Age-Profiles Of Mammographic Density In Women From 22 Diverse Countries: Insights Into A Tissue-Specific Marker Of Breast Cancer Risk From The International Consortium On Mammographic Density

Anya BURTON, IARC, France
DOS SANTOS SILVA I. 2 , HUI M. 3 , MASKARINEC G. 4 , VACHON C. 5 , PÉREZ-GÓMEZ B. 6 , BOYD N. 7 , MCCORMACK V. 1

1 Section of Environment and Radiation, International Agency for Research on Cancer, Lyon, France
2 Dept of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
3 Saw Swee Hock School of Public Health, National University of Singapore, Singapore
4 University of Hawaii Cancer Center, Honolulu, Hawaii, USA
5 Dept Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA
6 Cancer Epidemiology Unit, Instituto de Salud Carlos III and CIBERESP, Madrid, Spain
7 Princess Margaret Cancer Centre, Toronto, Canada

Purpose: Mammographic density (MD) is radio-opaque (white) breast tissue on a mammogram and is a strong breast cancer risk factor. MD varies over time within women and this age-profile may be related to Pike’s model of the breast tissue aging rate, with breast cancer risk being a function of accumulated breast tissue age. MD age-profiles have been studied in high breast cancer risk countries where westernized lifestyles prevail. In the International Consortium on Mammographic Density (ICMD), we investigated how MD is associated with age and menopausal transition across 22 countries, spanning the breast cancer incidence spectrum.
Methods: ICMD contains individual-level risk factor and MD data (read centrally using Cumulus) on 11755 breast cancer-free women in 40 ethnicity and location-specific population groups. Linear regression was used to estimate square-root percent MD (PMD) and absolute dense area (DA) in relation to age and menopausal status at mammography, adjusted for BMI, image type and population group.
Results: Mean (SD) age at mammography across ICMD was 52.5 years (8.2).  4890 pre and 6865 post-menopausal women were included. Overall, DA and PMD was lower in older women, with a difference in square-root DA per 10 years of -0.24 cm (95% confidence interval: -0.39,-0.08) at premenopausal ages, which was slightly larger at postmenopausal ages (-0.35 (-0.42,-0.27)). This association was present across all population groups and was more consistent for DA (between population group heterogeneity I2=6.2%) than for PMD (I2=41.5%). The difference in square-root DA between post and pre-menopausal women of the same age was pronounced (-0.52 (-0.63,-0.41): the equivalent of a drop from 16 cm2 to 11.5 cm2.
Conclusions: Lower PMD and DA with increasing age and particularly after menopausal transition were highly consistent and present across diverse countries, based on these cross-sectional data. They are likely to result from intrinsic biologically-driven changes.
Funding Source: NIH-R03CA167771