National Comprehensive Cancer Network

Philadelphia, Pennsylvania

Angela R. Bradbury, MD

800.325.4145 or 215.728.2795

Neal J. Meropol, MD

215.728.7041

Stuart R. Lessin, MD

215.214.1448

Veda N. Giri, MD

215.728.2406

Through the Community and Physician Awareness Program, Fox Chase makes primary care practitioners and members of the community aware of the genetic counseling and testing services and clinical trials available at Fox Chase-affiliated cancer programs in their communities.

Participants for the risk assessment programs are identified through their physicians, relatives, or are self-referred. All participants receive comprehensive education about their medical and personal risk factors for cancer, the role genetic factors play in cancer risk, cancer patterns in the family and the benefits and limitations of genetic testing, where appropriate. Participants also receive information about different screening options and other risk reduction measures based on their individualized risk.

The risk assessment programs hold pedigree review conferences to assign a cancer pattern and genetic risk status following a counseling session. The pedigree review team consists of a multidisciplinary group of health-care professionals. This includes medical oncologists, genetic counselors, nurses, health educators, and research coordinators. This system helps determine eligibility for genetic testing and/or other research opportunities based on the participant's family history via pedigree expansion and evaluation.

Eligibility for participation in genetic testing and related research projects is determined by careful analysis of the family pedigree and other personal risk factors.

All participants proceeding with genetic testing receive counseling regarding their genetic risk of cancer; the appropriateness of genetic testing; and the risks, benefits, and limitations of testing. Participants are also counseled on their eligibility for research or commercial genetic testing. Individualized cancer risk counseling is made available to each participant regardless of his or her eligibility or interest in genetic testing as part of a research protocol. (See description under "Research.")

Fox Chase uses a multi-staged process to obtain informed consent. Consent forms relate to specific research studies and cover any of the following: the collection of baseline data, family history data, or research-specific surveys (such as psychological surveys) and entering family history and other medical data into a research database. Consent forms may be sent by mail or obtained at the point of contact with participants.

At individualized counseling sessions, the goals and procedures of cancer risk counseling and/or research are fully discussed with a health professional trained in cancer risk assessment. Primary and secondary prevention is tailored to the individual level of risk. For individuals who proceed to genetic testing, the benefits, risks, and limitations of obtaining genetic information are discussed. Consent is obtained prior to having their blood drawn. A pre-test consent form is also obtained, allowing the counselor to disclose the patient's test results to a family member or friend in the event that the patient is not able to receive them due to death or severe trauma. The blood sample can either be sent to a commercial laboratory or to the genetic testing facility at Fox Chase Cancer Center, depending on the needs of the patient. If the participant is tested at Fox Chase, a second blood sample accompanied by a separate consent form is required for quality assurance.

During the disclosure session, the genetic test results, the implications of the results, and medical management recommendations are discussed with a genetic counselor and either a nurse practitioner or a physician. Another consent form allowing the risk assessment program to enter the patient's test results into their database is also offered at that time.

Participants eligible to take part in one of Fox Chase's cancer family registries or the Biosample Repository are given detailed information about the content of the data to be collected, potential uses of the data, safeguards to prevent unauthorized disclosure, and the kinds of information they will receive in feedback.

To preserve the privacy of participants, a series of security procedures have been implemented for stored data, DNA samples, and genetic test results. The database structure and data entry/retrieval interfaces have been made current and in compliance with HIPAA (Health Insurance Portability and Accountability Act of 1996) privacy regulations. Only numeric identifiers are stored with data, specimens, and study results. Hard-copy data collection instruments are in locked storage.

Participants receiving genetic results are counseled about security policies. Fox Chase will not share genetic test results with any party without consent. Patients are advised that Fox Chase cannot guarantee privacy once they have chosen to share results with another party.

All research protocols involving human subjects are reviewed and approved by the Fox Chase Cancer Center Institutional Review Board (IRB) prior to implementation.

