Mammographic density and breast cancer risk: current understanding and future prospects

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Abstract

Variations in percent mammographic density (PMD) reflect variations in the amounts of collagen and number of epithelial and non-epithelial cells in the breast. Extensive PMD is associated with a markedly increased risk of invasive breast cancer. The PMD phenotype is important in the context of breast cancer prevention because extensive PMD is common in the population, is strongly associated with risk of the disease, and, unlike most breast cancer risk factors, can be changed. Work now in progress makes it likely that measurement of PMD will be improved in the near future and that understanding of the genetics and biological basis of the association of PMD with breast cancer risk will also improve. Future prospects for the application of PMD include mammographic screening, risk prediction in individuals, breast cancer prevention research, and clinical decision making.

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Most cited references 72

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Projecting individualized probabilities of developing breast cancer for white females who are being examined annually.

M H Gail, L Brinton, D Byar … (1989)

To assist in medical counseling, we present a method to estimate the chance that a woman with given age and risk factors will develop breast cancer over a specified interval. The risk factors used were age at menarche, age at first live birth, number of previous biopsies, and number of first-degree relatives with breast cancer. A model of relative risks for various combinations of these factors was developed from case-control data from the Breast Cancer Detection Demonstration Project (BCDDP). The model allowed for the fact that relative risks associated with previous breast biopsies were smaller for women aged 50 or more than for younger women. Thus, the proportional hazards models for those under age 50 and for those of age 50 or more. The baseline age-specific hazard rate, which is the rate for a patient without identified risk factors, is computed as the product of the observed age-specific composite hazard rate times the quantity 1 minus the attributable risk. We calculated individualized breast cancer probabilities from information on relative risks and the baseline hazard rate. These calculations take competing risks and the interval of risk into account. Our data were derived from women who participated in the BCDDP and who tended to return for periodic examinations. For this reason, the risk projections given are probably most reliable for counseling women who plan to be examined about once a year.

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Of extracellular matrix, scaffolds, and signaling: tissue architecture regulates development, homeostasis, and cancer.

Celeste Nelson, Mina Bissell (2006)

The microenvironment influences gene expression so that the behavior of a cell is largely determined by its interactions with the extracellular matrix, neighboring cells, and soluble local and systemic cues. We describe the essential roles of context and organ structure in directing mammary gland development and differentiated function and in determining the response to oncogenic insults, including mutations. We expand on the concept of "dynamic reciprocity" to present an integrated view of development, cancer, and aging and posit that genes are like the keys on a piano: Although they are essential, it is the context that makes the music.

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Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women's Health Initiative Randomized Trial.

Rowan Chlebowski, Susan L Hendrix, Robert D. Langer … (2003)

The Women's Health Initiative trial of combined estrogen plus progestin was stopped early when overall health risks, including invasive breast cancer, exceeded benefits. Outstanding issues not previously addressed include characteristics of breast cancers observed among women using hormones and whether diagnosis may be influenced by hormone effects on mammography. To determine the relationship among estrogen plus progestin use, breast cancer characteristics, and mammography recommendations. Following a comprehensive breast cancer risk assessment, 16 608 postmenopausal women aged 50 to 79 years with an intact uterus were randomly assigned to receive combined conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) or placebo from 1993 to 1998 at 40 clinical centers. Screening mammography and clinical breast examinations were performed at baseline and yearly thereafter. Breast cancer number and characteristics, and frequency of abnormal mammograms by estrogen plus progestin exposure. In intent-to-treat analyses, estrogen plus progestin increased total (245 vs 185 cases; hazard ratio [HR], 1.24; weighted P<.001) and invasive (199 vs 150 cases; HR, 1.24; weighted P =.003) breast cancers compared with placebo. The invasive breast cancers diagnosed in the estrogen plus progestin group were similar in histology and grade but were larger (mean [SD], 1.7 cm [1.1] vs 1.5 cm [0.9], respectively; P =.04) and were at more advanced stage (regional/metastatic 25.4% vs 16.0%, respectively; P =.04) compared with those diagnosed in the placebo group. After 1 year, the percentage of women with abnormal mammograms was substantially greater in the estrogen plus progestin group (716 [9.4%] of 7656) compared with placebo group (398 [5.4%] of 7310; P<.001), a pattern which continued for the study duration. Relatively short-term combined estrogen plus progestin use increases incident breast cancers, which are diagnosed at a more advanced stage compared with placebo use, and also substantially increases the percentage of women with abnormal mammograms. These results suggest estrogen plus progestin may stimulate breast cancer growth and hinder breast cancer diagnosis.

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Author and article information

Journal

Journal ID (nlm-ta): Breast Cancer Res

Journal ID (iso-abbrev): Breast Cancer Res

Title: Breast Cancer Research : BCR

Publisher: BioMed Central

ISSN (Print): 1465-5411

ISSN (Electronic): 1465-542X

Publication date (Print): 2011

Publication date (Electronic): 1 November 2011

Publication date PMC-release: 1 May 2012

Volume: 13

Issue: 6

Page: 223

Affiliations

[1 ]Campbell Family Institute for Breast Cancer Research, Room 10-415, 610 University Avenue, Toronto, ON M5G 2M9, Canada

[2 ]Ontario Cancer Institute, 610 University Avenue, Toronto, ON M5G 2M9, Canada

[3 ]Imaging Research, 2075 Sunnybrook Health Sciences Centre, Bayview Avenue, Toronto, ON M4N 3M5, Canada

Article

Publisher ID: bcr2942

DOI: 10.1186/bcr2942

PMC ID: 3326547

PubMed ID: 22114898

SO-VID: f68b753b-99fa-47c9-99e7-63bdde2cb0a0

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Mammographic density and breast cancer risk: current understanding and future prospects

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Karger: Oncology

Most cited references 72

Projecting individualized probabilities of developing breast cancer for white females who are being examined annually.

Of extracellular matrix, scaffolds, and signaling: tissue architecture regulates development, homeostasis, and cancer.

Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women's Health Initiative Randomized Trial.

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