Dataset Information

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.

SUBMITTER: Burton A

PROVIDER: S-EPMC5493289 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Burton Anya A Maskarinec Gertraud G Perez-Gomez Beatriz B Vachon Celine C Miao Hui H Lajous Martín M López-Ridaura Ruy R Rice Megan M Pereira Ana A Garmendia Maria Luisa ML Tamimi Rulla M RM Bertrand Kimberly K Kwong Ava A Ursin Giske G Lee Eunjung E Qureshi Samera A SA Ma Huiyan H Vinnicombe Sarah S Moss Sue S Allen Steve S Ndumia Rose R Vinayak Sudhir S Teo Soo-Hwang SH Mariapun Shivaani S Fadzli Farhana F Peplonska Beata B Bukowska Agnieszka A Nagata Chisato C Stone Jennifer J Hopper John J Giles Graham G Ozmen Vahit V Aribal Mustafa Erkin ME Schüz Joachim J Van Gils Carla H CH Wanders Johanna O P JOP Sirous Reza R Sirous Mehri M Hipwell John J Kim Jisun J Lee Jong Won JW Dickens Caroline C Hartman Mikael M Chia Kee-Seng KS Scott Christopher C Chiarelli Anna M AM Linton Linda L Pollan Marina M Flugelman Anath Arzee AA Salem Dorria D Kamal Rasha R Boyd Norman N Dos-Santos-Silva Isabel I McCormack Valerie V

PLoS medicine 20170630 6

<h4>Background</h4>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.<h4>Methods and findings</h4>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 Inter ...[more]

PMID: 28666001

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Project description:BACKGROUND:Well-tolerated and commonly used medications are increasingly assessed for reducing breast cancer risk. These include metformin and statins, both linked to reduced hormone availability and cell proliferation or growth and sometimes prescribed concurrently. We investigated independent and joint associations of these medications with mammographic breast density (MBD), a useful biomarker for the effect of chemopreventive agents on breast cancer risk. METHODS:Using data from a cross-sectional study of 770 women (78% Hispanic, aged 40-61?years, in a mammography cohort with high cardiometabolic burden), we examined the association of self-reported "ever" use of statins and metformin with MBD measured via clinical Breast Imaging Reporting and Data System (BI-RADS) density classifications (relative risk regression) and continuous semi-automated percent and size of dense area (Cumulus) (linear regression), adjusted for age, body mass index, education, race, menopausal status, age at first birth, and insulin use. RESULTS:We observed high statin (27%), metformin (13%), and combination (9%) use, and most participants were overweight/obese (83%) and parous (87%). Statin use was associated with a lower likelihood of high density BI-RADS (RR?=?0.60, 95% CI?=?0.45 to 0.80), percent dense area (PD) (??=?-?6.56, 95% CI?=?-?9.05 to -?4.06), and dense area (DA) (??=?-?9.05, 95% CI?=?-?14.89 to -?3.22). Metformin use was associated with lower PD and higher non-dense area (NDA), but associations were attenuated by co-medication with statins. Compared to non-use of either medication, statin use alone or with metformin were associated with lower PD and DA (e.g., ??=?-?6.86, 95% CI: -?9.67, -?4.05 and ??=?-?7.07, 95% CI: -?10.97, -?3.17, respectively, for PD) and higher NDA (??=?25.05, 95% CI: 14.06, 36.03; ??=?29.76, 95% CI: 14.55, 44.96, respectively). CONCLUSIONS:Statin use was consistently associated with lower MBD, measured both through clinical radiologist assessment and continuous relative and absolute measures, including dense area. Metformin use was associated with lower PD and higher NDA, but this may be driven by co-medication with statins. These results support that statins may lower MBD but need confirmation with prospective and clinical data to distinguish the results of medication use from that of disease.

Project description:INTRODUCTION:Mammographic density is one of the strongest risk factors for breast cancer and is believed to represent epithelial and stromal proliferation. Because of the high heritability of breast density, and the role of the insulin-like growth factor (IGF) pathway in cellular proliferation and breast development, we examined the association between common genetic variation in this pathway and mammographic density. METHODS:We conducted a cross-sectional analysis among controls (n = 1,121) who were between the ages of 42 and 78 years at mammography, from a breast cancer case-control study nested within the Nurses' Health Study cohort. At the time of mammography, 204 women were premenopausal and 917 were postmenopausal. We genotyped 29 haplotype-tagging SNPs demonstrated to capture common genetic variation in IGF1, IGF binding protein (IGFBP)-1, and IGFBP-3. RESULTS:Common haplotype patterns in three of the four haplotype blocks spanning the gene encoding IGF1 were associated with mammographic density. Haplotype patterns in block 1 (p = 0.03), block 3 (p = 0.009), and block 4 (p = 0.007) were associated with mammographic density, whereas those in block 2 were not. None of the common haplotypes in the three haplotype blocks spanning the genes encoding IGFBP-1/IGFBP-3 were significantly associated with mammographic density. Two haplotype-tagging SNPs in IGF1, rs1520220 and rs2946834, showed a strong association with mammographic density. Those with the homozygous variant genotype for rs1520220 had a mean percentage mammographic density of 19.6% compared with those with the homozygous wild-type genotype, who had a mean percentage mammographic density of 27.9% (p for trend < 0.0001). Those that were homozygous variant for rs2946834 had a mean percentage mammographic density of 23.2% compared with those who were homozygous wild-type with a mean percentage mammographic density of 28.2% (p for trend = 0.0004). Permutation testing demonstrated that results as strong as these are unlikely to occur by chance (p = 0.0005). CONCLUSION:Common genetic variation in IGF1 is strongly associated with percentage mammographic density.

Dataset Information

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

Background

Methods and findings

Conclusions

Publications

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

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