Lower-Category Benign Breast Disease and the Risk of Invasive Breast Cancer

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Abstract
Background: The risk of invasive breast cancer associated with benign breast disease (BBD) other than atypical hyperplasia and in situ breast cancer, especially with nonproliferative diagnosis, has not been explored extensively. This report evaluates the risk of breast cancer associated with this lower-category BBD (LC-BBD). Methods: 11 307 women without prior history of atypical hyperplasia or in situ breast cancer at randomization (1992–1997) were identified from the cohort of the National Surgical Adjuvant Breast and Bowel Project’s Breast Cancer Prevention Trial. Pathologic findings from breast biopsy reports through August 2002 were reviewed, and Cox proportional hazards models were used to determine the relative risks (RRs) of breast cancer with 95% confidence intervals (CIs). The relative risks of breast cancer for LC-BBD were adjusted for treatment and for breast cancer risk as determined by the modified Gail model. Results: Of the 11 307 women, 1376 had LC-BBD, of whom 47 developed breast cancer, and of the 9931 women without LC-BBD, 291 developed breast cancer. The RR of breast cancer for women with LC-BBD relative to women without LC-BBD was 1.60 (95% CI = 1.17 to 2.19). Among women 50 years of age and older, the RR of breast cancer for those with LC-BBD was 1.95 (95% CI = 1.29 to 2.93). After adjustment for treatment and breast cancer risk, the RR of breast cancer for women with LC-BBD was 1.41 (95% CI = 1.03 to 1.94). Conclusions: Women with LC-BBD had a statistically significant increased risk of breast cancer. The elevation of breast cancer risk was especially evident in women 50 years of age and older. Furthermore, this risk was independent of that associated with key epidemiologic breast cancer risk factors.