Biography

After receiving an M.P.H. in epidemiology from the University of North Carolina at Chapel Hill, Dr. Brinton joined the NCI as a Staff Fellow in 1976. She earned a Ph.D. in epidemiology from The Johns Hopkins School of Hygiene and Public Health in 1979, and subsequently conducted postdoctoral research at Oxford University. Dr. Brinton was appointed Acting Chief of the Environmental Studies Section in 1984, and Chief of the Environmental Epidemiology Branch (now called the Hormonal and Reproductive Epidemiology Branch) in 1996. She served on the Executive Board of the Society for Epidemiologic Research, and was elected President of the organization in 1990. Dr. Brinton has received the PHS Special Recognition Award and the NIH Director's Award for innovative leadership in women's health research. In the fall of 2008 Dr. Brinton was honored with the University of North Carolina H.A. Tyroler Distinguished Alumni Award.

Research Interests

Despite extensive epidemiologic studies, the causes of a large proportion of cancers of the female breast and reproductive system are unknown. A number of etiologic leads have recently emerged, which we are pursuing in a variety of studies. Many of these efforts include biochemical components that will contribute to an increased understanding of the biologic mechanisms underlying observed relationships with risk factors.

Breast Cancer

In a major approach to understand the role of environmental factors on risk of breast cancer, we are examining their effects among subgroups defined by genetic markers. These markers include breast cancer susceptibility genes that are known to affect hormone or carcinogen metabolism. Two collaborative studies are underway, one at three U.S. centers and the other in Poland. Each study has a sample size large enough to achieve statistical power for evaluating gene-environment interactions. The Polish study is also assessing the relation between breast cancer risk and occupational exposures, as a large proportion of Polish women work outside their homes, often in industrialized settings. In addition, the study is examining risk associated with physical activity, as measured by accelerometers worn by the women during recreational, occupational, and household activities.

Bone density is recognized as a predictor of breast cancer risk, but the mechanism underlying this relationship is unknown. We are collaborating on a follow-up study of women previously screened for bone density to evaluate their risk of breast and other hormonally-related cancers. Sera collected earlier from these women, together with DNA that will be obtained from buccal cell swabs, offer the opportunity for assessing interrelationships among bone density, endogenous hormones, and genetic polymorphisms.

Gynecologic Cancers

We are pursuing research opportunities for expanding our knowledge about etiologic factors for endometrial and ovarian cancers. Since a large number of women are treated for these malignancies within the Gynecologic Oncology Group, we are developing mechanisms for integrating epidemiologic components into several ongoing clinical trials. The identification of molecular markers for early stage ovarian cancer and endometrial cancer of varying histologies is of particular interest.

Exposures Unique to Women

Clues about hormonal mechanisms of carcinogenesis may be derived from studies of cancer risk in populations with known hormonal alterations. A collaborative record-linkage study in Denmark and Sweden found that patients with endometriosis had significant excesses of non-Hodgkin's lymphoma and cancers of the ovary and breast. We are pursuing additional research to gain further insights into the pathology of the ovarian tumors. Plans are underway to study several other conditions linked to hormonal alterations, including some that are androgen related.

To address the long-term effects of silicone breast implants, we conducted a retrospective cohort study among women with augmentation mammoplasties, using a comparison group of women with other types of plastic surgery. Despite clinical evidence that implants interfere with the visualization of breast lesions, we found no evidence that implants were associated with altered breast cancer risk. Patients with breast implants, however, presented with somewhat later stages of breast cancer at diagnosis than other patients. Data from the study are also being analyzed to evaluate the incidence of other cancers and connective tissue disorders, as well as cause-specific mortality, among implant patients. In a study conducted in collaboration with Swedish investigators, we sought to determine reasons for a reduced risk of breast cancer observed among women who had breast reduction operations. Our study found that the reduction in risk appeared to be inversely related to the amount of breast tissue removed.