Participants enrolling in any of the risk-assessment programs' research or clinical services receive for their review and signature Fox Chase's Notice of Privacy Practice document and the HIPAA authorization form for each protocol in which they are enrolled.

The risk-assessment programs at Fox Chase offer genetic counseling and testing for the following cancers or syndromes (cancers grouped together). Research testing may also be available. Fox Chase's genetic counselors inform participants if they are eligible.

Cancer/Syndrome Gene

Breast & Ovarian Cancer BRCA1 & BRCA2

Hereditary Non-Polyposis Colon Cancer MSH2, MLH1, MSH6,

PMS2 Familial Adenomatous Polyposis Colon Cancer APC

MYH-Associated Polyposis MYH

Hereditary Prostate Cancer BRCA1 & BRCA2, others

Hereditary Melanoma & Basal Cell Nevus Syndrome CDK4, CDKN2A,
CMM & P16

Li-Fraumeni Syndrome P53, CHEK2

Cowden's Syndrome PTEN

Hereditary Breast and Colorectal Cancer CHEK2

Peutz-Jeghers Syndrome STK11

Multiple Endocrine Neoplasia, Type I MEN1

Multiple Endocrine Neoplasia, Type II,
Medullary Thyroid Carcinoma RET

von Hippel-Lindau VHL

The Clinical Molecular Genetics Laboratory is a CAP/CLIA-certified molecular testing laboratory in the Department of Pathology at Fox Chase Cancer Center. Quality control and quality improvement programs are appropriate in design and practice for the rigors of federally overseen clinical sample testing and ensure the integrity, specificity, and sensitivity of testing data. Proper sample identification is maintained throughout pre-analytical, analytical, and post-analytical monitoring. Results are always correlated in the context of all the data available, i.e., personal and family history, any former testing data and current scientific literature review. Molecular genetic test reports are released/transmitted in a manner adequate to maintain patient confidentiality at a level appropriate for the particular test. Computerized records are backed-up daily by the institution.

The risk-assessment programs also provide a clinical component where participants receive individualized cancer risk assessment based on an individual's medical, environmental, and family history. Medical records and pathology reports may also be reviewed or requested.

For all those undergoing genetic testing, Fox Chase uses a multi-stage informed consent counseling process, which includes education, counseling, a pre-test session, and disclosure counseling session. During a cancer risk counseling session and a pre-test session, benefits, risks, and limitations related to genetic testing are reviewed by a genetic counselor. The counselor also helps to examine any anticipated psychosocial and emotional concerns that genetic testing may generate and addresses any impact genetic testing poses for a family.

If the participant opts to receive test results, a disclosure counseling session is scheduled. During this session, patients receive their genetic test results from a genetic counselor. A nurse practitioner or physician is also present to review medical management, screening recommendations and risk-reduction options. Any psychosocial and emotional impact of test results to patients and their families are addressed at this time. A plan may be developed to communicate results to family and medical professionals.

During the individual counseling session and/or follow-up clinic visits, screening, medical management, and risk-reduction issues are reviewed. Resources and referrals are provided as needed.

Individualized screening recommendations are offered based on personal, medical, and family history and clinical findings.

Participants receive an explanation of findings and consideration of options for chemoprevention, screening, and surveillance, and risk-reducing surgery, if appropriate.

All participants are provided with information regarding support services. For example, the book Ovarian Cancer Risk-Reducing Surgery-A Decision-Making Resource has been written to help women in the complex decisions surrounding elective ovary removal and is provided as part of the counseling process.

Participants have the option of receiving medical evaluation and follow-up for breast and/or ovarian cancer risk in the state-of-the-art Prevention Pavilion at Fox Chase Cancer Center. The clinical component includes a comprehensive cancer risk evaluation of personal and medical history along with a physical evaluation. Both the patient and her referring physician will receive information about medical management, screening recommendations, and eligibility for enrolling in current prevention trials. The medical evaluation is a service that is billed to the client's health insurance provider.

