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Down-regulation of transforming growth factor-alpha by tamoxifen in human breast cancer
S Noguchi1, K Motomura, H Inaji
1Department of Surgery, Center for Adult Diseases, Osaka, Japan.
Background:
The influence of tamoxifen treatment on transforming growth factor-alpha (TGF-alpha) levels in human breast cancer rarely has been studied in vivo.
Methods:
Postmenopausal patients with estrogen receptor (ER)-positive and progesterone receptor (PR)-positive primary breast cancer underwent two fine-needle aspiration biopsies (FNA) of the tumors. Between the two FNAs, 10 patients received no treatment (control group), and the other 10 patients received tamoxifen (20 mg/day) for 10 (8-12) days (TAM group). TGF-alpha levels in FNA samples were assayed by enzyme immunoassay.
Results:
No significant difference was found in TGF-alpha levels between the first and second FNA samples in the control group. On the other hand, in the TAM group, TGF-alpha levels in the second FNA samples (2.5 +/- 0.5; mean +/- SEM ng/mg.DNA) were significantly (P < 0.01) lower than those in the first (4.5 +/- 0.8). Studies on the influence of tamoxifen treatment on TGF-alpha levels in ER-negative and PR-negative breast cancer showed that TGF-alpha levels were not affected by tamoxifen treatment. Positivity of epidermal growth factor receptor (EGFR) was 60% in ER-negative and PR-negative breast cancer and 30% in ER-positive and PR-positive breast cancer.
Conclusions:
Tamoxifen downregulates TGF-alpha levels in ER-positive and PR-positive breast cancers through ER. The significance of TGF-alpha as an autocrine growth factor appears to be more important in ER-negative and PR-negative breast cancer with high EGFR positivity than in ER-positive and PR-positive breast cancer with low EGFR positivity.
Insights
Tamoxifen treatment significantly reduces transforming growth factor-alpha (TGF-alpha) levels in estrogen receptor-positive breast cancer. This effect was not observed in receptor-negative cancers, suggesting a role for estrogen receptors in tamoxifen
Area of Science:
- Oncology
- Endocrinology
- Molecular Biology
Background:
- Transforming growth factor-alpha (TGF-alpha) role in breast cancer is understudied, especially in vivo.
- Tamoxifen is a common treatment for estrogen receptor-positive (ER+) breast cancer.
Purpose of the Study:
- To investigate the in vivo effect of tamoxifen on TGF-alpha levels in human breast cancer.
- To explore the relationship between TGF-alpha, tamoxifen, and hormone receptor status in breast cancer.
Main Methods:
- Fine-needle aspiration (FNA) biopsies were performed on ER+/PR+ breast cancer patients.
- Patients received either tamoxifen treatment or no treatment (control) between biopsies.
- TGF-alpha levels were quantified using enzyme immunoassay.
Main Results:
- Tamoxifen significantly decreased TGF-alpha levels in ER+/PR+ breast cancer patients.
- No significant change in TGF-alpha levels was observed in the control group.
- Tamoxifen did not affect TGF-alpha levels in ER-negative and PR-negative breast cancer, which had higher EGFR positivity.
Conclusions:
- Tamoxifen downregulates TGF-alpha in ER+/PR+ breast cancers, mediated by estrogen receptors.
- TGF-alpha may play a more critical autocrine growth factor role in ER-/PR- breast cancers with high EGFR expression.