Background: Transforming growth factors-β (TGF-βs) regulate mammary epithelial cell division. Loss of expression of TGF-β receptor II (TGF-β- RII) is related to cell proliferation and tumor progression. Breast epithelial hyperplastic lesions lacking atypia (EHLA) are associated with a mild elevation in breast cancer risk. We investigated the expression of TGF- β-RII in EHLA arid the risk of subsequent invasive breast cancer. Methods: We conducted a nested case-control study of women with biopsy-confirmed EHLA who did not have a history of breast cancer or atypical hyperplasia of the breast. Case patients (n = 54) who subsequently developed invasive breast cancer were matched with control patients (n = 115) who did not. Formalin- fixed, paraffin-embedded sections of breast biopsy specimens of all 169 patients with EHLA were studied by immunohistochemical analysis with antibodies against TGF-β-RII. AII P values are two-sided. Results: Women with breast EHLA and 25%-75% TGF-βRII-positive cells or less than 25% TGF- β-RII-positive cells had odds ratios of invasive breast cancer of 1.98 (95% confidence interval [CI] = 0.954.1) or 3.41 (95% CI = 1.2-10.0), respectively (P for trend = .008). These risks are calculated with respect to women with EHLA that had greater than 75% TGF-β-RII expression. Women with a heterogeneous pattern of TGF-β-RII expression in their normal breast lobular units and either greater than 75%, 25%-75%, or less than 25% positive cells in their EHLA had odds ratios for breast cancer risk of 0.742 (95% CI = 0.3- 1.8), 2.85 (95% CI = 1.1-7.1), or 3.55 (95% CI = 1.010.0), respectively (P for trend = .003). These risks are relative to women with a homogeneous pattern of expression in their normal lobular units and greater than 75% positive cells in their EHLA. Conclusion: This study indicates that loss of TGF-β-RII expression in epithelial cells of EHLA is associated with increased risk of invasive breast cancer.
ASJC Scopus subject areas
- Cancer Research