Attenuation of breast cancer risk in benign breast disease

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Background: Benign breast disease is a common condition in women. Much research has been devoted to studying benign breast disease (BBD) lesions to investigate how these lesions alter a woman’s risk of developing breast cancer (BC). In a Detroit-based multi-ethnic cohort of women with biopsy-proven BBD we observed that fibrosis and fibroadenoma were protective against BC progression from BBD.
 Methods: To further dissect out the attenuation of risk conferred by fibroadenoma, these lesions were investigated with respect to lesion size and degree and type of epithelial proliferation in a case-control (1:3 match) cohort of 872 women nested within the parent cohort of 4,970 women with BBD.
 Results: In the parent cohort, fibrosis was shown to attenuate the risk of developing breast cancer. The risk of developing breast cancer was 37% lower among women with fibrosis compared to those without fibrosis (RR: 0.63; 95% CI 0.45, 0.87; p=0.0053) after adjusting for other parameters. In the nested case-control study, fibroadenoma was shown to attenuate the risk of progression to breast cancer. The odds of breast cancer was reduced by 35% in women with fibroadenoma compared to those without fibroadenoma (OR: 0.65; 95% CI: 0.46, 0.94; p=0.02) after adjusting for other parameters. This reduction in risk of breast cancer was seen regardless of whether the fibroadenoma was proliferative or nonproliferative. In addition, the size of the fibroadenoma was found to be inversely related to breast cancer risk. The average size of fibroadenoma was 1.14 cm (std =0.76) in women who developed breast cancer versus 1.56 cm (std =1.196) in women who did not progress to breast cancer (p=0.0002). Also, the size of the fibroadenoma was found to be inversely related to the degree and type of epithelial proliferation of the associated fibroadenoma. Nonproliferative fibroadenomas were on average larger in size than proliferative fibroadenomas which tended to be larger than fibroadenomas associated with atypical hyperplasia. 
 Conclusion: Stromal elements are shared features among fibrosis and fibroadenoma lesions. Women with a diagnosis of fibrosis in the parent cohort had an attenuated risk of progression to breast cancer. Also, in the nested case-control study, women with fibroadenoma were less likely to develop breast cancer. Fibroadenoma size was associated with type and degree of epithelial proliferation and breast cancer risk.
 Support: NIH CA 70923