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Vol. 10 Issue 1, Winter 2005

Breast Cancer and the Environment Research Centers (BCERC)
The Ribbon 

Origins and directions of the BCERC

Readers of The Ribbon are familiar with the variety of scientific disciplines needed in order to effectively begin to answer the outstanding questions about breast cancer risk. Readers are also familiar with the important role of other professionals - such as clinicians - as well as the many possible roles of the breast cancer advocate community. We now have a federally funded network in place that embraces the concept of scientists, clinicians and advocates sharing a place at the table, called the Breast Cancer and the Environment Research Centers (BCERC). The four Centers are based at the University of Cincinnati, the Fox Chase Cancer Center in Philadephia, Michigan State University, and the University of California at San Francisco. The Centers are set to make significant progress in advancing a fundamental question with regard to breast cancer risk: understanding mammary gland development.

As Dr. Jose Russo, Director of the Fox Chase BCERC and chairperson of the first scientific meeting of the Centers in November of this past year, described in his opening remarks at that meeting, this is "a converging point for scientists … seeking an answer to the single question of how the normal breast develops and how the perturbation of the normal process of development predisposes this organ to develop cancer." And what does perturb the normal process of development? The approach of the Centers in seeking answers is to examine the influence of early environmental exposures on the early onset of puberty, a key indicator of subsequent breast cancer risk.

This emphasis, describes Dr. Leslie Reinlib of the National Institute of Environmental Health Sciences (NIEHS) and Program Director of the BCERC, was born of groundbreaking work to contact all those with a stake in breast cancer risk research. In a documentary (available on DVD; see box on page 5) on the Centers, Dr. Reinlib describes how the agency asked those contacted and brought together what they thought was missing from the research to date. From the wealth of ideas collected, there was a consensus on the importance of focusing on early environment exposures.

Dr. Reinlib explains that it is these scientific questions about normal breast development, and exposures that affect normal breast development and onset of puberty, combined with the commitment to "engage the community in a continuing conversation," that characterize the BCERC.

A model of coordination, integration and inclusion

The NIEHS and the National Cancer Institute (NCI) jointly awarded grants to establish four Breast Cancer and the Environment Research Centers. The specific areas of emphases and partnerships of each are described below. As a network, all contribute to the central research questions. Advocate partners aligned with each Center are diverse and help carry out the work of the "Community Outreach and Translation Core" (COTC) of the Centers.

Efforts across Centers are governed by a steering committee. There is also a Working Group, with scientist and breast cancer advocate representation, that reviews the progress of the Centers and has responsibilities toward the development of overall public health messages. See in this issue the review of the October 2004 BCERF Cancer and Environment Forum, which featured Karen Miller discussing the Working Group, and Karli Mennuti-Woods discussing one of the COTC projects. Dr. Suzanne Snedeker, BCERF Director of Translational Research, is a member of the Working Group. Dr. Snedeker has a unique role thus far within this structure: she served as a scientist-mentor at the first scientific meeting of the BCERC this past November.

This kind of role for scientists, as well as the participation in and structure of this meeting represent some of the many ways that the BCERC effort marks a turning point in cooperation amongst scientists, advocates, and others. For example, at this first BCERC meeting, 80 out of the 220 participants were advocates. This intensive two-day meeting had several features and events designed to help integrate the advocates. Aside from Dr. Snedeker's role to informally assist with understanding of scientific concepts, there was a working dinner at which scientific topics were previewed, and "Talk with the Experts" sessions to enhance understanding of presentations. Dr. Snedeker presented a pre-conference talk for the advocates entitled "Evaluating Chemicals and Breast Cancer Risk: Existing and Emerging Concepts." Presentations were in the format of plenary lectures, mini symposia, and poster sessions, all under the heading of "Emerging Topics in Breast Cancer and the Environment Research." Speakers and session abstracts from this meeting can be viewed at http://www.bcerc.org/princeton/

The central research question and methods

There are periods of vulnerability in the development of the mammary gland when exposures to environmental agents may impact the breast that can influence breast cancer risk in adulthood. This is the hypothesis embraced by the BCERC. What is unique and new about the BCERC approach to examining this hypothesis? The four Centers will be functioning as a coordinated whole, using both of the major scientific approaches to studying breast cancer risk: laboratory work with experimental animals and cell cultures, and epidemiology, the study of health and disease in human populations.

The laboratory research project addresses the development of the mammary gland over the life span (the shorter life span of the animals being advantageous in this work), and tests how environmental exposures affect this development. Each of the four Centers pursues a different, complementary aspect of this work.

The coordinated epidemiological study project is enrolling 1,200 girls across the country to learn about the exposures in the environments in which they live and learn, and how these exposures, as well as genetic determinants, affect mammary gland development and the onset of puberty. The research design is prospective, meaning it follows the participants over time, monitoring exposures and effects throughout the course of the study. The three Centers performing epidemiological studies - Cincinnati, Fox Chase, and the University of California at San Francisco Centers - have spent the first year coming up with core questions and protocols to examine how the environment may modify puberty in girls. The Centers have developed common protocols for clinical evaluations, obtaining medical histories, and measuring exposures. The three Centers complement each other by providing participants with different racial and ethnic backgrounds, and because of the different geographic and demographic settings, different environmental exposures.

Investigators involved with this project point out that, unlike most laboratory or epidemiological studies on breast cancer risk which monitor mammary tumor development or breast cancer cases, these studies are not looking for those end points. The enormous contribution that the Centers will make toward understanding the breast cancer process relates entirely to developmental processes that occur long before a breast tumor or breast cancer case typically arises. It is only in advancing understanding of these "windows of vulnerability," and influences on those windows that will lead us to increased possibilities for breast cancer risk reduction.

