Screen-positive rates and agreement among six family history screening protocols for breast/ovarian cancer in a population-based cohort of 21- to 55-year-old women.
OBJECTIVE
Mutations in the BRCA1 and BRCA2 genes are responsible for approximately 2% of breast cancers by age 70 years. Professional and governmental groups recommend using family history protocols as an initial step in identifying women and families for mutation testing. We assess screen-positive rates and levels of agreement between these protocols.


METHODS
We applied six family history screening protocols to a population-based cohort of 321 women, age 21 to 55 years, who reported their personal and family history of breast and ovarian cancer.


RESULTS
The proportion of women and families identified as candidates for mutation testing ranged from 4.4% to 7.8%, depending on the protocol. The protocols had low or fair agreement (kappa <0.75 for 14 of 15 comparisons), but all identified six women (1.9%, 95% confidence interval 0.7%-4.0%) as screen positive. When the effect of missing ages of cancer onset was modeled, these rates increased (range 6.5%-11.5%), and nine women (2.8%) were screen positive by all protocols.


CONCLUSIONS
Given limitations of family history as a screening test for hereditary cancer related to BRCA1/2 mutations, 1% to 2% of women in the general population should initially be identified for mutation testing. One way to achieve this would be to require that multiple screening protocols agree.
Palomaki
Glenn E
GE
Foundation for Blood Research, Scarborough, ME, USA.
McClain
Monica R
MR
Steinort
Klaus
K
Sifri
Randa
R
LoPresti
Leigh
L
Haddow
James E
JE
D000328:Adult; D017668:Age of Onset; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005820:Genetic Testing / Q000379:methods*; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics*; D010375:Pedigree; D011159:Population Surveillance; D012307:Risk Factors; D014481:United States / Q000453:epidemiology