Increasing breast density elevates cancer risk

Women with large breasts are at greater risk of developing breast cancer, reveals a study, indicating the important role of mammographic density as first measured in determining subsequent risk.

On the other hand, some women with lower density at baseline but an increasing trajectory over time are also at increased risk of breast cancer, suggesting the importance of identifying those with a growing density trajectory.

“Our findings also suggest that the trajectory of breast density, in addition to its single measurement, should be carefully considered when predicting breast cancer risk and should be incorporated into future breast cancer risk prediction models,” the investigators said.

In this retrospective cohort study, data from the national breast cancer screening program, embedded in the National Health Insurance database in Korea, were analysed. The investigators assessed breast density using the four category Breast Imaging Reporting and Data System (BI-RADS) classification. They also used a group-based trajectory modelling to identify breast density trajectories.

A total of 1,747,507 women (mean age 61.4 years) who underwent four biennial mammographic screening between 2009 and 2016 were included in the analysis. Five breast density trajectory groups were identified among the participants. [BMJ 2024;387:e079575]

Women with persistently fatty breast tissue were included in group 1, while those with fatty breast tissue at baseline but increased breast density over time were included in group 2. Groups 3 to 5 involved women with denser breasts, with a slight decrease in density in the long run.

Women in group 2 showed a 1.60-fold (95 percent confidence interval [CI], 1.49–1.72) higher risk of breast cancer than those in group 1. Those in groups 3 (adjusted hazard ratio [aHR], 1.86, 95 percent CI, 1.74–1.98), 4 (aHR, 2.49, 95 percent CI, 2.33–2.65), and 5 (aHR, 3.07, 95 percent CI, 2.87–3.28) also had increased risks compared with participants in group 1.

These results were consistent across age groups, regardless of changes in menopausal status or BMI.

“Breast density remains one of the most readily identifiable mammographic features and previous studies have explored the association between changes in breast density and breast cancer risk,” the investigators said. [Radiology 2023;306:e220291; JAMA Oncol 2023;9:808-814; J Natl Cancer Inst 2007;99:386-395; Cancer 2020;126:4687-4696; Int J Cancer 2014;135:1740-1744]

“The findings from these studies are generally consistent with our results, which indicate that a reduction in breast density is associated with a lower risk of breast cancer compared with women with stable or increasing breast density,” they added. [J Natl Cancer Inst 2020;112:391-399; Tutor Quant Methods Psychol 2009;5:11-24; Breast 2019;46:108-115]

Hormone therapy

In earlier studies, use of postmenopausal hormone replacement therapy (HRT) has been shown to increase breast density over time. In the current study, HRT use was higher in group 2 than in those with an initial BI-RADS density category 1 with a declining trend. [JNCI Cancer Spectr 2019;3:pkz004; JAMA 2001;285:171-176]

“Additionally, among women with increased density, the proportion of women whose BMI changed from overweight to normal was higher than that in the other trajectory groups,” the investigators said. 

“Considering the association between weight loss and increased breast density, weight reduction could be partially attributed to increased breast density in these populations,” they added. [BMC Med Imaging 2018;18:10; Cancer Epidemiol Biomarkers Prev 2015;24:1724-1730]