Long Island Breast Cancer Study Project 1995 Status Report

Status Report

October 18, 1995

The Long Island Breast Cancer Study Project (LIBCSP) was established to examine the role of selected environmental and occupational factors in the development of breast cancer. Potential risk factors under study, as mandated by Congress, include: contaminated drinking water, sources of indoor and ambient air pollution, pesticides, electromagnetic fields, hazardous and municipal waste, and other toxic chemicals. The LIBCSP research is supported and coordinated by the National Cancer Institute (NCI) in collaborations with the National Institute of Environmental Health Sciences (NIEHS).

The LIBCSP intends to stay on the cutting edge of breast cancer research by incorporating recent molecular and genetic findings wherever appropriate into the ongoing studies. Following are brief summaries of the research components that are underway:

• Columbia University has started a comprehensive, population-based case-control study of breast cancer among Long Island women. The approximately 4,000 study participants will be recruited over a one-year period, beginning in summer 1996. Dr. Marilie Gammon at Columbia University leads a collaborative team of investigators that includes a network of New York area cancer centers and Long Island Hospitals. Dr. Cristina Leske of the University Medical Center at Stony Brook is leading a companion project to study the effects of electromagnetic field (EMF) exposures on participants in the case-control study.
• In 1994, Dr. Steve Stellman of the American Health Foundation began his study of breast cancer risk in relation to accumulated levels of organochlorine pesticides in fatty tissue. In collaboration with the Long Island Jewish Hospital and the North Shore University Hospital, the researchers are collecting breast tumor tissue samples from women who undergo breast surgery, as well as fatty tissue from women having other surgeries. Over 100 breast cancer patients and 200 women without breast cancer have already been recruited. Intake of polycyclic aromatic hydrocarbons from foods will also be examined, as well as occupational exposures and exposure to electromagnetic fields. NCI has recently supplemented the original grant to allow more women to be studied and to study women in Schoharie County, New York, as mandated.
• A study on the feasibility of a Geographic Information System (GIS) for Long Island has been completed by Dr. Jerome Barancik of the Brookhaven National Laboratory. An inventory of over 400 data resources has been developed. Later this fall, a broad, competitive request for proposals will be issued to solicit design and implementation of the GIS. The environmental and other data in the GIS for Long Island will be linked to participants in the LIBCSP case-control studies according to residential histories and job locations.
• NCI and NIEHS are currently reviewing a number of research proposals to explore the use of GIS technology in environmental and cancer research. These projects should lead to a sharp focus on the value of visualization of data and the use of GIS as a research tool.
• Dr. Susan Harlap and colleagues at the Memorial Sloan-Kettering Institute for Cancer Research are conducting a pilot study of genetic differences in estrogen metabolism in women. Estrogen metabolite levels in women with breast cancer will be compared against those in a similar group without breast cancer.
• Dr. Michael Wigler of Cold Spring Harbor Laboratory is currently examining genetic changes in breast tumor tissue from patients on Long Island using a new technique called representational difference analysis. Certain point mutations in genes may be linked to environmental exposures, and certain mutations may be characteristic of specific environmental exposures.
• Dr. Eliot Rosen and colleagues of the Long Island Jewish Medical Center are evaluating how scatter factor (a growth factor) may regulate the growth of breast tumors. This study will look for biologic differences in tumors from breast cancer patients from Long Island as compared to Detroit and Los Angeles.
• Dr. Tony Zheng at Yale University is conducting a case-control study to examine organochlorine pesticide levels in breast fatty tissue and blood, and breast cancer risk in Connecticut. This project was supplemented to include Tolland County, as mandated, The research is ahead of schedule with nearly 200 women already enrolled.
• Dr. Dorothy Lane at the School of Medicine, SUNY at Stony Brook, is conducting a study entitled "Reducing the Barriers to the use of Breast Cancer Screening." This project is investigating if barriers to the use of mammography or delays in diagnosis are related to increased rates of breast cancer mortality in the Long Island area. Over 8,900 Long Island women have participated in a telephone survey about breast cancer screening, and a physician survey is underway.
• Dr. Rubie Senie at Memorial Sloan-Kettering Institute for Cancer Research will be establishing a multi-center registry of over 1,600 breast cancer families, with an emphasis on ethnic diversity of the participants. This will form part of an international cooperative registry developed by NCI to study susceptibility factors for breast cancer and the impact of environment and lifestyle.
• Columbia University, NYU Medical Center and the Albert Einstein College of Medicine have been awarded funds from NCI and NIEHS to support planning for research programs focusing on environmental factors in relation to breast cancer. These exploratory grants will allow these centers to develop new measures and techniques that may expedite the results from the LIBCSP.

