Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0010200 (cough)
 23,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amplification of the human epidermal growth factor receptor 2 protein (HER2) in primary breast carcinomas has been shown to correlate with poor clinical prognosis for certain patients. Trastuzumab (Herceptin, Genentech, Inc., South San Francisco, California) is a highly purified recombinant DNA-derived humanized monoclonal immunoglobulin G1 kappa antibody that binds with high affinity and specificity to the extracellular domain of the HER2 receptor. In vitro and in vivo preclinical studies have shown that administration of trastuzumab alone or in combination with paclitaxel or carboplatin significantly inhibits the growth of breast tumor-derived cell lines that overexpress the HER2 gene product. At therapeutic doses in breast cancer patients, the mean half-life of trastuzumab is 5.8 days. Trastuzumab serum concentrations reach steady state with mean trough and peak concentrations of 79 microg/mL and 123 microg/mL, respectively. In a 222-patient, single-arm clinical study, treatment with a loading dose of trastuzumab 4 mg/kg administered IV followed by weekly IV doses of 2 mg/kg produced an overall response rate of 14% (2% complete remission and 12% partial remission). The beneficial effects were greatest in patients with the greatest degree (3+) of HER2 protein overexpression. In another clinical study, 469 women with metastatic breast carcinoma were randomized to a paclitaxel or anthracycline-plus-cyclophosphamide regimen with or without trastuzumab. The overall response rate was significantly greater in the trastuzumab-plus-chemotherapy group than in the chemotherapy-alone cohort. The magnitude of observed effects was greatest with pacli taxel plus trastuzumab. The most common adverse effects attributed to trastuzumab in clinical studies were fever and chills, pain, asthenia, nausea, vomiting, increased cough, diarrhea, headache, dyspnea, infection, rhinitis, and insomnia. Trastuzumab in combination with chemotherapy can lead to cardiotoxicity, leukopenia, anemia, diarrhea, abdominal pain, and infection. Trastuzumab has been approved by the US Food and Drug Administration as a single agent for the treatment of patients who have metastatic breast cancer involving overexpression of the HER2 protein and who have received 1 or more chemotherapy regimens; in combination with paclitaxel, it has been approved for the treatment of such patients who have not received chemotherapy.
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PMID:Trastuzumab, a recombinant DNA-derived humanized monoclonal antibody, a novel agent for the treatment of metastatic breast cancer. 1021 34

BACKGROUND: Totally implantable venous access devices are widely used for infusion of chemotherapy or parenteral nutrition. Device associated complications include technical operative problems, infections, paravasal infusions and catheter or punction chamber dislocation. CASE PRESENTATION: We present the case of a 49-year-old patient with the rare complication of a intrapulmonal catheter dislocation of a totally implantable venous access system. Treosulfane for chemotherapy of metastatic breast cancer was infused via the catheter causing instant coughing and dyspnoea which lead to the diagnosis of catheter dislocation. The intrapulmonal part of the catheter was removed under thoracoscopic control without further complications. CONCLUSION: Intrapulmonal catheter dislocation is a rare complication of a totally implantable venous access device which can not be avoided by any prophylactic measures. Therefore, the infusion system should be tested before each use and each new symptom, even when not obviously related to the catheter should be carefully documented and evaluated by expert physicians to avoid severe catheter-associated complications.
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PMID:Intrapulmonal dislocation of a totally implantable venous access device. 1582 10

The Drug Safety Information Section of the Division of Safety Information on Drug, Food and Chemicals has been providing bulletins titled "Overseas Drug Safety Information" in Japanese since 2003. These bulletins comprise summarized and translated reports of important post-marketing drug safety information that are published by foreign regulatory agencies such as the US Food and Drug Administration (FDA) and the European Medical Agency. A new issue of the bulletin is posted every two weeks on the website of the National Institute of Health Sciences, Japan; to date (May 2013), a total of 280 issues have been posted, covering approximately 2400 foreign news items and articles since its inception. Recently, visits to the bulletin website have been increasing: the number of hits for each issue totaled 570,000 in fiscal 2012. Among the "Overseas Drug Safety Information" issued in the past five years, I briefly describe here several topics which interested me: erythropoietin-stimulating agents in chronic kidney disease and their cardiovascular risk; bisphosphonates and atypical femur fracture; effectiveness of oral liquid cough medicines containing codeine in children; bevacizumab for metastatic breast cancer; and congenital abnormality associated with the use of antiepileptic drugs by pregnant women. I also describe the potential safety signals identified by FDA using its Adverse Event Reporting System, and their importance in ensuring the safe use of drugs in the post-marketing phase.
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PMID:[Topics from "Overseas Drug Safety Information" in the past five years]. 2434 Jun 68

