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Clinical Utility of BRCA Testing. Mark Robson, MD September 7, 2012. Pharoah PD et al. N Engl J Med 2008;358:2796-2803. Risk Factors. Not modifiable Age Gender Age menarche Age menopause Histologic RF (eg ADH) Mammo density. Potentially modifiable Age FFTP Breast feeding Obesity
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Clinical Utility of BRCA Testing Mark Robson, MD September 7, 2012
Risk Factors • Not modifiable • Age • Gender • Age menarche • Age menopause • Histologic RF (eg ADH) • Mammo density • Potentially modifiable • Age FFTP • Breast feeding • Obesity • Alcohol • HRT • Radiation exposure
Importance of family history Pharoah et al, Int J Cancer 1997; 71: 800
Mechanisms of familial risk • Chance • Shared socio-cultural risk factors • Shared environmental exposures
* * * 92 Dx 45 d. 89 86 * * Dx 59 d. 62 Dx 72 73 68 71 * 36 Dx 36
Causes of Hereditary Breast Cancer • BRCA1 & BRCA2 • PTEN • TP53 • CDH1 • LKB1/STK11
BRCA1 and BRCA2 mutations in BCKurian et al, CEBP 2009;18:1084-91 Category A Category B Category A: BC <35, B/L BC with first before 50, prior OC, 1+ FDR with BC or OC
BRCA1 and BRCA2 mutations in OC Zhang et al, Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer. Gynecol Oncol 2011;121:353
NCCN Criteria for BRCA testing Personal History of BC No Personal History of BC Epithelial ovarian cancer Male BC Pancreas with 2+ relatives with breast, ovary, or pancreas cancer Unaffected with FDR or SDR meeting criteria • Dx ≤ 45 • Dx ≤ 50 with: • 1 or more relative with BC ≤ 50 or • 1 or more relative with OC • Bilateral with first ≤ 50 • TNBC ≤ 60 • Any age with 2+ relatives with breast or ovary any age • Any age with 2+ relatives with pancreas • Any age with relative with male BC • Any age if Ashkenazi
Impact on management of affected • Choice of local therapy • Choice of systemic therapy • Surgical prevention of second primaries
Risks to unaffected carriersChen & Parmigiani JCO 2007;25:1329 Breast Ovary
Diagnostic yield of surveillance strategies True positive diagnoses per 1000 screens Kuhl et al, J Clin Oncol 2010;28:1450
Risk-Reducing Salpingo-Oophorectomy • Peritoneal cancers may occur • Unexpected cancers in ~4% • Also ↓breast cancer risk • Survival benefit
Risk-Reducing Salpingo-Oophorectomy • Peritoneal cancers may occur • Unexpected cancers in ~4% • Also ↓breast cancer risk • Survival benefit