We will conduct a nested case-control study of women who participated in the Breast Cancer Detection Demonstration Project (BCDDP). All women who underwent breast biopsy revealing benign breast parenchyma during the screening phase of the BCDDP will be eligible for inclusion in the study if they did not have a previous history of breast cancer. All such women who develop breast cancer during subsequent follow-up will be included in the case group for the study. Each case patient will be matched with two control patients. Control patients will be matched to case patients by project center, age, and date of entry biopsy (within 6 months). The entry biopsy of all case and control patients will be assessed using Page's histologic classification scheme. This review will be done independently without knowledge of the patient's subsequent cancer outcome. Dr. Page will discuss the nuances of his classification scheme with the pathologists prior to, but not after, the start of review of study material. Dr. Winfield will classify the mammograms from study subjects at the time of their entry biopsy. These mammograms will be assessed with respect to parenchymal pattern (Wolf's criteria), calcifications, asymmetry, mass density, architectural distortion, and focal duct dilatation. This review will also be conducted without knowledge of the patient's subsequent cancer outcome. 17,012 women underwent benign breast biopsy during the screening phase of the BCDDP. A median follow-up time of 8.75 years is available on these women; 490 developed breast cancer during follow-up. The BCDDP data base includes the patient's date of birth, family history of breast cancer, menstrual history and status, reproductive history, and exogenous female hormone history. We will use conditional logistic regression analysis to assess the individual and combined effects of the histologic, mammographic and non-anatomic risk factors in the study. Our previous research has indicated that 70% of women who undergo benign breast biopsy are not at increased breast cancer risk while 4% of these women have a fivefold increase in the risk of this disease. In this study we will determine whether our previous results can be confirmed in a different population of subjects using different pathologists. If our previous results are corroborated, it will be possible to reassure the majority of patients with benign breast disease that they are not at enhanced cancer risk while identifying a small minority of these patients who need to be followed with great care.
