Report on the New York Breast Cancer Study
The Ribbon

Jessica Mandell, MS
Genetic Counselor and Research Coordinator, New York Breast Cancer Study, Bronxville, NY

Women who inherit specific mutations in the BRCA1 and BRCA2 genes are predisposed in their lifetimes to develop breast and ovarian cancer, as well as other possible cancers. Some women with inherited mutations, however, do not develop any cancer. And for women with cancer, age at onset, disease progression and lifestyle factors vary widely, even in the same family.

The goal of the New York Breast Cancer Study is to help answer such questions surrounding inherited breast and ovarian cancer. This genetic and epidemiological project is designed and directed by two leaders in cancer genetics and genetic counseling: Mary-Claire King, PhD, American Cancer Society Professor and Laboratory Director in the Division of Medical Genetics at the University of Washington in Seattle, and Joan H. Marks, MS, Creator and Director Emerita of the Health Advocacy and the Human Genetics Masters Programs at Sarah Lawrence College in Bronxville, New York.

King and Marks united in the mid-1990s soon after the isolation of the BRCA1 and BRCA2 genes and at the rise of genetic counseling as a recognized service in cancer care. King and Marks amassed a team of medical specialists in the metropolitan New-York area and in 1996 began searching for the three most common BRCA1 and BRCA2 mutations in Jewish women and families with breast cancer and evaluating the lifestyle and social factors which may impact cancer development.

Today, the study has enrolled over 800 participants and has expanded to include 13 medical centers: Albert Einstein College of Medicine, Beth Israel Medical Center, Columbia Presbyterian Medical Center, Memorial Sloan-Kettering Cancer Center, New York University Medical Center and Strang Cancer Prevention Center in New York City; North Shore University Hospital on Long Island; White Plains Hospitals Center in White Plains, New York; Stamford Hospital/Bennett Center in Stamford, Connecticut; Hackensack University Medical Center in Hackensack, New Jersey; and three private oncology/radiology practices in New York City.

Integrating molecular genetics, genetic counseling and epidemiology, the investigators seek to identify genetic and environmental factors important in the control of breast or ovarian cancer and to apply what is learned from Jewish families in New York to the general population of individuals confronting the reality of breast and ovarian cancer in their lives.

The Genetic Mission

A primary goal of the New York Breast Cancer Study is to determine the actual (empiric) risk of breast cancer, ovarian cancer, or both, by age, among women who carry one of the three founder BRCA1 or BRCA2 mutations in the Jewish population. These mutations are 185delAG and 5382insC in the BRCA1 gene, and 6174delT in the BRCA2 gene.

To date, 650 women have joined the study, with more enrolling every day. Each collaborating medical center identifies eligible women from their patient population and invites them to participate. Eligible women must be Jewish, diagnosed with invasive breast cancer between 1994 and the present, and living in the New York area. Women do not need a family history of cancer to participate, limiting the bias of family history in the assessment of BRCA gene mutations.

Enrollment procedures are carefully designed. Women are first offered genetic counseling to assess their family and lifestyle histories and to review the benefits and limitations of genetic testing. Participants may either receive their test results or enroll anonymously and may withdraw at any time. Participation is free of charge, and test results are protected by a Certificate of Confidentiality from the National Institutes of Health.

Each participant signs an informed consent and provides a blood sample for genetic testing. Genotyping for the three founder BRCA mutations is carried out at the University of Washington. Results are returned through a post-test consultation with the genetic counselor and medical team at the participant's hospital, ensuring that each woman understands the implications of her results and receive appropriate medical follow-up.

Epidemiological Aims

Epidemiological goals of the study include identifying the differences in environmental risk factors between women with and without BRCA gene mutations who develop breast and/or ovarian cancer and women with mutations who remain cancer free. These comparisons may uncover environmental influences on breast/ovarian cancer that are preventable and thus may imply new routes towards fighting these diseases.

Toward these aims, all participants are asked to complete a specially designed questionnaire on their breast and ovarian health history, hormonal and reproductive history, social history, diet, exercise, smoking and alcohol use, and radiation, pesticide and related chemical exposures. For anonymous participants, questionnaires and blood samples are numbered so that test results can still be linked to environmental risk factors for epidemiological analysis.

