Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Hereditary Breast and Ovarian Cancer Syndrome

Syndrome

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Breast Neoplasms

Neoplastic Syndromes, Hereditary

Genetic Diseases, Inborn

Breast Diseases

Skin Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Blood Draw and Baseline Questionnaire: Participants will have their blood drawn for the study and complete a baseline questionnaire about their current cancer screening practices and concern regarding cancer.

Patients identified with a mutation in a gene not commonly tested for prior to the advent of multiplex panel testing. This excludes BRCA1, BRCA2, MLH1, MSH2, MSH6, PMS2, EPCAM, APC, MYH unless a patient tested positive for one of these 9 genes but did not meet clinical criteria for the underlying syndrome (n = 124). These participants will be asked to complete questionnaires for the duration of the study (up to 60 months after enrollment) at 3 months, 6 months, 12 months, 24 months, 36 months, 48 months, and 60 months.

Blood Draw and Baseline Questionnaire: Participants will have their blood drawn for the study and complete a baseline questionnaire about their current cancer screening practices and concern regarding cancer.

Patients identified with a variant of unknown significance of any gene of any nonBRCA (BRCA1 and BRCA2) or non-Lynch syndrome gene (MLH1, MSH2, MSH6, PMS2 and EPCAM).

Target accrual is 100. These participants will be asked to complete questionnaires for the duration of the study (up to 60 months after enrollment) at 3 months, 6 months, 12 months, 24 months, 36 months, 48 months, and 60 months.

Blood Draw and Baseline Questionnaire: Participants will have their blood drawn for the study and complete a baseline questionnaire about their current cancer screening practices and concern regarding cancer.

Patients who test negative for all the genes tested. Target goal is 50 for Stanford (100 for the study). These participants will be asked to complete questionnaires for the duration of the study (up to 60 months after enrollment) at 3 months, 6 months, 12 months, 24 months, 36 months, 48 months, and 60 months.

Blood Draw and Baseline Questionnaire: Participants will have their blood drawn for the study and complete a baseline questionnaire about their current cancer screening practices and concern regarding cancer.

All other participants who do not meet any of the above criteria or fall into one of these groups after the target goal is met for that group.

These participants will be asked to complete questionnaires for the duration of the study (up to 60 months after enrollment) at 3 months, 6 months, 12 months, 24 months, 36 months, 48 months, and 60 months.

Questionnaires

Participants will have their blood drawn for the study and complete a baseline questionnaire about their current cancer screening practices and concern regarding cancer.

Blood Draw and Baseline Questionnaire

Gregory Idos, MD

This study is about understanding the use of a genetic test (Myriad Genetics myRisk panel) that analyzes 25 genes related to different hereditary cancer conditions. The investigators hope to learn more about how this type of genetic test is used clinically. The investigators also hope to understand more about the experience of individuals and families who undergoing this test of genetic testing.

If a patient is identified as fulfilling one of the screening criteria, possible participants should be referred to the Cancer Genetics Clinic for further evaluation for possible enrollment into the study. A pre-clinic questionnaire will be sent to the patients prior to their assessment in cancer genetics clinic in order to obtain baseline information that will be used to inform changes during follow-up. Assessments performed exclusively to determine eligibility for this study will be done only after obtaining informed consent. Assessments performed for clinical indications (not exclusively to determine study eligibility) may be used for baseline values even if the studies were done before informed consent was obtained.

All screening procedures must be performed on the day of registration unless otherwise stated. The screening procedures include:

1. Medical history -Complete medical and surgical history, family history including a multi-generation family pedigree, and social history
2. Demographics - Age, gender, race, ethnicity
3. Review subject eligibility criteria
4. Physical exam including vital signs, height and weight
5. Blood draw for correlative studies
6. DNA from whole blood will be isolated

Intervention Procedure:

Approximately 15 ml of blood will be drawn at the time of enrollment (one time blood draw) and sent to Myriad Genetics and Laboratories for analysis of 25 genes using next generation sequencing. This platform will sequence 25 genes in one experimental run and the results will be sent back to the cancer genetics clinic for interpretation and disclosure.

