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 & 34 others 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 H. 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 F. Boyd, Isabel dos Santos Silva, Valerie A. McCormack

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    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.

    Original languageEnglish
    Article numbere1002335
    Pages (from-to)1-20
    Number of pages20
    JournalPLoS Medicine
    Volume14
    Issue number6
    DOIs
    Publication statusPublished - 30 Jun 2017

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    Cross-Sectional Studies
    Breast Neoplasms
    Mammography
    Population Groups
    Linear Models
    Breast
    Breast Density
    Risk Reduction Behavior
    Meta-Analysis
    Life Style
    Body Mass Index

    Cite this

    Burton, A., Maskarinec, G., Perez-Gomez, B., Vachon, C., Miao, H., Lajous, M., ... McCormack, V. A. (2017). Mammographic density and ageing: A collaborative pooled analysis of cross-sectional data from 22 countries worldwide. PLoS Medicine, 14(6), 1-20. [e1002335]. https://doi.org/10.1371/journal.pmed.1002335
    Burton, Anya ; Maskarinec, Gertraud ; Perez-Gomez, Beatriz ; Vachon, Celine ; Miao, Hui ; Lajous, Martín ; López-Ridaura, Ruy ; Rice, Megan ; Pereira, Ana ; Garmendia, Maria Luisa ; Tamimi, Rulla M. ; Bertrand, Kimberly ; Kwong, Ava ; Ursin, Giske ; Lee, Eunjung ; Qureshi, Samera A ; Ma, Huiyan ; Vinnicombe, Sarah ; Moss, Sue ; Allen, Steve ; Ndumia, Rose ; Vinayak, Sudhir ; Teo, Soo-Hwang ; Mariapun, Shivaani ; Fadzli, Farhana ; Peplonska, Beata ; Bukowska, Agnieszka ; Nagata, Chisato ; Stone, Jennifer ; Hopper, John ; Giles, Graham ; Ozmen, Vahit ; Aribal, Mustafa Erkin ; Schüz, Joachim ; van Gils, Carla H. ; Wanders, Johanna O. P. ; Sirous, Reza ; Sirous, Mehri ; Hipwell, John H. ; Kim, Jisun ; Lee, Jong Won ; Dickens, Caroline ; Hartman, Mikael ; Chia, Kee-Seng ; Scott, Christopher ; Chiarelli, Anna M. ; Linton, Linda ; Pollan, Marina ; Flugelman, Anath Arzee ; Salem, Dorria ; Kamal, Rasha ; Boyd, Norman F. ; dos Santos Silva, Isabel ; McCormack, Valerie A. / Mammographic density and ageing : A collaborative pooled analysis of cross-sectional data from 22 countries worldwide. In: PLoS Medicine. 2017 ; Vol. 14, No. 6. pp. 1-20.
    @article{fb54898c96f94d3b85ac9353c9c464d8,
    title = "Mammographic density and ageing: A collaborative pooled analysis of cross-sectional data from 22 countries worldwide",
    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.",
    author = "Anya Burton and Gertraud Maskarinec and Beatriz Perez-Gomez and Celine Vachon and Hui Miao and Mart{\'i}n Lajous and Ruy L{\'o}pez-Ridaura and Megan Rice and Ana Pereira and Garmendia, {Maria Luisa} and Tamimi, {Rulla M.} and Kimberly Bertrand and Ava Kwong and Giske Ursin and Eunjung Lee and Qureshi, {Samera A} and Huiyan Ma and Sarah Vinnicombe and Sue Moss and Steve Allen and Rose Ndumia and Sudhir Vinayak and Soo-Hwang Teo and Shivaani Mariapun and Farhana Fadzli and Beata Peplonska and Agnieszka Bukowska and Chisato Nagata and Jennifer Stone and John Hopper and Graham Giles and Vahit Ozmen and Aribal, {Mustafa Erkin} and Joachim Sch{\"u}z and {van Gils}, {Carla H.} and Wanders, {Johanna O. P.} and Reza Sirous and Mehri Sirous and Hipwell, {John H.} and Jisun Kim and Lee, {Jong Won} and Caroline Dickens and Mikael Hartman and Kee-Seng Chia and Christopher Scott and Chiarelli, {Anna M.} and Linda Linton and Marina Pollan and Flugelman, {Anath Arzee} and Dorria Salem and Rasha Kamal and Boyd, {Norman F.} and {dos Santos Silva}, Isabel and McCormack, {Valerie A.}",
    note = "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.S., Istanbul, Turkey; UK-EPSRC and EP/K020439/1 (JHi), Breast Cancer Campaign (2007MayPR23), Cancer Research UK (G186/11; C405/A14565), Da Costa 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 the Susan G. Komen Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.",
    year = "2017",
    month = "6",
    day = "30",
    doi = "10.1371/journal.pmed.1002335",
    language = "English",
    volume = "14",
    pages = "1--20",
    journal = "PLoS Medicine",
    issn = "1549-1277",
    publisher = "Public Library of Science",
    number = "6",