Other aspects of the LIBCSP

• A LIBCSP Town Meeting held on March 13, 1995 at the Marriott Wind Watch in Hauppauge was well attended. Scientists participating in the LIBCSP gave presentations and the members of the audience and the press asked lively questions. Representatives of the Congressional Delegation from Long Island, the New York State Legislature, and local officials also attended.
• An ad hoc Advisory Committee to the LIBCSP has been established, which includes eminent epidemiologists, experts in GIS, and community representatives. The Advisory Committee met formally for the first time in March 1995. As needs arise, Advisory Committee members are consulted directly, and the community representatives on the Committee have met several times. The next meeting with the full Advisory Committee is being scheduled for early 1996. These meetings are open to the public and will likely be held approximately once a year or more frequently as needed.
• In keeping with the NCI promise to have community involvement in the LIBCSP, community representatives have participated as voting members on two peer review panels to date. In addition, NCI representatives, and LIBCSP scientists, have attended all meetings of the Long Island Breast Cancer Network.
• NCI's Surveillance, Epidemiology, and End Results Program (SEER) will report the results of reabstracting tumor registry cases to the Network later this fall. Dr. Mark Baptiste of the New York State Health Department and Dr. Maria Schymura, the recently appointed Director of the New York State Tumor Registry, will join Dr. Brenda Edwards of the NCI in presenting the results. At that time, the important role played by tumor registrars and the cooperation of individuals on Long Island in creating cancer maps will be acknowledged. As a result of expert assistance offered by NCI to the New York State Tumor Registry, and the recent award of a Centers for Disease Control and Prevention (CDC) grant, the registry procedures are rapidly improving in the State.
• NCI regrets the departure of Senior Science Writer Clarissa Wittenberg, who was a valuable liaison in the LIBCSP. Ms. Wittenberg has accepted the position of Director of Communications for the National Institute for Child Health and Human Development at NIH. NCI is currently seeking a replacement, and during this time we will ensure that essential communication will continue to be provided.

Annual Ad Hoc Advisory Committee Meeting Soon

The annual meeting of the Ad Hoc Advisory Committee to the Long Island Breast Cancer Study Project (LIBCSP) will be held Monday afternoon, September 22, through Wednesday noon, September 24, at the Wind Watch Marriott, Hauppauge, Long Island. Many of the investigators working on the LIBCSP are scheduled to give updates on their research. The annual meeting, which is open to the public, is always well attended. Last year, about 100 advisors, scientists, and community members came. To register, contact Shelia Lindsay, TASCON, Inc., 301-907-3844, ext. 247; fax: 301-907-9655- e-mail: slindsay@TASCON.com. Preregistration is important to ensure that enough information kits are available for everyone. An environmental working group will meet the morning of the first day of the annual meeting at the same hotel.

New Appointments to the Advisory Committee

Two new members were recently appointed to the Ad Hoc Advisory Committee to the LIBCSP: Mary B. Daly, MD, PhD, Director of the Family Risk Assessment Program, Fox Chase Cancer Center, Philadelphia, and Victoria White, a breast cancer educator, member of the New York State Women's Advisory Council, Vice President of the African American Health Education and Development Foundation, Chairperson of the Women of Color Coalition, and resident of Hempstead, Long Island. Sixteen scientists and community representatives serve on the committee as members or ex-officio members.

Columbia Case-Control Study Nears End of Recruitment Phase

Marilie Gammon, PhD, and colleagues at Columbia University are in the home stretch of enrolling participants in their landmark study of environmental pollutants and risk of breast cancer on Long Island. The study focuses on DDT, commonly used as a pesticide, and polycylic aromatic hydrocarbons (PAH), a ubiquitous pollutant caused by incomplete combustion of various chemicals including diesel fuel and cigarette smoke. All women in Nassau and Suffolk counties who were newly diagnosed with breast cancer during the one-year period that ended July 31, 1997 (cases) are eligible to participate. The study also includes a comparison group (controls) -- an equal number of women who do not have breast cancer and who were randomly selected from the general population of the same two Long Island counties.

For the next several months, the researchers will continue to contact and interview eligible cases and controls. Study participants are asked to complete an in-person interview and to provide a blood and urine sample. About 1,600 cases and 1,600 controls are expected to participate by the end of 1997. A random sample of participants who have resided in their homes for at least 15 years are also asked to permit collection of house dust, tap water, and yard soil samples (home study). About 340 cases and 345 controls will be selected for this component of the study.

The study has received $529,798 in additional funding from NCI for several supplementary projects that will enhance the study. First, a supplementary study will be conducted to evaluate the effect of breast cancer treatment on measurement of DDT and PAH in the blood samples. Second, the original study protocol includes laboratory analyses of blood and urine specimens from a random sample of study participants. However, the supplemental funding now provides for the analysis of all blood and urine samples donated by African-American participants. In addition, every African-American study participant who has resided in her home for at least 15 years will be asked to participate in the home study. Third, supplemental funds will be used to enhance the quality control testing for the laboratory analyses of the water samples. Last, the funding will cover additional expenses associated with the extensive and complex data collection process for this unique study.

The Long Island Breast Cancer Network, a coalition of breast cancer advocacy groups, has worked closely with the breast cancer researchers, providing input and support to the study. For example, when the researchers informed the Network about the difficulty in convincing women without breast cancer to participate in the interview, the member breast cancer organizations made great efforts to increase the visibility of the study, including sponsoring public service announcements in the media.

In preparation for the analyses of polychlorinated biphenyls (PCB) from dust in the home study as well as for application in other epidemiologic studies, the researchers have suggested a possible set of PCB functional groupings, based on existing literature and structure activity considerations (for example, whether the PCB congener is estrogenic, antiestrogenic, or immunotoxic). PCBs are organochlorine compounds. Mary Wolff, PhD, of Mount Sinai School of Medicine; David Camann, of Southwest Research Institute; Marilie Gammon, PhD, of Columbia University; and Steven Stellman, PhD, describe the groupings in "Proposed PCB Congener Groupings for Epidemiologic Studies," Environmental Health Perspectives, January 1997, vol. 105, no. 1, p. 13-14.

EMF and Breast Cancer Study "In The Field"

The field research phase for the Electromagnetic Fields (EMF) and Breast Cancer on Long Island Study is in progress under Cristina Leske, MD, MPH, of the State University of New York at Stony Brook. By measuring EMFs in the homes of women who are long-term residents of Long Island, Dr. Leske and her colleagues seek to determine whether a relationship exists between EMF exposure and breast cancer. Researchers are now interviewing eligible women about EMF exposure, and visiting their homes to take EMF measurements, including spot and 24- hour measurements, ground current measurement, and assessment of the external power lines. The study population is drawn from participants in the Columbia Case-Control Study who have lived in their current residences at least 15 years. About 600 women who have had breast cancer, and 600 women who have not had breast cancer are expected to participate. No published study to date has included actual measurements of EMF inside the homes of women who have breast cancer and healthy women. The National Institute of Environmental Health Sciences (NIEHS) provided $100,000 in additional funding, and $38,500 for purchase of 18 Emdex 11 meters for EMF measurement.

EMF result from the flow of electric current, and common sources include power lines, electrical wiring, and appliances. No clear relationship between EMF and breast cancer has been found, but researchers hypothesize that they may be linked to breast cancer through the hormone melatonin, which could affect estrogen production. According to the hypothesis, a decrease in melatonin production may result from EMF exposure and cause an increase in estrogen.

