Mammographic density and ageing: A collaborative pooled analysis of cross-sectional data from 22 countries worldwide

Abstract

Background

Mammographic density (MD) is one of the strongest breast cancer risk factors. Its age-related characteristics have been studied in women in western countries, but whether these associations apply to women worldwide is not known.

Methods and findings

We examined cross-sectional differences in MD by age and menopausal status in over 11,000 breast-cancer-free women aged 35–85 years, from 40 ethnicity- and location-specific population groups across 22 countries in the International Consortium on Mammographic Density (ICMD). MD was read centrally using a quantitative method (Cumulus) and its square-root metrics were analysed using meta-analysis of group-level estimates and linear regression models of pooled data, adjusted for body mass index, reproductive factors, mammogram view, image type, and reader. In all, 4,534 women were premenopausal, and 6,481 postmenopausal, at the time of mammography. A large age-adjusted difference in percent MD (PD) between post- and premenopausal women was apparent (–0.46 cm [95% CI: −0.53, −0.39]) and appeared greater in women with lower breast cancer risk profiles; variation across population groups due to heterogeneity ( I ²) was 16.5%. Among premenopausal women, the √PD difference per 10-year increase in age was −0.24 cm (95% CI: −0.34, −0.14; I ² = 30%), reflecting a compositional change (lower dense area and higher non-dense area, with no difference in breast area). In postmenopausal women, the corresponding difference in √PD (−0.38 cm [95% CI: −0.44, −0.33]; I ² = 30%) was additionally driven by increasing breast area. The study is limited by different mammography systems and its cross-sectional rather than longitudinal nature.

Conclusions

Declines in MD with increasing age are present premenopausally, continue postmenopausally, and are most pronounced over the menopausal transition. These effects were highly consistent across diverse groups of women worldwide, suggesting that they result from an intrinsic biological, likely hormonal, mechanism common to women. If cumulative breast density is a key determinant of breast cancer risk, younger ages may be the more critical periods for lifestyle modifications aimed at breast density and breast cancer risk reduction.

Abstract

Valerie McCormack and colleagues reveal reduced breast density with increased age in women from different ethnic groups; however increased breast density in young women is a cancer risk.

Author summary

Why was this study done?

• Breast density, a measure of the amount of dense to fatty tissue in the breast, is a strong marker of breast cancer risk.

• Breast density determinants have been studied in high-income countries, but not in women worldwide.

What did the researchers do and find?

• We studied how breast density differed by age and menopausal status in diverse groups of women from 22 countries worldwide.

• For over 11,000 women, mammograms were read centrally and risk factor data harmonised.

• We found that, regardless of the country and ethnic group of women, breast density was much lower in postmenopausal than in premenopausal women of the same age.

• Additionally, as a relative proportion of breast area, breast density was lower in older women both among premenopausal and postmenopausal women. Among premenopausal women, breast density changed with age without an increase in breast area, but among postmenopausal women, the latter also increased.

What do these findings mean?

• That this change in breast density with age is seen internationally suggests that the change is due to a universal biological mechanism inherent to all women.

• If cumulative breast density is a key determinant of breast cancer risk, younger ages may be the more critical periods for lifestyle modifications aimed at breast density and breast cancer risk reduction.