Meeting Summaries

Emerging Topics in Breast Ca & the Environment

The Breast Cancer and the Environment Research Centers program is a network of collaborative research centers comprised of teams including scientists, clinicians, and breast cancer advocates focused on how chemical, physical, and social factors in the environment interact with genetic factors to affect mammary gland development.

Jointly supported by the National Institute of Environmental Health Sciences and the National Cancer Institute, this program will span seven years with annual funding levels of $5 million per year, for a total commitment of $35 million.

Report on “Emerging Topics in Breast Cancer and the Environment Research” by Ann E. Fonfa, President, The Annie Appleseed Project. November 4-6, 2004

This was a gathering of researchers, government and advocates cosponsored by the National Institute of Environmental Health Sciences (NIEHS), National Cancer Institute (NCI), Avon Foundation, and Susan G. Komen Cancer Foundation. It was the first scientific meeting of the folks involved in the Breast Cancer and Environmental Research Centers recently established and a report-back to the community of advocates.

In my opinion, the advocates raised most of the interesting questions. This is often the case. Some say we are naïve, and some of the questions were. So what? We ask things that no else seems to think about, we ask things from a perspective that is often ignored.

Thus our full participation in a meeting like this almost guarantees a new approach. Many of the advocates present were in fact graduates of the National Breast Cancer Coalition’s Project LEAD training program.

The first evening featured an advocate dinner with speakers. I was completely enthralled by Claudia S. Miller, MD (UT Health Science Ctr) who is not only a cancer survivor herself, but very aware of chemicals and sensitivities that may develop to them.

Her presentation was very exciting and informative. She has an interest in HRT and why only some women develop breast cancer after use. The leaders of each of the research centers spoke briefly to introduce themselves and their specific research agendas. Robert Hiatt, MD, Ph.D, (UCSF Comprehensive Cancer Ctr), spoke about cell biology and imaging of live tissue.

In cooperation with Kaiser Permanente they are part of a large study that will follow young girls six to eight years old.

Suzanne Snedecker, Ph.D. (Cornell University, Sprecher Inst for Comparative Cancer Research) spoke about the 42 chemicals already identified as breast cancer-related toxins.

Frank Biro, MD, (Principal Investigator, Project 2. U Cincinnati Children’s Hosp Med Ctr), spoke about their interest in obesity, energetics, dietary factors and mammary gland development.

And Sandra Haslam discussed progesterone and its actions, mentioning they were doing translational work (in rats and mice).

After opening remarks by Jose Russo, MD, FACP, opened the meeting with a moment of silence for those lost to breast cancer, still a KILLER disease. He talked about this meeting as the beginning of a journey of exploration that actually began thirty years ago for some researchers.

Leslie Reinlib, PhD (NIEHS), gave an introductory talk about the four Centers “designed to better understand how early environmental exposures influence female puberty and development of” mammary glands.

This will involve an exploration of the agents in the food, air and local areas. There will be collaboration among all Centers for a study of 1500 young girls from various ethnicities and religions across the country.

Genetic signatures and biomarkers will be examined to help understand the gene-environment interactions. There is a National Advisory Environmental Health Sciences Council Working group, which is made up of advocates, and scientists, which will provide guidance and constructive criticism to the Centers.

The first plenary session was about ‘Risk Communication’s, delivered by G.L. Kreps, George Mason University, Fairfax, VA. He told the audience that collaboration with the media is a necessity in getting information to the public.

From the CDC meeting on Cancer in 2003, I learned that most public health messages could take as long as forty years to get out properly. Hopefully the Internet and broader communication tools will/are changing this.

In fact Dr. Krebs did talk a bit about ‘targeted’ audiences.

The next presenter, C.B. Ambrose, Dept of Epidemiology, Roswell Park Cancer Institute, Buffalo, NY, gave the audience ‘An Epidemiological Perspective’. The main point was that better understanding of factors; genetic and environmental “that impact age at puberty and menarche” could be helpful in the prevention of breast cancer.

Daniel Medina, PhD, Dept of Molecular and Cellular Biology, College of Medicine, Houston, TX. gave a talk “Microenvironment and Breast Cancer”.

His abstract stated “Evaluation of risk factors over the past 50 years has definitely linked only radiation as a significant external risk factor for breast cancer. Other factors such as pesticides, industrial chemicals, pollution, etc., have not been implicated as risk factors.

Current data would suggest that dietary factors and lifestyle are the primary determinants of breast cancer. The contribution of specific dietary components is a subject of current scientific investigation.”

