Focus: Prevention and Environmental Factors Implicated in Breast Cancer

Identifying and understanding the underlying causes of breast cancer--be it environmental triggers or mistakes of biology--are critical to achieving our ultimate goal of prevention and cure. Since 1993, BCRF-funded researchers have contributed to important breakthroughs in determining environmental effects on not only the risk of developing both primary and recurrent breast cancer but also lifestyle prevention strategies to improve patient survival.

An example is the critical support BCRF provided to Regina Santella, PhD, Mary Beth Terry, PhD, and Ruby Senie, PhD at Columbia University in their work with the Long Island Breast Cancer Study. This project focuses on environmental pollutants and their possible link to the high breast cancer incidence rate in that region and has now extended to examining the underlying biological processes impacting breast cancer risk in these women. BCRF has also funded related investigations on breast cancer in populations outside the US, in Africa, Asia, Latin America, and the Middle East.

Several of BCRF's current environmental initiatives center on modifiable lifestyle factors, including research by Walter Willett, MD, Dr.PH (Harvard University School of Public Health) and Graham Colditz, MD, Dr.PH (Washington University School of Medicine), who are examining the impact of diet and exercise on breast cancer risk at different stages of life. The defining aim of all these efforts is so that we can develop ways to reduce risk effectively.

"When we as epidemiologists talk about 'environment,' we usually are referring to pretty much everything except genetics," explained Dr. Willett, who is the world's most cited expert on nutritional science. "If we look at this very broad definition of environment, we have learned quite a bit about breast cancer."

For example, many risk factors seem to be most influential during childhood and adolescence, a phenomenon not unique to breast cancer, but different from that of heart disease or diabetes where factors acting within a few years of diagnosis are most important. Studies on survivors of the atomic bombing of Nagasaki and Hiroshima showed that in women over age 40, even big doses of radiation had limited effect on their breast cancer risk. However, if the women were irradiated when they were children or young adults, several decades later, an increase in breast cancer risk was seen.

"We have to wait decades to see the full impact of environmental factors on breast cancer," commented Dr. Willett. "This long delay between the 'cause' and the actual initial effects on breast cancer creates some tremendous challenges for researchers of environmental risk factors for breast cancer." Dr. Willett also pointed out that another challenge confronting scientists is that some environmental factors, such as exposure to pesticides, are difficult to measure.

Alongside work on the environmental causes of breast cancer, BCRF has funded several seminal studies on cancer prevention. Through her BCRF-funded research related to the New York Breast Cancer Study, Mary-Claire King, PhD (University of Washington), who is world-renowned for locating the first breast cancer (BRCA1) gene and proving that some forms of the disease are hereditary, made the groundbreaking observation that regular exercise and healthy weight as teenagers can delay the onset of breast cancer in women who carry the BRCA mutation. Building on Dr. King's work, Dr. Graham Colditz has further enriched our knowledge of the important impact of lifestyle during adolescence in adult breast cancers, in particular the harmful effects of excessive alcohol intake on breast cancer risk.

Recent advances by Andrew Dannenberg, MD (Weill Cornell Medical College), Clifford Hudis, MD (Memorial Sloan-Kettering Cancer Center), and others whose investigations into the biology of obesity, inflammation, and breast cancer formation have also significantly advanced prevention studies. This work complements BCRF's investigations on tumor biology and improved treatment strategies, and provides new insights essential to the development of possible interventions.

Because BCRF is dedicated to eradicating breast cancer by whatever means possible, including prevention, we recognize the pressing need to better understand causative factors that might be effectively reduced or eliminated. Therefore, research projects led by Michael Sporn, PhD and Karen Liby, PhD (Dartmouth Medical School) on chemoprevention of breast cancer, and a series of studies aimed at the creation of vaccines to prevent breast cancer recurrence and, ultimately, its development, are at the forefront of our efforts.

In all, the spectrum of projects listed above exemplifies some of the key areas of concern we are most enthusiastic about supporting in order to achieve the ultimate goal of cure and prevention.

"It takes a village," said Dr. Mary-Claire King. "Catalyst exactly explains the role BCRF has had for our research, and BCRF has saved the lives of many women by making out-of-the-box work possible by us all."

Selected BCRF projects on breast cancer prevention:

Robert Benezra, PhD - biology of breast cancer metastasis

Andrew J. Dannenberg, MD - biology of obesity, inflammation pathway, and breast cancer development

Susan M. Domchek, MD and Robert H. Vonderheide, MD, D.Phil - breast cancer vaccine

H. Shelton Earp, MD - breast cancer vaccine

Carol J. Fabian, MD - use of omega-3 fatty acids as breast cancer prevention agent in high-risk women

John Forbes, MB BS and Jack Cuzick, PhD - clinical trials for prevention of primary breast cancer and recurrence/metastasis

Silvia Formenti, MD and Robert J. Schneider, PhD - biology of breast cancer metastasis

Teresa Gilewski, MD and Govind Ragupathi, PhD - breast cancer vaccine

Daniel A. Haber, MD, PhD - biology of breast cancer metastasis

Rachel Hazan, PhD and Larry Norton, MD - biology of breast cancer metastasis

Clifford Hudis, MD - biology of obesity, inflammation pathway, and breast cancer

Stephen D. Hursting, PhD, MPH - comparing the effectiveness of weight loss strategies (total calorie restriction vs. carbohydrate restriction, vs. adding high dose omega-3 fatty acids to diet, etc.) in breast cancer prevention

Seema Khan, MD - development of anti-progesterone patch for breast cancer prevention

Gordon B. Mills, MD, PhD - biology of obesity and its role in cancer development

Electra D. Paskett, PhD - nutrition and lifestyle studies for breast cancer prevention

Regina Santella, PhD and Mary Beth Terry, PhD - discovery of biomarkers for breast cancer risk assessment

Dipali Sharma, PhD - use of honokiol as breast cancer prevention

Pamela J. Goodwin, MD, MSc, FRCPC and Lois Shepherd, MD - metformin trial for breast cancer prevention

Michael B. Sporn, MD and Karen T. Liby, PhD - development of chemoprevention drugs

Vered Stearns, MD - weight-loss program for women with early breast cancer to prevent against recurrence and metastasis

Robert A. Weinberg, PhD - biology of breast cancer metastasis

Jedd Wolchok, MD, PhD, Alan Houghton, MD, and Larry Norton, MD - breast cancer vaccine development