Raised mammographic density: causative mechanisms and biological consequences

Authorship

Raised mammographic density: causative mechanisms and biological consequences by Michael J. Sherratt, James C. McConnell and Charles H. Streuli

2016

Affiliations of authors

Faculties of Life and Medical and Human Sciences, University of Manchester, Oxford Road, Manchester

Key outtakes

  • “High mammographic density is the most important risk factor for breast cancer, after ageing.”
  • “Epidemiologically, the risk of developing breast cancer is significantly greater in those women with raised MD (‘mammographic density’).”
  • “MD is therapeutically modifiable, patient tolerance to long-term endocrine treatments (‘Tamoxifen’) is low…”
  • “MD is highly variable between women, ranging from a minimum of 3 % by volume, to very high levels of 25 % (Volpara measurements; the latter high level is equivalent to 75 % density in VAS).”
  • “The current understanding of the link between MD and breast cancer was reviewed extensively in 2014, with over 180 of the previous papers on this topic examined. Numerous studies, originating in 1976, have revealed that high MD is strongly linked with the susceptibility for breast cancer.”
  • “Indeed, women with high-dense breasts have a four-to sixfold greater risk of getting cancer than those with the lowest MD density.”
  • “More recently, it was found that the percentage of high MD is a stronger risk factor for breast cancer than absolute dense area.”
  • “Breast cancer is a major disease that affects 12 % of the female population at some point during their lifetime, and is the global cause of death for nearly 500,000 women per year.”
  • “Although there is a link between BMI and cancer, there is no direct association between BMI and MD.”
  • “Regardless of the role played by cellular hypertrophy, an altered stromal composition in women aged 50–69 years correlates with increased MD, although there is no difference in the amount of epithelial lobules or ducts.”
  • “It seems likely that raised MD is associated with a complex pattern of upregulation and downregulation of ECM proteins.”
  • “There are several therapeutic strategies to reduce or eliminate breast cancer from those who have it. The American Cancer Society sanctions six major kinds of treatment, including surgery, radiation therapy, chemotherapy, hormone therapy, targeted therapy, and bone-directed therapy.”
  • “With high MD now being recognised as a major risk factor for cancer, the therapeutics that are used so far to reduce density and thereby to potentially protect against cancer arising from high MD mainly include selective ER modulators. For example, the anti-oestrogenic compounds tamoxifen, its relatives such as raloxifene and aromatase inhibitors, are prescribed to patients with high MD but yet have no signs of acquiring breast cancer.”
  • “Interestingly, breast cancer-specific survival occurred in tamoxifen-treated women who showed a reduction in MD.”
  • “…taking advantage of combined strategies to detect and/or revert high MD could reduce the incidence and mortality of breast cancer by more than 20 %.”

Paper

The full paper can be found here: Click here

 

 

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Mammographic Densities and Breast Cancer Risk

Authorship

Mammographic Densities and Breast Cancer Risk by N.F. Boyd, G.A. Lockwood, L.J. Martina, J.A. Knight, J.W. Byng, M.J. Yae and D.L. Tritchler of Division of Epidemiology and Statistics, Ontario Cancer Institute, Toronto, Canada, Division of Preventive Oncology, Cancer Care Ontario, Toronto, Canada, Imaging Research, Sunnybrook Health Sciences Centre, Toronto, Canada

1998

Key outtakes

  • “Individuals with extensive areas of radiologically dense breast tissue on the mammogram have been found to have a risk of breast cancer that is four to six times higher than women with little or no density. In this paper, we propose a model for the relation- ship of mammographic densities”
  • “Considerable evidence now indicates that mammographic densities are strongly related to the risk of breast cancer.”
  • “Because mammographic densities are strongly related to risk of breast cancer, factors that cause mammographic density also are likely to contribute to the causes of cancer. The identification of factors that change density may lead to the development of methods for preventing breast cancer.”
  • “We propose that the risk of breast cancer associated with mammographically dense breast tissue is due to the combined effects of two processes: cell proliferation (mitogenesis), and damage to the DNA of dividing cells (mutagenesis).”
  • “An association between the mammographic pattern of the breast and risk of breast cancer was first proposed in 1976 by the late John Wolfe, using a four category classification …”
  • “…at least 15 cohort studies… have since confirmed that Wolfe’s classification of mammographic pattern is associated with variations in risk of breast cancer…”
  • “Definitions of the categories of density compared varied between studies, but all found significantly elevated summary odds ratios between extreme categories of the classification used.”
  • “Odds ratios varied between 2.8 and 6.0 for different observers and types of density, but each of the eight studies contained an odds ratio of at least 4.0.”
  • “Two studies showed persistence of increased risk associated with extensive dense tissue for at least 5 years, and one showed that risk persisted for at least 10 years.”
  • “Risk of hyperplasia was 30 times greater, and risk of atypical hyperplasia and in situ carcinoma was 8 times greater in women with extensive densities compared to those with none.”
  • “The evidence that the tissue responsible for mammographic densities is hormonally responsive comes from the consistent associations found with age, which is at least partly due to the effect of menopause, and from the observed effects of exogenous hormones on the radiology of the breast.”
  • “Mammographic densities consistently are associated with a much greater relative risk of breast cancer than are other risk factors.”
  • “…mammographic densities are associated with a much larger attributable risk of breast cancer than atypical hyperplasia or BRCA1 and BRCA2 mutations. Further, in contrast to other risk factors, mammographic densities can be changed by hormonal or dietary interventions.”
  • “…abundant evidence indicates that mammographic densities are related to risk of breast cancer from middle age onward…”
  • “Several aspects of the association of mammographic densities with breast cancer risk meet criteria for causality and suggest that mammographic densities may be closely related to factors that are important causes of this disease.”

Paper

The full paper can be found here: Click here