Although reports indicate that ovulation-stimulating drugs may predispose to ovarian cancer, the studies are limited by small numbers and imprecise information on causes of infertility and medication use. To clarify this relationship, an ongoing large retrospective cohort study is reviewing detailed medical data on women who were evaluated and treated for infertility as long ago as the 1960s. Questionnaires are being administered to collect additional data on subsequent health events and other risk factors. In a separate study, we are evaluating cancer risk among children conceived following their mother's use of ovulation-stimulating drugs.

Keywords

breast cancer, endometrial cancer, genetics, hormones, gynecological conditions, breast implants, genetic polymorphisms, genital cancers, ovulation-stimulating drugs

Selected Publications

• Lacey JV Jr, et al. "Oral contraceptives as risk factors for cervical adenocarcinomas and squamous cell carcinomas." Cancer Epidemiol Biomarkers Prev 1999; 8:1079-1087.
• Brinton LA, et al. "Tubal ligation and risk of breast cancer." Br J Cancer 2000; 82:1600-1604.
• Butler L, et al. "Menstrual risk factors and early-onset breast cancer." Cancer Causes Control 2000; 11:451-458.
• Brinton LA, et al. "Breast cancer following augmentation mammoplasty." Cancer Causes Control 2000; 11:819-827.

Collaborators

DCEG Collaborators

• Aaron Blair, Ph.D.; Joseph F. Fraumeni, Jr., M.D.; Mitchell Gail, M.D., Ph.D.; Montserrat Garcia-Closas, M.D., Dr.P.H.; Allan Hildesheim, Ph.D.; Robert Hoover, M.D., Sc.D.; James Lacey, Jr., Ph.D.; Charisee Lamar, Ph.D.; Jay Lubin, Ph.D.; Pamela Mink, Ph.D.; Catherine Schairer, Ph.D.; Mark Sherman, M.D.; Patricia Stewart, Ph.D.; Stephanie Weinstein, Ph.D.; Regina Ziegler, Ph.D.

Other NCI Collaborators

• William Anderson, M.D.

Other Scientific Collaborators

• John Baron, M.D.; Linda Titus-Ernstoff, Ph.D., Dartmouth University Medical School, Hanover, NH
• Douglas C. Bauer, M.D., University of California at San Francisco, San Francisco, CA
• Valerie Beral, Oxford University, Oxford, United Kingdom
• Donna Brogan, Ph.D., Emory University, Atlanta, GA
• S. Lori Brown, Ph.D., Food and Drug Administration, Rockville, MD
• Celia Byrne, Ph.D., Harvard Medical School, Boston, MA
• Ralph Coates, Ph.D., Centers for Disease Control and Prevention, Atlanta, GA
• Theodore Colton, Sc.D., Boston University School of Public Health, Boston, MA
• Janet Daling, Ph.D.; Kathleen Malone, Ph.D.; Polly Newcomb, Ph.D.; Janet Stanford, Ph.D.. Fred Hutchinson Cancer Research Center, Seattle, WA
• Kathleen Egan, Ph.D., Harvard Medical School, Boston, MA
• Marilie Gammon, Ph.D., Columbia University, New York, NY
• Susanne Kruger-Kjaer, Danish Cancer Registry, Copenhagen, Denmark
• Emmet Lamb, M.D., Stanford University, Palo Alto, CA
• Jolanta Lissowska, Ph.D., Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
• L. Joseph Melton, III, M.D., Mayo Clinic, Rochester, MN
• Kamran Moghissi, M.D., Wayne State University, Detroit, MI
• Humberto Scoccia, M.D., University of Illinois, Chicago, IL
• Janet Schoenberg, M.P.H., New Jersey State Department of Health, Trenton, NJ
• Xiao-Ou Shu, M.D., Ph.D., Vanderbilt University, Nashville, TN
• Carolyn Westhoff, M.D., Columbia University, New York, NY
• Witold Zatonski M.D., Ph.D., Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology