Objective: To compare the effect of different endocrine therapy drugs on liver function in patients with early breast cancer. Methods: A retrospective cohort study was conducted to include 4 318 patients with early breast cancer who received adjuvant endocrine therapy in Department of Breast Surgery, Peking Union Medical College Hospital from January 1, 2013 to December 31, 2021. All the patients were female, aged (51.2±11.3) years (range: 20 to 87 years), including 1 182 patients in the anastrozole group, 592 patients in the letrozole group, 332 patients in the exemestane group, and 2 212 patients in the toremifene group. The mixed effect model was used to analyze and compare the liver function levels of patients at baseline, 6, 12, 18, 24, 36, 48, 60 months of medication, and 1 year after drug withdrawal among the three aromatase inhibitors (anastrozole, letrozole, exemestane) and toremifene. Results: ALT and AST of the 4 groups were significantly higher than the baseline level at 6 months (all P<0.01), and there were no significant differences in total bilirubin, direct bilirubin and AST levels among all groups one year after drug withdrawal (P: 0.538, 0.718, 0.061, respectively). There was no significant difference in the effect of all groups on AST levels (F=2.474, P=0.061), and in the effect of three aromatase inhibitors (anastrozole, letrozole, and exemestane) on ALT levels (anastrozole vs. letrozole, P=0.182; anastrozole vs. exemestane, P=0.535; letrozole vs. exemestane, P=0.862). Anastrozole and letrozole had significantly higher effects on ALT levels than toremifene (P<0.01, P=0.009). The proportion of abnormal liver function in each group increased significantly at 6 months compared with baseline, and then the proportion showed a decreasing trend over time. Conclusions: Three aromatase inhibitors (anastrozole, letrozole, and exemestane) and toremifene can significantly increase the level of ALT and AST in patients with breast cancer, and the levels can gradually recover to the baseline after 1 year of drug withdrawal. The effect of non-steroidal aromatase inhibitors (anastrozole, letrozole) on ALT levels is greater than toremifene.
Female ; Humans ; Anastrozole ; Aromatase Inhibitors/therapeutic use* ; Bilirubin ; Breast Neoplasms/drug therapy* ; Letrozole ; Liver ; Retrospective Studies ; Toremifene ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over

BACKGROUND: The present study describes our 10-year experience with uveoretinal adverse events that manifest because of chemotherapy. METHODS: A retrospective chart review was performed for all patients who presented to the ophthalmologic department while undergoing systemic chemotherapy between July 2005 and June 2015. RESULTS: A total of 55 patients (mean age, 51.2 years, 38 women [69.1%]) suspected of having uveoretinal disease owing to the use of chemotherapeutic agents alone were enrolled. Breast cancer was the predominant disease (36.4%); noninfectious anterior uveitis (21.8%) was the most common condition. Bilateral involvement was observed in 16 patients (29.1%). Although cisplatin (21.8%) was the most commonly used drug, daunorubicin, cytarabine, tamoxifen, toremifene, and imatinib were also frequently used. The median duration until ophthalmologic diagnosis was 208.5 days (range, 19–5,945 days). The proportion of patients with final visual acuity (VA) < 20/40 Snellen VA (0.5 decimal VA) was 32.7%. However, no relationship was observed between final VA < 20/40 and age, sex, therapeutic agents, and metastasis. CONCLUSION: Uveoretinal complications were mostly mild to moderate and exhibited a favorable response to conservative therapy. A considerable number of patients exhibited significant irreversible loss of vision after cessation of the causative chemotherapeutic agent. Ophthalmological monitoring is required during chemotherapy.
Antineoplastic Agents ; Breast Neoplasms ; Cisplatin ; Cytarabine ; Daunorubicin ; Diagnosis ; Drug Therapy ; Drug-Related Side Effects and Adverse Reactions ; Female ; Humans ; Imatinib Mesylate ; Molecular Targeted Therapy ; Neoplasm Metastasis ; Retrospective Studies ; Tamoxifen ; Toremifene ; Uveitis ; Uveitis, Anterior ; Visual Acuity

Aged ; Aged, 80 and over ; Androgen Antagonists/pharmacology* ; Androgens/blood* ; Cohort Studies ; Gonadotropin-Releasing Hormone/antagonists & inhibitors* ; Hormones/blood* ; Humans ; Luteinizing Hormone/blood* ; Male ; Middle Aged ; Orchiectomy ; Prostatic Neoplasms/surgery* ; Toremifene/therapeutic use*

