the Breast Cancer Surveillance Consortium from January 1, 1996, to December 31, 2012, for US women aged 65 years or older who underwent screening mammography. Data were analyzed from January 1, 2018, to December 31, 2020. Exposures: Breast Imaging Reporting and Data System breast density category, age, and BMI. Main Outcomes and Measures: The 5-year cumulative incidence of invasive breast cancer by level of breast density (almost entirely fat, scattered fibroglandular densities, or heterogeneous or extreme density) and age (65-74 vs ≥75 years) was calculated using weighted means. Cox proportional hazards models were fit to estimate the association of breast density with invasive breast cancer risk. The likelihood ratio test was used to test the interaction between BMI and breast density. Results: A total of 221 714 screening mammograms from 193 787 women were included in the study; a total of 38% of the study population was aged 75 years or older. Of the mammograms, most were from women aged 65 to 74 years (64.6%) and non-Hispanic White individuals (81.4%). The 5-year cumulative incidence of invasive breast cancer increased in association with increasing breast density among women aged 65 to 74 years (almost entirely fatty breasts: 11.3 per 1000 women 95% CI, 10.4-12.5 per 1000 women; scattered fibroglandular densities: 17.2 per 1000 women 95% CI, 16.1-17.9 per 1000 women; extremely or heterogeneously dense breasts: 23.7 per 1000 women 95% CI, 22.4-25.3 per 1000 women) and among those aged 75 years or older (fatty breasts: 13.5 per 1000 women 95% CI, 11.6-15.5; scattered fibroglandular densities: 18.4 per 1000 women 95% CI, 17.0-19.5 per 1000 women; extremely or heterogeneously dense breasts: 22.5 per 1000 women 95% CI, 20.2-24.2 per 1000 women). Extreme or heterogeneous breast density was associated with increased risk of breast cancer compared with scattered fibroglandular breast density in both age categories (65-74 years: hazard ratio HR, 1.39 95% CI, 1.28-1.50; ≥75 years: HR, 1.23 95% CI, 1.10-1.37). Women with almost entirely fatty breasts had a decrease of approximately 30% (range, 27%-34%) in the risk of invasive breast cancer compared with women with scattered fibroglandular breast density (65-74 years: HR, 0.66 95% CI, 0.58-0.75; ≥75 years: HR, 0.73; 95% CI, 0.62-0.86). Associations between breast density and breast cancer risk were not significantly modified by BMI (for age 65-74 years: likelihood ratio test, 2.67; df, 2; P = .26; for age ≥75 years, 2.06; df, 2; P = .36). Conclusions and Relevance: The findings suggest that breast density is associated with increased risk of invasive breast cancer among women aged 65 years or older. Breast density and life expectancy should be considered together when discussing the potential benefits vs harms of continued screening mammography in this population.