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- Title
Transforming growth factor-beta and breast cancer risk in women with mammary epithelial hyperplasia.
- Authors
Gobbi, Helenice; Dupont, William D.; Gobbi, H; Dupont, W D; Simpson, J F; Plummer, W D Jr; Schuyler, P A; Olson, S J; Arteaga, C L; Page, D L
- Abstract
<bold>Background: </bold>Transforming growth factors-beta (TGF-betas) regulate mammary epithelial cell division. Loss of expression of TGF-beta receptor II (TGF-beta-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-beta-RII in EHLA and the risk of subsequent invasive breast cancer.<bold>Methods: </bold>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-beta-RII. All P values are two-sided.<bold>Results: </bold>Women with breast EHLA and 25%-75% TGF-beta-RII-positive cells or less than 25% TGF-beta-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-beta-RII expression. Women with a heterogeneous pattern of TGF-beta-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.<bold>Conclusion: </bold>This study indicates that loss of TGF-beta-RII expression in epithelial cells of EHLA is associated with increased risk of invasive breast cancer.
- Subjects
TRANSFORMING growth factors-beta; HYPERPLASIA; BREAST cancer; BIOCHEMICAL mechanism of action; DISEASE risk factors; BREAST; BREAST tumors; CELL division; COMPARATIVE studies; EPITHELIUM; GENE expression; GROWTH factors; IMMUNOHISTOCHEMISTRY; LONGITUDINAL method; RESEARCH methodology; MEDICAL cooperation; RESEARCH; EVALUATION research; RELATIVE medical risk; CASE-control method; DISEASE progression; DUCTAL carcinoma; ODDS ratio
- Publication
JNCI: Journal of the National Cancer Institute, 1999, Vol 91, Issue 24, p2096
- ISSN
0027-8874
- Publication type
journal article
- DOI
10.1093/jnci/91.24.2096