AS134 - Serum estrogen hormone metabolites, hormone replacement therapy and the risk of breast cancer
Investigator Names and Contact Information
Francesmary Modugno (fm@cs.cmu.edu)
Introduction/Intent
There is substantial evidence linking both exogenous and endogenous estrogens to breast cancer risk. Hormone replacement therapy (HRT), the most common source of exogenous estrogens, has also been associated with increased risk. However, not all women using HRT will develop breast cancer, suggesting genetic and/or other factors that modify the risk associated with HRT. In particular, our preliminary data suggests that body mass index (BMI) and HRT interact to determine how estrogen is metabolized and therefore affect a woman’s risk of breast cancer. We have found that in women with low BMI, estrogen is usually metabolized to 2-OH estrone, the less genotoxic estrogen metabolite. However, our data indicate that HRT use causes a shift from the 2-OH metabolite to the 16-OH metabolite. The 16-OH metabolite is more genotoxic and has been associated with breast cancer risk. In women with a high BMI, HRT does not appear to alter estrogen metabolism as much. Hence, among HRT users, production of the 16-OH metabolite is inversely associated with BMI; this is exactly the opposite of the association found among non-HRT users. This suggests that the increase in risk associated with HRT use among thin women may be mediated by estrogen metabolism.
The objective of this proposal is to prospectively evaluate the extent to which BMI and estrogen metabolism are related to breast cancer associated with HRT use. We will specifically test the following hypotheses: Among postmenopausal women using HRT:
a). the risk of breast cancer is higher for women with higher serum 16-OH levels
b). lower BMI is associated with higher serum 16-OH levels
c). therefore: the risk of breast cancer increases with decreasing BMI
We will also test the relationship between serum 2-OH levels, the 2:16-OH ratio, BMI and breast cancer risk.
Results/Findings
Some of the publications related to this ancillary study are:
Ms209 - Modugno F, Kip KE, Cochrane B, Kuller L, Klug TL, Rohan TE, Chlebowski RT, Lasser N, Stefanick ML. Obesity, hormone therapy, estrogen metabolism and risk of postmenopausal breast cancer. Int J Cancer. 2006 Mar 1;118(5):1292-301
For a complete, up-to-date list of WHI papers related to this ancillary study, please use the searchable Bibliography section of this website. To search for papers by study number, access the Simple Search, and enter the study number in the “Related Studies” field.
Data Dictionaries and Study Documentation
This section displays all study-related data dictionaries and study-related files. The investigators for this study will upload the datasets, data dictionaries, and other study-related files. Study-related files will be made available to the public one year after the completion of the ancillary study, with the exception of the datasets, which will only be available to those with a Data Distribution Agreement. Those will be available to those with permission to download and will appear as a download link next to the data dictionary
Data Dictionaries
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Study Documents
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NameAS134 Matching Summary 2-11-03.pdf | Description |