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
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
AU - dos-Santos-Silva, Isabel
AU - McCormack, Valerie
N1 - Publisher Copyright:
© 2017 Burton et al.
PY - 2017/6
Y1 - 2017/6
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.
UR - http://www.scopus.com/inward/record.url?scp=85021821442&partnerID=8YFLogxK
U2 - 10.1371/journal.pmed.1002335
DO - 10.1371/journal.pmed.1002335
M3 - Article
C2 - 28666001
AN - SCOPUS:85021821442
SN - 1549-1277
VL - 14
JO - PLoS Medicine
JF - PLoS Medicine
IS - 6
M1 - e1002335
ER -
