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

Burton A 1 , Maskarinec G 2 , Perez-Gomez B 3 , Vachon C 4 , Miao H 5 , Lajous M 6 Show all authors , López-Ridaura R 6 , Rice M 7 , Pereira A 8 , Garmendia ML 8 , Tamimi RM 9 , Bertrand K 10 , Kwong A 11 , Ursin G 12 , Lee E 13 , Qureshi SA 14 , Ma H 15 , Vinnicombe S 16 , Moss S 17 , Allen S 18 , Ndumia R 19 , Vinayak S 19 , Teo SH 20 , Mariapun S 21 , Fadzli F 22 , Peplonska B 23 , Bukowska A 23 , Nagata C 24 , Stone J 25 , Hopper J 26 , Giles G 26 , Ozmen V 27 , Aribal ME 28 , Schüz J 1 , Van Gils CH 29 , Wanders JOP 29 , Sirous R 30 , Sirous M 31 , Hipwell J 32 , Kim J 33 , Lee JW 33 , Dickens C 34 , Hartman M 4 , Chia KS 35 , Scott C 4 , Chiarelli AM 36 , Linton L 37 , Pollan M 3 , Flugelman AA 38 , Salem D 39 , Kamal R 39 , Boyd N 37 , Dos-Santos-Silva I 40 , McCormack V 1

Affiliations 

  • 1 Section of Environment and Radiation, International Agency for Research on Cancer, Lyon, France
  • 2 University of Hawaii Cancer Center, Honolulu, Hawaii, United States of America
  • 3 Instituto de Salud Carlos III, Madrid, Spain
  • 4 Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America
  • 5 Saw Swee Hock School of Public Health, National University of Singapore, Singapore
  • 6 Instituto Nacional de Salud Pública, Cuernavaca, Mexico
  • 7 Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
  • 8 Instituto de Nutrición y Tecnología de los Alimentos, Universidad de Chile, Santiago, Chile
  • 9 Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
  • 10 Slone Epidemiology Center, Boston University, Boston, Massachusetts, United States of America
  • 11 Division of Breast Surgery, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
  • 12 Cancer Registry of Norway, Oslo, Norway
  • 13 Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, United States of America
  • 14 Norwegian Centre for Migrant and Minority Health (NAKMI), Oslo, Norway
  • 15 Department of Population Sciences, City of Hope National Medical Center, Duarte, California, United States of America
  • 16 Division of Cancer Research, Ninewells Hospital and Medical School, Dundee, United Kingdom
  • 17 Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom
  • 18 Department of Diagnostic Radiology, Royal Marsden NHS Foundation Trust, London, United Kingdom
  • 19 Aga Khan University Hospital, Nairobi, Kenya
  • 20 Breast Cancer Research Group, University of Malaya Medical Centre, University of Malaya, Kuala Lumpur, Malaysia
  • 21 Cancer Research Malaysia, Subang Jaya, Malaysia
  • 22 Breast Cancer Research Unit, Faculty of Medicine, University of Malaya Cancer Research Institute, University of Malaya, Kuala Lumpur, Malaysia
  • 23 Nofer Institute of Occupational Medicine, Łódź, Poland
  • 24 Department of Epidemiology & Preventive Medicine, Graduate School of Medicine, Gifu University, Gifu, Japan
  • 25 Centre for Genetic Origins of Health and Disease, University of Western Australia, Crawley, Western Australia, Australia
  • 26 Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia
  • 27 Faculty of Medicine, Istanbul University, Istanbul, Turkey
  • 28 Department of Radiology, School of Medicine, Marmara University, Istanbul, Turkey
  • 29 Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
  • 30 Isfahan University of Medical Sciences, Isfahan, Iran
  • 31 Radiology Department, Isfahan University of Medical Sciences, Isfahan, Iran
  • 32 Centre for Medical Image Computing, University College London, London, United Kingdom
  • 33 Asan Medical Center, Seoul, Republic of Korea
  • 34 Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
  • 35 Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore
  • 36 Ontario Breast Screening Program, Cancer Care Ontario, Toronto, Ontario, Canada
  • 37 Princess Margaret Cancer Centre, Toronto, Ontario, Canada
  • 38 National Cancer Control Center, Lady Davis Carmel Medical Center, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
  • 39 Woman Imaging Unit, Radiodiagnosis Department, Kasr El Aini, Cairo University Hospitals, Cairo, Egypt
  • 40 Department of Non-communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, United Kingdom
PLoS Med, 2017 Jun;14(6):e1002335.
PMID: 28666001 DOI: 10.1371/journal.pmed.1002335

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 (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.

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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