Request for Proposals for Geographic Information System Announced Soon

A Request for Proposals (RFP) for implementation of a geographic information system (GIS) to support the LIBCSP will be issued this fall. A GIS is a computerized database management system capable of storing, manipulating, displaying, and analyzing various types of data that can be referenced by geographic location. A prototype, health-related GIS (GIS-H) will be developed for use by researchers to investigate relationships between breast cancer and estimated exposures to environmental contamination on Long Island. The science of developing GISs to help study relationships between environmental factors and cancer is in its infancy, and poses many challenges. A technical team of experts has been assisting NCI to develop the RFP. In the process, NCI and its assembled team hosted public workshops on Long Island so that community members could learn about GIS, and to discuss questions about breast cancer that they would like researchers to be able to answer with the aid of the proposed system. Three workshop sessions were held over a two-day period last November in order to maximize opportunity for public participation, and between 60 and 70 community members attended. The technical team also met with Long Island researchers to discuss their needs. The contract for development of the GIS-H will be awarded in 1998. (Award date subsequently changed to 1999.)

Early Findings Suggest Estrogens Detected in Urine May Be Biomarkers for Breast Cancer

Long Island researchers reported in July that differences in the way women's bodies process the natural hormone estrogen may be related to breast cancer risk. Estrogen is metabolized by two main, competing pathways, either to 2-hydroxyestrone or to 16 hydroxyestrone. Preliminary studies have suggested that the balance between the estrogen metabolite 16 hydroxyestrone, which has been associated with breast cancer, and 2 hydroxyestrone, which has not, may affect risk for the disease. Geoffrey Kabat, PhD, of the State University of New York at Stony Brook, and Leon Bradlow, PhD, of Strang Cancer Research Laboratory, and colleagues, examined the ratio between the two metabolites in urine. They found that postmenopausal women with very low levels of the "good" metabolite relative to the "bad" metabolite had a greatly increased risk of breast cancer, compared to women with high levels of the "good" metabolite. The researchers say that because of the small number of study participants, further study is needed to confirm their findings. The research is reported in "Urinary Estrogen metabolites and Breast Cancer: A Case-Control Study," in the July issue of Cancer Epidemiology, Biomarkers & Prevention, vol. 6, no. 7, p. 505-509.

Laboratory Procedures Providing Accurate Measurements

Steven Stellman, PhD, of the American Health Foundation, reported at the annual meeting of the Society of Epidemiology in June the results of analyses of adipose tissue and blood for organochlorine pesticides and PCBs. He found that assays of either blood or adipose tissue can be useful measures of human body burden if risk estimates are adjusted for age and body mass. Dr. Stellman is principal investigator of a hospital-based, case-control study to investigate breast cancer risk in relation to levels of organochlorine compounds, such as PCBs, and chlorinated pesticides, such as DDT. Levels of these compounds are being analyzed in both adipose tissue and blood serum. The researchers collected breast tissue samples taken from 390 women who had breast cancer surgery and fatty tissue from 714 women who had other surgeries at Long Island Jewish Medical Center, New Hyde Park; North Shore University Hospital, Manhasset; and Bassett HealthCare, Inc., Cooperstown, New York. Bassett HealthCare, Inc., serves Schoharie County, an area included in the Congressional mandate for research on breast cancer risk on Long Island. Analysis of the data are now underway.

Breast and Ovarian Cancer Family Registry Welcomes Participants

The Metropolitan New York Registry for families with a history of breast or ovarian cancer is now recruiting families who have a history of either or both of these cancers. The participants are asked to contribute information, and blood and urine samples that can be used for studies on the causes of these diseases. The registry began enrolling participants in November 1996 and expects to recruit 1,600 families. Family members who have had these cancers as well as those who have not, are included, and both male and female family members are welcome. The availability of this ready resource of information and specimens will help speed research on the causes of these diseases, susceptibility to them, and the impact of environment and lifestyle on their development. The ultimate aim is to find avenues to prevent the cancers, and improve methods for early detection and treatment. The confidentiality of registry participants is assured; all data and specimens will have personal identifying information removed before qualified researchers are given access to them. The registry, which is directed by Ruby Senie, PhD, of Columbia University, is one of six NCI-fund breast and ovarian cancer family registries located in the United States, Canada, and Australia. Individuals interested in learning more about the Metropolitan New York Registry or enrolling may call 1-888-METRO-08.

