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Background: Women with proliferative benign breast lesions are at increased risk of breast cancer, and some studies have provided evidence that microscopic calcifications in such lesions enhance the risk.Purpose: This study was performed to determine whether calcifications on mammograms are predictive of subsequent breast cancer.Methods: Data for this study were collected on women enrolled at four of the clinics that participated in the Breast Cancer Detection and Demonstration Project (BCDDP). The presence, morphology, and distribution of calcifications visualized on baseline mammograms for 686 women who developed breast cancer over a 7- to 10-year period of follow-up were compared with those for 1357 controls who remained cancer free. We also compared presence and types of calcifications in breasts in which cancer subsequently developed with those in the contralateral breast.Results: Calcifications were evident at baseline in at least one breast in 381 (55.5%) of 686 cases and in 606 (44.7%) of 1357 controls. The estimated relative risk (RR) of breast cancer was 1.68 in women with calcifications, compared with those having none. There was a statistically significant trend of increasing risk with number of breasts with calcifications; RR increased from 1.28 to 2.14 in women with calcifications in one and both breasts, respectively. In women with unilateral calcifications, RR was greater for the breast in which the calcification occurred (1.48) than for the opposite breast (1.08). The elevated risk persisted for more than 6 years from identification of the calcification, suggesting that these lesions were not indicative of existing carcinomas detected later. Risk was greatest in women with clustered calcifications of any morphology or linearly distributed punctate calcifications (RR = 3.64), and the cancer in women with such calcifications was 4.65 times more likely to occur in the involved breast than in the contralateral breast. Multiple and scattered punctate calcifications, and those of any number or distribution that were ring-shaped or linear, were also associated with subsequent risk of breast cancer (RR = 2.09 and 1.76, respectively) but were not strongly predictive of the side on which the breast cancer occurred. Risk was not altered in women with single punctate or large conglomerate calcifications, although the cancers that subsequently occurred in women with the latter lesions were over three times more likely to develop in the breast with the calcification than in the opposite breast.Conclusions: These findings are consistent with previously reported relationships between breast cancer and specific histologic types of noninvasive breast lesions. Some types of mammographic calcifications appear to be independent risk factors for breast cancer.Implications: If these results are confirmed by other investigators, mammographic calcifications could serve as an additional indicator of women at high risk for breast cancer who may benefit from intensified follow-up. [ABSTRACT FROM AUTHOR]