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Association between Breast Density and Subsequent Breast Cancer Following Treatment for Ductal Carcinoma In situ

Departments of ¹ Surgery, ² Medicine, and ³ Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California; ⁴ Group Health Center for Health Studies, Seattle, Washington; ⁵ Applied Research Program, DCCPS, National Cancer Institute, Bethesda, Maryland; and ⁶ Department of Pathology, University of Vermont, College of Medicine, Burlington, Vermont

Requests for reprints: E. Shelley Hwang, University of California, San Francisco Cancer Center, 1600 Divisadero Avenue, B606 San Francisco, CA 94115. Phone: 415-353-7908; Fax: 415-353-9571. E-mail: shelley.hwang{at}ucsfmedctr.org

Background: Risk of invasive cancer following treatment for ductal carcinoma in situ (DCIS) is associated with both treatment- and tumor-related factors. However, it is unknown whether stromal factors such as breast density may also influence subsequent invasive breast events. We investigated whether breast density is an independent predictor of subsequent breast events among women treated for DCIS.

Population: A prospective cohort study of 3,274 women ages 30 to 93 in the Breast Cancer Surveillance Consortium treated with lumpectomy for DCIS between 1993 and 2005. All subjects had an American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) breast density measure recorded prior to diagnosis.

Methods: Ipsilateral and contralateral breast cancer following lumpectomy for DCIS were ascertained through state tumor registries, regional Surveillance Epidemiology and End Results program or pathology databases. A Cox proportional hazard model was used to compare adjusted risk of breast cancer among women with high (BI-RADS 3 or 4) versus low (BI-RADS 1 or 2) breast density.

Results: During a median follow-up period of 39 months (0-132 months), 133 women developed invasive breast cancer. After adjusting for age and radiation treatment, high breast density was associated with increased hazard for contralateral (hazard ratio, 3.1; 95% confidence interval, 1.6-6.1) but not ipsilateral (hazard ratio, 1.0; 95% confidence interval, 0.6-1.6) invasive breast events.

Conclusion: High breast density is associated with contralateral, but not ipsilateral, invasive breast cancer following lumpectomy for DCIS. Thus, women with DCIS and high breast density may especially benefit from antiestrogenic therapy to reduce the risk of contralateral invasive disease. (Cancer Epidemiol Biomarkers Prev 2007;16(12):2587–93)