Next-generation sequencing of primary and metachronous metastatic cancer lesions may impact patient care. We present a case of relapsed metastatic breast cancer with a dominant pulmonary lesion originally identified as lung adenocarcinoma. A 72-year-old, never-smoker woman with a protracted cough was found to have a large lung mass and regional lymphadenopathy on a chest CT. Lung mass biopsy showed adenocarcinoma with focal TTF-1 (thyroid transcription factor 1) positivity, favoring a lung primary. In addition to stereotactic brain radiation for cerebral metastases, she was started on carboplatin/pemetrexed. As part of the workup, the tumor was analyzed by a 50-gene targeted mutation panel, which detected 3 somatic mutations: ERBB2 (HER2) D769H activating missense mutation, TP53 Y126 inactivating truncating mutation, and SMARCB1 R374Q missense mutation. Of note, the patient had a history of stage IIA triple-negative grade 3 invasive ductal carcinoma of the left breast 1.5 years ago and received neoadjuvant chemotherapy and adjuvant radiation, and underwent a lumpectomy. Further analysis of her primary breast tumor showed a mutational profile identical to that of the lung tumor. Fluorescence in situ hybridization revealed HER2 amplification in the lung tumor, with a HER2/CEP17 ratio of 3.9. The patient was diagnosed with recurrent HER2-positive metastatic breast carcinoma with a coexisting ERBB2 (HER2) activating mutation. Chemotherapy was adjusted to include dual HER2-targeted therapy containing trastuzumab and pertuzumab, resulting in an ongoing partial response. This case demonstrates that a unique genetic mutational profile can clarify whether a tumor represents a metastatic lesion or new malignancy when conventional morphological and immunohistochemical methods are indeterminate, and can directly impact treatment decisions.
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PMID:Cancer Signature Investigation: ERBB2 (HER2)-Activating Mutation and Amplification-Positive Breast Carcinoma Mimicking Lung Primary. 2628 40

Everolimus has been used in patients with hormone receptor-positive breast cancer. This study reports that treatment with everolimus alone induced severe pulmonary injury in a patient with systemic metastatic breast cancer. A 58-yearold woman with systemic metastatic breast cancer was treated with everolimus alone for 4 weeks and developed severe cough and dyspnea. Computed tomography (CT) scan of the chest showed a progressive lung tumor accompanied by bilateral pulmonary homogeneous ground-glass opacity, especially in the inferior lobe of the left lung. Laboratory examinations revealed a high frequency of monocytes, higher levels of serum alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and C-reactive protein as well as mild hypoxemia and hypocarbia. However, she had no evidence of infection with mycoplasma pneumoniae, chlamydia, pneumocystis, tuberculosis, influenza A virus, and was negative for serum galactomannan (GM) antigen assay. She was suspected to have drug-induced interstitial pneumonia. Everolimus treatment was stopped, and treated with methylprednisolone and empiric antibiotic therapy for 7 days. She received further corticosteroid treatment and felt much better, accompanied by clearance of lung inflammation; she was discharged from hospital. Our experience suggests that treatment with everolimus alone may cause severe pulmonary injury and should be considered carefully in cases of patients with systemic metastatic breast cancer.
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PMID:Treatment with everolimus for a patient with systemic metastatic breast cancer results in severe pulmonary injury: a case report. 2693 4

The lung is a common location for malignant metastases. However, endobronchial metastases from nonpulmonary neoplasms are rare. Metastatic breast cancer usually occurs in 2-3 years of the disease course. A 65-year-old woman visited our hospital for the evaluation of dry cough. The patient had a history of breast cancer, which was treated with modified radical mastectomy and axillary dissection 10 years ago; she was then treated with aromatase inhibitor for 5 years. Chest X-ray revealed right hilum enlargement. Thorax computed tomography revealed a 35-mm diameter mass that was localized in the right hilum. Fiberoptic bronchoscopy was performed, and an endobronchial lesion was observed in the right main lobe carina. Pathological evaluation revealed that the mass was a metastasis of the invasive ductal carcinoma of the breast. Weekly paklitaxel chemotherapy was initiated because of the symptomatic disease. We reported the case of a patient with breast cancer who had an endobronchial metastasis. Her disease-free interval was 10 years. This case indicates that a long-term follow-up of breast cancer is necessary, and biopsies must be performed to make a final diagnosis when any suspicious hilum enlargement is observed.
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PMID:Late Endobronchial Pulmonary Metastasis in a Patient with Breast Cancer. 2975 15

A 70-year-old woman with lung metastases from a breast cancer presented with worsening cough and dyspnoea. She recently had a pleurodesis for a malignant pleural effusion. Chest CT scans demonstrated various radiological changes leading to diagnostic challenges. Differential diagnoses included empyema, pleural disease progression, pulmonary oedema, pneumonitis, lymphangitis and atypical infections. She deteriorated despite a multimodality treatment strategy. Postmortem examination confirmed that lung changes were consistent with a bronchoalveolar carcinoma unrelated to the known metastatic breast cancer. The eventual knowledge of this diagnosis was reassuring to the treating medical team and a comfort to the relatives who witnessed the lack of response to standard treatment.
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PMID:Bronchoalveolar carcinoma as an unsuspected cause for worsening shortness of breath in a patient with metastatic breast cancer. 3041 46