© 1999 by Oxford University Press
Journal of the National Cancer Institute, Vol. 91, No. 24, 2096-2101,
December 15, 1999
© 1999 Oxford University Press
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Transforming Growth Factor-ß and Breast Cancer Risk in Women With Mammary Epithelial Hyperplasia
Affiliations of authors: H. Gobbi, Department of Pathology, Vanderbilt University School of Medicine, Nashville, TN, and Department of Anatomic Pathology, School of Medicine, Federal University of Minas Gerais, Brazil; W. D. Dupont, W. D. Plummer, Jr., P. A. Schuyler (Department of Preventive Medicine), J. F. Simpson, S. J. Olson (Department of Pathology), C. L. Arteaga (Departments of Medicine and Cell Biology), D. L. Page (Departments of Pathology and Preventive Medicine), Vanderbilt University School of Medicine, Nashville, TN.
Correspondence to: William D. Dupont, Ph.D., Department of Preventive Medicine, Vanderbilt University School of Medicine, A-1124 Medical Center North, Nashville, TN 37232-2637 (e-mail: bill.dupont{at}vanderbilt.edu).
BACKGROUND: Transforming growth factors-ß (TGF-ßs) regulate mammary epithelial cell division. Loss of expression of TGF-ß receptor II (TGF-ß-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-ß-RII in EHLA and 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-ß-RII. All P values are two-sided. RESULTS: Women with breast EHLA and 25%-75% TGF-ß-RII-positive cells or less than 25% TGF-ß-RII-positive cells had odds ratios of invasive breast cancer of 1.98 (95% confidence interval [CI] = 0.95-4.1) 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-ß-RII expression. Women with a heterogeneous pattern of TGF-ß-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 = 1.0-10.0), 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-ß-RII expression in epithelial cells of EHLA is associated with increased risk of invasive breast cancer.
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