Prevention and Risk Reduction: The Environment of the Disease

Overview: Despite our knowledge of breast cancer genes and other risk factors, the cause of breast cancer in most women is unknown. There are causes of the disease that cannot be explained by the analysis of 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 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 Total
Prevention & Risk Reduction grants awarded in 2003:

8

16%
Funded amount:

$2,687,259

23%

Prevention & Risk Reduction Portfolio Summary:

Four new grants were awarded in the CBCRP priority issue of Etiology to study the causes of breast cancer. Women who are obese may be more or less likely to develop breast cancer depending upon the age their obesity occurs. Obese women during the menstrual years have a lower risk, while risk increases for women who are obese after menopause. Catherine Carpenter at the University of California, Los Angeles, will study different forms of genes in relationship to breast cancer, the hypothesis being that genes that increase the likelihood of obesity may also increase women's chances of developing breast cancer. Several candidate genes (e.g., the leptin-receptor gene OBR, which has never been studied in relationship to breast cancer) will be genotyped to see if various forms of these genes are related to chances of developing breast cancer or obesity. Next, Christina Clarke Dur at the Northern California Cancer Center received a New Investigator Award to examine “The Hygiene Hypothesis and Breast Cancer Risk.” Dr. Clarke Dur will contact women with and without breast cancer to find out about their exposures relevant to hygiene. Dr. Clarke Dur will then use statistical analysis to determine if breast cancer cases have a different profile of immunodevelopmental exposures than control groups. The hypothesis to be tested is whether reduced or delayed exposure to microbes, or living in a mostly disease-free, sanitized environment hampers development of a healthy immune system. An underdeveloped immune system might subsequently influence breast cancer development by weakening responses against tumors, increasing estrogen production, or both. Next, Sally Glaser also from the Northern California Cancer Center is using an innovative, STEP award to examine a suggested link between EBV (Epstein-Barr Virus) and breast cancer. She will use a powerful gene amplification technique called “real-time PCR” to determine how much, if any, EBV is present in very small tissue samples provided by breast cancer patients. Another method, called “laser capture microdissection”, will be used to determine whether EBV is inside cancer cells or merely in the surrounding normal cells. Dr. Glaser will then begin identifying the characteristics of women (e.g., age, race/ethnicity, socioeconomic status, extent of disease spread, prognosis) who have EBV-associated breast cancers. Finally, prolactin is important to breast development both during puberty and pregnancy, and is the primary hormone responsible for milk production after pregnancy. Human and animal studies have supported the role of prolactin as a possible hormonal risk factor for breast cancer. Brian Henderson at the University of Southern California will take advantage of the multiethnic Hawaii/LA cohort, and, using an IDEA award study the breast cancer risk association between genetic variations in prolactin and the prolactin receptor. Using high-throughput laboratory techniques and novel statistical methods, this project will be the first to comprehensively evaluate genetic variations in PRL and the prolactin receptor in relation to breast cancer risk.

Four new CBCRP grants focus on the priority issue of Prevention and Risk Reduction. Two grants involve animal studies of novel breast cancer chemoprevention agents. Michael DeGregorio at the University of California, Davis received a STEP award to assess the ability of ginseng, a natural remedy that has been used to treat numerous ailments for several thousand years in the Orient, to prevent the development of breast cancer. In another STEP award, Kristen Kulp at the Lawrence Livermore National Laboratory will investigate whether Essiac® Herbal Tea, a commercially available complementary therapy, has protective properties that may have an effect on breast cancer risk. Dr. Kulp will study breast cell damage caused by PhIP, which is an ubiquitous food mutagen formed during high-temperature cooking of protein rich foods, especially meat. She will use cell lines and rat models treated with Essiac® Herbal Tea to see whether this prevents cell DNA damage or tumor formation caused by PhIP. Next, Christopher Haiman from the University of Southern California received a New Investigator award to study subtle variations in the BRCA1 and BRCA2 familial breast cancer genes that might be associated with sporadic breast cancer risk. It is also not known what percentage, if any, of the racial/ethnic variation in breast cancer risk may be explained by subtle variations in these genes. Dr. Haiman will use a novel genetic haplotype (i.e., a combination of genotypes on the same chromosome that tend to be inherited as a group) approach that exploits the ancestral relationship between common variations in the DNA to identify genetic markers of sporadic breast cancer risk in a large-scale multiethnic epidemiologic study of African-Americans, Latinas, Japanese, Whites and Hawaiians in Los Angeles and Hawaii. Finally, Susan Neuhausen at the University of California, Irvine will examine African American breast cancer mortality, employing a molecular epidemiology approach. The aim is to identify genes in the insulin-like growth factor (IGF) pathway that are important for breast cancer occurrence and progression. Dr. Neuhausen will compare specific genetic changes in DNA from African American women with and without breast cancer, and then analyze the data for the effects of genetic changes, for gene-gene interactions and lifestyle factors. She will correlate these lifestyle factors, such as body mass index, with breast cancer risk, age at which it was diagnosed, and tumor characteristics.

Prevention & Risk Reduction Grants Funded in 2003:

Etiology Priority Issue

Genetics, Obesity, and Breast Cancer Risk
Catherine Carpenter
University of California, Irvine
Request for Applications Award
3 years; $533,527

The Hygiene Hypothesis and Breast Cancer Risk
Christina Clarke Dur
Northern California Cancer Center
New Investigator Award
3 years; $366,997

Epstein-Barr Virus in Breast Cancer Tissues
Sally Glaser
Northern California Cancer Center
STEP Award
2 years; $275,564

Prolactin and Breast Cancer Risk in a Multiethnic Cohort
Brian Henderson
University of Southern California
IDEA
1.5 years; $162,311

Prevention Priority Issue

Preventing Breast Cancer with Ginseng
Michael DeGregorio
University of California, Davis
STEP Award
1year; $99,708

Common Genetic Variation & Breast Cancer: A Genomic Approach
Christopher Haiman
University of Southern California
New Investigator Award
3 years; $462,925

Studying the interaction of an Essiac Tea and Food Mutagen
Kristen Kulp
Lawrence Livermore National Laboratory
STEP Award
2 years; $363,760

The IGF Pathway & Breast Cancer Risk in African Americans
Susan Neuhausen
University of California, Irvine
Request for Applications Award
3 years; $422,467