Family Testing

When a participant is found to carry a BRCA mutation, the next phase of the study involves genetic counseling and testing for this family, with the goal of better understanding the inheritance and penetrance of these gene mutations and identifying other types of cancers that may be associated.

The first step is determining which side of the family the mutation originated and then inviting into the study those relatives who may be carriers. Relatives are contacted by a genetic counselor with the help of the original study participant, and may enroll no matter where they live or whether or not they have had cancer. Genetic counseling and blood sampling are coordinated in each relative's local area. Relatives complete the study questionnaire and may receive their test results or participate anonymously. Several hundred relatives have now enrolled in the study from across the United States and Canada, Israel, France, Sweden and England.

Longer Term Goals

Long term goals of the project include examining whether other mutations in the BRCA genes, or other genes all together, can explain the cancer histories in families that do not to carry a common BRCA mutation.

Another goal is to assess the impact of genetic counseling in the cancer predisposition testing process via a questionnaire on patients' perceptions of this experience and the influence of genetic test results on future cancer care choices.

Current graduate students of the Human Genetics Program at Sarah Lawrence College also serve as research assistants, gaining necessary training in cancer counseling as well as in developing and managing clinical genetics research.

Maintaining sensitivity to the needs of participants remains a consistent focus. An Advisory Board of cancer patients and professionals provides oversight to the study, in particular to issues of patient's rights.

Over the next year, the study will continue collecting invaluable research data for the medical community while at the same time benefiting women and families with cancer. With its carefully designed objectives, the inclusion of relatives in the project, and the comprehensive counseling and testing services offered to each individual, the New York Breast Cancer Study remains unique to research of its kind.

As Research Coordinator for the New York Breast Cancer Study, Jessica oversees the activities at all collaborating centers, counsels patients, and is the primary coordinator of family enrollment. Jessica also organizes the data on each participant and extracts DNA from all blood samples for genetic testing. For more information on inherited breast cancer or the New York Breast Cancer Study, please contact Jessica Mandell at (914) 395-2239.

References

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Ford, D.K. et al. Risks of cancer in BRCA1 mutation carriers. Lancet 343:692-695. 1994.

Friedman, E. et al. Double heterozygotes for the Ashkenazi founder mutations in BRCA1 and BRCA2 genes. Am J Hum Genet 4:1224-7. 1998.

Friedman, L.S. et al. Novel inherited mutations and variable expressivity of BRCA1 alleles, including the founder mutation in Ashkenazi Jewish families. Amer J Human Genet 57:1284-1297. 1995.

Hall, J.M. et al. Linkage of early-onset familial breast cancer to chromosome 17q21. Science 250:1684-1689. 1990.

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Levy-Lahad, E. et al. Founder BRCA1 and BRCA2 mutations in Ashkenazi Jews in Israel: frequency and differential penetrance in ovarian cancer and in breast-ovarian cancer families. Am J Hum Genet 5:1059-67. 1997.

Newman, B. et al. The Carolina Breast Cancer Study: Integrating population-based epidemiology and molecular biology. Breast Cancer Res Treat 35:51-60. 1995.

Roa, B.B. et al. Ashkenazi Jewish population frequencies for common mutations in BRCA1 and BRCA2. Nat Genet 2:185-7. 1996.

Schubert, E.L. et al. BRCA2 in American families with breast or ovarian cancer. Amer J Human Genet 60:1031-1040. 1997.

Struewing, J.P. et al. The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. New Engl J Med 336:1401-1408. 1997.

Tavtigian, S.V. et al. The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds. Nature Genet. 12:333-337. 1996.

Tonin, P. et al. Frequency of recurrent BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer families. Nat Med 2:1179-1183. 1996.

Wooster, R.et al. Identification of the breast cancer susceptibility gene BRCA2. Nature 378:789-792. 1995.

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Report on the New York Breast Cancer Study The Ribbon

Report on the New York Breast Cancer Study
The Ribbon