Originally published as JCO Early Release 10.1200/JCO.2005.04.0345 on January 8 2007

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Ductal Carcinoma In Situ in BRCA Mutation Carriers

E. Shelley Hwang, Jane L. McLennan, Dan H. Moore, Beth B. Crawford, Laura J. Esserman, John L. Ziegler

From the University of California, San Francisco (UCSF) Cancer Risk Program and the Carol Franc Buck Breast Care Center, UCSF Comprehensive Cancer Center, San Francisco CA

Address reprint requests to E. Shelley Hwang, MD, MPH, University of California, San Francisco Cancer Center, 1600 Divisadero Ave, Box 1710, San Francisco, CA 94143-1710; e-mail: shelley.hwang{at}ucsfmedctr.org

PURPOSE: The current literature suggests that ductal carcinoma in situ (DCIS) of the breast is infrequently diagnosed in patients with BRCA germline mutations. We studied women at high risk of hereditary breast cancer syndromes who underwent testing for BRCA1 and BRCA2 to estimate DCIS prevalence and incidence in known BRCA-positive women compared with high-risk women who were mutation negative.

METHODS: We analyzed breast event outcomes in a retrospective cohort of 129 BRCA-positive and 269 BRCA-negative women undergoing genetic testing for a BRCA mutation between September 1996 and December 2003 at University of California, San Francisco. We estimated the frequency of DCIS and invasive cancer and time to breast events from birth using a Cox proportional hazard model for competing risks. Histologic grade of DCIS was also compared between groups.

RESULTS: Among BRCA carriers, 48 (37%) had DCIS (with or without invasive cancer) compared with 92 noncarriers (34%). Univariate analysis showed that both DCIS and invasive cancer had an earlier onset in mutation carriers than in noncarriers, although on a per-woman basis, this difference was not statistically significant. High-grade DCIS was more common in BRCA1 mutation carriers than in patients without a mutation (P = .02).

CONCLUSION: DCIS is equally as prevalent in patients who carry deleterious BRCA mutations as in high familial-risk women who are noncarriers, but occurs at an earlier age. Our results argue for the consideration of DCIS as a criterion for BRCA risk assessments with appropriate weighting in prediction models such as BRCAPRO.

published online ahead of print at www.jco.org on January 8, 2007.

Supported in part by a gift from the Avon Foundation, private donors, and a National Cancer Institute Comprehensive Cancer Center Support Grant (NCI/NIH Grant No. P30 CA82103).

Presented in part at the 27th Annual Meeting of Annual Breast Cancer Symposium, December 8-11, 2004, San Antonio, TX.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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