Critical assessment of new risk factors for breast cancer: considerations for development of an improved risk prediction model

Santen, Richard J.; Boyd, Norman F.; Chlebowski, Rowan T.; Cummings, Steven R.; Cuzick, Jack; Dowsett, Mitch; Easton, Douglas F.; Forbes, John F.; Key, Tim; Hankinson, Susan E.; Howell, Anthony; Ingle, James N.

doi:10.1677/erc-06-0045

Cited by 176 publications

(134 citation statements)

References 88 publications

(64 reference statements)

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“…This mechanism of estrogen production can lead to local estrogen levels in breast tumors that are as much as 10-fold higher compared with the circulation. In fact, a recent publication assessing breast cancer risk factors listed BMI and weight gain between the ages of 20 and 50 years as second only to Gail Model parameters [quantitative breast density, free estradiol, parity (yes/no), and age of menopause] in importance (79). The association between obesity and breast cancer risk is complex, varying by breast cancer subtype and by menopausal status.…”

Section: Cancermentioning

confidence: 99%

Morbidity and mortality associated with obesity

Abdelaal

Roux

Docherty

2017

Annals of Translational Medicine

735

459

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Obesity and its repercussions constitute an important source of morbidity, impaired quality of life and its complications can have a major bearing on life expectancy. The present article summarizes the most important co-morbidities of obesity and their prevalence. Furthermore, it describes classification and grading systems that can be used to assess the individual and combined impact of co-morbid conditions on mortality risk. The literature was screened for assessment tools that can be deployed in the quantification of morbidity and mortality risk in individual patients. Thirteen specific domains have been identified that account for morbidity and mortality in obesity. Cardiovascular disease (CVD) and cancer account for the greatest mortality risk associated with obesity. The King's Criteria and Edmonton Obesity Staging System (EOSS) were identified as useful tools for the detection and monitoring of individual patient mortality risk in obesity care. The stark facts on the complications of obesity should be capitalized on to improve patient management and knowledge and referred to in the wider dissemination of public health messages aimed at improving primary prevention.

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Section: Cancermentioning

confidence: 99%

Morbidity and mortality associated with obesity

Abdelaal

Roux

Docherty

2017

Annals of Translational Medicine

735

459

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“…This conclusion is based on the observations that several oestrogen-related events such as early menarche, age at menopause, plasma oestrogen levels, BMI, and menopausal hormone therapy (MHT) are all associated with an increased risk of breast cancer ( Fig. 8; Santen et al 2007). Two large multi-center studies demonstrated a linear relationship between breast cancer risk and increasing oestradiol ( Fig.…”

Section: Mechanisms Of Oestrogen Associated Carcinogenesismentioning

confidence: 99%

Celebrating 75 years of oestradiol

Simpson

Santen

2015

Journal of Molecular Endocrinology

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Oestrogens exert important effects on the reproductive as well as many other organ systems in both men and women. The history of the discovery of oestrogens, the mechanisms of their synthesis, and their therapeutic applications are very important components of the fabric of endocrinology. These aspects provide the rationale for highlighting several key components of this story. Two investigators, Edward Doisy and Alfred Butenandt, purified and crystalized oestrone nearly simultaneously in 1929, and Doisy later discovered oestriol and oestradiol. Butenandt won the Nobel Prize for this work and Doisy's had to await his purification of vitamin K. Early investigators quickly recognized that oestrogens must be synthesized from androgens and later investigators called this process aromatization. The aromatase enzyme was then characterized, its mechanism determined, and its structure identified after successful crystallization. With the development of knock-out methodology, the precise effects of oestrogen in males and females were defined and clinical syndromes of deficiency and excess described. Their discovery ultimately led to the development of oral contraceptives, treatment of menopausal symptoms, therapies for breast cancer, and induction of fertility, among others. The history of the use of oestrogens for postmenopausal women to relieve symptoms has been characterized by cyclic periods of enthusiasm and concern. The individuals involved in these studies, the innovative thinking required, and the detailed understanding made possible by evolving biologic and molecular techniques provide many lessons for current endocrinologists. Discovery of oestrogenThe concept that substances secreted by one organ could then be transported internally to another via the blood stream is the underpinning of the field of endocrinology. The 'father of physiology', Claude Bernard, articulated the concept of internal secretion by describing how the liver produces glucose, which then travels to and is utilized by other tissues in the body. This concept underlies studies on the ovaries, which became a focus of investigation later in the century. In 1896, Emil Knauer, a 29-year-old Austrian, excised the ovaries of adult rabbits and then re-implanted pieces into different locations in the same animals (Watkins 2007 Doisy then enlisted a nurse in the obstetrics clinic to supply each pregnant patient with a 1 gal jug and ask for her urine. This provided the needed material but was fraught with difficulties. Suspected to be a bootlegger because of the large jugs of yellow material in his car, one of Doisy's drivers was nearly arrested until he suggested using the sniff test with the response 'My god, it is urine'. Doisy, then being recruited to St Louis University, continued his efforts to purify the active substance. Each extract was tested with a bioassay and its effect on uterine stimulation. Urine, the material of choice for study, was initially extracted with a very large countercurrent apparatus (Fig. 1). Costing the exorbitan...

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“…The difference in risk between women with extremely dense, as opposed to predominantly fatty breasts is approximately 4-to 6-fold (15). Incorporation of density into the standard risk prediction models is associated with some improvement in risk prediction (16,17).…”

Section: Introductionmentioning

confidence: 99%

Assessing Individual Breast Cancer Risk within the U.K. National Health Service Breast Screening Program: A New Paradigm for Cancer Prevention

Evans

Warwick

Astley

et al. 2012

Cancer Prevention Research

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109

121

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The aim of this study is to determine breast cancer risk at mammographic screening episodes and integrate standard risk factors with mammographic density and genetic data to assess changing the screening interval based on risk and offer women at high risk preventive strategies. We report our experience of assessing breast cancer risk within the U.K. National Health Service Breast Screening Program using results from the first 10,000 women entered into the "Predicting Risk Of breast Cancer At Screening" study. Of the first 28,849 women attending for screening at fifteen sites in Manchester 10,000 (35%) consented to study entry and completed the questionnaire. The median 10-year Tyrer-Cuzick breast cancer risk was 2.65% (interquartile range, 2.10-3.45). A total of 107 women (1.07%) had 10-year risks 8% or higher (high breast cancer risk), with a further 8.20% having moderately increased risk (5%-8%). Mammographic density (percent dense area) was 60% or more in 8.3% of women. We collected saliva samples from 478 women for genetic analysis and will extend this to 18% of participants. At time of consent to the study, 95.0% of women indicated they wished to know their risk. Women with a 10-year risk of 8% or more or 5% to 8% and mammographic density of 60% or higher were invited to attend or be telephoned to receive risk counseling; 81.9% of those wishing to know their risk have received risk counseling and 85.7% of these were found to be eligible for a risk-reducing intervention. These results confirm the feasibility of determining breast cancer risk and acting on the information in the context of population-based mammographic screening. Cancer Prev Res; 5(7);

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Critical assessment of new risk factors for breast cancer: considerations for development of an improved risk prediction model

Cited by 176 publications

References 88 publications

Morbidity and mortality associated with obesity

Morbidity and mortality associated with obesity

Celebrating 75 years of oestradiol

Assessing Individual Breast Cancer Risk within the U.K. National Health Service Breast Screening Program: A New Paradigm for Cancer Prevention

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