The influence of family history and histological stratification on breast cancer risk in women with benign breast disease: a meta-analysis

Benign breast disease (BBD) is an important risk factor for subsequent breast cancer. However, it is unclear whether breast cancer risk is higher in cases of atypical ductal hyperplasia (ADH) than atypical lobular hyperplasia (ALH). Furthermore, it is unclear whether family history increases risk in women with various subtypes of BBD. We searched the electronic database of PubMed for case-control studies about the subsequent breast cancer risk of BBD, and a meta-analysis was conducted. Of ten inclusive studies, nine were eligible for subsequent breast cancer risk of histological subtype, including 2,340 cases and 4,422 controls, and four were eligible for investigating the influence of family history on subtypes of BBD, including 1,377 cases and 2,630 controls. Relative to non-proliferative disease (NP), all subtypes of BBD increased subsequent risk, and risk for women with ALH (OR = 5.14, 95% CI 3.52-7.52) may be higher than for women with ADH (OR = 2.93, 95% CI 2.16-3.97). Compared to women without family history and proliferative disease, women with a first-degree family history and atypical hyperplasia (AH) were at highest risk (OR = 4.87, 95% CI 2.89-8.20). Relative to women without family history, women with a first-degree family history had an increased breast cancer risk in different histological subtypes of BBD except for AH (OR = 1.39, 95% CI 0.82-2.37). This meta-analysis strongly suggested that women with AH, especially for ALH and AH combined with a first-degree family history, were at high risk, for whom risk-reduction options should be considered.