Prophylactic bilateral mastectomy

Metcalfe, Kelly; Goel, Vivek; Lickley, Lavina; Semple, John L.; Narod, Steven A.

doi:10.1002/cncr.10680

Cited by 31 publications

(15 citation statements)

References 26 publications

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“…Nonetheless, the strongest basis for breast cancer prevention among women with elevated risk is through hormonal intervention. (46,63,64) However, both surgical and pharmacologic preventive techniques have serious negative long-term consequences that may be unacceptable to many women. The results of this study suggest potential value in exercise interventions that might address the same hormonal issues but with fewer serious side effects and less deleterious impact on quality of life.…”

Section: Discussionmentioning

confidence: 99%

Exercise lowers estrogen and progesterone levels in premenopausal women at high risk of breast cancer

Kossman

Williams

Domchek

et al. 2011

Journal of Applied Physiology

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Kossman DA, Williams NI, Domchek SM, Kurzer MS, Stopfer JE, Schmitz KH. Exercise lowers estrogen and progesterone levels in premenopausal women at high risk of breast cancer. J Appl Physiol 111: 1687-1693, 2011. First published September 8, 2011 doi:10.1152/japplphysiol.00319.2011.-Experimental and clinical data support a role for estrogens in the development and growth of breast cancer, and lowered estrogen exposure reduces breast cancer recurrence and new diagnoses in high-risk women. There is varied evidence that increased physical activity is associated with breast cancer risk reduction in both pre-and postmenopausal women, perhaps via lowered estrogen levels. The purpose of this study was to assess whether exercise intervention in premenopausal women at increased breast cancer risk reduces estrogen or progesterone levels. Seven healthy premenopausal women at high risk for breast cancer completed a seven-menstrual-cycle study. The study began with two preintervention cycles of baseline measurement of hormone levels via daily first-morning urine collection, allowing calculation of average area under the curve (AUC) hormone exposure across the menstrual cycle. Participants then began five cycles of exercise training to a maintenance level of 300 min per week at 80 -85% of maximal aerobic capacity. During the last two exercise cycles, urinary estradiol and progesterone levels were again measured daily. Total estrogen exposure declined by 18.9% and total progesterone exposure by 23.7%. The declines were mostly due to decreased luteal phase levels, although menstrual cycle and luteal phase lengths were unchanged. The study demonstrated the feasibility of daily urine samples and AUC measurement to assess hormone exposure in experimental studies of the impact of interventions on ovarian hormones. The results suggest value in exercise interventions to reduce hormone levels in high-risk women with few side effects and the potential for incremental benefits to surgical or pharmacologic interventions. menstrual cycle; BRCA1/2 mutation carriers EXPERIMENTAL AND CLINICAL data support a role for estrogens in the development and growth of breast cancer, with the primary hypothesis being that estrogens interact with receptors in a manner that increases cell proliferation rates (7, 70). Lowering endogenous estrogen levels via bilateral oopherectomy or blocking estrogen effects with selective estrogen receptor modulators such as tamoxifen and raloxifene reduce the rate of initial diagnoses among women at high risk of developing breast cancer (11,29,38,34,36,55). Early onset of menarche, late first full-term pregnancy, and late menopause, factors that increase lifetime estrogen exposure, have all been associated with higher rates of breast cancer. On the other hand, there is conflicting epidemiologic evidence of a link between premenopausal endogenous estrogens and breast cancer risk. Of seven studies identified, four observed a significant inverse association of endogenous estrogens with breast cancer risk in premenopausal w...

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Section: Discussionmentioning

confidence: 99%

Exercise lowers estrogen and progesterone levels in premenopausal women at high risk of breast cancer

Kossman

Williams

Domchek

et al. 2011

Journal of Applied Physiology

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“…Both strategies have advantages and disadvantages and are a subject of considerable scientiWc controversy (Lostumbo et al 2004;Metcalfe et al (2002). The pros and cons are signiWcant for a mutation carrier who has to decide which strategy she should opt for.…”

Section: Introductionmentioning

confidence: 99%

Prevalence of pre-malignant and malignant lesions in prophylactic mastectomy specimens of BRCA1 mutation carriers: comparison with a control group

