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Breast Cancer Res Treat. 2011 Jan;125(1):169-73. doi: 10.1007/s10549-010-0923-y. Epub 2010 May 11.

No evidence of excess breast cancer risk among mutation-negative women from BRCA mutation-positive families.

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1
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

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00004007 NCT00045214.

PMID:
20458532
PMCID:
PMC3110729
DOI:
10.1007/s10549-010-0923-y
[Indexed for MEDLINE]
Free PMC Article
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