Ann’s NOTE: Many advocates, probably most, are absolutely persuaded that when scientists start looking in the ‘right’ places and in the ‘right’ ways, connections to pesticides, industrial chemicals, pollution, etc. will be FOUND. Currently it is very rare for more than one chemical ‘insult’ to be studied at a time.

Usually one application of one carcinogenic chemical is given to an animal. This is NO way compares to the human condition. Dr. Medina calls for study of specific dietary components. We suggest combinations of dietary components will be the best to study.

In some circles, it is stated that nutrition does not impact breast cancer. Who will pick up the ball?

Dr. Medina discussed the many studies on immigrants that point to environment as being more important than homeland. This casts implications on the gene theory of cancer causes. It relies on the fact that some countries, mostly Asian, have much lower cancer rates than the U.S.

When people emigrate, they are at lower risk. But over time, they and their children show increased risks of cancer. Is this dietary? Or are there substances in the air and water as well as the soil and food supply, that cause these changes of risk?

Researchers say this has yet to be determined.

He characterized protective factors as fiber, vegetables and fruits, intake of monosaturated fats (rather than hydrogenated, saturated or polyunsaturated), vit E and vit D. He ‘believes’ that estrogen and progesterone are protective if given for a short time.

In response to a question he stated that abortion or miscarriage do not confer increased risk nor do they offer a protective benefit.

Glen Talaska, PhD, University of Cincinnati School of Medicine discussed “How Carcinogens are Evaluated and Defined at an Agency Level”. From the abstract:

“Evidence is evaluated by a team of experts and a ‘web of causation’ is constructed that includes data from human epidemiological and animal experimental studies. The experts are drawn from backgrounds that include exposure assessment, toxicology, medicine, genetics and epidemiology.”

There are several international bodies looking at this area as well as U.S. based. He is involved with the international Agency for Research on Cancer (IARC) and the American Conference of Governmental Industrial Hygienists (ACGIH). Other groups include German MAC Commission, NIOSH/OSHA (US regulatory agencies), the National Toxicology Program, VSEPA and the California EPA.

IARC uses a risk assessment approach. Hazard is looked at as the main problem – with checking of dose/response, assessing population exposure, and characterizing risk is filtered through politics, business and the diverse views of many countries.

Working groups are formed that collect and provide critical reviews of the literature in draft reports. Subgroups prepare consensus drafts and at plenary meetings, a monograph is written which allows for minority reports. He did say, in response to question, that advocates are often involved.

I wanted to ask why it is accepted that new compounds can be used without proving safety? But then again, how long would anything need to be studied to determine this? I do not accept that genetically-modified/engineered foods are safe yet FDA and other regulatory agencies find no issues with them.

Charles Atkin, PhD, Dept of Communications, Michigan State University, spoke about the media and its coverage of medical/breast cancer stories. The most commonly discussed topic is treatment, then awareness, then risk, prevention, detection and prevalence.

Unsurprisingly the top story of 2004 is considered to be HRT related, followed by aspirin reducing/antibiotics increasing risk, genes and mammography issues.

Dr. Atkin felt that prevention was underrepresented. This topic might include weight loss/exercise, protective parental actions and collective policy iniatives.

He suggested there were very few comprehensive overviews or discussions. Lots of authoritative sources were used, researchers, physicians, medical or research centers, less often government agencies, foundations or corporations. Advocates are often contacted.

Ann’s NOTE: It is my experience that answers are often shaped by the media to fit the preconceived notions. A great example of this is when a new treatment is discussed. The interviewer often believes it is very important and tries to get an advocate to say that.

Many of us are less easily impressed the longer we watch how the system works. And almost everyone interviewed has complained that their statements were changed or abridged.

In response to Dr. Atkin’s statement on exercise, I asked whether cancer centers include exercise programs, or nutritional information in their usual offerings to patients. Naturally most do not.

Dr. Kami Silk, Dept of Communications, Michigan State University, spoke about “The Role of Health Literacy and Numeracy in Cancer Communications”. This talk pointed out that “Human beings process information within psychological and socio-cultural frameworks that assist them in assessing risks and decision-making.”

Luz Claudio, PhD, gave an excellent talk about how to motivate community involvement entitled “How to Communicate with the Underserved Population”. She works with the Community Outreach and Translation Core of the Mount Sinai School of Medicine Breast Cancer and the Environment Research Ctr. in New York City.

The Center she is connected with has placed advertising in the New York Times suggesting parents should try to feed their children organic foods. (I like that).