Adenosarcoma of the uterus is a rare biphasic tumor containing benign glandular epithelial and malignant mesenchymal components. The tumor has been reported to be associated with antiestrogen therapy, particularly tamoxifen, but there have been a few case reports with MRI. We present two cases of MRI findings of uterine adenosarcoma after antiestrogen therapy, tamoxifen and toremifene in breast cancer patients. The tumor presents as a large polypoid mass occupying the endometrial cavity, and may protrude into the vagina. On MRI, the tumor typically shows solid components with scattered small cysts and heterogeneous enhancement. These findings are not significantly different from conventional adenosarcoma.
Adenosarcoma* ; Breast Neoplasms ; Estrogen Receptor Modulators ; Humans ; Magnetic Resonance Imaging* ; Tamoxifen ; Toremifene ; Uterus ; Vagina

OBJECTIVETo explore the regulation mechanism of the reversal of breast cancer resistance protein-mediated multidrug resistance by toremifene.

METHODSTwo recombinant plasmids (pcDNA3-promoter-BCRP and pcDNA3-CMV-BCRP) were designed to express the wild-type full-length BCRP cDNA enforced driven by its endogenous promoter containing a functional ERE and a CMV promoter as control, respectively. Two recombinant plasmids were transfected into ERα-positive MCF-7 and ERα-negative MDA-MB-231 breast cancer cell lines. Four kinds of BCRP expressing cell lines of MCF-7/Promoter-BCRP, MCF-7/CMV-BCRP, MDA-MB-231/Promoter-BCRP and MDA-MB-231/CMV-BCRP were established in which BCRP was promoted by the BCRP promoter and a CMV promoter as control, respectively. The drug resistant cells were treated with toremifene. Then RT-PCR, Western blot, mitoxantrone efflux assays and cytotoxicity assay were performed to detect the reversal function of BCRP by toremifene on the drug resistance cell lines.

RESULTSToremifene significantly downregulated BCRP mRNA levels in a dose-dependent manner in ERα-positive MCF-7/Promoter-BCRP cells than that of untreated control cells. In MCF-7/Promoter-BCRP cells, toremifene at the dose of 0.1, 1 and 10 µmol/L decreased BCRP mRNA expression by 29.5% (P < 0.05), 68.1% (P < 0.01) and 97.4% (P < 0.01), respectively. After being treated with toremifene and 17β-estradiol, the BCRP mRNA level in MCF-7/Promoter-BCRP cells was 64.2% ± 1.3%, significantly higher than that of toremifene treatment control cells (3.8% ± 0.2%,P < 0.01). Furthermore, the effect of toremifene on BCRP protein is similar in BCRP mRNA. Toremifene obviously increased the mitoxantrone fluorescence intensity and decreased the efflux activity by 47.3% (P < 0.05) in MCF-7/promoter-BCRP cells when compared with the untreated control, whereas intracellular accumulation of mitoxantrone obviously decreased and the efflux activity increased by 61.5% were observed in combination with 17β-estradiol when compared with toremifene treatment alone. The results therefore suggested that toremifene reversed mitoxantrone resistance in MCF-7/Promoter-BCRP cells. However, in MCF-7/CMV-BCRP, MDA-MB-231/Promoter-BCRP and MDA-MB-231/CMV-BCRP cells, toremifene or in combination with 17β-estradiol did not affect intracellular mitoxantrone uptake.

CONCLUSIONTaken together, our findings indicate that expression of BCRP is downregulated by toremifene, via a novel transcriptional mechanism which might be involved in the ERE of BCRP promoter through ER-mediated to inactivate the transcription of BCRP gene.

ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; ATP-Binding Cassette Transporters ; genetics ; metabolism ; Antineoplastic Agents ; pharmacology ; Antineoplastic Agents, Hormonal ; administration & dosage ; pharmacology ; Breast Neoplasms ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; Cytomegalovirus ; genetics ; Dose-Response Relationship, Drug ; Down-Regulation ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Estradiol ; pharmacology ; Estrogen Receptor alpha ; metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Mitoxantrone ; pharmacology ; Neoplasm Proteins ; genetics ; metabolism ; Plasmids ; Promoter Regions, Genetic ; RNA, Messenger ; metabolism ; Recombinant Proteins ; genetics ; metabolism ; Response Elements ; genetics ; Toremifene ; administration & dosage ; pharmacology

BACKGROUND AND OBJECTIVEMale breast cancer (MBC) in China usually has been studied retrospectively with small sample size, and studies analyzing the prognostic factors are rare. This study was to investigate the prognostic factors of Chinese patients with MBC based on the data from a single institute with a relatively large sample.

METHODSClinical data of 72 patients with histopathologically confirmed MBC who received treatment at Sun Yat-sen University Cancer Center between January 1969 and March 2009, were collected. Kaplan-Meier, log-rank test and Cox regression model were used for statistical analysis.

