Boyd NF, Martin LJ, Yaffe MJ, Minkin SMammographic density: a hormonally responsive risk factor for breast cancer. J Br Menopause Soc 12: 186-193

The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, Toronto, Ontario, Canada.
Menopause International (formerly Journal of the British Menopause Society) 01/2007; 12(4):186-93. DOI: 10.1258/136218006779160436
Source: PubMed


Mammographic density refers to radiologically dense breast tissue, and reflects variations in the tissue composition of the breast. It is positively associated with collagen and epithelial and non-epithelial cells, and negatively associated with fat. There is extensive evidence that mammographic density is a risk factor for breast cancer, independent of other risk factors, and is associated with large relative and attributable risks for the disease. The epidemiology of mammographic density, notably the inverse association with age, is consistent with it being a marker of susceptibility to breast cancer. Cumulative exposure to mammographic density may be an important determinant of the age-specific incidence of breast cancer in the population. All risk factors for breast cancer must ultimately exert their influence by an effect on the breast, and these findings suggest that, for at least some risk factors, this influence includes an effect on the number of cells and the quantity of collagen in the breast, which is reflected in differences in mammographic density. Many of the genetic and environmental factors that influence the risk of breast cancer affect the proliferative activity and quantity of stromal and epithelial tissue in the breast, and these effects are reflected in differences in mammographic density among women of the same age. Some of these influences include endogenous and exogenous hormones, and the menopause. A better understanding of the factors that influence the response of breast tissue to these hormonal exposures may lead to an improved understanding of the aetiology of mammographic density and of breast cancer.

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    • "Mammographic breast density is a strong predictor of breast cancer with odds ratios (ORs) varying from 1.8 to 6.0 (Henderson and Feigelson, 2000; Ursin et al, 2003; Boyd et al, 2006; Martin et al, 2006; Tamimi et al, 2007; Vachon et al, 2007; Ginsburg et al, 2008; Ghosh and Vachon 2010; Kerlikowske et al, 2010). Mammographic breast density is a reflection of the amount of fat, connective, and epithelial tissue in the breast (Warren, 2004). "
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    ABSTRACT: We investigated associations of known breast cancer risk factors with breast density, a well-established and very strong predictor of breast cancer risk. This nested case-control study included breast cancer-free women, 265 with high and 860 with low breast density. Women were required to be 40-80 years old and should have a body mass index (BMI) <35 at the time of the index mammogram. Information on covariates was obtained from annual questionnaires. In the overall analysis, breast density was inversely associated with BMI at mammogram (P for trend<0.001), and parity (P for trend=0.02) and positively associated with alcohol consumption (ever vs never: odds ratio 2.0, 95% confidence interval 1.4-2.8). Alcohol consumption was positively associated with density, and the association was stronger in women with a family history of breast cancer (P<0.001) and in women with hormone replacement therapy (HRT) history (P<0.001). Parity was inversely associated with density in all subsets, except premenopausal women and women without a family history. The association of parity with density was stronger in women with HRT history (P<0.001). The associations of alcohol and parity with breast density appear to be in reverse direction, but stronger in women with a family history of breast cancer and women who ever used HRT.
    British Journal of Cancer 02/2012; 106(5):996-1003. DOI:10.1038/bjc.2012.1 · 4.84 Impact Factor
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    • "Mammographic density is strongly correlated with hormone exposure profiles of women [7]. Several hormonal risk factors for breast cancer have been found to influence mammographic density in a similar fashion to their respective associations with risk for the disease [8]. "
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    ABSTRACT: Several studies have examined the effect of genetic variants in genes involved in the estrogen metabolic pathway on mammographic density, but the number of loci studied and the sample sizes evaluated have been small and pathways have not been evaluated comprehensively. In this study, we evaluate the association between mammographic density and genetic variants of the estrogen metabolic pathway. A total of 239 SNPs in 34 estrogen metabolic genes were studied in 1,731 Swedish women who participated in a breast cancer case-control study, of which 891 were cases and 840 were controls. Film mammograms of the medio-lateral oblique view were digitalized and the software Cumulus was used for computer-assisted semi-automated thresholding of mammographic density. Generalized linear models controlling for possible confounders were used to evaluate the effects of SNPs on mammographic density. Results found to be nominally significant were examined in two independent populations. The admixture maximum likelihood-based global test was performed to evaluate the cumulative effect from multiple SNPs within the whole metabolic pathway and three subpathways for androgen synthesis, androgen-to-estrogen conversion and estrogen removal. Genetic variants of genes involved in estrogen metabolism exhibited no appreciable effect on mammographic density. None of the nominally significant findings were validated. In addition, global analyses on the overall estrogen metabolic pathway and its subpathways did not yield statistically significant results. Overall, there is no conclusive evidence that genetic variants in genes involved in the estrogen metabolic pathway are associated with mammographic density in postmenopausal women.
    Breast cancer research: BCR 03/2010; 12(2):R19. DOI:10.1186/bcr2488 · 5.49 Impact Factor
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    • "The following variables were assessed as potential confounders: age, body mass index (BMI), race/ethnicity, study site, education level, household income, age at menarche, parity, menopausal status, oral contraceptive use, other hormone use, alcohol consumption, and family history of breast cancer [43–46]. In addition, a combined variable race/ethnicity-study site was created, because each study site recruited women from a single race/ethnic group in addition to non-Hispanic whites. "
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    ABSTRACT: The opposing carcinogenic and antiestrogenic properties of tobacco smoke may explain why epidemiologic studies have not consistently reported positive associations for active smoking and breast cancer risk. A negative relation between mammographic density, a strong breast cancer risk factor, and active smoking would lend support for an antiestrogenic mechanism. We used multivariable linear regression to assess the associations of active smoking and secondhand smoke (SHS) exposure with mammographic density in 799 pre- and early perimenopausal women in the Study of Women's Health Across the Nation (SWAN). We observed that current active smoking was associated with 7.2% lower mammographic density, compared to never active smoking and no SHS exposure (p = 0.02). Starting to smoke before 18 years of age and having smoked > or =20 cigarettes/day were also associated with statistically significantly lower percent densities. Among nulliparous women having smoked > or =20 cigarettes/day was associated with 23.8% lower density, compared to having smoked < or = 9 cigarettes/day (p<0.001). Our findings support the hypothesis that tobacco smoke exerts an antiestrogenic effect on breast tissue, but counters the known increased risk of breast cancer with smoking prior to first full-term birth. Thus, our data suggest that the antiestrogenic but not the carcinogenic effects of smoking may be reflected by breast density.
    Cancer Causes and Control 11/2009; 21(2):301-11. DOI:10.1007/s10552-009-9462-4 · 2.74 Impact Factor
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