Hereditary Factors in Breast Cancer

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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 - PowerPoint PPT Presentation


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Hereditary Factors in Breast CancerJessica Ray, MS, CGCGenetic Counselor

1OBJECTIVES:Discuss who should consider genetic counseling and genetic testingDiscuss risks for cancers associated with BRCA1/2 mutationCancer Risk Reduction OptionsImportant Points of Genetic TestingCost of Genetic Testing and Insurance Issues

2Reasons for Seeking Genetics ConsultationTo learn aboutPersonal risk for cancerChildrens risk for cancerFamilys risk for cancerRisks for developing cancer if you have a cancer geneRecommendations for screening, surveillance, and/or treatmentEducational informationTo obtain genetic DNA testing

J Med Genet 2000; 37:866-874







9Key Flags that Warrant Genetic CounselingSignificant family medical history-breast, ovarian, prostate, colon, melanoma, pancreatic, or other cancers Cancer occurs in every generationEarly age of onset (< 50 years)Male breast cancerBilateral cancer, or multiple primary cancers in one individualKnown family genetic mutationEthnicity Ashkenazi Jewish ancestry10



13A BRCA Mutation Increases Risk of Second CancerJNCI 1999;15:1310-6JCO 1998;16:2417-25Lancet 1998;351:316-21JCO 2004;22:2328-35Lancet 1994;3343:692-50204060Ovarian CancerBreast Cancerafter 5 yrsBreast Cancer by age 70General PopulationBRCA Mutation16%Up to 11%Up to 27% Up to 11%Up to 64%Risk of Cancer (%)* no statistic available*

14Slide 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.

15Average Age of Diagnosis Hereditary Sporadic

Breast 41Prostate63Ovarian 40-50Breast62Prostate71Ovarian 6016RISK REDUCTION OPTIONSSurveillanceAlternate Mammogram and Breast MRI every 6 monthsCA-125 and Pelvic/Ovarian Ultrasound annuallyProphylactic SurgeriesProphylactic Bilateral/Unilateral Mastectomy = 90% reduction in breast cancer riskProphylactic Bilateral Oophorectomy = 96% reduction in ovarian cancer riskIf PBO performed pre-menopausally, also gives a 50% reduction in breast cancer riskChemopreventionTamoxifen, Raloxifene17When 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 conditionThe test can be adequately interpretedThe results will aid in diagnosis or influence the medical or surgical management of the patient or family members at hereditary risk of cancer

18ASCO 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 testingBRCA1 and BRCA2 testing is available only at Myriad Genetic LaboratoriesIn 2001, added 5 specific large rearrangements in BRCA1August 2006, new panel added to detect large rearrangement in both BRCA1 and BRCA2Cost of full sequencing of both BRCA1 and BRCA2 genes is $4,000, Cost of testing for a known family mutation is $47520GINA-Genetic Information Nondiscrimination ActProhibits use of an individuals genetic information in setting eligibility or premium or contribution amounts by group and individual insurersProhibits health insurers from requesting or requiring an individual to take a genetic testDoes not prohibit medical underwriting based on current health statusProhibits use of an individuals genetic information by employers in employment decisions such as hiring, firing, job assignments, and promotionsProhibits employers from requesting, requiring, or purchasing information about an individual employee or family member21Final Take Home MessageEvidence that many women overestimate their risk of developing breast cancerGenetic testing may provide accurate risk assessments for both breast and ovarian cancerNot 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 AZCC22