title: No evidence of excess breast cancer risk among mutation-negative women from BRCA mutation-positive families.
abstract: This analysis addresses risk of breast cancer among women in BRCA-positive families who test negative for the family mutation. We compared the number of prospectively diagnosed breast cancers in 395 mutation-negative women from 28 BRCA1/2-positive families to an age-, race-, and calendar time-specific expected number of breast cancers derived from the SEER 9 Cancer Registry. Study participants contributed a total of 7008.1 person-years of follow-up. The mean age at study entry was 31.3 years; mean follow-up was 17.7 years. Ten women developed breast cancer yielding an observed-to-expected ratio of 0.82 (95% CI 0.39-1.51). Adjustment for possible reduction in breast cancer risk due to oophorectomy by two different methods resulted in O/E ratios in the range of 0.80-0.99. Stratification by degree of relatedness to the nearest mutation carrier did not substantially alter these results, however, women with at least one-first degree relative with breast cancer appeared to have a slightly increased, though not statistically significant, risk of breast cancer (O/E ratio = 1.33, 95% CI 0.41-2.91). Our data suggest that breast cancer risk among mutation-negative women from BRCA1/2 mutation-positive families is similar to that observed in the general population, with a possible slight increase in risk among mutation-negative women with a family history of breast cancer in a first degree relative. Although this is the largest prospective cohort yet assembled to address this important question, the number of breast cancer events is still relatively small.
authors.affiliation: Division of Medical Oncology, University of Washington/Seattle Cancer Care Alliance, 825 Eastlake Ave, E., G3-630, Seattle, WA 98109, USA. Lkorde@u.washington.edu
authors.forename: Larissa A
authors.initials: LA
authors.lastname: Korde
authors.forename: Christine M
authors.initials: CM
authors.lastname: Mueller
authors.forename: Jennifer T
authors.initials: JT
authors.lastname: Loud
authors.forename: Jeffery P
authors.initials: JP
authors.lastname: Struewing
authors.forename: Kathy
authors.initials: K
authors.lastname: Nichols
authors.forename: Mark H
authors.initials: MH
authors.lastname: Greene
authors.forename: Phuong L
authors.initials: PL
authors.lastname: Mai
mesh_terms: D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000517:prevention & control; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D010052:Ovariectomy; D010375:Pedigree; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D018426:SEER Program; D013997:Time Factors; D014481:United States
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human
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