Endometrial mullerian adenosarcoma after toremifene treatment in breast cancer patients: a case report / 부인종양

Toremifene is an anti-estrogen which has been shown to be effective in the treatment of breast cancer, and is thought to be a less uterotrophic agent than tamoxifen. The risk assessment concerning endometrial cancer has been inconclusive because of its rare use up to the mid-1990s. We report a case of an adenosarcoma, which is a very rare type of uterine malignancy, after toremifene treatment for 5 years in a breast cancer patient. After 1 year of toremifene use, the patient had a benign Mullerian adenofibroma. After an additional 4 years of toremifene treatment, the endometrial polypoid lesion was transformed into a Mullerian adenosarcoma. Although toremifene is a promising anti-estrogenic agent in the treatment of breast cancer patients, clinicians should not neglect the possibility of a uterine malignancy.

Clinical efficacy of toremifene combined with second line drugs novelbine/cisplatin on advanced non-small cell lung cancer / 肿瘤

Objective:To make a prospective study on the effectiveness and safety of toremifene (TOR) combined with novelbine/cisplatin (NP) in the treatment of patients with advanced non-small cell lung cancer (NSCLC) whose first line platinum-based chemotherapy was failure. Methods:Forty-four patients with stage ⅡB-Ⅳ NSCLC, who failed in the first line cisplatin-based chemotherapy from January 2004 to February 2006, were enrolled in this study. All the patients received TOR combined with NP second line chemotherapy for two cycles. The response rate and adverse reaction were evaluated. The survival rate was analyzed.Results:The 44 patients received average 1.8 cycles of chemotherapy (1-3 cycles). The response of 37 patients could be evaluated including 21 patients who received NP regimen before and 16 patients who received platinum-based chemotherapy. After second line therapy, 4 of the 37 patients had partial response (PR), 19 had stable disease (SD), 14 had progressive disease (PD), and no patient had complete response (CR). The total response rate (CR+PR) was 10.8% (4/37). The disease-controlling rate (CR+PR+SD) was 62.2% (23/37). The response rate and disease-controlling rate of squamous cell lung cancer (SCC) were 27.3% (3/12) and 72.7% (8/12), which were significantly higher than adenocarcinoma [0% (0/18) and 44.4% (8/18), P<0.05]. The median survival time was 8.2 months, the median time for SD was 4.0 months (1.0-10.2 months), and the 1-year survival rate was 24.4%. The median survival time and 1-year survival rate of SCC patients had no significant difference compared with adenocarcinoma patients (9.2 vs 7.1 months; 33.3% vs 27.7%, P＝0.72). There was no significant difference in survival rate between male and female patients. One patient stopped therapy for liver function injury (hyperbilirubinemia). The adverse reactions induced by chemotherapy mainly included gastrointestinal reaction, bone marrow suppression, and liver function injury. No serious adverse reaction occurred. Conclusion:The clinical efficacy of second line TOR combined with NP regimen is similar with the first line regimen for NSCLC patients, especially for SCC patients. The frequency of adverse reaction is not increased.

Toremifene as an Adjuvant Hormone Therapy for Estrogen Receptor Positive early Breast Cancer: Therapeutic Efficacy and Effect on Endometrium / 한국유방암학회지

PURPOSE: This study was conducted to evaluate the use of toremifene as an adjuvant hormonal therapy for estrogen recepter (ER) positive early breast cancer patients in terms of therapeutic efficacy and effect on endometrium as compared with tamoxifen. METHODS: Between January 2001 and December 2003, 451 patients with stage 0, I and II breast cancer, received adjuvant hormone therapy that consisted of either tamoxifen (N=387) or toremifene (N=64). The recurrence rate and survival rate were compared between two groups and the incidence of of endometrial event was evaluated in 273 of the patients. RESULTS: The median follow up period was 57 months and the median hormonal therapy period was 51 months. During the follow up period, there were 3 (2.0%) recurrence in the stage I tamoxifen group, 19 recurrences (8.7%) and 3 deaths (1.4%) in the stage II tamoxifen group (n=219), however there were no instances of recurrence or death in all of the toremifene group. In addition, endometrial cancer developed in 2 patients in the tamoxifen group, but in no patients in toremifene group during the follow up period. Further 21 of the patients who began treatment using tamoxifen changed to toremifene due to adverse side effects. The toremifene was well tolerated by 15 of the patients that changed treatment regimes. CONCLUSION: Toremifene was found to be as effective and safe as tamoxifen, when used as an adjuvant hormonal therapeutic agent in ER-positive early breast cancer, therefore toremifene may be a good option in place of tamoxifen for patients who are experiencing adverse effects as a result of tamoxifen treatment.

