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Who is at risk?
Susan Domchek, MD
Director, Basser Research Center
Risk/Benefit
• Breast cancer risk assessment models exist
– Gail model (first degree relatives with breast
cancer, reproductive factors)
– Claus model (family history of breast cancer)
– Tyrer-Cusick, BRCAPro, BOADICEA
– Significant limitations of these models
– Can be quite hard to use
– Poor discrimination
Risk/Benefit
• Better models are needed
–
–
–
–
Particularly for the “bad cancers”
Those <50
ER, PR, HER2 negative cancer
Can genetics help us?
• Those known to be at increased risks
– Individuals carrying mutations in key genes
• BRCA1, BRCA2, TP53, PTEN, CDH1, STK11
– Those with mantle radiation
– Very strong family history of breast cancer
Commercially available panels
• Now being marketed
• “Low penetrance” panels (SNP panels)
• Brevagen
• DeCode
• 23andme
• “Moderate penetrance” panels
• BreastNext (Ambrey Genetics)
• BROCA (University of Washington)
S
e arc
h E
form
search_bl
S earch
-5aP
ATM, BARD1, BRIP1, CDH1, CHEK2, MRE11A,
MUTYH, NBN, PALB2, PTEN, RAD50, RAD51C, STK11,
TP53
What about overdiagnosis?
• Several studies have suggested that 25-30% of
breast cancer are “overdiagnosed”
– Would never have caused harm
– We only hurt people
• Zackrisson et al, BMJ 2006; Esserman et al, JAMA 2009;
• Can we tell which ones these are?
– Maybe we are getting somewhat better
– Oncotype
The Recurrence Score® Reveals the Underlying Biology
16 CANCER RELATED GENES
Estrogen
Proliferation
HER2
Invasion
ER
PR
Bcl2
SCUBE2
Ki-67
STK15
Survivin
Cyclin B1
MYBL2
GRB7
HER2
Stromelysin 3
Cathepsin L2
GAPDH
RPLPO
Others
CD68
GSTM1
BAG1
5 REFERENCE GENES
Beta-actin
Paik et al. N Engl J Med. 2004;351:2817-2826.
GUS
TFRC
B20: proportion of patients
distant recurrence-free at 10 years
Population
Tam 10yr DRFS
Tam + Chemo
(95% CI)
10yr DRFS (95% CI)
All Patients
87.8%
92.2%
(651)
(83.3%, 92.3%)
(89.4%, 94.9%)
(N=227)
(N=424)
Low Risk (RS<18)
96.8% (93.7%, 99.9%)
95.6% (92.7%, 98.6%)
(N=353)
(N=135)
(N=218)
Int Risk (RS 18-30)
(N=134)
90.9% (82.5%, 99.4%)
89.1% (82.4%, 95.9%)
(N=45)
(N=89)
High Risk (RS>31)
60.5% (46.2%, 74.8%)
88.1% (82.0%, 94.2%)
(N=164)
(N=47)
(N=117)
Net Reduction
in Overall CT Recommendation
AFTER RS
BEFORE RS
CT + HT
HT
Total
CT + HT
271
41
312
HT
297
303
600
Total
568
344
912
Before RS testing, 62% of patients (568 of 912) were recommended adjuvant
CT+HT
After RS testing, 34% of patients (312 of 912) were recommended adjuvant
CT+HT  28% net reduction in CT
Hornberger J, et al. SABCS 2010. Poster P2-09-06.
What else is important?
• Need for chemotherapy
• Need for mastectomy