Mammographic density and ageing: A collaborative pooled analysis of cross-sectional data from 22 countries worldwide.
Anya Burton, Gertraud Maskarinec, Beatriz Perez-Gomez, Celine Vachon, Hui Miao, Martín Lajous, Ruy López-Ridaura, Megan Rice, Ana Pereira, Maria Luisa Garmendia, Rulla M Tamimi, Kimberly Bertrand, Ava Kwong, Giske Ursin, Eunjung Lee, Samera A Qureshi, Huiyan Ma, Sarah Vinnicombe, Sue Moss, Steve Allen, Rose Ndumia, Sudhir Vinayak, Soo-Hwang Teo, Shivaani Mariapun, Farhana Fadzli, Beata Peplonska, Agnieszka Bukowska, Chisato Nagata, Jennifer Stone, John Hopper, Graham Giles, Vahit Ozmen, Mustafa Erkin Aribal, Joachim Schüz, Carla H Van Gils, Johanna O P Wanders, Reza Sirous, Mehri Sirous, John Hipwell, Jisun Kim, Jong Won Lee, Caroline Dickens, Mikael Hartman, Kee-Seng Chia, Christopher Scott, Anna M Chiarelli, Linda Linton, Marina Pollan, Anath Arzee Flugelman, Dorria Salem, Rasha Kamal, Norman Boyd, Isabel Dos-Santos-Silva, Valerie McCormack
Journal: PLoS medicine
2017;14(6):e1002335
PMID: 28666001
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.
Address:
Section of Environment and Radiation, International Agency for Research on Cancer, Lyon, France.; University of Hawaii Cancer Center, Honolulu, Hawaii, United States of America.; Instituto de Salud Carlos III, Madrid, Spain.; CIBERESP, Madrid, Spain.; Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America.; Saw Swee Hock School of Public Health, National University of Singapore, Singapore.; Instituto Nacional de Salud Pública, Cuernavaca, Mexico.; Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.; Instituto de Nutrición y Tecnología de los Alimentos, Universidad de Chile, Santiago, Chile.; Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.; Slone Epidemiology Center, Boston University, Boston, Massachusetts, United States of America.; Division of Breast Surgery, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China.; Department of Surgery and Cancer Genetics Center, Hong Kong Sanatorium and Hospital, Hong Kong, China.; Hong Kong Hereditary Breast Cancer Family Registry, Hong Kong, China.; Cancer Registry of Norway, Oslo, Norway.; Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, United States of America.; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, United States of America.; Norwegian Centre for Migrant and Minority Health (NAKMI), Oslo, Norway.; Department of Population Sciences, City of Hope National Medical Center, Duarte, California, United States of America.; Division of Cancer Research, Ninewells Hospital and Medical School, Dundee, United Kingdom.; Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom.; Department of Diagnostic Radiology, Royal Marsden NHS Foundation Trust, London, United Kingdom.; Aga Khan University Hospital, Nairobi, Kenya.; Breast Cancer Research Group, University of Malaya Medical Centre, University of Malaya, Kuala Lumpur, Malaysia.; Cancer Research Malaysia, Subang Jaya, Malaysia.; Cancer Research Malaysia, Subang Jaya, Malaysia.; Breast Cancer Research Unit, Faculty of Medicine, University of Malaya Cancer Research Institute, University of Malaya, Kuala Lumpur, Malaysia.; Biomedical Imaging Department, University of Malaya Medical Centre, University of Malaya, Kuala Lumpur, Malaysia.; Nofer Institute of Occupational Medicine, Łódź, Poland.; Department of Epidemiology & Preventive Medicine, Graduate School of Medicine, Gifu University, Gifu, Japan.; Centre for Genetic Origins of Health and Disease, University of Western Australia, Crawley, Western Australia, Australia.; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.; Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia.; Faculty of Medicine, Istanbul University, Istanbul, Turkey.; Department of Radiology, School of Medicine, Marmara University, Istanbul, Turkey.; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.; Isfahan University of Medical Sciences, Isfahan, Iran.; Radiology Department, Isfahan University of Medical Sciences, Isfahan, Iran.; Centre for Medical Image Computing, University College London, London, United Kingdom.; Asan Medical Center, Seoul, Republic of Korea.; Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.; Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America.; Department of Surgery, Yong Loo Lin School of Medicine, Singapore.; Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore.; Ontario Breast Screening Program, Cancer Care Ontario, Toronto, Ontario, Canada.; Princess Margaret Cancer Centre, Toronto, Ontario, Canada.; National Cancer Control Center, Lady Davis Carmel Medical Center, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.; Woman Imaging Unit, Radiodiagnosis Department, Kasr El Aini, Cairo University Hospitals, Cairo, Egypt.; Department of Non-communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, United Kingdom.
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MeSH Terms:
Adult,
Aged,
Aged, 80 and over,
Aging,
Breast Density,
Cross-Sectional Studies,
Female,
Humans,
Middle Aged,
Perimenopause,
Postmenopause,
Premenopause