Earlier this year, the registry received supplemental funding from NCI for a study of Ashkenazi Jewish family members who are enrolled in the registry and who wish to receive genetic counseling and testing for the presence of the BRCA1 and BRCA2 gene mutations. Studies have shown that mutations in BRCA1 and BRCA2 are associated with increased risk for breast and ovarian cancers. NCI is providing $671,975 over three years for this activity.

Exploratory Study Looks at Environmental Exposures, Residence, and Breast Cancer Risk

Ms. Erin O'Leary, now at the State University of New York at Stony Brook, is conducting a pilot investigation to determine whether length of residence in close proximity to hazardous waste sites, industrial sites, toxic release inventory sites, prior land use (for example, farm land), and exposure to various chemicals in the drinking water, may increase risk for breast cancer on Long Island. The study population was selected from a cohort of New York State residents in 1980 who had lived at least 18 years in their current residences and had completed a mail questionnaire. Within the cohort, 3,101 women from Long Island answered the questionnaire. From this Long Island group, Ms. O'Leary is now comparing data on about 100 women who had been diagnosed with breast cancer (cases) as of 1992, to data on 200 randomly selected Long Island women who had not had breast cancer (controls). Data on each woman's residence is being linked with data on environmental exposures to pesticides, solvents, PAHs, and metals. Prior land use for each address is also being assessed. This is being conducted under the direction of Jo Freudenheim, PhD, State University of New York at Buffalo, where Ms. O'Leary was previously located.

Tolland County, Connecticut, Study Enrollment Nears Completion

Enrollment is nearly completed for an exploratory case-control study of women in Tolland County, Connecticut, in which the relationship between exposure to organochlorine compounds and risk for breast cancer is being examined. For this study, Tongzhang Zheng, MD, ScD, of Yale University, and colleagues are enrolling a total of 150 women who have been diagnosed with breast cancer, and 150 women who have not had cancer. Each study participant is providing a blood sample for the organochlorine compound analyses, and answering a questionnaire about environmental exposures, medical and diet history, alcohol usage, smoking, and lifetime residences. The study recently received $70,995 in additional funding to support analyses of blood samples. The Congressional mandate for research on breast cancer risk on Long Island included study of Tolland County.

Breast Cancer Growth Factor May Provide Clues to Development of the Disease

Eliot Rosen, MD, PhD, of Long Island Jewish Medical Center, is evaluating how a growth factor called scatter factor may regulate the growth of breast cancer. He and his colleagues have found that levels of scatter factor are higher in invasive breast cancers than in non-invasive cancers. Further, they have found that scatter factor causes human breast cancer cells to move faster and to be more invasive in cell cultures. It induces the breast cells to produce an enzyme that degrades tissue, thus facilitating tumor invasion. It also stimulates the formation of new blood vessels, an essential step for tumor growth and spread. These findings were reported in "Scatter Factor Protein Levels in Human Breast Cancers," American Journal of Pathology, vol. 149, no. 5, November 1996, p. 1707-1712. Now, the researchers are comparing levels of scatter factor in breast cancer tissue taken from women who live on Long Island with those of women who live in other geographic areas.

Can Women Be Encouraged to Improve Their Breast Cancer Screening Practices?

Dorothy Lane, MD, MPH, of the State University of New York, is investigating whether a telephone counseling intervention aimed at women who are known to under use breast cancer screening can with, or without, an accompanying educational intervention for their physicians, increase use of breast cancer screening. In a first step of the study, Dr. Lane and colleagues surveyed more than 8,900 Long Island women, ages 50-80, by telephone about their use of breast cancer screening, and over 540 doctors by questionnaire. The researchers identified over 3,400 women who had not received mammograms in the past two years and the past two years prior to that. Fifty-three percent of the women who were under users of mammography were 65 years-of-age and older, and 47 percent of the under users were 50 to 64 years-of-age. (Forty-five percent of women in the 65 years-of-age and older age group under use mammography, and 34 percent of women in the 50 to 64 years-of-age group under use it.) The chief reasons given for not getting mammograms were procrastination and not believing a mammogram was needed — the latter reason given more frequently by women in the older age group. The researchers found that over 80 percent of the women who were under users of mammography had less than a college degree, the majority (58 percent) had family incomes of under $35,000, and most were homemakers or were retired. Dr. Lane and colleagues are now in the intervention phase of the study and are testing the effectiveness of telephone counseling and physician education. Over 1,100 women have been reached and counseled by telephone, and a second mailing of information and motivational materials is under way. The physician intervention component is also in progress.

