quetiapine-fumarate and Breast-Neoplasms

Breast cancer is more common in female patients with schizophrenia than in the general population. It is not known whether treatment with prolactin-increasing antipsychotics contributes to increased odds of breast cancer.. We used Finnish nationwide registers of hospital treatment, prescription drug purchases, and cancer diagnoses to do a nested case-control study. Of women with schizophrenia, those with breast cancer (cases) were matched by age and duration of illness with five women without cancer (controls). Cases and controls were aged 18-85 years and exclusion criteria were any previous cancer diagnoses, receipt of organ transplant, mastectomy, or diagnosis of HIV. The main analysis was the association between cumulative exposure to prolactin-increasing drugs and breast cancer. The analyses were done with conditional logistic regression, by adjusting for comorbid conditions and concomitant medications. Ethnicity data were not available.. Of 30 785 women diagnosed with schizophrenia between 1972 and 2014, 1069 were diagnosed with breast cancer between Jan 1, 2000, and Dec 31, 2017. Compared with 5339 matched controls, 1-4 years cumulative exposure (adjusted odds ratio [OR] 0·95, 95% CI 0·73-1·25) or 5 or more years exposure (adjusted OR 1·19, 0·90-1·58) to prolactin-sparing antipsychotics (including clozapine, quetiapine, or aripiprazole) was not associated with an increased risk of breast cancer in comparison with minimal exposure (<1 year). When compared with less than 1 year of exposure to prolactin-increasing antipsychotics (all other antipsychotics), 1-4 years of exposure was not associated with an increased risk, but exposure for 5 or more years was associated with an increased risk (adjusted OR 1·56 [1·27-1·92], p<0·001). The risk for developing lobular adenocarcinoma associated with long-term use of prolactin-increasing antipsychotics (adjusted OR 2·36 [95% CI 1·46-3·82]) was higher than that of developing ductal adenocarcinoma (adjusted OR 1·42 [95% CI 1·12-1·80]).. Long-term exposure to prolactin-increasing, but not to prolactin-sparing, antipsychotics is significantly associated with increased odds of breast cancer. Monitoring prolactinemia and addressing hyperprolactinemia is paramount in women with schizophrenia being treated with prolactin-increasing antipsychotics.. Finnish Ministry of Social Affairs and Health.

Topics: Adult; Aged; Antipsychotic Agents; Breast Neoplasms; Carcinoma, Lobular; Case-Control Studies; Clozapine; Female; Finland; Humans; Middle Aged; Prolactin; Quetiapine Fumarate; Schizophrenia

Bone loss is one of the major complications of advanced cancers such as breast cancer, prostate cancer, and lung cancer. Extensive research has revealed that the receptor activator of NF-κB ligand (RANKL), which is considered to be a key factor in osteoclast differentiation, plays an important role in cancer-associated bone resorption. Therefore, agents that can suppress this bone loss have therapeutic potential. In this study, we detected whether quetiapine (QUE), a commonly used atypical antipsychotic drug, can inhibit RANKL-induced osteoclast differentiation in vitro and prevent human breast cancer-induced bone loss in vivo. RAW 264.7 cells and bone marrow-derived macrophages (BMMs) were used to detect inhibitory effect of QUE on osteoclastogenesis in vitro. Mouse model of breast cancer metastasis to bone was used to test suppressive effect of QUE on breast cancer-induced bone loss in vivo. Our results show that QUE can inhibit RANKL-induced osteoclast differentiation from RAW 264.7 cells and BMMs without signs of cytotoxicity. Moreover, QUE reduced the occurrence of MDA-MB-231 cell-induced osteolytic bone loss by suppressing the differentiation of osteoclasts. Finally, molecular analysis revealed that it is by inhibiting RANKL-mediated MAPK and NF-κB signaling pathways that QUE suppressed the osteoclast differentiation. We demonstrate, for the first time, the novel suppressive effects of QUE on RANKL-induced osteoclast differentiation in vitro and human breast cancer-induced bone loss in vivo, suggesting that QUE may be a potential therapeutic drug for osteolysis treatment.

Topics: Animals; Bone Resorption; Breast Neoplasms; Cell Differentiation; Cell Line, Tumor; Dibenzothiazepines; Female; Humans; Macrophages; MAP Kinase Signaling System; Mice; NF-kappa B; Osteoclasts; Quetiapine Fumarate; RANK Ligand; Signal Transduction

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antipsychotic Agents; Bevacizumab; Breast Neoplasms; Dibenzothiazepines; Drug Costs; Drug Labeling; Health Services Accessibility; Insurance, Health, Reimbursement; Legislation, Drug; Midodrine; Off-Label Use; Prescription Drugs; Quetiapine Fumarate; United States; Vasoconstrictor Agents

Several studies have reported the findings of fluorine-18-labeled fluoro-2-deoxy-D: -glucose positron emission tomography (FDG-PET) in benign lung disease with diffuse pulmonary injury; however, the characteristics and effectiveness of FDG-PET imaging for interstitial pneumonitis have not been substantiated. We report two cases of drug-induced pneumonitis in two patients treated for breast cancer who were diagnosed by FDG-PET examination. Both the cases showed diffuse interstitial infiltration in the bilateral lungs on computed tomography, but the degree of FDG accumulation was different. It is probable that the degree of FDG accumulation reflected the activity of the drug-induced pneumonitis. The present cases show very interesting FDG-PET imaging findings of diffuse lung disease.

Topics: Aged; Anxiety Disorders; Brain Neoplasms; Breast Neoplasms; Dibenzothiazepines; Female; Fluorodeoxyglucose F18; Humans; Middle Aged; Neoplasm Recurrence, Local; Paclitaxel; Pneumonia; Positron-Emission Tomography; Quetiapine Fumarate; Sensitivity and Specificity; Tomography, X-Ray Computed; Whole Body Imaging