Randomization of the patient Population:

After results are given to the patient they will be randomized into 4 groups:

* Patients identified with a mutation in a gene not commonly tested for prior to the advent of multiplex panel testing. This excludes BRCA1, BRCA2, MLH1, MSH2, MSH6, PMS2, EPCAM, APC, MYH unless a patient tested positive for one of these 9 genes but did not meet clinical criteria for the underlying syndrome (Stanford accrual goal is 62/USC 62)
* Patients identified with a variant of unknown significance (VUS) of any gene of any nonBRCA (BRCA1 and BRCA2) or non-Lynch syndrome gene (MLH1, MSH2, MSH6, PMS2 and EPCAM).

Stanford target accrual is 50 and 50 for USC.

* Patients who test negative for all the genes tested. Target goal is 50 for Stanford/50 for USC for the study.
* All other participants who do not meet any of the above criteria or fall into one of these groups after the target goal is met for that group. Only participants who are in the 1st three groups will be asked to complete questionnaires for the duration of the study (up to 60 months after enrollment)

Follow-up Procedures:

Patients (as noted above) will be followed at 3 months, 6 months, 12 months, 24 months, 36 months, 48 months, and 60 months

• At 3 months and 6 months after disclosure of genetic testing results, follow up questionnaires will ask if participants had initiated or intend to undergo any of the following risk reducing interventions and/or treatment: (i) Cancer surveillance/screening: breast MRI, mammograms, self-breast examinations, thyroid ultrasound, dermatology exams, urinalysis, upper endoscopy, colonoscopy, endometrial biopsy, transvaginal ultrasound, or other imaging (i.e. whole body rapid MRI) (ii) Chemoprevention/Behavior Modification: Tamoxifen, Oral Contraceptives (OCP), Raloxifene, Sulindac, Abstinence from Smoking (iii) Prophylactic procedures: Mastectomy, TAHBSO, polypectomy, total and segmental colectomy (iv) Cancer Treatment: aggregated pharmacologic and radiation therapy.

Cancer Genetics Hereditary Cancer Panel Testing

University of Southern California (USC) Norris Comprehensive Cancer Center and Stanford Cancer Institute Cancer Genetics Hereditary Cancer Panel Testing

Develop a resource (repository and database) with banked specimens, HCP panel results, pre-clinical and follow up information and impact of the HCP results

Summarize results of the HCP testing in terms of genes found with mutations and the frequency of mutation. The investigators will review expected versus actual off target or incidental findings from HCP testing. Off target findings will be classified into clinical actionable versus variants of uncertain significance (VUS). Incidence rates of off target mutations will be quantified and types of mutations will be qualitatively described.

Summarize the medical management of these subjects - prior to testing after results disclosure of testing, and over the subsequent 5 years. The investigators will descriptively report changes to medical management from pre-cancer risk assessment and HCP testing and post-cancer risk assessment and HCP testing. For each patient, the investigators will determine whether the HCP result leads to a change in recommendation in regards to the risk reducing interventions and treatment.

Perform descriptive analyses of information gained, in terms of reported patient experience and understanding of HCP testing. The investigators will measure the time it takes to reach a diagnosis with panel testing as compared to the sum of the average turnaround time (based on measurements supplied by Myriad Genetics) for sequential testing of single candidate genes. Bayesian models will be developed to measure the effect of an HCP actionable mutation result or an HCP VUS results on the final differential diagnosis of the patient. The Bayesian paradigm allows one to update the likelihood or probability of the event under consideration as more information becomes available.

In addition to the questionnaire that subjects will complete about their intent to undergo risk-reducing interventions (Specific Aim 5), subjects will also complete a questionnaire to measure concerns and psychosocial issues associated with genetic testing.

Spots Global Cancer Trial Database for blood draw and baseline questionnaire