Kroiss

Winkler

Kalteis

et al. 2008

J Cancer Res Clin Oncol

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“…Metcalfe et al 50 reviewed patterns of practice in 124 bilateral prophylactic mastectomies performed within Ontario, Canada, during the years 1991-1999. Since 1995, when genetic testing for BRCA became available, the frequency of total mastectomy (compared to subcutaneous mastectomy) increased among women with a positive family history from 81.3% to 94.0% (pϭ0.07).…”

Section: Discussionmentioning

confidence: 99%

Prevention of breast cancer in women who carry BRCA1 or BRCA2 mutations: A critical review of the literature

Calderon‐Margalit

Paltiel

2004

Intl Journal of Cancer

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The purpose of our study was to review the evidence for the efficacy of surveillance for early detection, bilateral prophylactic mastectomy, prophylactic oophorectomy and chemoprevention in preventing breast cancer and improving survival of BRCA1 or BRCA2 carriers. A critical review of journal articles published between 1998 and 2004 identified by searches of MEDLINE, PubMed and references of retrieved articles was undertaken. None of the current evidence is based on randomized studies. The efficacy of surveillance for early detection of breast cancer among BRCA1 or BRCA2 carriers is not yet established. Screening with clinical breast examination and mammography showed lower sensitivity in BRCA1 or BRCA2 carriers than in the general population. Screening with MRI might offer higher sensitivity rates than mammography. Prophylactic mastectomy was shown to significantly reduce the risk of breast cancer by 89.5-100%. However, of all strategies reviewed, mastectomy was the least acceptable to women at high risk. Tamoxifen Approximately 7% of breast cancer cases are estimated to be due to breast cancer susceptibility genes. 1 In the last decade, 2 such susceptibility genes, BRCA1 and BRCA2, were identified on the long arms of chromosomes 17 and 13, respectively. The highest population prevalence rates of BRCA1 and BRCA2 were described among Ashkenazi Jews at about 2.5%; 2-4 these mutations include 5382insC and 185delAG in BRCA1, and 6174delT in BRCA2 with prevalence rates of 0.13%, 1.09% and 1.52%, respectively. 2 In Iceland, 1 common founder BRCA2 mutation, 999del5, occurs in 0.6% [95% Confidence Interval (95% CI): 0.1-1.7] of the general population. 5 Among breast cancer patients, the prevalence of BRCA1 and BRCA2 mutations varies according to ethnicity, age and family history of the patients, ranging between 0% and 3.3% in black and white American women unselected for family history to 10% among Spanish breast cancer patients younger than 40 years at diagnosis and 19% and among French Canadian breast cancer patients younger than 36 years at diagnosis with a positive family history of breast cancer. 6 -9 Among unselected Icelandic breast cancer patients, the prevalence is 10.4%, 10 while among Ashkenazi Jewish breast-cancer patients, the overall prevalence is 12-25%, with a range of 18 -75% according to age at diagnosis and family history of breast or breast-ovarian cancer. [11][12][13] The estimated cumulative lifetime risk of breast cancer for women who carry mutations in BRCA1 or BRCA2 ranges from as high as 80% 14,15 to less than 60%. 3,16 In a meta-analysis of 22 studies, among first-degree relatives of 500 index patients with BRCA mutations, the average lifetime cumulative risks for breast cancer were 65% (95% CI: 44 -78%) and 45% (31-56%) in BRCA1 and BRCA2 mutation carriers, respectively. There was evidence for variation in risk by mutation position for both genes. 17 Much higher estimates were reported in the recently published New York Breast Cancer Study (NYBCS), where the lifetime risk of breast cancer ...

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Prophylactic bilateral mastectomy

Cited by 31 publications

References 26 publications

Exercise lowers estrogen and progesterone levels in premenopausal women at high risk of breast cancer

Exercise lowers estrogen and progesterone levels in premenopausal women at high risk of breast cancer

Prevalence of pre-malignant and malignant lesions in prophylactic mastectomy specimens of BRCA1 mutation carriers: comparison with a control group

Prevention of breast cancer in women who carry BRCA1 or BRCA2 mutations: A critical review of the literature

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