Clinical Utility of BRCA Testing
Mark Robson, MDSeptember 7, 2012
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Pharoah PD et al. N Engl J Med 2008;358:2796-2803.2
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
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Importance of family history
Pharoah et al, Int J Cancer 1997; 71: 800 4
Mechanisms of familial risk
• Chance
• Shared socio-cultural risk factors
• Shared environmental exposures
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Dx 45d. 89
92 86
73 68 Dx 59d. 62
Dx 72
Dx 36 36
71
* **
* *
*
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Causes of Hereditary Breast Cancer
• BRCA1 & BRCA2• PTEN• TP53• CDH1• LKB1/STK11
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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
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BRCA1 and BRCA2 mutations in OC
Zhang et al, Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselectedpatients with invasive ovarian cancer. Gynecol Oncol 2011;121:353
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NCCN Criteria for BRCA testing
Personal History of BC • 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
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
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Impact on management of affected
• Choice of local therapy
• Choice of systemic therapy
• Surgical prevention of second primaries
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Risks to unaffected carriersChen & Parmigiani JCO 2007;25:1329
Breast Ovary
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Management of breast cancer risk 14
Author N cancers/ N screened % detected by modality
MMG US MRI
Kriege 45/1909 40% 71%
Warner 22/236 36% 33% 77%
Kuhl 43/529 33% 39% 91%
Lehman 4/367 25% 100%
Leach 33/649 40% 77%
Lehman 6/171 33% 17% 100%
Sardanelli 18/278 59% 65% 94%
MRI surveillance in women at risk
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Diagnostic yield of surveillance strategies
Kuhl et al, J Clin Oncol 2010;28:1450
True positive diagnoses per 1000 screens
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Management of ovarian cancer risk 17
Risk-Reducing Salpingo-Oophorectomy
•Peritoneal cancers may occur
•Unexpected cancers in ~4%
•Also ↓ breast cancer risk
•Survival benefit
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Risk-Reducing Salpingo-Oophorectomy
•Peritoneal cancers may occur
•Unexpected cancers in ~4%
•Also ↓ breast cancer risk
•Survival benefit
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Impact of RRSO
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Potential impact of intervention
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Potential impact of intervention
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