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Transforming growth factor-beta and breast cancer risk in women with mammary epithelial hyperplasia.
- Source :
-
Journal of the National Cancer Institute [J Natl Cancer Inst] 1999 Dec 15; Vol. 91 (24), pp. 2096-101. - Publication Year :
- 1999
-
Abstract
- Background: 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.<br />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-beta-RII. All P values are two-sided.<br />Results: 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.<br />Conclusion: 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 :
- Adult
Aged
Breast Neoplasms pathology
Carcinoma, Ductal, Breast pathology
Case-Control Studies
Cell Division
Disease Progression
Epithelium pathology
Female
Follow-Up Studies
Gene Expression
Humans
Hyperplasia
Immunohistochemistry
Middle Aged
Odds Ratio
Risk
Transforming Growth Factor beta immunology
Breast pathology
Breast Neoplasms chemistry
Carcinoma, Ductal, Breast chemistry
Transforming Growth Factor beta analysis
Subjects
Details
- Language :
- English
- ISSN :
- 0027-8874
- Volume :
- 91
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- Journal of the National Cancer Institute
- Publication Type :
- Academic Journal
- Accession number :
- 10601380
- Full Text :
- https://doi.org/10.1093/jnci/91.24.2096