The Importance of Iden0fying Women at Risk for BRCA1/2 Muta0ons for Referral to Cancer Gene0cs Services

Transcription

1 The Importance of Iden0fying Women at Risk for BRCA1/2 Muta0ons for Referral to Cancer Gene0cs Services Cecelia Bellcross, PhD, MS, CGC Emory University School of Medicine Department of Human Gene0cs Alliance Webinar 11/21/14

2 Breast Cancer Genomics Familial:15-20% Hereditary: 5-10% Sporadic: 70-75%

3 Hereditary Breast and Ovarian Cancer Syndrome (HBOC) Inherited muta0ons in the BRCA1 or BRCA2 genes account for: ~3-5% of all breast cancers ~15 + % of all ovarian cancers (fallopian tube, primary peritoneal) Prostate Ca age 58 Ov Ca age 52 Br Ca age 46 Br Ca age 48 Bilat Br Ca ages 33, 38 Br Ca age 40 Br Ca age 31 Br Ca age 35

4 Red Flags for BRCA1/2 Muta0ons Ø Early onset breast cancer (< age 50) Ø Ovarian* cancer Ø Triple nega0ve breast cancers (ER/PR/Her2) Ø Mul0ple cases of breast and/or ovarian cancer in the same family Ø Breast and ovarian* cancer in the same woman Ø Bilateral breast cancer (at least one < age 50) Ø Male breast cancer Ø Ashkenazi Jewish heritage *Fallopian tube/primary peritoneal

5 Prevalence of BRCA1/2 Muta0ons Percent BRCA1 BRCA2 Gen Pop Jewish Dx any age Jewish Dx < 45 Fam Hist Br Ca Fam Hist Ov Ca General Population Women with Breast Cancer

6 BRCA1/2- Associated Cancers: Life0me Risks breast cancer (50% 85%) 2nd breast cancer (40-60%) ovarian cancer (BRCA1:20-45%) (BRCA2:10-20%) male breast cancer (5-10%) Risks for other cancers also appear to be increased 2-5 fold: pancrea0c, melanoma, prostate < 65

7 Management Options for BRCA1/2 Mutation Carriers Ø Early clinical surveillance (begin by age 25) annual or semi annual: Ø clinical breast exam, mammogram, breast MRI Ø CA125, transvaginal ultrasound (uncertain efficacy) Ø Chemopreven0on Ø tamoxifen Ø oral contracep0ves

8 Breast MRI vs. Mammogram in High Risk Women Kriege-04 Warner-04 MARIBS-05 BRCA 1/2 carriers* MRI Mammo *Warner, JCO 2011

9 Management Op0ons for BRCA1/2 Muta0on Carriers Ø Prophylac0c mastectomy 90%+ reduc0on in breast cancer risk Ø Prophylac0c bilateral salpingoophorectomy Ø 80-96% reduc0on in ovarian/fallopian tube cancer risk Ø 50%+ reduc0on in breast cancer risk Ø Reduc0on in all cause and breast & ovarian cancer- specific mortality (Domcheck, JAMA, 2010)

10 Impact of Genetic Test Results Breast, dx 45 Bonnie: Risk for second breast cancer Risk for ovarian cancer Breast, dx 54 d. 62 Bonnie Breast, dx 42 BRCA1 muta-on 36 Sara Sara: Nega-ve for BRCA1 muta-on found in sister No increased risk for breast or ovarian cancer beyond anyone in the general population. = True Nega*ve

11 Cancer Gene0c Counseling Ø Collect and review detailed personal and family cancer histories Ø Assess likelihood for a hereditary cancer syndrome and cancer risk probabili0es Ø Determine appropriateness of gene0c tes0ng, who best to test, and which test to order Ø Educate pa0ent about cancer gene0cs, personal risks, pros/cons/limita0ons of gene0c tes0ng including possible test results

12 Cancer Gene0c Counseling- cont. Ø Address pa0ent s risk percep0ons and psychosocial concerns Ø Review op0ons of screening, management, risk reduc0on Ø Coordinate tes0ng and insurance coverage Ø Post- test disclosure session Ø implica0ons of test results for pa0ent/family Ø management plan based on result Ø addi0onal tes0ng needed/available Ø psychosocial adjustment to results/implica0ons

13 United States Preven0ve Services Task Force (USPSTF) 2005 Recommenda0on Ø.women whose family history is associated with an increased risk for deleterious muta0ons in the BRCA1 or BRCA2 genes [should] be referred for gene0c counseling and evalua0on for BRCA tes0ng. Healthy People 2020 Genomics Objec0ve Ø Increase the propor0on of women with a family history of breast and/or ovarian cancer who receive gene0c counseling

14 Ø Standard 2.3: Risk Assessment and Gene0c Counseling Ø All programs are required to provide cancer risk assessment as well as gene0c counseling and tes0ng, on- site or by referral, by a qualified gene0cs professional [who has] Ø extensive experience and educa0onal background in gene0cs, cancer gene0cs, counseling, and hereditary cancer syndromes to provide risk assessment and empathe0c gene0c counseling to pa0ents with cancer and their families

15 2013 USPSTF Recommenda0on The USPSTF recommends that primary care providers screen women who have family members with breast, ovarian, tubal, or peritoneal cancer with 1 of several screening tools designed to iden0fy a family history that may be associated with an increased risk for poten0ally harmful muta0ons in breast cancer suscep0bility genes (BRCA1 or BRCA2). Women with posi0ve screening results should receive gene0c counseling and, if indicated a:er counseling, BRCA tes0ng. (B recommenda*on)

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17 B- RST Valida0on Measure BD BR MII FH Overall* Sensi*vity % Specificity % AUC (95% CI) 0.88 ( ) 0.87 ( ) 0.87 ( ) 0.90 ( ) 0.90 ( ) *High- risk by at least one of the models = actual posi0ve state BD = BOADICEA Model; BR = BRCAPRO Model; MII = Myriad II Tables; FH = Family History Assessment Tool, AUC = Area under the curve Bellcross et al. Genet Med. 2009;11:783 Bellcross et al. Genet Med. 2010;12:240

18 Public Health Implica0ons Approximately 1/400 individuals carry a muta0on in BRCA1/2 (1/40 individuals of Jewish descent) This implies ~ 800,000 plus BRCA1/2 muta0on carriers in the US the majority of which have not been iden0fied Iden0fica0on of an individual with a BRCA1/2 muta0on allows for live saving interven0ons which reduce morbidity and mortality associated with early onset breast cancer and ovarian cancer For each BRCA1/2 muta0on carrier iden0fied, mul0ple family members are at risk and can benefit from the knowledge of their muta0on status