    }

    Burton, A, Maskarinec, G, Perez-Gomez, B, Vachon, C, Miao, H, Lajous, M, López-Ridaura, R, Rice, M, Pereira, A, Garmendia, ML, Tamimi, RM, Bertrand, K, Kwong, A, Ursin, G, Lee, E, Qureshi, SA, 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, ME, Schüz, J, van Gils, CH, Wanders, JOP, Sirous, R, Sirous, M, Hipwell, JH, Kim, J, Lee, JW, Dickens, C, Hartman, M, Chia, K-S, Scott, C, Chiarelli, AM, Linton, L, Pollan, M, Flugelman, AA, Salem, D, Kamal, R, Boyd, NF, dos Santos Silva, I & McCormack, VA 2017, 'Mammographic density and ageing: A collaborative pooled analysis of cross-sectional data from 22 countries worldwide', PLoS Medicine, vol. 14, no. 6, e1002335, pp. 1-20. https://doi.org/10.1371/journal.pmed.1002335

    Mammographic density and ageing : A collaborative pooled analysis of cross-sectional data from 22 countries worldwide. / Burton, Anya; Maskarinec, Gertraud; Perez-Gomez, Beatriz; Vachon, Celine; Miao, Hui; Lajous, Martín; López-Ridaura, Ruy; Rice, Megan; Pereira, Ana; Garmendia, Maria Luisa; Tamimi, Rulla M.; Bertrand, Kimberly; Kwong, Ava; Ursin, Giske; Lee, Eunjung; Qureshi, Samera A; Ma, Huiyan; Vinnicombe, Sarah; Moss, Sue; Allen, Steve; Ndumia, Rose; Vinayak, Sudhir; Teo, Soo-Hwang; Mariapun, Shivaani; Fadzli, Farhana; Peplonska, Beata; Bukowska, Agnieszka; Nagata, Chisato; Stone, Jennifer; Hopper, John; Giles, Graham; Ozmen, Vahit; Aribal, Mustafa Erkin; Schüz, Joachim; van Gils, Carla H.; Wanders, Johanna O. P.; Sirous, Reza; Sirous, Mehri; Hipwell, John H.; Kim, Jisun; Lee, Jong Won; Dickens, Caroline; Hartman, Mikael; Chia, Kee-Seng; Scott, Christopher; Chiarelli, Anna M.; Linton, Linda; Pollan, Marina; Flugelman, Anath Arzee; Salem, Dorria; Kamal, Rasha; Boyd, Norman F.; dos Santos Silva, Isabel; McCormack, Valerie A. (Lead / Corresponding author).

    In: PLoS Medicine, Vol. 14, No. 6, e1002335, 30.06.2017, p. 1-20.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Mammographic density and ageing

    T2 - A collaborative pooled analysis of cross-sectional data from 22 countries worldwide

    AU - Burton, Anya

    AU - Maskarinec, Gertraud

    AU - Perez-Gomez, Beatriz

    AU - Vachon, Celine

    AU - Miao, Hui

    AU - Lajous, Martín

    AU - López-Ridaura, Ruy

    AU - Rice, Megan

    AU - Pereira, Ana

    AU - Garmendia, Maria Luisa

    AU - Tamimi, Rulla M.

    AU - Bertrand, Kimberly

    AU - Kwong, Ava

    AU - Ursin, Giske

    AU - Lee, Eunjung

    AU - Qureshi, Samera A

    AU - Ma, Huiyan

    AU - Vinnicombe, Sarah

    AU - Moss, Sue

    AU - Allen, Steve

    AU - Ndumia, Rose

    AU - Vinayak, Sudhir

    AU - Teo, Soo-Hwang

    AU - Mariapun, Shivaani

    AU - Fadzli, Farhana

    AU - Peplonska, Beata

    AU - Bukowska, Agnieszka

    AU - Nagata, Chisato

    AU - Stone, Jennifer

    AU - Hopper, John

    AU - Giles, Graham

    AU - Ozmen, Vahit

    AU - Aribal, Mustafa Erkin

    AU - Schüz, Joachim

    AU - van Gils, Carla H.

    AU - Wanders, Johanna O. P.

    AU - Sirous, Reza

    AU - Sirous, Mehri

    AU - Hipwell, John H.

    AU - Kim, Jisun

    AU - Lee, Jong Won

    AU - Dickens, Caroline

    AU - Hartman, Mikael

    AU - Chia, Kee-Seng

    AU - Scott, Christopher

    AU - Chiarelli, Anna M.

    AU - Linton, Linda

    AU - Pollan, Marina

    AU - Flugelman, Anath Arzee

    AU - Salem, Dorria

    AU - Kamal, Rasha

    AU - Boyd, Norman F.

    AU - dos Santos Silva, Isabel

    AU - McCormack, Valerie A.

    N1 - 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.S., Istanbul, Turkey; UK-EPSRC and EP/K020439/1 (JHi), Breast Cancer Campaign (2007MayPR23), Cancer Research UK (G186/11; C405/A14565), Da Costa 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 the Susan G. Komen Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

    PY - 2017/6/30

    Y1 - 2017/6/30

    N2 - 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.

    AB - 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.

    U2 - 10.1371/journal.pmed.1002335

    DO - 10.1371/journal.pmed.1002335

    M3 - Article

    VL - 14

    SP - 1

    EP - 20

    JO - PLoS Medicine

    JF - PLoS Medicine

    SN - 1549-1277

    IS - 6

    M1 - e1002335

    ER -