From the abstract: “The Community Outreach and Translation Core…aims to provide a vehicle for bi-directional communications between scientists conducting the research …and community members who participate in the study”. “Educational activities draw from the considerable wealth of knowledge already present in the community”. Claudio offered information as well as photos of actively involved children and parents.

In response to a question from me, she told the audience that exercise is part of the programs being offered, along with nutrition and much more.

Mary Wolff, PhD, Dept of Community and Preventive Medicine, Mount Sinai School of Medicine, spoke next. Her topic “Early Life Environment and Breast Cancer”. She discussed the different rates of breast cancer distinguished by ethnicity and age of puberty. She asked how environment fits into this picture? From the abstract: “Therefore, a combination of factors and likely a complex interaction of risks are responsible for breast cancer as well as timing of puberty”. “Strong environmental data support a role for environmental toxins in determining whether puberty will be early or late.

She mentioned that vitamin C appears protective in girls with high BMI. In response to a question from the audience, she suggested good things to eat would include fruits and vegetables. A new paper from Denmark seems to show that height, not age at menarche creates risk. (Algren et al 2004)

Frank Biro, MD, Cincinnati Children’s Hospital Medical Center, University of Cincinnati spoke about “Pathways through Puberty: Body Habitus as an Environmental Determinant of Health”.

He reported on the NHLBI Growth and Health Study, a multi-site study that recruited nine and ten year old girls, and followed them into early adulthood recording pubertal changes. From the abstract: “Mean onset of puberty was 10.2 and 9.6 years in white and black girls, respectively, and age at menarche was 12.6 and 12.0”.

“Girls who demonstrate breast development as the initial manifestation of puberty have earlier menarche, greater central adiposity, and greater bone density, all of which are epidemiological factors associated with breast cancer.”

And unfortunately few of these characteristics are under our control.

Lawrence Kushi, ScD, spoke on “Does What We Eat Make a Difference in Long-Term Breast Cancer Risk”? He is with the Division of Research, Kaiser Permanente in Oakland, CA.

The clues as to what we eat are international studies, epidemiological studies relating to food or nutrient intake and disease risk, prospective studies, and retrospective studies.

From the abstract: “Observations from these areas of research do suggest that if diet does influence breast cancer risk, the recommendations that may result would be consistent with dietary guidelines for prevention of other chronic diseases.

Ann’s NOTE: As I often ask at meetings, “why don’t we recommend healthy eating, ie the dietary guidelines mentioned above, RIGHT NOW? There is no down-side to eating fresh fruit/vegetables, low salt/sugar, whole grains, etc. And the answer usually is we are not sure, we have to study each element, it’s too soon to say, etc. I do not have to remind this audience that people are dealing with and dying of cancer every single day. Why wait to make changes within our grasp? The worst that happens is we reduce our risk of heart disease, diabetes, and high blood pressure!

The next presentation was by Coral Lamartiniere, PhD, Dept of Pharmacology and Toxicology, UAB Comprehensive Cancer Ctr, U of Alabama, Birmingham on “Timing of Exposure and How Environmental Chemicals Can Alter Susceptibility for Breast Cancer”.

From the abstract: “We are testing the hypothesis that timing of exposure to hormonally-active environmental chemicals can predetermine susceptibility for mammary cancer.” He talked about working with toxic compounds (endocrine disruptors) but using a green tea component (EGCG), resveratrol (from red wine) and genistein (from soy) to offset toxicity. Studies were in rats of course. He presented published evidence that genistein, given in the diet prepubertally, was protective against chemically-induced mammary cancers.

I wanted to ask what happened if the babies of rats exposed to the toxins were nursed by untreated females but did not get the chance.

The next talk was by Karam El-Bayoumi, PhD, of Hershey Medical Center, Penn State University on “Environmental Carcinogens That May Be Involved in Human Breast Cancer Etiology”.

El-Bayoumi published an early paper on breast cancer and the environment (1992). He suggested the following environmental ‘insults’ may be risk factors:

Gas and Diesel Exhaust

Carbon Black & Toner

Soil, Water, Food and Beverages

Indoor Exposures – household cleaners and other chemicals

Cigarette Smoke

From the audience came a suggestion to study rodent strains that are tumor-resistant.

Max Wicha, University of Michigan, Comprehensive Cancer Center, spoke on “Stem Cells in the Normal Human Breast and Breast Cancer”.

Embryonic stem cells can differentiate to all cells of any body, any tissue. Adult stem cells can become the tissue it came from, ie. liver stays liver tissue. Only stem cells can undergo full renewal and completely duplicate themselves.

