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

 

 

Advertisements

Mammographic Features and Breast Cancer Risk: Effects With Time, Age, and Menopause Status

Authorship

Mammographic Features and Breast Cancer Risk: Effects With Time, Age, and Menopause Status by Celia Byrne, Catherine Schairer, John Wolfe, Navin Parekh, Martine Salane, Louise A. Brinton, Robert Hoover, Robert Haile of Environmental Epidemiology Branch, Division of Cancer Etiology, National Cancer Institute, Bethesda, MD, the Department of Radiology, Hutzel Hospital, Detroit, MI and Department of Epidemiology. University of California. Los Angeles, School of Public Health.

1995

Study scope/scale

Analysis of detailed information from a large, nested case—control study with 16 years of follow-up. This study used information from both screening and follow-up phases of the Breast Cancer Detection Demonstration Project, a nationwide program that offered annual breast cancer screening for more than 280 000 women from 1973 to 1980.

Key outtakes

  • “The purpose of this study was twofold: 1) to evaluate the associations between mammographic features and other breast cancer risk factors and 2) to assess effects of mammographic features on breast cancer risk by time, age, and menopause status.”
  • “Of the breast cancer risk factors assessed in the participants, high- density mammographic parenchymal patterns, as measured by the proportion of breast area composed of epithelial and stromal tissue, had the greatest impact on breast cancer risk. Of the breast cancers in this study, 28% were attributable to having 50% or greater breast density.”
  • “…consistent twofold to sixfold increased risk of breast cancer associated with various categorizations of patterns of mammographic features.”
  • “Increasing total breast size was not associated with higher breast cancer risk in this study.”
  • “Regardless of the age of the women at the time of the mammographic examination, breast cancer risk rose with increasing percent density. The relative magnitude of this increase, however, was somewhat greater for older women. Mammographic density measured from either premenopausal or postmenopausal mammograms was associated with an increased risk of breast cancer.”
  • “For women with any mammographic density, the breast cancer risk rose twofold. For those women with breast density of 75% or more, the breast cancer risk rose more than fourfold.”
  • “In contrast to these other recognized risk factors (28) in which substantially elevated risks apply to a relatively small segment of the population, a large segment of the population has sufficient mammographic density to place it in categories with markedly elevated risk.”
  • “The implications of the high prevalence of mammographic density to the attributable risk or etiologic fraction are obvious. Assuming that density is involved in a causal manner with breast cancer risk, then in our study the presence of any density was responsible for 46.2% of all breast cancers, breast density of 50% or more accounted for 28.2%, and breast density of 75% or more explained 8.2% of all breast cancers.”
  • “…because the proportion of the breast occupied by mammographic density is one risk factor that may identify a group at high risk for breast cancer, the implications of the findings of this study for intervention, both for screening strategies and prevention trials, should be considered.”
  • ” This study, with information from 16 years of the BCDDP, has demonstrated that an easily measured feature from a screening mammographic examination—the percent breast density— had a greater effect on breast cancer risk than most other breast cancer risk factors and could not be explained by these other factors. In addition, percent breast density was not an artifact of a masking bias and applied to women of all ages. Thus, in efforts either to prevent breast cancers or to detect breast cancers earlier, the impact of the percent breast density on breast cancer risk can no longer be ignored.”

Paper

The full paper can be found here: Click here