Mammographic density and ageing: A collaborative pooled analysis of cross-sectional data from 22 countries worldwide.
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Garmendia, Maria Luisa
Tamimi, Rulla M
Qureshi, Samera A
Aribal, Mustafa Erkin
Van Gils, Carla H
Wanders, Johanna O P
Lee, Jong Won
Chiarelli, Anna M
Flugelman, Anath Arzee
MetadataShow full item record
AbstractMammographic 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.
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 (I2) 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; I2 = 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]; I2 = 30%) was additionally driven by increasing breast area. The study is limited by different mammography systems and its cross-sectional rather than longitudinal nature.
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.
CitationPLoS Med. 2017, 14 (6):e1002335
SponsorsFunding: This work was supported by grant R03CA167771 from the US National Cancer Institute of the National Institutes of Health, and by the International Agency for Research on Cancer. Original studies were supported, according to country, by: Australia-Australian National Breast Cancer Foundation (to JSt), MCCS by VicHealth, Cancer Council Victoria and Australian NHMRC grants 209057, 251553 and 504711, cases and their vital status were ascertained through the Victorian Cancer Registry and the Australian Institute of Health and Welfare, including the National Death Index and the Australian Cancer Database; Canada-the National Cancer Institute of Canada (to NB); Chile-Fondecyt 11100238 (to MLG), 1120326, 1130277, 3130532, World Cancer Research Fund 2010/245, Ellison Medical Foundation Grant (to AP); Iran-Isfahan University of Medical Sciences; Israel-The Israel Cancer Association; Rep. of Korea: Asan Medical Center, Seoul, Republic of Korea, Grant No. 2010-0811; Malaysia-Sime Darby LPGA Tournament, the Ministry of Education University Malaya High Impact Research Grant UM.C/HIR/MOHE/06 and University Malaya Research Grant No RP046B-15HTM; Mexico-Ministry of Education of Mexico and ISSSTE's Medical Directorate staff and regional office in Jalisco for technical and administrative support, National Council of Science and Technology (Mexico) and the American Institute for Cancer Research (10A035); Netherlands EPIC- NL-Europe against Cancer Programme of the European Commission (SANCO), Dutch Ministry of Health, Dutch Cancer Society, ZonMW the Netherlands Organisation for Health Research and Development, and the World Cancer Research Fund; Poland-Polish-Norwegian Research Programme (PNRF±243±AI±1/07); Singapore-Clinician Scientist Award from National Medical Research Council and National University Cancer Institute Singapore (NCIS) Centre grant programme from National Medical Research Council; South Africa-Pink Drive; Spain-Spain's Health Research Fund (Fondo de Investigacion Santiaria) PI060386 and PS09/0790, and Spanish Federation of Breast Cancer Patients (FECMA) EPY1169-10; Turkey-Roche Mustahzarlari San. A. ., Istanbul, Turkey; UK-EPSRC and EP/K020439/1 (JHi), Breast Cancer Campaign (2007MayPR23), Cancer Research UK (G186/11; C405/A14565), DaCosta Foundation; US-National Cancer Institute R01CA85265, R37 CA54281, R01 CA97396, P50 CA116201, R01 CA177150, R01 CA140286, Cancer Center Support Grant CA15083; CA131332, CA124865, UM1 CA186107, UM1 CA176726 and he Susan G. Komen Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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