New Statistical Methodology Suggests Elevated Breast Cancer Mortality in Parts of Northeast

Martin Kulldorff, PhD, of the National Cancer Institute, and colleagues have developed an innovative statistical technique that shows that women living in a broad stretch of the metropolitan northeastern United States, which includes Long Island, are slightly more likely to die from breast cancer than women in other parts of the Northeast. The study does not explain why these women are at higher risk of death, and the researchers note that the increase may be due to differences in well-established risk factors for breast cancer which they were unable to include in the analysis. The study is published in "Breast Cancer Clusters in the Northeast United States: A Geographic Analysis," in the July 15 issue of the American Journal of Epidemiology, vol. 146, no. 2, p. 161-170.

Environmental Exposure Working Group Formed, Review of Chemicals Underway

An environmental exposure working group has been formed to evaluate the exposure assessment methodologies in place in the LIBCSP, such as environmental sampling of water and soil, biological sampling for organochlorine pesticides and polyaromatic hydrocarbon exposure, and questionnaire assessment of occupation and environmental sources of carcinogens. The group is composed of scientists and a member of the Long Island community. It will meet at 9:30 a.m. the morning prior to the convening of the annual meeting of the Ad Hoc Advisory Committee to the LIBCSP on September 22, and at the same hotel.

In response to requests from Long Island community members for study of additional chemicals, the NCI asked the Environmental Protection Agency for assistance in evaluating the regulatory status and relevant testing results for these chemicals. EPA's Richard Hill, MD, PhD, science advisor, Office of Prevention, Pesticides and Toxic Substances, has been providing data on many of the chemicals. Other data are coming from the National Institute of Environmental Health Sciences' National Toxicology Program. Ruth Allen, PhD, of NCI/EPA, and Gwen Collman, PhD, of NIEHS, are collecting and organizing the information. Dr. Allen is in regular contact with community members on the progress, and in April, hosted a community workshop on Long Island with experts on environmental exposure assessment.

Separately, Dr. Gammon, of the Columbia Case-Control Study, and her staff conducted a review of the chemicals of interest, based on fewer data sources, and presented their results to concerned community members.

News Reports Published on LIBCSP

Newsday published a feature article about the LIBCSP that prominently featured the Columbia Case-Control Study and reported on its progress and that of the other Project studies. "Update: The Long Island Breast Cancer Study," by reporter Ridgley Ochs, appeared in the newspaper's December 10, 1996, issue.

Another article describing the detailed work and tools required "in the field" to collect environmental and laboratory samples during the home visits to the women who are participating in the Columbia Case-Control Study and the Electromagnetic Fields and Breast Cancer Study, appeared in "Details Seen as Critical to Long Island Study," in The Journal of the National Cancer Institute, December 4, 1996, vol. 88, no. 23, p. 1711-1713.

Community Liaisons Named to Studies

The community representatives on the Ad Hoc Advisory Committee to the LIBCSP recently assigned community liaisons to each of the research projects that make up the Project and to other NCI-funded studies that may be relevant to Long Island. The liaisons welcome the opportunity to establish relationships with the investigators and follow the progress of their research. The community representatives and members of the Long Island community believe that they can provide investigators unique perspective that could enhance their research. Ideally, they would like to be involved in the research process and serve as advisors. They have had advisory roles in the Columbia Case-Control and the EMF and Breast Cancer Studies, and have been helpful to investigators of some other studies. Linda Anderson, Director of Communications for the LIBCSP, NCI, has provided the community representatives and liaisons information about the studies to help them launch their liaison effort. A list of the liaisons and their project assignments is available on request.