- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00340262
Bone Mineral Density and Subsequent Cancer Risk
Recent cohort studies demonstrated reduced breast cancer risks among women with a history of fractures or low bone mineral density (BMD). In the Study of Osteoporotic Fractures, each standard deviation increase in distal radius BMD was associated with a 50% increased risk over three years of follow-up, while in the Framingham study, women in the highest quartile of metacarpal bone mass had a 3.5-fold higher risk than women in the lowest quartile. The impact of the severity and timing of bone loss on risk has not yet been investigated, and the extent to which other risk factors (family history, anthropometric factors, physical activity, and exogenous hormones) modify the relationship with BMD is unknown.
To elaborate on these research questions, we are conducting a follow-up study of 22,695 postmenopausal women who volunteered for the Fracture Intervention Trial (FIT), a trial of the bone-enhancing drug alendronate. This large cohort includes extensive baseline information on major breast cancer risk factors, and thus is ideal for evaluating potential interactions with BMD and the effects of BMD on other cancer sites. Endometrial cancer has been reported to occur more frequently among women with a history of fracture, but no previous studies have specifically investigated its relationship to BMD.
We are investigating whether BMD of the proximal femur predicts breast cancer risk; whether breast cancer risk factors among postmenopausal women modify the relationship with BMD; whether BMD predicts endometrial or other cancers; and whether measurable biomarkers offer further etiologic clues about BMD and cancer risk.
We have contacted the surviving members of FIT to ascertain incident cancers. Risk factors and fracture history are being updated through a self-administered questionnaire. To supplement the serum samples collected at baseline, we are using a nested case-control study approach to collect buccal cell specimens, which may be useful for measuring a variety of biomarkers, including endogenous hormones and genetic polymorphisms involved in either bone growth (e.g., vitamin D receptor) or hormone metabolism (e.g., CYP17, COMT). Retrieval of operative and pathology reports is being used to validate self-reported cancers. The social security numbers and contacts names provided by FIT participants when they completed the baseline questionnaire are facilitating comprehensive follow-up and a National Death Index search for those who cannot be located. The baseline data, the established cooperation of this study population, and the collection of additional biospecimens should enable this study to answer important questions about BMD in breast and endometrial cancers.
Study Overview
Status
Conditions
Detailed Description
Recent cohort studies demonstrated reduced breast cancer risks among women with a history of fractures or low bone mineral density (BMD). In the Study of Osteoporotic Fractures, each standard deviation increase in distal radius BMD was associated with a 50% increased risk over three years of follow-up, while in the Framingham study, women in the highest quartile of metacarpal bone mass had a 3.5-fold higher risk than women in the lowest quartile. The impact of the severity and timing of bone loss on risk has not been investigated, and the extent to which other risk factors (family history, lifestyle, and exogenous hormones) modify the relationship with BMD is unknown.
To elaborate on these research questions, we conducted a follow-up study of postmenopausal women who volunteered for the Fracture Intervention Trial (FIT), a trial of the bone-enhancing drug alendronate. The BFIT follow-up study includes 15,595 of the 22,695 FIT volunteers. Surviving members of FIT were contacted to ascertain incident cancers and to provide updated risk factor and fracture history through a self-administered questionnaire. To supplement baseline serum samples, we used a nested case-control approach to collect buccal cell specimens for biomarker measurement, including endogenous hormones and genetic polymorphisms involved in either bone growth (e.g., vitamin D receptor) or hormone metabolism (e.g., CYPI7, COMT). Operative and pathology reports were used to validate self-reported cancers. The social security numbers and contact names provided by FIT participants at baseline facilitated comprehensive follow-up and a National Death Index search for those who could not be located.
This large cohort includes extensive baseline information on major breast cancer risk factors, and thus is ideal for evaluating potential interactions with BMD and the effects of BMD on other cancer sites. Endometrial cancer has been reported to occur more frequently among women with a history of fracture, but no previous studies have investigated its relationship to BMD. We are investigating whether proximal femur BMD predicts breast cancer risk; whether breast cancer risk factors among postmenopausal women modify the relationship with BMD; whether BMD predicts cancer risk; and whether biomarkers offer etiologic clues about BMD and cancer risk. Currently, we are examining: 1) the relationship of serum adipocytokines to endometrial cancer risk, and 2) the relationships of serum estrogens and metabolites to postmenopausal breast cancer risk. The baseline and follow-up data and the collection of additional biospecimens should enable us to answer important questions about BMD and other cancers.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Maryland
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Bethesda, Maryland, United States, 20892
- National Cancer Institute (NCI), 9000 Rockville Pike
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
- INCLUSION CRITERIA:
Women previously enrolled in FIT and provided informed consent.
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
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FIT Participants
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incident cancer diagnosis
Time Frame: Through December 2003
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breast, endometrial, ovarian, colorectal
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Through December 2003
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Britton L Trabert, Ph.D., National Cancer Institute (NCI)
Publications and helpful links
General Publications
- Kuller LH, Cauley JA, Lucas L, Cummings S, Browner WS. Sex steroid hormones, bone mineral density, and risk of breast cancer. Environ Health Perspect. 1997 Apr;105 Suppl 3(Suppl 3):593-9. doi: 10.1289/ehp.97105s3593.
- Newcomb PA, Trentham-Dietz A, Egan KM, Titus-Ernstoff L, Baron JA, Storer BE, Willett WC, Stampfer MJ. Fracture history and risk of breast and endometrial cancer. Am J Epidemiol. 2001 Jun 1;153(11):1071-8. doi: 10.1093/aje/153.11.1071.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 999900019
- OH00-C-N019
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