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

 

 

Acceptance of adjuvant therapy and quality of life issues

Authorship

Acceptance of adjuvant therapy and quality of life issues by Lesley Fallowfield

2005

Affiliations of authors

Cancer Research UK Psychosocial Oncology Group, Brighton & Sussex Medical School, University of Sussex.

Key outtakes

  • “Studies show that 40% women do not adhere to tamoxifen because of side effects affecting Quality of Life (QoL).”
  • “Most novel therapies appear, initially at least, to have much better profiles than the standard treatment that has been in use for much longer.”
  • “In one such study, 72 pre-menopausal women who had taken part in a clinical trial of adjuvant goserelin and/or tamoxifen… Symptoms such as weight gain, hot flushes, fatigue and night sweats were commonly reported.”
  • “Another study compared the symptoms reported on QoL questionnaires by 581 women who had been taking 2–3 years of tamoxifen… Hot flushes, weight gain, night sweats, loss of libido and sleeping difficulties were frequently reported by the women as severe…”
  • “In the pre-menopausal women, the effects of a premature menopause and fertility loss following adjuvant chemotherapy exerts a profoundly deleterious impact on QoL.”
  • “Adjuvant endocrine therapy Until recently, tamoxifen was the gold standard in adjuvant endocrine treatment,but despite the efficacy of the drug, the serious side effects such as thromboembolic problems, stroke and endometrial cancer limit its use.”
  • “Tamoxifen also has many nonlife threatening side effects, which also affect QoL.”
  • “Although the drugs appear to be reasonably well-tolerated in the trial settings in which they have been tested, there are significant, non-life threatening problems that women must endure.”
  • “The worst symptoms of endocrine therapy are the vasomotor problems with hot flushes, night sweats and cold sweats being apparent…”
  • “Joint pains with particularly troubling arthralgia are something to watch and if in the future the fracture rate increases then this will have a detrimental effect upon QoL.”

Paper

The full paper can be found here: Click here

Risk-Benefit Profiles of Women Using Tamoxifen for Chemoprevention

Authorship

Risk-Benefit Profiles of Women Using Tamoxifen for Chemoprevention by Hazel B. Nichols, Lisa A. DeRoo, Daniel R. Scharf, Dale P. Sandler

2015

Affiliations of authors

Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC (HBN); Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway (LAD); Westat, Durham, NC (DS); Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC (DPS).

Study scope/scale

The Sister Study, a cohort of 50,884 US and Puerto Rican women age 35 to 74 years enrolled from 2003 to 2009.

Key outtakes

  • “Tamoxifen has been US Food and Drug Administration–approved for primary prevention of breast cancer since 1998 but has not been widely adopted, in part because of increased risk of serious side effects.”
  • “…20% of women who used tamoxifen had insufficient evidence that the benefits of tamoxifen outweigh the risk of serious side effects.”
  • “After 4.5 years, 46% of women had discontinued tamoxifen.”
  • “While the majority of women who used tamoxifen for primary prevention of breast cancer were likely to benefit, substantial discontinuation of tamoxifen before five years and use by women at risk of serious side effects may attenuate benefits for breast cancer prevention.”
  • “An estimated 15% of US women age 35 to 79 years are eligible for breast cancer chemoprevention; however, less than 5% may have favorable risk-benefit profiles.”
  • “National estimates indicate that less than 1% of eligible women use tamoxifen for prevention.”
  • “…substantial nonadherence to the recommended five-year course of tamoxifen has been reported in prevention trials.”
  • “…risk of serious side effects (endometrial cancer, stroke, pulmonary embolism, deep vein thrombosis, and cataract)…”
  • “At 4.5 years, 46% of tamoxifen users had discontinued use.”
  • “Tamoxifen users were 49% more likely (95% CI = 1.05 to 2.11) to report cataract…”
  • “Recent trials of aromatase inhibitors (23,24) show important benefits for breast cancer prevention; however, their use is limited to postmenopausal women. Until alternative therapies for premenopausal women become available, tamoxifen will continue to have an important role in breast cancer primary prevention.”
  • “…review of studies examining decision making surrounding tamoxifen use concluded that higher perceived breast cancer risk increased willingness to consider tamoxifen for prevention, but few other characteristics have been identified.”

Paper

The full paper can be found here: Click here