Clinical Significance of Germline BRCA Mutations

Study Overview
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Brief Summary
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The goal of this study is to help us learn more about the roles of genes in cancers that run in families. Sometimes, we are born with genes that are changed or altered. Gene changes are called mutations. Mutations may be passed down from parent to child. Some mutations cause a high risk for cancer. There are two major genes for breast and ovarian cancer. These genes are called BRCA --for breast cancer. If you have a mutation in these genes special actions may be needed. For a person with a known mutation, we will suggest ways to screen for cancer or prevent it. Not everything is known about cancer genes and mutations. The cancer screening we suggest may not always be effective. The aim of this study is to explore these questions. If you agree we will stay in touch with you to follow your medical history. We will also ask you about your family. This will allow us to measure the cancer risks of known mutations. The study will also look for other cancer genes we do not know about. Whether or not you take part in this study, you may have gene testing. If you take part in this study and wish to know, we will tell your BRCA gene test results. Beginning in 2019, a subset of participants will be given a follow-up questionnaire regarding their health and well-being. The investigators may perform genetic testing on the blood or saliva sample in one of two ways: analysis for mutations in the BRCA1 and BRCA2 genes alone or as part of a panel of genes associated with breast cancer predisposition. New technologies are being employed for identification of patients with a susceptibility for developing breast cancer and thus analysis of multiple genes at one time may be offered to you. If this multi-gene testing applies to the patient, a question and answer sheet about this testing will be provided to them by their genetic counselor.

Official Title
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Clinical Significance of Germline BRCA Mutations

Conditions
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Breast Cancer, Ovarian Cancer

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Families referred for genetic counseling consultation at Memorial Hospital Individuals self-referred or physician referred for genetic counseling due to a concern about increased risk for breast cancer, regardless of family history or ethnic origin. Individuals enrolled in MSK protocol 97-029 Germline BRCA1 and BRCA2 mutations in Jewish Women Affected by Breast Cancer Individuals who present for genetic counseling consultation at Memorial Hospital after undergoing genetic testing at an outside institution. Member of a family with breast cancer who wishes to provide a DNA sample for research purposes Individuals enrolled on protocol 12-245 with germline variants in genes associated with risk for breast or ovarian cancer, or absent such variants in the presence of a family history or other phenotypic features of interest including but not limited to: triple negative breast cancer, early onset of disease, and/or synchronous or metachronous breast and ovarian cancer. Exclusion Criteria: -Patients will be excluded from this study if: he/she has physical, cognitive or psychiatric conditions that interfere with ability to give meaningful informed consent; he/she cannot read, write or communicate in English; he/she is less than 18 years of age.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To obtain DNA samples | for the purpose of estimating relative risk of BRCA1 ,BRCA2 and other gene mutations for breast cancer incidence in families with breast or ovarian cancer. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To obtain clinical and follow-up information on individuals being tested for BRCA mutations, in order to assess penetrance & phenotypic correlations of specific mutations, & to describe the outcome of medical or surgical interventions in heterozygotes. |  | 2 years | 
| To establish a confidential registry/repository containing data on specific mutations and genomic variants and clinical feature as well as DNA for future gene discovery. |  | 2 years |