Person:

Baer, Heather

Introduction: Alcohol consumption is a well-established risk factor for breast cancer. Some studies have suggested that the risk of breast cancer associated with alcohol consumption is greater for women with a history of benign breast disease (BBD). We hypothesized that among women with biopsy-confirmed BBD, recent alcohol consumption would increase the risk of breast cancer in women with proliferative breast disease to a greater extent than in women with nonproliferative breast disease. Methods: We conducted a nested case–control study in the Nurses' Health Study I and II. The cases (n = 282) were women diagnosed with incident breast cancer, with a prior biopsy-confirmed breast disease. The controls (n = 1,223) were participants with a previous BBD biopsy, but without a diagnosis of breast cancer. Pathologists reviewed benign breast biopsy slides in a blinded fashion and classified the BBD as nonproliferative, proliferative without atypia, or atypical hyperplasia, according to standard criteria. Results: Women with nonproliferative breast disease consuming ≥ 15 g of alcohol per day had a nonsignificant 67% increased risk of breast cancer (odds ratio = 1.67; 95% confidence interval 0.65 to 4.34) compared with nondrinkers. There was no evidence that recent alcohol consumption increased the risk of breast cancer to a greater extent in women with proliferative BBD than among women with nonproliferative BBD (P for interactio n = 0.20). Conclusion: Contrary to our a priori hypothesis, there was no evidence that recent alcohol consumption increased the risk of breast cancer to a greater extent among women with proliferative BBD than among women with nonproliferative BBD.

Introduction: At least four major categories of invasive breast cancer that are associated with different clinical outcomes have been identified by gene expression profiling: luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) and basal-like. However, the prevalence of these phenotypes among cases of ductal carcinoma in situ (DCIS) has not been previously evaluated in detail. The purpose of this study was to compare the prevalence of these distinct molecular subtypes among cases of DCIS and invasive breast cancer. Methods: We constructed tissue microarrays (TMAs) from breast cancers that developed in 2897 women enrolled in the Nurses' Health Study (1976 to 1996). TMA slides were immunostained for oestrogen receptor (ER), progesterone receptor (PR), HER2, cytokeratin 5/6 (CK5/6) and epidermal growth factor receptor (EGFR). Using these immunostain results, cases were grouped into molecularly defined subtypes. Results: The prevalence of the distinct molecular phenotypes differed significantly between DCIS (n = 272) and invasive breast cancers (n = 2249). The luminal A phenotype was significantly more frequent among invasive cancers (73.4%) than among DCIS lesions (62.5%) (p = 0.0002). In contrast, luminal B and HER2 molecular phenotypes were both more frequent among DCIS (13.2% and 13.6%, respectively) as compared with invasive tumours (5.2% and 5.7%, respectively) (p < 0.0001). The basal-like phenotype was more frequent among the invasive cancers (10.9%) than DCIS (7.7%), although this difference was not statistically significant (p = 0.15). High-grade DCIS and invasive tumours were more likely to be HER2 type and basal-like than low- or intermediate-grade lesions. Among invasive tumours, basal-like and HER2 type tumours were more likely to be more than 2 cm in size, high-grade and have nodal involvement compared with luminal A tumours. Conclusion: The major molecular phenotypes previously identified among invasive breast cancers were also identified among cases of DCIS. However, the prevalence of the luminal A, luminal B and HER2 phenotypes differed significantly between DCIS and invasive breast cancers.