Prevention and Risk Reduction: The Environment of the Disease

Despite the identification of breast cancer genes and other risk factors, the disease strikes women seemingly at random. There are causes of the disease that cannot be explained by studying tumors in the laboratory setting. What are environmental and biological factors that interact to increase a woman's risk of developing breast cancer? How do these factors increase the risk and impact different communities of women in California? Knowing what causes breast cancer will allow us to take steps to prevent it.

Two of CBCRP's Priority Issues are represented in this section:

Funding Data:

 

Proportion of CBCRP's Total

Prevention & Risk Reduction grants awarded in 2002:

7

10%

Funded Amount:

$1,477,269

10%

Prevention & Risk Reduction Portfolio Summary:

Catherine Blake, a doctoral student at the University of California, Irvine, was funded to develop a computer program to help scientists rapidly identify new risk factors associated with breast cancer. She intends to semi-automate both the extraction of data from the breast cancer medical literature and the meta-analysis by which conclusions are drawn from multiple studies on the same topic. If scientists are able to explore secondary information in the literature faster and more comprehensively, then they may also be able to reduce publication bias by including articles that were not specifically studying a given risk factor.

Two grants will examine the role of the androgen receptor (AR) in breast cancer. The AR is a steroid hormone receptor that mediates the affects of the steroid hormones testosterone and 5α-dihydrotestosterone. There are contradictory studies in cell lines, animal, and human studies about the role of androgen in affecting breast cancer risk. Elizabeth Lillie, a doctoral student at the University of Southern California, proposes to test the hypothesis that there is an association between AR activity, as measured by genotyping variations in the AR gene (AR polymorphism), and percent mammographic density, which is a known risk factor for breast cancer, and to determine whether the AR polymorphism is associated with more advanced forms of breast cancer. Wei Wang, also a doctoral student at the University of Southern California, will undertake a human population study that will incorporate genetic markers to study differences among individuals in one specific androgen pathway (the PSA pathway) in order to try to determine how androgens act to influence breast cancer risk. The molecular epidemiologic approach he will use is a powerful method that may overcome some of the deficiencies in the previous human studies on this topic.

Bradley Ekstrand, a postdoctoral fellow at Stanford University, will investigate a novel approach to the prediction and prevention of breast cancer. Cells from women with and without breast cancer will be exposed to X-rays and the genetic response to the X-rays will be measured using a microarray. The resulting data from women without breast cancer will be compared to those with breast cancer. A computer-based statistical method will be used to identify the genes whose responses to X-rays predict the patients with breast cancer. If successful, this strategy would allow breast cancer risk assessments to be based on genetic factors specific to each woman.

There is a large and compelling body of evidence implicating estrogen in human breast cancer. Diet is also thought important, although its role is less clear; however, dietary fiber may play an important role in estrogen metabolism and may therefore be an important determinant of circulating estrogen levels in the body, and thus affect breast cancer risk. Malcolm Pike at the University of Southern California will conduct a study into this issue, which is innovative in that it: (1) utilizes an ideal population where the traditional diet is rich in dietary fiber, (2) comprises two generations of Mexican origin women where differences in breast cancer rates provide powerful evidence on the extent to which the causes are due to changes in environmental factors, and (3) utilizes two methods of quantifying fiber intake—that of a food frequency questionnaire as well as a biochemical marker.

A full term pregnancy (FTP) before the age 20 reduces breast cancer risk in women. It does the same in rats and mice exposed to potent chemical carcinogens, perhaps by permanently reducing secretion (in parous animals who have given birth) of some hormones associated with breast cancer. Satyabrata Nandi at the University of California, Berkeley, intends to optimize and analyze the physiological and molecular bases of a short-term (7-21 days) protective hormone treatment (PHT) that he has developed using pregnancy levels of estrogen. In rats who have never given birth, this treatment reduced mammary cancer incidence by over 80% and multiplicity of tumors by over 90%. The eventual goal is for this PHT to serve as a paradigm for safe and efficient human breast cancer prevention.

Part of CBCRP's goal is to continually bring fresh ideas and new approaches into breast cancer research. One way of doing this is to support the training of highly qualified students. Ronald Ross at the University of Southern California will continue with the third cycle of CBCRP support for a training program emphasizing multidisciplinary interests, which include pathology, molecular biology, cell biology, and cancer control. Trainees are matched to an appropriate faculty mentor with an active breast cancer research program.

Prevention & Risk Reduction Grants Funded in 2002:

Using Scientific Text to Identify Breast Cancer Risk-Factors
Blake, Catherine
University of California, Irvine
Dissertation Award
1 year, $29,136

Using Microarrays to Estimate Breast Cancer Risk
Ekstrand, Bradley
Stanford University
Postdoctoral Fellowship
2 years, $86,400

The Androgen Receptor and Mammographic Density
Lillie, Elizabeth
University of Southern California
Dissertation Award
2 years, $59,998

Breast Cancer Prevention with Estrogen
Nandi, Satyabrata
University of California, Berkeley
Prevention RFA Award
3 years, $812,340

Fiber, Estrogen and Breast Cancer in Mexican American Women
[Tax Check-off!]
Pike, Malcolm
University of Southern California
STEP award
2 years, $159,697

USC/NCCC Breast Cancer Research Training Program
Ross, Ronald
University of Southern California
Training Program
3 years, $269,698

Androgen Receptor Gene and PSA Gene in Breast Cancer Risk
Wang, Wei
University of Southern California
Dissertation Award
2 years, $60,000

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