Adjusting the estimated proportion of breast cancer cases associated with BRCA1 and BRCA2 mutations: public health implications.
OBJECTIVE
Mutations in BRCA1 or BRCA2 genes increase breast cancer risk. Assuring reliability of information about these mutations is increasingly important to the health care community; mutation testing is becoming more widespread. We describe a methodology for assessing such information.


METHODS
Our approach integrates four interdependent epidemiologic parameters: (1) the probability of developing breast cancer, (2) the proportion of breast cancer cases with a BRCA1 or BRCA2 mutation, (3) the proportion of women that carries a mutation, and (4) the proportion of women with a mutation that develops cancer. We assess the plausibility of estimates of these parameters from published reports and commonly accessed information sources.


RESULTS
Assuming a fixed probability of developing breast cancer, the following estimates for the other three epidemiologic parameters are derived for women by age 70: 1% to 2% of all breast cancer cases are associated with a BRCA1 or BRCA2 mutation; 1 in 300 to 1 in 465 women carry a mutation; and 35 to 65% of mutation carriers develop breast cancer. Within these ranges, however, only selected combinations are plausible. The proportion of mutation-related breast cancer is lower than listed in some common information sources (1 to 2% vs 6%). Also, penetrance is somewhat lower and the carrier rate somewhat higher.


CONCLUSIONS
The four epidemiologic parameters can be integrated to test their plausibility. BRCA1 and BRCA2 mutations are associated with only one-third as many breast cancer cases in the general population as reported by commonly accessed information sources.
McClain
Monica R
MR
Foundation for Blood Research, Scarborough, Maine, USA.
Palomaki
Glenn E
GE
Nathanson
Katherine L
KL
Haddow
James E
JE
D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D019683:Penetrance; D015995:Prevalence; D012307:Risk Factors
D019313:BRCA1 Protein; D024682:BRCA2 Protein; D009363:Neoplasm Proteins