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

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 differenc...

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Main Authors:	Burton, A., Maskarinec, G., Perez-Gomez, B., Vachon, C., Miao, H., Lajous, M., López-Ridaura, R., Rice, M., Pereira, A., Garmendia, M.L., Tamimi, R.M., Bertrand, K., Kwong, A., Ursin, G., Lee, E., Qureshi, S.A., Ma, H., Vinnicombe, S., Moss, S., Allen, S., Ndumia, R., Vinayak, S., Teo, S.H., Mariapun, S., Fadzli, F., Peplonska, B., Bukowska, A., Nagata, C., Stone, J., Hopper, J., Giles, G., Ozmen, V., Aribal, M.E., Schüz, J., Van Gils, C.H., Wanders, J.O.P., Sirous, R., Sirous, M., Hipwell, J., Kim, J., Lee, J.W., Dickens, C., Hartman, M., Chia, K.S., Scott, C., Chiarelli, A.M., Linton, L., Pollan, M., Flugelman, A.A., Salem, D., Kamal, R., Boyd, N., dos-Santos-Silva, I., McCormack, V.
Format:	Article
Published:	Public Library of Science 2017
Subjects:	R Medicine
Online Access:	http://eprints.um.edu.my/19218/ http://dx.doi.org/10.1371/journal.pmed.1002335
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id	my.um.eprints.19218
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institution	Universiti Malaya
building	UM Library
collection	Institutional Repository
continent	Asia
country	Malaysia
content_provider	Universiti Malaya
content_source	UM Research Repository
url_provider	http://eprints.um.edu.my/
topic	R Medicine
spellingShingle	R Medicine Burton, A. Maskarinec, G. Perez-Gomez, B. Vachon, C. Miao, H. Lajous, M. López-Ridaura, R. Rice, M. Pereira, A. Garmendia, M.L. Tamimi, R.M. Bertrand, K. Kwong, A. Ursin, G. Lee, E. Qureshi, S.A. Ma, H. Vinnicombe, S. Moss, S. Allen, S. Ndumia, R. Vinayak, S. Teo, S.H. Mariapun, S. Fadzli, F. Peplonska, B. Bukowska, A. Nagata, C. Stone, J. Hopper, J. Giles, G. Ozmen, V. Aribal, M.E. Schüz, J. Van Gils, C.H. Wanders, J.O.P. Sirous, R. Sirous, M. Hipwell, J. Kim, J. Lee, J.W. Dickens, C. Hartman, M. Chia, K.S. Scott, C. Chiarelli, A.M. Linton, L. Pollan, M. Flugelman, A.A. Salem, D. Kamal, R. Boyd, N. dos-Santos-Silva, I. McCormack, V. Mammographic density and ageing: A collaborative pooled analysis of cross-sectional data from 22 countries worldwide
description	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.
format	Article
author	Burton, A. Maskarinec, G. Perez-Gomez, B. Vachon, C. Miao, H. Lajous, M. López-Ridaura, R. Rice, M. Pereira, A. Garmendia, M.L. Tamimi, R.M. Bertrand, K. Kwong, A. Ursin, G. Lee, E. Qureshi, S.A. Ma, H. Vinnicombe, S. Moss, S. Allen, S. Ndumia, R. Vinayak, S. Teo, S.H. Mariapun, S. Fadzli, F. Peplonska, B. Bukowska, A. Nagata, C. Stone, J. Hopper, J. Giles, G. Ozmen, V. Aribal, M.E. Schüz, J. Van Gils, C.H. Wanders, J.O.P. Sirous, R. Sirous, M. Hipwell, J. Kim, J. Lee, J.W. Dickens, C. Hartman, M. Chia, K.S. Scott, C. Chiarelli, A.M. Linton, L. Pollan, M. Flugelman, A.A. Salem, D. Kamal, R. Boyd, N. dos-Santos-Silva, I. McCormack, V.
author_facet	Burton, A. Maskarinec, G. Perez-Gomez, B. Vachon, C. Miao, H. Lajous, M. López-Ridaura, R. Rice, M. Pereira, A. Garmendia, M.L. Tamimi, R.M. Bertrand, K. Kwong, A. Ursin, G. Lee, E. Qureshi, S.A. Ma, H. Vinnicombe, S. Moss, S. Allen, S. Ndumia, R. Vinayak, S. Teo, S.H. Mariapun, S. Fadzli, F. Peplonska, B. Bukowska, A. Nagata, C. Stone, J. Hopper, J. Giles, G. Ozmen, V. Aribal, M.E. Schüz, J. Van Gils, C.H. Wanders, J.O.P. Sirous, R. Sirous, M. Hipwell, J. Kim, J. Lee, J.W. Dickens, C. Hartman, M. Chia, K.S. Scott, C. Chiarelli, A.M. Linton, L. Pollan, M. Flugelman, A.A. Salem, D. Kamal, R. Boyd, N. dos-Santos-Silva, I. McCormack, V.
