Transforming growth factor-beta and breast cancer risk in women with mammary epithelial hyperplasia.
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.


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.


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.


CONCLUSIONS
This study indicates that loss of TGF-beta-RII expression in epithelial cells of EHLA is associated with increased risk of invasive breast cancer.
Gobbi
H
H
Department of Pathology, Vanderbilt University School of Medicine, Nashville, TN 37232-2637, USA.
Dupont
W D
WD
Simpson
J F
JF
Plummer
W D
WD
Schuyler
P A
PA
Olson
S J
SJ
Arteaga
C L
CL
Page
D L
DL
D000328:Adult; D000368:Aged; D001940:Breast / Q000473:pathology*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry* / Q000473:pathology; D016022:Case-Control Studies; D002455:Cell Division; D018450:Disease Progression; D004848:Epithelium / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D008875:Middle Aged; D016017:Odds Ratio; D012306:Risk; D016212:Transforming Growth Factor beta / Q000032:analysis* / Q000276:immunology
D016212:Transforming Growth Factor beta