A Randomized Study of the Effects of Tibolone on Bone Density, Menopausal Symptoms, and Breast Density in High-Risk Women After Prophylactic Oophorectomy

Background: The carcinogenic effect of exogenous steroid hormones on the breasts is a matter of debate, causing confusion for physicians at the time of making prescriptions. This article, as part of a quadruple series about exogenous sex hormones and breast disorders, reviews the association of breast cancer and hormone replacement therapy (HRT) in the general population, women with benign breast disorders, women with personal or family history of breast cancer, and BRCA carriers. Methods: We accomplished an extensive search of the literature by using relevant keywords to identify pertinent cohort studies, clinical trials, and reviews. Then, we extracted all points regarding the question. Results: An extensive literature exists on the risk of breast cancer following HRT in the general population, and HRT has been mentioned as a risk factor for breast cancer, especially in recent, long-term users of combined formulations. However, there is still no consensus about it. Conversely, few studies have considered challenging issues like the use of HRT in breast cancer survivors and high-risk women. Conclusion: HRT up to 5 years can safely be used for management of menopausal symptoms in healthy women, and those with low-risk benign breast disorders. On the contrary, its use in high-risk women should be limited to refractory menopausal symptoms after describing potential harms to the patient.

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Decreased TGFβ signaling and increased COX2 expression in high risk women with increased mammographic breast density

Breast Cancer Research and Treatment ◽

10.1007/s10549-009-0350-0 ◽

2009 ◽

Vol 119 (2) ◽

pp. 305-314 ◽

Cited By ~ 40

Author(s):

Wei Tse Yang ◽

Michael T. Lewis ◽

Kenneth Hess ◽

Helen Wong ◽

Anna Tsimelzon ◽

...

Keyword(s):

High Risk ◽

Breast Density ◽

Mammographic Breast Density ◽

Tgfβ Signaling ◽

High Risk Women ◽

Cox2 Expression

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Is screening and/or prophylactic oophorectomy for ovarian cancer of value in high risk women?

Human Reproduction ◽

10.1093/oxfordjournals.humrep.a019566 ◽

1997 ◽

Vol 12 (2) ◽

pp. 203-204 ◽

Cited By ~ 3

Author(s):

M. Bowman

Keyword(s):

Ovarian Cancer ◽

High Risk ◽

Prophylactic Oophorectomy ◽

High Risk Women

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BRCA1 and BRCA2 germline mutation carriers have a lower breast density compared to high risk women without such mutations

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.1517 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 1517-1517

Author(s):

P. Sharma ◽

J. R. Klemp ◽

B. F. Kimler ◽

Q. J. Khan ◽

E. J. Smith ◽

...

Keyword(s):

Breast Cancer ◽

Family History ◽

High Risk ◽

Breast Density ◽

Genetic Factors ◽

Mammographic Breast Density ◽

Mutation Status ◽

High Risk Women ◽

Mutation Carriers ◽

Chi Square Analysis

1517 Background: High mammographic breast density, a known risk factor for breast cancer is influenced by both genetic and non genetic factors. It is not clear if there are differences in breast densities between BRCA1/2 mutation carriers and high-risk non carriers. The aim of this study was to compare breast density in high-risk women with and without BRCA1/2 mutation. Methods: Women at high risk for development of breast cancer (based on family history, prior precancerous disease or prior breast cancer) who underwent genetic testing at the University of Kansas Breast Cancer Prevention Center between 1998 and 2005 were identified under an IRB approved protocol. BRCA1/2 full sequencing was performed at Myriad Genetic Laboratories. The earliest digitized mammogram of these subjects was identified from a preexisting mammogram database. All mammograms had to be prior to/at least one year from any chemoprevention intervention. For subjects with prior breast cancer, mammogram of the uninvolved breast was used. Breast density was assessed on the left craniocaudal mammographic view by computer assisted method, Cumulus. Frequencies of categorical variables were assessed using chi-square analysis. Continuous variables were assessed using Mann-Whitney non parametric test. Multiple regression analysis was used to investigate whether differences are due to variables other than mutation status. Results: The study population consisted of 284 high-risk women who underwent BRCA1/2 testing and for whom a mammogram was available. 30 (11%) had BRCA1 and/or 2 deleterious mutation. There was no difference between mutation carriers and non-carriers for BMI, 5 year Gail risk, parity, menopausal status and HRT use. Mutation carriers were younger (median age 42 vs. 46, p=0.020) and more likely to have a positive family history (100% vs. 85%, p=0.020). Older age (p<0.001), higher BMI (p<0.001) and having a BRCA1/2 mutation (p=0.025) were significantly associated with a lower breast density. Conclusion: Among high risk women, possession of a deleterious BRCA1/2 mutation is associated with lower breast density after adjusting for factors known to affect breast density. This suggests that breast density may be governed by genetic factors other than BRCA1/2 mutation status. No significant financial relationships to disclose.

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