From the abstract: “We have developed an in vitro culture system in which primary human epithelial cells isolated from reduction mammoplasties are cultured as “mammospheres” on non-adhererent surfaces. We have demonstrated that these mammospheres are highly enriched in undifferentiated cells capable of both self-renewal as well as differentiation to all three lineages of the mammary gland: myoepithelial cells, ductal epithelial cells, and alveolar epithelial cells. They also contain estrogen receptor positive proliferative progenitor cells.”

Only 1-2% of tumor cells are stem cells, and only 2 out of 10 are actually malignant. Tumor shrinkage doesn’t necessarily target stem cells. He thinks testicular cancer stem cells respond to chemotherapy and that is why this cancer responds so well. There is evidence that leukemia, multiple myeloma and brain cancers may also have stem cells

Thus we must find therapies that ‘kill’ the cancer stem cells without damaging other stem cells. He believes tumor regression is an inadequate endpoint.

Sandra Haslam, Dept of Physiology: Breast Cancer and the Environment Research Center, Michigan State University spoke on “Hormonal Regulation of Normal Mammary Gland Development”. She talked about progesterone as a “potent breast mitogen” and Her abstract stated that “recent epidemiological studies suggest that it plays an important although undefined role in breast cancer”.

Zena Werb, Dept of Anatomy, University of CA, San Francisco, spoke on “Epthelial-Stromal Interactions in Mammary Development and Neoplasia”.

From the abstract: “The extracellular matrix (ECM), stromal cells, and the inflammatory infiltrate all impact epithelial patterning and importantly, carcinogenesis” within the gland. Possible “links between breast and bone biology are just now becoming evident.”

The final planned speaker was Dr. Susan Love but she was unable to attend.

The meeting features some posters, some of which were presented by advocates.

Marin Breast Cancer Watch showed “Enhancing Community Involvement in the Research Process” which discussed ways to “foster ongoing cross communication and dialogue” among concerned parties.

The Breast Cancer Fund had “Campaign for Safe Cosmetics” which presented information in collaboration with Alliance for a Healthy Tomorrow, Commonweal, Environmental Working Group, Friends of the Earth, Healthcare without Harm, National Environmental Trust, and National Black Environmental Justice Network Women’s Voices for the Earth. This abstract discussed the “chemical ingredients linked to cancer and birth defects that are found in “brand-name personal care products –soap, shampoos, toothpaste and makeup.

It highlighted the lack of oversight by FDA “which allows the $35 billion cosmetics industry to use unlimited amounts of industrial chemicals in personal care products with no required testing , no monitoring of health effects, and without fully disclosing ingredients on the label.”

The Breast Cancer Fund had a second abstract entitled: “State of the Evidence 2004: What is the Connection Between the Environment and Breast Cancer?

Their conclusions:

“It is essential, based on existing scientific evidence, to initiate policy changes that will reduce exposure to toxic chemicals and radiation. At the same time, research into possible environmental causes of breast cancer must continue and expand, including studies on

Timing of exposures (period of vulnerability)

Multiple exposures

Chronic exposures (such as occupational exposures and second-hand smoke

Differences in exposures and disparities in health outcomes

“Building a Working Partnership” was presented by Breast Cancer Alliance of Greater Cincinnati, National Breast Cancer Coalition, Pink Ribbon Girls, Patterns, Inc. and the University of Cincinnati.

From the abstract: The benefits of community-based participatory research and collaborative education methods accrue to the community participants as well as the researchers and improves the research agenda. The acceptance of these methods in bio-medical research is demonstrated by the growing number of nIH-sponsored Requests for Applications (RFA) that require one of both of these as program areas.

It seemed to me that the advocates felt that more should be known by now. Our frustrations are that things always seem to be done in the same way. For the most part that involves one exposure of one chemical per lifetime in an animal. This in no way resembles real life.

Some start is being made on looking at things differently. Whenever anyone other than a researcher or someone who works in the chemical industry discusses environmental pollutions, there is agreement of its involvement in cancer.

However this consortium of environmental centers is wonderful and we welcome it.

Ann Fonfa received a scholarship to attend, from the Susan G. Komen Foundation.

Further update 6/29/07 At the time the above was written, Ann Fonfa was simply an (independent) advocate attending the meeting. Subsequently she was appointed to be an advocate within the grant for this project.

Here is a link to the Breast Cancer and Environmental Research Centers website – www.bcerc.org


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