Hereditary Factors in Breast Cancer Jessica Ray, MS, CGC Genetic Counselor

OBJECTIVES: Discuss who should consider genetic counseling and genetic testing Discuss risks for cancers associated with BRCA1/2 mutation Cancer Risk Reduction Options Important Points of Genetic Testing Cost of Genetic Testing and Insurance Issues

Reasons for Seeking Genetics Consultation To learn about Personal risk for cancer Children’s risk for cancer Family’s risk for cancer Risks for developing cancer if you have a “cancer gene” Recommendations for screening, surveillance, and/or treatment Educational information To obtain genetic DNA testing J Med Genet 2000; 37:866-874

Key Flags that Warrant Genetic Counseling Significant family medical history-breast, ovarian, prostate, colon, melanoma, pancreatic, or other cancers Cancer occurs in every generation Early age of onset (< 50 years) Male breast cancer Bilateral cancer, or multiple primary cancers in one individual Known family genetic mutation Ethnicity – Ashkenazi Jewish ancestry

A BRCA Mutation Increases Risk of Second Cancer Up to 64% General Population 60 BRCA Mutation Up to 27% 40 Risk of Cancer (%) Up to 11% 20 16% Up to 11% * Slide 8 : A BRCA Mutation Increases the Risk of a Second Cancer Women who have developed breast cancer are at greatly increased risk of a second cancer if they carry a mutation in BRCA1 or BRCA2. Their risk of developing ovarian cancer is 10 times higher than women with early-onset breast cancer who do not have mutations, 1 or at least 16% in their lifetime.2 There are no current statistics for the general population. In addition, mutations in these genes greatly increase the risk of a second breast cancer.3-5 The risk of a contralateral breast cancer is increased up to 64% by age 70, 3 or 27.1% within five years of the initial diagnosis5 in women with BRCA1 mutations. Mutations in BRCA2 increase these risks to about 50% by age 70,4 or 23.5% within five years of the first breast cancer. 5 References: 1. Frank TS, Manley SA, Olopade OI, et al. Sequence analysis of BRCA1 and BRCA2: correlation of mutations with family history and ovarian cancer risk. JCO 1998;16:2417-2425. 2. The Breast Cancer Linkage Consortium. Cancer Risks in BRCA2 Mutation Carriers. JNCI 1999;15:1310-1316. 3 Ford D, Easton DF, Bishop DT, Narod SA, Goldgar DE, Breast Cancer Linkage Consortium. Risks of cancer in BRCA1-mutation carriers. Lancet 1994;343:692-695. 4. Verhoog LC, Brekelmans CTM, Seynaeve C, et al. Survival and tumour characteristics of breast-cancer patients with germline mutations of BRCA1. Lancet 1998;351:316-321. 5. Metcalfe K, Lynch HT, Ghadirian P, et al. Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. JCO 2004;22:2328-2335. Ovarian Cancer Breast Cancer Breast Cancer by after 5 yrs age 70 * no statistic available JNCI 1999;15:1310-6 JCO 1998;16:2417-25 Lancet 1998;351:316-21 JCO 2004;22:2328-35 Lancet 1994;3343:692-5

Average Age of Diagnosis Hereditary Sporadic Breast 62 Prostate 71 Ovarian 60 Breast 41 Prostate 63 Ovarian 40-50

RISK REDUCTION OPTIONS Surveillance Alternate Mammogram and Breast MRI every 6 months CA-125 and Pelvic/Ovarian Ultrasound annually Prophylactic Surgeries Prophylactic Bilateral/Unilateral Mastectomy = 90% reduction in breast cancer risk Prophylactic Bilateral Oophorectomy = 96% reduction in ovarian cancer risk If PBO performed pre-menopausally, also gives a 50% reduction in breast cancer risk Chemoprevention Tamoxifen, Raloxifene

When Do You Offer Testing? American Society of Clinical Oncology recommends offering genetic testing when: The individual has a personal or family history of features suggestive of a genetic cancer susceptibility condition The test can be adequately interpreted The results will aid in diagnosis or influence the medical or surgical management of the patient or family members at hereditary risk of cancer

ASCO recommends genetic testing only in the setting of pre- and post-test counseling, which should includes discussion of possible risks and benefits of cancer early detection and prevention modalities

Commercial BRCA testing BRCA1 and BRCA2 testing is available only at Myriad Genetic Laboratories In 2001, added 5 specific large rearrangements in BRCA1 August 2006, new panel added to detect large rearrangement in both BRCA1 and BRCA2 Cost of full sequencing of both BRCA1 and BRCA2 genes is $4,000, Cost of testing for a known family mutation is $475

GINA-Genetic Information Nondiscrimination Act Prohibits use of an individual’s genetic information in setting eligibility or premium or contribution amounts by group and individual insurers Prohibits health insurers from requesting or requiring an individual to take a genetic test Does not prohibit medical underwriting based on current health status Prohibits use of an individual’s genetic information by employers in employment decisions such as hiring, firing, job assignments, and promotions Prohibits employers from requesting, requiring, or purchasing information about an individual employee or family member

Final Take Home Message Evidence that many women overestimate their risk of developing breast cancer Genetic testing may provide accurate risk assessments for both breast and ovarian cancer Not everyone found to have a BRCA1/2 mutation will develop cancer! Negative genetic test result DOES NOT mean No Increased Risk!! What do we offer women at high risk for breast and ovarian cancer who test negative commercially for a BRCA1/2 mutation? HIGH RISK BREAST CANCER CLINIC AT AZCC