Benign breast disease and breast cancer risk

Abstract

1089

Introduction: Benign breast disease (BBD) is an established risk factor for breast cancer (BC), but only a minority of women with BBD ultimately develop BC. To identify the subset of women at greatest risk for breast cancer at the time of BBD diagnosis, we have established a large historical cohort of women with BBD in which we can test more specific means of risk prediction, using clinical, histopathologic and molecular tools. Methods: The Mayo Clinic Surgical Index was used to identify all women ages 18-85 who had an open breast biopsy with benign findings at the Mayo Clinic between 1/1/67 and 12/31/91. The availability of tissue slides and blocks on these patients was verified through linkage to the Pathology Index. Medical record review was performed to verify eligibility and to identify subsequent occurrences of breast cancer diagnosed or treated at Mayo. A study-specific questionnaire is being used to collect risk factor data on the cohort and to identify breast cancers diagnosed outside of Mayo. Results: This 25-year cohort includes 11,782 women with 181,284 person years of follow-up. The median age at BBD diagnosis was 50.0 years. Some family history of BC was present in 40% of those surveyed; 21% had an affected first-degree relative. Thus far, 705 women are known to have developed BC, at a median of 9.2 years after their BBD. The interval from BBD to BC is 15 years, 23%. The cancer occurred in the same breast as the BBD in 279 women (40%), the opposite breast in 189 (27%) and both breasts in 18 (3%). Side is pending for 219 (31%). The estimated 5-yr, 10-yr and 15-yr BC incidence rates are 2.0%, 4.1%, and 6.4%, respectively for women with BBD from 1982-1991 (follow-up ongoing for 1967-81 group). The histopathologic review has been completed for 3,004 of the BBD specimens. Non-proliferative disease was found in 65.8%, proliferative disease without atypia in 28.6% and atypia (atypial ductal hyperplasia or atypial lobular hyperplasia) in 3%. Incorporating time from BBD to BC, histology, and side of BBD vs BC, we are exploring a panel of biomarkers as indicators of possible BC precursors or a background field change. Conclusions: We have assembled a large cohort of patients with BBD with extensive follow-up for breast cancer, excellent participation on a risk factor survey, and sufficient quantities of well-characterized tissues to permit independent evaluation of established and novel molecular markers. Supported by grants from the national Komen Foundation, the Breast Cancer Research Foundation, and DOD Breast Cancer Center of Excellence award DAMD 17-02-1-0473.