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Contribution to consortial activities for clarifying the etiology of male breast cancers

Principal Investigator
Name
Louise Brinton
Degrees
-
Institution
NCI, DCEG, HREB
Position Title
-
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
2008-0252
Initial CDAS Request Approval
Jan 28, 2010
Title
Contribution to consortial activities for clarifying the etiology of male breast cancers
Summary
The etiology of male breast cancer has been difficult to clarify, given its relative rarity. Most previous studies have been of case-control designs, raising questions about the influence of recall biases. The identification of risk factors through prospective analyses is needed, although it is difficult to assemble sufficient numbers of cases in any individual study. A consortial approach is therefore being proposed, in which data from a number of studies will be pooled to derive sufficient power to fully explore the role of a variety of potential risk factors. Cohorts with biologic material collected prior to disease onset will be especially valuable for clarifying biologic mechanisms underlying identified risk factors. Of specific interest, given our current knowledge of male breast cancers, is the assessment of endogenous hormones and genetic markers. Questionnaire data and biologic samples (sera, DNA) are being sought for contribution to this consortial effort. This study is a valuable resource for adding to our knowledge of the etiology of male breast cancers. As of October 2008, 31 incident cases of male breast cancer had developed in both arms of the trial, making it one of the largest cohorts with biologic material.Only one previous cohort study has been undertaken of male breast cancer. This investigation, conducted by the investigators involved with the current proposal, was undertaken within the NIH-AARP Diet and Health Study. This study importantly identified increased risks associated with a family history of breast cancer, obesity, lack of physical activity, and previous bone fractures. These risk factors suggest an important role for endogenous hormones, particularly the balance of bioavailable estrogens to androgens. There is also clearly a genetic component of the disease, which needs to be further understood through the measurement of both highly penetrant genes (e.g., BRCA1 and BRCA2) and common genetic polymorphisms.
Aims

This proposal will assemble cohort of sufficient sizes to identify and contribute male breast cancer cases (at least 20 from each cohort) and non-cases for pooled analyses. With these data, the specific aims of this proposal will be to: 1) Using questionnaire data, conduct pooled analyses to assess the extent to which male breast cancer is influenced by a family history of breast cancer (in both male and female relatives); obesity; physical inactivity; histories of certain medical conditions, such as liver diseases, diabetes, bone fractures and osteoporosis; cigarette smoking; alcohol consumption; and other putative risk factors suggested in previous investigations. The PLCO-specific variables of interest are listed in Appendix III. 2) Using biologic samples from PLCO and other studies, conduct assays to assess the influence on male breast cancer risk of various levels of different estrogens, estrogen metabolites, androgens, and the ratio of estrogens to androgens. 3) Using biologic samples from PLCO and other studies, conduct assays to assess the influence on male breast cancer risk of various genes (both highly penetrant genes such as BRCA1 and BRCA2 and more common polymorphisms, particularly those involved in hormone metabolism and those that have been identified as predictive of female breast cancers).

Collaborators

Louise Brinton (NCI, DCEG)
Stephen Chanock (NCI, DCEG)
Gretchen Gierach (NCI, DCEG)
Isaacs Claudine (Georgetown University)
Tim Veenstra (SAIC-Frederick)

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