The four Centers and their activities

Fox Chase Cancer Center. Located in Philadelphia, the Fox Chase BCERC has as its scientific collaborators the University of Alabama and the Mount Sinai School of Medicine in New York City. As participants of BCERF's October 29 New York City forum heard about from Karli Woods-Mennuti (see page 6), key community partners are health and science educators and activists in East Harlem, the New York City Parks Foundation, and the breast cancer group SHARE: Self-Help for Women with Breast or Ovarian Cancer.

In its laboratory studies, the Fox Chase team will study several hormonal disrupting chemicals, such as bisphenol A and butyl benzyl phthalate, suspected to influence mammary development during important windows of exposure. Dr. Jose Russo, the leader of this effort and long established expert in the field of mammary gland biology says of the Fox Chase Center:

"We have a long-lasting commitment to breast cancer research, demonstrated through pioneer work that has identified critical windows of susceptibility to carcinogenic and environmental exposures. Our Center provides a broad and comprehensive armamentarium encompassing varied populations, clinical and basic sciences, and bioinformatics expertise that will be immediately translated to the population it will serve through carefully orchestrated programs under the guidance of advocates. Our goal is to identify the genomic signature of the differentiated mammary gland that will allow us to use it as a surrogate marker for understanding the effect of xenobiotic agents and predicting markers of prevention of breast cancer."

University of Cincinnati Center. The University of Cincinnati joins with the Cincinnati Children's Hospital Medical Center in examining the effect of dietary factors and obesity on puberty and cancer initiation. Dietary factors to be addressed include dietary fatty acids and phytoestrogens, both of which have been the subject of much scientific controversy, with regard to their health effects, in recent years. The thirteen community partners, including breast and general cancer organizations and various public health-oriented groups, will join in a COTC project they have called "Growing Up Female: Environmental Factors in Female Development and Disease." This project has five committees covering education, research, editorial issues, funding, and special projects (currently focusing on African American women and breast/cervical health and cancer). In addition to the COTC work, a representative from the breast cancer advocacy community attends meetings for the epidemiology and biology projects.

Dr. Sue Heffelfinger, Director of this Center, explains,

"The biology groups from each of the Centers are asking complementary questions in the broad base question of environmental determinants of puberty. Our Center is focused on the interaction of the hormonal state with adiposity and mammary development. We are studying adipose distribution in the body, as well as specific fatty acid effects as influenced by diet. Various studies examine these interactions through the lifespan of the animal. These studies are particularly complementary to those at the University of Alabama on endocrine disruptors and those at Michigan State on hormonal expression patterns in the mammary gland, being performed in similar model systems."

This Center's particular epidemiologic interest concerns the pathway through puberty. Extensive studies to test for correlations among these pathways and factors such as environmental chemical exposure, antenatal exposures, diet, physical activity, psychosocial factors, body habitus, and genetic polymorphisms are planned. Biochemical studies for hormonal levels at and before puberty will also be very important.

Michigan State University (MSU) Center. Dr. Sandra Haslam, Center Director at MSU, brings 25 years of experience to studying the effects of hormones such as estrogen and progesterone on breast development, and how breast development impacts cancer susceptibility. Her team will use mouse and rat models to focus specifically on gaps in knowledge in the understanding of in utero, postnatal, and pubertal environmental influences on the activity of the estrogen and progesterone receptors. Dr. Haslam believes

"understanding how hormones, in particular progesterone, regulate growth and function of the normal breast is key to understanding how hormones impact breast cancer risk."

Dr. Haslam and her science colleagues will be joined by colleagues in the Department of Communication at MSU; they will work with community partners of this Center - such as the Great Lakes Division of the American Cancer Society, Michigan Department of Community Health, Michigan Environmental Council, Faith Access to Community Economic Development and the Lansing Affiliate of the Susan G. Komen Foundation - to transmit information to the people of Michigan. They will also develop public health messages for broader BCERC and national use.

University of California at San Francisco - Bay Area Center. Dr. Robert Hiatt, Director of the Bay Area Breast Cancer and the Environment Research Center (BABCERC), says that their Center has enjoyed a close working relationship with its community partners under the leadership of Janice Barlow, Director of Marin Breast Cancer Watch. Advocates meet with the Center's scientific teams, and are also active on their own, organizing community outreach and education programs that translate the science to the public.

The BABCERC basic science project uses mouse models to understand the normal development of the breast and what can go wrong under the influence of environmental factors such as radiation and chemical exposures. The BABCERC scientists have special expertise in understanding the influence of the stroma of breast, or the supporting tissues around ductal cells of the breast, on the development of cancer in ductal cells. As Dr. Hiatt says,

"As the principal investigator of the BABCERC my goals are to use this opportunity to make some major contributions to the understanding of the environment and other determinants of pubertal maturation and the onset of menarche. If we understand this critical period in the maturation of women and the development of the human breast, we can expect to find better ways to prevent, diagnose and treat breast cancer."

Dr. Snedeker at Cornell BCERF concurs with this optimism. "That's the 'thinking outside the box' aspect to these studies. Without this information on early events and their impact on the normal development of the breast, we can't expect to fully understand the basic breast cancer process." Visit www.bcerc.org -- still under development - for information on funders, background, and the November 2004 meeting, and more information to come as the Centers proceed with the work of this exciting research network. Box: DVD: Breast Cancer and the Environment Research Centers Limited numbers of this documentary are available on DVD as of this date. Eventually the documentary will be available on the BCERC web site, www.bcerc.org. If you are interested in obtaining a DVD, please contact either: Dr. Fathima Sheriff (215) 728-5344 or FS_Sheriff@fccc.edu Dr. Jose Russo (251) 728-4782 or J_russo@fccc.edu

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Last Update 02.04.05