Clinical and histologic aspects of proliferative and non-proliferative benign breast disease

It has been known for years that benign breast disease is correlated with an increased risk for the development of breast cancer. Over the years, there have been many studies linking histological changes in benign breast biopsies and subsequent risk of breast cancer. In many of these reports, there was no attempt to standardize criteria and often the patient population under study was relatively small. Over the past decade, three large groups have agreed to use the same definition of benign changes and a unified set of criteria for the diagnosis of these lesions. The results from these three groups [Nashville, Nurses Health Study (NHS), and the Breast Cancer Detection Demonstration Project (BCDDP)] are strikingly similar. All three studies reported that if the biopsy revealed proliferative disease without atypia, the subsequent risk was ∼1.5x. If the biopsy revealed atypical hyperplasia (AH), the risk was ∼4–5x. If the patients with AH had a family history of breast cancer, their subsequent risk approached that of patients with in situ carcinoma (∼8–10x). In addition to family history, menopausal status seemed to play a role. In patients with AH, the breast cancer risk was much higher in pre- than post-menopausal patients. While the classification scheme proposed by Page and co-workers is useful in assigning different levels of risk to women with benign breast disease, it has not been universally accepted. Our major short-term goal should be to encourage pathologists to apply these criteria in a reproducible manner in their daily practice. Our long-term goals should first include a refining of the criteria for AH, especially atypical ductal hyperplasia. A second important area for future study is to further analyze the interaction between histological, biological, and epidemiological factors (such as family history, menopausal status, exogenous hormone use, and dietary factors) on subsequent breast cancer risk. Accomplishing these goals will require a combination of careful histopathological evaluation and application of new biological markers to breast specimens from women in large cohorts with long-term follow-up.