Objective To explore the effect of toremifene on estrogen receptor （ER） expression and tumor micro-angiogenesis in rat Lewis lung carcinoma. Methods Cell suspension of rat Lewis lung carcinoma was implanted into 40 female Wistar rats subcutaneously. The rats were randomly divided into a control group，a estradiol group （0.006 mg/mL），a low dose toremifene group （0.25 mg/mL） and a high dose toremifene group （5 mg/mL）. Tumor size was measured every 3 days and the tumor growth curve was charted. On 15th day，the tumor weight and the growth inhibition rate were measured. Immunohistochemical method was used to detect the expressions of estrogen receptor α （ERα），estrogen receptor β （ERβ），vascular endothelial growth factor （VEGF），and platelet endothelial cell adhesion molecule-1 （PECAM-1）. Integral optical density （IOD） of ERα，ERβ and VEGF was calculated by image analysis software. Quantitative method of Weidner with PECAM-1 was employed for microvessel density （MVD） count. Results Tumor size of the four groups all presented a quadratic function growth trend with time （Plt;0.05）. Tumor growth speed was slower in toremifene groups of low and high doses than that in the control group and the estradiol group. The growth inhibition rate of the estradiol group，the low dose toremifene group and the high dose toremifene group was －15.1%，22.6%，and 45.1%，respectively. The expressions of ERα，VEGF，and MVD in the estradiol group were significantly higher than those in the control group，the low dose toremifene group and the high dose toremifene group （all Plt;0.05）. The expressions of ERα，VEGF，and MVD in the low dose toremifene group were significantly lower than those in control group，but higher than those in high dose toremifene group （all Plt;0.05）.The expression of ERα was positively related to VEGF （r=0.664，Plt;0.05） and MVD（r=0.593，Plt;0.05）. Conclusion Toremifene can inhibit tumor growth，which maybe involved in inhibiting ERα mediated VEGF expression.
ObjectiveTo explore the role of toremifene in postmenopausal operable patients with luminal subtype of breast cancer in China. MethodsA total of 618 eligible patients diagnosed with luminal subtype of breast cancer from January 2000 to December 2009 in the Cancer Center of Sun Yat-sen University were analyzed. One hundred and fifteen patients were treated with toremifene(toremifene group) and 503 patients were treated with tamoxifen(tamoxifen group) as adjuvant endocrine therapy. Survival was compared by Kaplan-Meier with log-rank test in two groups. Cox analysis was used to compare different prognostic factors. ResultsThe general clinical data had no significant differences between the toremifene group and tamoxifen group (P > 0.05). After a median follow-up of 76 months, there was no statistical difference in the 5-year disease free survival rate and 5-year overall survival rate between the toremifene group and the tamoxifen group (5-year disease free survival rate:78.5% versus 85.5%, P=0.083;5-year overall survival rate:86.4% versus 92.0%, P=0.334). Univariated analysis showed that the histological grade, tumor size, lymph node status, TNM stage, HER-2 positive expression were associated with the disease free survival rate and overall survival rate(P < 0.05). Multivariated analysis showed that the tumor size and lymph node status were the independent risk factors of disease free survival rate and overall survival rate for postmenopausal operable patients with luminal subtype of breast cancer(P < 0.05). HER-2 positive expression was the independent risk factor in predicting disease free survival rate for patients with tamoxifen or toremifene. There was no grade 3 or 4 toxicity for all the patients according to CTC AE 4.0 grade. ConclusionsSimilar benefit is found in disease free survival rate and overall survival rate in Chinese postmenopausal patients with operable luminal subtype of breast cancer between patients receiving toremifene and tamoxifen with tolerable adverse effects. HER-2 status is associated with disease free survival rate.