Some women with histologically identifiable breast biopsies, such as lobular carcinoma in situ (LCIS), atypical ductal hyperplasia (ADH), or atypical lobular hyperplasia (ALH), are at a higher relative risk of breast cancer. The risk may be further increased when there is a positive family history. The clinical component of the Margaret Dyson Family Risk Assessment Program provides patients the opportunity to meet clinicians with special training in breast diseases (consultant surgeon, breast physician). Preventive measures such as chemoprevention with tamoxifen, other drugs when their role in prevention has been established, or surgery are highlighted during these discussions.

The GI Tumor Risk Assessment Program brings together doctors, researchers, and other health-care professionals to educate patients and families about ways to reduce their cancer risk. GI-TRAP offers one-on-one and/or family-based risk counseling, genetic evaluation, and when appropriate physical examination. Recommendations are tailored on how to reduce the risk of cancer. In addition, opportunities for research participation are offered.

The Prostate Cancer Risk Assessment Program provides comprehensive evaluation of prostate cancer risk based on personal medical history along with a physical examination and prostate specific antigen (PSA) blood test. PRAP uses the percent-free PSA blood test for men with a total PSA of 1.5 ng/ml as part of its criteria for prostate biopsy. Current literature and PRAP data show that use of the percent-free PSA blood test to determine appropriateness of biopsy increases cancer detection and decreases unnecessary biopsies. Men with normal findings on examination and PSA blood test are screened on an annual basis; men with abnormal findings undergo further diagnostic studies (e.g. biopsy, endorectal MRI). The medical examination and the PSA blood test are services billed to the participant's health insurance provider.

The Melanoma Family Risk Assessment Program provides cancer risk assessment, cancer prevention, and early detection of melanoma and complements Fox Chase's state-of-the-art services of staging and treatment. Staff is dedicated to helping prevent melanoma and other forms of skin cancer.

A study is under way focusing on African American, Hispanic, and Asian women with breast cancer or a strong family history of breast/ovarian cancer to collect environmental, lifestyle, medical, and family history; and blood and tissue samples. The purpose of this research is to estimate the prevalence of BRCA1 and BRCA2 mutations in each of the racial/ethnic groups and to search for new genes and gene alterations that may prove to be associated with cancer development.

The purpose of the counseling research is to test communication strategies for providing genetic risk information, to prepare individuals for taking part in genetic testing research, and to evaluate the psychosocial and clinical impact of genetic risk information.

An interactive multimedia program using compact disc interactive (CD-i) technology has been developed for use with individuals in the Dyson program . It is designed to improve patient satisfaction with decision-making regarding genetic testing by improving comprehension of their personal cancer risk and improving knowledge regarding cancer genetic testing options.

Fox Chase has several chemoprevention clinical trials under way aimed at reversing pre-cancerous abnormalities.

The National Cancer Institute and the National Surgical Adjuvant Breast and Bowel Project have sponsored the Study of Tamoxifen and Raloxifene (STAR) for postmenopausal women at increased risk of breast cancer. While this study is closed to accrual and study results are published in JAMA, women enrolled continue to be followed as per protocol.

Genomic Markers of Breast Cancer Prevention Induced by HCG in Women at High Risk is a study that will measure the gene expression in breast epithelium obtained from asymptomatic, nulliparous, premenopausal high risk women at baseline, after treatment with self-injections of recombinant human chorionic gonadotropin (r-hCG) at 12 weeks and at 39 weeks from baseline. The breast epithelial cells are collected via fine needle aspirate. This trial will not only explore the physiological basis of breast cancer prevention and treatment, but will also establish novel biomarkers predictive of risk and prevention.

Final analysis is under way for this prospective study that compares a group of women who chose prophylactic oophorectomy to reduce risk of ovarian cancer with a control group. The groups were matched in age, race, education, marital status, and BRCA-gene mutation testing status. Findings show statistically significant short-term differences between groups, with the surgery group experiencing more hot flashes, night sweats, and cold sweats; decreased physical and social functioning; and decreased sexual activity, frequency, and pleasure. Given that the majority of women were premenopausal at the time of surgery, the abrupt drop in hormone levels after ovary removal accounts for the symptoms reported. This is a key area for clinical intervention that Fox Chase is addressing.