Role of estrogen receptor/progesterone receptor in toremifene-induced reversal of multidrug resistance in MCF7/ADR cells / 肿瘤

Objective: To study the reversing effect of toremifene (TOR) on multidrug resistance (MDR) in drug-resistant (MCF7/ADR) cell lines and its relationship with expression of estrogen receptor/progesterone receptor (ER/PR) in vitro. Methods: SRB method was used to determine the reversal time of toremifene on MDR in MCF7/ADR cells. Flow cytometry was applied to analyze the change in rhodamine 123 fluorescence in MCF7/ADR cells after addition of toremifene. The effect of toremifene on P-glycoprotein (P-gp) expression in MCFT/ADR cells was examined by western blot. Immunohistochemistry was applied to analyze the effect of toremifene on expression of ER/PR. Results: TOR (5, 10, and 20 mol/L) increased the in vitro cytotoxicity of doxorubicin in drug-resistant breast cancer cells (reversing times: 1.5-fold, 7.0-fold and 35.4-fold, respectively) but had no significant effect on drug-sensitive MCF7/S cells. Toremifene significantly enhanced intracellular accumulation of rhodamine 123 in drug-resistant MCF7/ADR cells. The intracellular fluorescence was close to sensitive MCF7/S cells. P-gp had negative expression in MCF7/S cells and was positively expressed in MCF7/ADR cells. TOR (5, 10, and 20 mol/L) had no significantly inhibitory effect on the expression of P-gp in MCF7/ADR cells. The expression of ER was positive and the expression of PR was weak in MCF7/S cells. Both ER and PR were negatively expressed in McF7/ ADR cells. Conclusion: TOR significantly reverses the MDR in MCF7/ADR cells, which is independent of the expression of ER/PR. The possible mechanism may be due to suppression of P-gp expression in MCF7/ADR cells.

Mitogen-activated protein kinase pathway in antitumor effect of toremifene / 上海第二医科大学学报

Objective To study the antitumor effect of toremifene on MCF7 cell lines,and investigate the role of mitogen-activated protein kinase pathway. Methods Inhibitory effect of toremifene alone or combined with MEK inhibitor PD98059 on MCF7 cells was measured by SRB test,and that on phosphorylated ERK was detected by Western blotting.Results Toremifene exhibited a concentration-dependent inhibitory effect on the activity of MCF7 cells.Phosphorylated ERK was significantly inhibited by 5,10 and 20 mmol/L toremifene.Combined with PD98059,toremifene had a significantly enhanced cytotoxity effect,which exceeded that of application alone. Conclusion Mitogen-activated protein kinase pathway may play an important role in the antitumor effect of toremifene which is independent of estrogens.Combined with PD98059,the antitumor effect of toremifene can be reinforced,indicating a synergistic effect of these two drugs.

Toremifene-associated endometrial polyp: A case report and review of the literature / 대한산부인과학회잡지

Antiestrogens have been widely used in the treatment of breast cancer patients. Although tamoxifen is one of the most prevalent antiestrogens, some reported its hepatocarcinogenic effects and the long-term treatment may increase the risk of endometrial and gastrointestinal cancer. Toremifene is an interesting new antiestrogen and have a similar antitumor efficacy as tamoxifen, with less side-effect including less uterotrophic effect compared to tamoxifen, in mice. we report a case of endometrial polyp which were associated with toremifene use, in postmenopausal woman with breast cancer, with a brief review of literature.

Comparison of Tamoxifen and Toremifene as Adjuvant Treatment in Node-negative Postmenopausal Breast Cancer

PURPOSE: To evaluate the differences in therapeutic efficacy and toxicity profiles between adjuvant toremifene and tamoxifene in postmenopausal breast cancer patients. METHODS: Toremifene 40 mg (n=115) and tamoxifen 20 mg (n =116) were administered daily for more than 2 years after curative surgery for lymph node-negative breast cancer. Toxicity profiles were compared between the two groups and the patient survival rate was also analyzed. RESULTS: Sweating and hot flashes were the most common symptoms in the two groups (toremifene vs. tamoxifen= 47.8% vs. 49.1%). Increase of vaginal discharge (39.1% vs. 36.2%) and weight gain (21.7% vs. 24.1%) were the next following adverse effects. There was no significant difference in adverse effect between the two groups. During the median follow-up period of 25 months (range: 9~38 months), five (4.3%) and four (3.3%) patients treated by toremifene and tamoxifen, respectively, had recurrent disease. CONCLUSION: The clinical outcome and adverse effect profiles of toremifene were similar to those of tamoxifen. Toremifene at 40 mg/day seems to be as safe and effective as tamoxifen at 20 mg/day in the treatment of postmenopausal, node-negative, breast cancer. However, a longer follow-up study is needed to verify this.

Synergistic effects of toremifene and anti-tumor drugs on human lung cancer cell lines A549 / 中国癌症杂志

Purpose:To study the activity of toremifene and its synergistic effect with anti-tumor drugs on human lung adenocarcinoma cell line A549,which might be expected to provide a new mode of therapy for the clinical management of lung cancer.Methods:The cytotoxic effects of these agents on human lung cancer cell line A549 were measured by a tet- razolium-based volorimetric assay (MTT assay).Results:Toremifene can inhibit the growth of A549 cell directly.The A value of the low dose toremifene combined with anti-tumor drugs were lower than that of anti-tumor drugs alone.Toremifene combined with VCR,ADM,DDP and VP-16 showed better effects.Conclusions:Toremifene combined with chemotherapy drugs shows significant synergistic anti-tumor effect on A549 cell.This might provide experimental evidence for lung cancer therapy.