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Energy Balance, Anthropometry, Hormone Therapy and Risk of Breast Cancer.

Principal Investigator
Name
Regina Ziegler
Institution
NCI, DCEG, EBP
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
2007-0039
Initial CDAS Request Approval
Jun 12, 2007
Title
Energy Balance, Anthropometry, Hormone Therapy and Risk of Breast Cancer.
Summary
Energy restriction remains one of the most effective ways known to prevent breast cancer in animal models. However, energy intake has not been consistently associated with risk of breast cancer in humans. We previously demonstrated in PLCO that energy intake is positively and significantly associated with breast cancer risk, even after adjusting for current body mass index (BMI) and recent physical activity. In addition, when we estimated the joint effect of energy intake, BMI, and physical activity, women with the most favorable energy balance had more than twice the risk of breast cancer of women with the least favorable energy balance. These provocative results were based on ~700 incident breast cancer cases in the screening arm of PLCO. We want to determine if we can replicate these results with the ~1500 incident breast cancer cases that have now accrued in the screening arm of PLCO and have prospectively collected dietary data from the baseline DQx, and also with the ~1500 incident breast cancer cases that have now accrued in both arms of the Trial and have prospectively collected dietary data from the DHQ, which was administered ~4 years after baseline. In addition, we will explore the relative contributions of recent BMI, BMI at 50 y, BMI at 20 y, recent weight gain, adult weight gain, and height to risk of breast cancer, with emphasis on independent and joint effects. We anticipate that all these anthropometric factors, other than BMI at 20 y, will be associated with increased risk. In all these analyses we will need to consider hormone therapy. The influence of BMI on breast cancer risk is generally not seen in women currently on hormone therapy, and is attenuated among recent users. We will examine the joint effects of hormone therapy and BMI, with particular attention to the importance of absolute levels of BMI and other anthropometric indicators and the years elapsed since ending hormone therapy.
Aims

1) In the screening arm of the PLCO Trial, we will attempt to replicate our previously published findings on the independent and joint effects of energy intake, current BMI, and recent physical activity on risk of breast cancer. Energy intake and physical activity will be estimated with the DQX, which was administered at baseline to subjects assigned to screening. In the PLCO screening arm, almost twice as many women have now been diagnosed with incident breast cancer as were utilized in our earlier analyses. We are particularly interested in whether we continue to see a statistically significant increase in breast cancer risk with energy intake after adjusting aggressively for BMI and physical activity. 2) We will also use the DHQ, administered ~ four years after baseline to subjects assigned to both arms of the Trial, to estimate energy intake. We will then be able to investigate the independent and joint effects of energy intake, current BMI, and recent physical activity on risk of breast cancer among women in both arms of the Trial. We wish to know whether using the DHQ --- a more detailed, more widely used, and more current dietary questionnaire than the DQx --- alters the results noted for the DQx. 3) We will investigate the independent and joint effects of current BMI, BMI at age 50, BMI at age 20, adult weight gain, recent weight gain, and height on risk of breast cancer. Women in both arms of the Trial will be utilized. 4) We will also explore how current and recent hormone therapy modifies the relationships studied in specific aim 3. Of particular interest are the details of the interaction: how long it takes after stopping hormone therapy for the effects of body size on breast cancer risk to be observed, and whether absolute levels of body size modulate the hormone therapy-breast cancer relationships. 5) When the data from the risk factor questionnaire administered at the end of the PLCO trial are available, we will use the updated information on hormone therapy, anthropometry, and physical activity to improve exposure assessment in the analyses described above.

Collaborators

Jeanine Genkinger
Catherine Schairer (BB/EBP/DCEG/NCI)
Laura Sue (EBP/DCEG/NCI)

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