RESULTSThe 5-year overall survival rate was 72.4%, and the survival rates for stage I, II, III, and IV were 100%, 74.2%, 57.2%, and 0%, respectively. Univariate analysis showed that the tumor size (P < 0.001), axillary lymph node status (P = 0.001), TNM stage (P = 0.001), operation model (with vs. without: P < 0.001; classic radical resection vs. modified radical resection, P = 0.336) and endocrine therapy(P = 0.02) significantly influenced the survival. Multivariate Cox regression showed that TNM stage (P = 0.035), operation model (P = 0.021) and endocrine therapy (P = 0.019) were independent prognostic factors for MBC.

CONCLUSIONSEarly diagnosis and comprehensive treatment strategy consisting of surgery and endocrine treatment is essential to improve the survival of the patients with MBC, and TNM stage, operation and endocrine treatment are the significant prognostic factors for MBC.

Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents, Hormonal ; therapeutic use ; Bone Neoplasms ; secondary ; Breast Neoplasms, Male ; pathology ; surgery ; therapy ; Carcinoma, Ductal, Breast ; pathology ; secondary ; surgery ; therapy ; Carcinoma, Intraductal, Noninfiltrating ; pathology ; secondary ; surgery ; therapy ; Carcinoma, Lobular ; pathology ; secondary ; surgery ; therapy ; Chemotherapy, Adjuvant ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Male ; Mastectomy ; methods ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Proportional Hazards Models ; Radiotherapy, Adjuvant ; Retrospective Studies ; Survival Rate ; Tamoxifen ; therapeutic use ; Toremifene ; therapeutic use ; Tumor Burden

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.
Adenofibroma ; Adenosarcoma ; Breast ; Breast Neoplasms ; Endometrial Neoplasms ; Female ; Humans ; Risk Assessment ; Tamoxifen ; Toremifene

This study was aimed to investigate the reversible effect of tetrandrine, toremifene and their combination on multidrug resistance of K562/A02 cell line. The IC(50) (the concentration causing 50% inhibition of cell growth) of adriamycin (ADR) were assayed by MTT method, the expression of MDR1 mRNA was measured by RT-PCR, the concentration of p-glycoprotein (P-gp) and intracellular ADR were detected by flow cytometry. The results showed that the IC(50) of ADR on K562/A02 and K562 cells were 57.43 and 1.16 mg/L, respectively. The IC(50) of ADR on K562/A02 cells after treatment with tetrandrine, toremifene and both combination were 14.12, 20.74 and 9.14 mg/L respectively, but both drugs did not influence the IC(50) of ADR on K562 cells. Pretreating K562/A02 cells with toremifene (2.5 micromol/L), tetrandrine (1 micromol/L) or both for 72 hours partially restored the sensitivity of K562/A02 cells to ADR. Tetrandrine and toremifene (alone or combination) elevated the ADR concentration in K562/A02, down regulated the expressions of P-gp and MDR1 mRNA. It is concluded that multidrug resistance of K562/A02 cells can be partially reversed by tetrandrine or toremifene, the combination of both drugs shows a higher synergistic reversal effect.
Antineoplastic Agents, Hormonal ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Benzylisoquinolines ; pharmacology ; Doxorubicin ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Drug Synergism ; Humans ; K562 Cells ; Toremifene ; pharmacology

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.
Breast Neoplasms* ; Breast* ; Endometrial Neoplasms ; Endometrium* ; Estrogens* ; Female ; Follow-Up Studies ; Humans ; Incidence ; Recurrence ; Survival Rate ; Tamoxifen ; Toremifene*

OBJECTIVETo study the toxic effect of toremifene (TOR) and its synergistic effect with cisplatin (DDP) on human lung adenocarcinoma cell line A549.

METHODSThe cytotoxic effects of these agents on human lung cancer cell line A549 were monitored by a tetrazolium-based colorimetric assay (MTT assay). The cell cycle and DNA content were detected by flow cytometer technic. p21 expression level was monitored by Western blot.

RESULTSToremifene inhibited the growth of A549 cell, with > or = 5 micromol/L significantly enhancing the chemosensitivity of cisplatin. TOR enhanced the antitumor activity of DDP at S, G(2) and M phases of cells. And p21 expression was increased after TOR and DDP had been given.

CONCLUSIONToremifene (> or = 5 micromol/L) combined with cisplatin shows significant synergistic anti-tumor effect on A549 cells.

Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; Cell Division ; drug effects ; Cisplatin ; pharmacology ; Drug Resistance, Neoplasm ; Drug Screening Assays, Antitumor ; Drug Synergism ; Humans ; Lung Neoplasms ; pathology ; Toremifene ; pharmacology ; Tumor Cells, Cultured