Effects Of Antiestrogen Therapy Research Articles

Changes in ER beta versus ER alpha in short-term studies of antiestrogen therapies.

Abstract Abstract #5113 Background: Fulvestrant (Faslodex™) is a novel estrogen receptor (ER) antagonist with no agonist effects used in the treatment of postmenopausal women with advanced breast cancer. Compared with other antiestrogen therapies, fulvestrant has a distinct and different mode of action; on binding to the ER it induces a rapid and dose-dependent degradation of ER alpha and concomitant decreases in progesterone receptor (PgR) levels and Ki67 labeling index (LI). The action of fulvestrant on ER beta is unknown and has been investigated in relation to other biomarkers in this study.
 Methods: This randomized, multicenter study included postmenopausal patients with previously untreated breast tumors (stage T1-T3) that were either ER+ or ER unknown. Patients were randomized to receive a single intramuscular dose of fulvestrant (50 mg [n=39], 125 mg [n=38], or 250 mg [n=44]), continuous daily tamoxifen (Nolvadex™) (20 mg/day [n=36]), or matching tamoxifen placebo (n=33) for 14–21 days prior to surgery. The effects of antiestrogen therapy on ER beta 1 and ER beta 2 levels and the relationship between these effects and changes in ER alpha, PgR and Ki67 LI were investigated. Effects on ER (alpha and beta) and PgR were determined by immunohistochemistry and expressed as mean percentage change from baseline H-score. Ki67 LI was determined as described previously1 and was expressed as median percentage change from baseline.
 Results: There was no overall treatment effect following placebo or antiestrogen therapy on ER beta 1 H-score (p=0.8537) or ER beta 2 H-score (p=0.5494). There were no significant differences between the individual fulvestrant dose groups, tamoxifen and placebo for mean changes in either ER beta 1 (50 mg: +34.8%, 125 mg: +42.8%, 250 mg: +15.5%; tamoxifen: +29.8%; placebo: +29.7%) or ER beta 2 (50 mg: +87.9%, 125 mg: +82.9%, 250 mg: +97.4%; tamoxifen: +98.1%; placebo: +64.2%). No correlations were observed between changes in ER beta 1 and changes in ER beta 2, nor between either ER beta 1 or 2 and ER alpha, PgR or Ki67 LI.
 Conclusion: Changes in ER beta did not correlate with fulvestrant dose (50 mg, 125 mg, or 250 mg) or other variables that have previously been shown to be related to fulvestrant activity. This study does not support the investigation of ER beta 1 or 2 as markers of the biological activity of fulvestrant high dose (500 mg/month) in ongoing trials such as FIRST and CONFIRM.
 1Robertson et al. Cancer Res 2001; 61: 6739-6746. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5113.

Preliminary results of postoperative adjuvant treatment with tamoxifen in colorectal cancer

To investigate estrogen receptor (ER) expression and the effects of anti-estrogen therapy on the prognosis of colorectal carcinoma. ER was measured in fresh colorectal cancer tissues by Dextran-coated charcoal (DCC) assay. The relationships between ER expression and clinicopathological parameters in colorectal cancer were analyzed. Tamoxifen was administrated postoperatively as adjuvant treatment. The positive rate of ER in colorectal tumor tissues was 37.0%. The 5-year survival rates of tamoxifen group and control group were 66.7% and 72.5% respectively, and there was no significant difference between the two groups. The distant metastasis rate of Tamoxifen group was significantly lower than that of control group (3% versus 20%). Some colorectal carcinomas are hormone-dependent tumors, and anti-estrogen therapy has no effect on them.

The effects of anti‐estrogen therapy on lymphocyte functions in breast cancer patients

The effects of anti-estrogen therapy (tamoxifen or toremifene) on in vitro lymphocyte functions were investigated in breast cancer patients. We found that the amount of DNA synthesis, with or without PWM stimulation, was decreased in all cancer patient groups compared to normal controls. The number of Ig-secreting cells was enhanced in unstimulated peripheral blood lymphocyte cultures but decreased in PWM-stimulated cultures. This occurred in all cancer patient groups investigated, with or without anti-estrogen therapy, as compared to healthy controls. On the other hand, subsequent samples with two-month intervals showed that anti-estrogens can increase PFC responses and inhibit DNA synthesis of peripheral blood lymphocytes in more than half of the patients. Interestingly, the enhancing dexamethasone effect, which usually causes an increase in the number of Ig-secreting cells in PWM-stimulated cultures, was also seen more often in anti-estrogen-treated patients. These results suggest that anti-estrogens may have immunoregulatory effects in vivo.