author_sort	Burton, A.
title	Mammographic density and ageing: A collaborative pooled analysis of cross-sectional data from 22 countries worldwide
title_short	Mammographic density and ageing: A collaborative pooled analysis of cross-sectional data from 22 countries worldwide
title_full	Mammographic density and ageing: A collaborative pooled analysis of cross-sectional data from 22 countries worldwide
title_fullStr	Mammographic density and ageing: A collaborative pooled analysis of cross-sectional data from 22 countries worldwide
title_full_unstemmed	Mammographic density and ageing: A collaborative pooled analysis of cross-sectional data from 22 countries worldwide
title_sort	mammographic density and ageing: a collaborative pooled analysis of cross-sectional data from 22 countries worldwide
publisher	Public Library of Science
publishDate	2017
url	http://eprints.um.edu.my/19218/ http://dx.doi.org/10.1371/journal.pmed.1002335
_version_	1643690922139975680
spelling	my.um.eprints.192182018-09-13T04:09:35Z http://eprints.um.edu.my/19218/ Mammographic density and ageing: A collaborative pooled analysis of cross-sectional data from 22 countries worldwide Burton, A. Maskarinec, G. Perez-Gomez, B. Vachon, C. Miao, H. Lajous, M. López-Ridaura, R. Rice, M. Pereira, A. Garmendia, M.L. Tamimi, R.M. Bertrand, K. Kwong, A. Ursin, G. Lee, E. Qureshi, S.A. Ma, H. Vinnicombe, S. Moss, S. Allen, S. Ndumia, R. Vinayak, S. Teo, S.H. Mariapun, S. Fadzli, F. Peplonska, B. Bukowska, A. Nagata, C. Stone, J. Hopper, J. Giles, G. Ozmen, V. Aribal, M.E. Schüz, J. Van Gils, C.H. Wanders, J.O.P. Sirous, R. Sirous, M. Hipwell, J. Kim, J. Lee, J.W. Dickens, C. Hartman, M. Chia, K.S. Scott, C. Chiarelli, A.M. Linton, L. Pollan, M. Flugelman, A.A. Salem, D. Kamal, R. Boyd, N. dos-Santos-Silva, I. McCormack, V. R Medicine 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. Public Library of Science 2017 Article PeerReviewed Burton, A. and Maskarinec, G. and Perez-Gomez, B. and Vachon, C. and Miao, H. and Lajous, M. and López-Ridaura, R. and Rice, M. and Pereira, A. and Garmendia, M.L. and Tamimi, R.M. and Bertrand, K. and Kwong, A. and Ursin, G. and Lee, E. and Qureshi, S.A. and Ma, H. and Vinnicombe, S. and Moss, S. and Allen, S. and Ndumia, R. and Vinayak, S. and Teo, S.H. and Mariapun, S. and Fadzli, F. and Peplonska, B. and Bukowska, A. and Nagata, C. and Stone, J. and Hopper, J. and Giles, G. and Ozmen, V. and Aribal, M.E. and Schüz, J. and Van Gils, C.H. and Wanders, J.O.P. and Sirous, R. and Sirous, M. and Hipwell, J. and Kim, J. and Lee, J.W. and Dickens, C. and Hartman, M. and Chia, K.S. and Scott, C. and Chiarelli, A.M. and Linton, L. and Pollan, M. and Flugelman, A.A. and Salem, D. and Kamal, R. and Boyd, N. and dos-Santos-Silva, I. and McCormack, V. (2017) Mammographic density and ageing: A collaborative pooled analysis of cross-sectional data from 22 countries worldwide. PLoS Medicine, 14 (6). e1002335. ISSN 1549-1676 http://dx.doi.org/10.1371/journal.pmed.1002335 doi:10.1371/journal.pmed.1002335
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Mammographic density and ageing: A collaborative pooled analysis of cross-sectional data from 22 countries worldwide

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