Breast Cancer Risk Registry: Fox Chase expanded its research base to include six of the 26 community hospitals within Fox Chase Cancer Center Partners.

Cooperative Family Registry for Breast Cancer Studies (CFRBCS): Fox Chase is one of six sites for this international registry.

Ovarian Cancer Consortium for Research and Surveillance (OCCRS): This is an ongoing collection of blood, tissue, and epidemiologic data from families with ovarian cancer, providing a rich resource for ongoing research into prevention, detection, and treatment of ovarian cancer.

Proteomic Validation Study: The goal of this multi-institutional study coordinated by the National Cancer Institute is to develop a protein fingerprint of ovarian cancer relapse as the next step in validating what may become an improved early detection test for women at risk for ovarian cancer.

The Benign Breast Registry to Assess Valid Endpoints (BeBrave) is collecting medical information and pathology samples from previous breast biopsies showing benign breast disease. The goals of this registry are to find new and better ways to predict which biopsy-proven benign findings need closer follow-up and to better distinguish who is at risk for getting breast cancer.

The Fox Chase Cancer Center Biosample Repository is dedicated to the collection and distribution of human subject biosamples and accompanying personal and family cancer history data. Patients and their family members at Fox Chase Cancer Center are introduced to the Biosample Repository and are invited to sign an informed consent. Willing participants are asked to contribute a blood sample and to complete family history, risk factor, and demographic questionnaires. Available biosamples are distributed by the repository for use in interdivisional advisory committee and IRB-approved research projects. In collaboration with the tumor bank facility, the Biosample Repository is able to match peripheral blood samples to tumor tissue. The repository has banked samples from more than 10,000 individuals. Specimens available include plasma, serum, red blood cells, viable leukocytes, and DNA.

The Gastrointestinal Tumor Risk Assessment Program Registry is collecting information from individuals at high risk of getting colorectal and other gastrointestinal cancers based on their personal and family medical history, as well as psychosocial indicators. Registry information and blood or tissue samples enable Fox Chase scientists to continue their work toward determining the causes of gastrointestinal cancer and prevention strategies.

The Prostate Cancer Risk Registry (PCRR) serves as a unique resource for further study of the interaction between environmental factors and genetic susceptibility patterns. It provides a mechanism for exploring the early, pre-malignant biologic markers of prostate cancer. It allows for the prospective assessment of quality of life in unaffected men, which has never been reported.

In addition, the PCRR facilitates the evaluation of the impact of prostate cancer risk counseling and decision models for prostate cancer screening in a community setting. The existence of a PCRR that represents a spectrum of racial and ethnic groups, specifically targets African American men, and is fully integrated into the mainstream of community health care is particularly relevant in light of the wealth of genetic information that will emerge from the intense efforts of the Human Genome Project over the next several years. The PCRR collects blood specimens and questionnaire data from men at risk for prostate cancer and men who have been diagnosed and treated for prostate cancer.

Communicating Genetic Test Results to the Family: This study, funded by the National Cancer Institute, is targeted to families in which a genetic alteration has been identified. First-degree relatives of individuals who have tested positive are given educational materials to help them better understand their genetic risk and make an informed decision about pursuing genetic counseling and/or testing.

Preference Shift & Spousal Utility for Cancer Treatments: This PRAP study was designed to evaluate differences in preferences between men participating in a prostate cancer-screening program and their spouses/partners, and evaluate shifts in men's preference when responses are elicited with input from the female spouse/partner. Using the Time Trade-off technique, partners were interviewed separately, then jointly, to determine their preferences and potential shifts in preferences for prostate cancer screening and treatment options. While active recruitment to this study has ended, the findings of this study, which are under analysis, will have relevance to outcomes research and will also have application to clinical decision-making.