Targeted Therapy for Breast Cancer

WOS: 000325118800007PubMed ID: 23988612Breast cancer is a heterogeneous group of diseases that are clinically subdivided as hormone receptor-positive, human epidermal growth factor receptor 2-positive (HER2+), and triple-negative breast cancer, to guide therapeutic interventions. Agents that target estrogen receptor (ER) and HER2 are among the most successful cancer therapeutics. However, de novo or acquired resistance is common, despite the development of newer agents against these pathways. As our understanding of tumor biology improves, novel targets are being identified. Notably, inhibitors against several pathways [including, among others, the phosphoinositide 3-kinase/mammalian target of rapamycin (PI3K/mTOR), cell-cycle regulation, heat shock protein, and epigenetic pathways] have demonstrated promising activity in clinical trials, and the mTOR-inhibitor everolimus has been approved for advanced or metastatic aromatase inhibitor-resistant ER+ breast cancer. At present, there are no established targeted agents for triple-negative breast cancer (negative ER, progesterone receptor, and HER2). Although poly(ADP-ribose) polymerase inhibitors have shown promising activity in BRCA-related cancers, its value in the treatment of triple-negative breast cancers remains to be demonstrated. In this Review, we present a basic understanding of the major targeted agents in current practice and under development for the treatment of breast cancer in the context of the three clinical subgroups.Siteman Cancer Center; Foundation for Barnes-Jewish Hospital; Susan G. Komen FoundationSusan G. Komen Breast Cancer Foundation; CALGB Clinical Investigator AwardSupported by the Siteman Cancer Center and Foundation for Barnes-Jewish Hospital, the Susan G. Komen Foundation, and the CALGB Clinical Investigator Award

Antrasiklinlere Bağlı Elektro-Mekanik Değişiklikler: Kardiyotoksisiteyi Erken Dönemde Öngörmede Strain Ekokardiyografinin Repolarizasyon Belirteçleri ile Birlikte Kullanımı

Objective: The aim of the study was to describe the acute cardiotoxic effects of anthracycline chemotherapy in echocardiographic strain and electrocardiographic repolarization parameters in patients with breast cancer. Methods: A total of 35 consecutive patients (all females, mean age: 48.9 +/- 11.8 years) who received chemotherapy due to breast cancer were prospectively included. Pre-treatment (T0) and third month (T2) 2-dimensional strain echocardiography and electrocardiography were performed. Additionally, within 3 hours of the first dose of chemotherapy (T1), additional electrocardiographic images were obtained. All mechanical and electrical parameters from different time intervals (T0, T1, and T2) were compared with each other. Results: In the acute period after treatment, electrocardiographic repolarization parameters were prolonged and this prolongation continued to the third month (QT corrected with Bazett formula [440.10 +/- 27.63 (T0), 468.00 +/- 38.98 (T1), 467.86 +/- 35.09 (T2)], QT dispersion [49.85 +/- 19.52 (T0), 69.54 +/- 16.06 (T1), 57.63 +/- 14.42 (T2)], and T-wave peak-to-end interval [94.00 +/- 45.46 (T0), 131.20 +/- 17.79 (T1), 120.00 +/- 18.32 (T2)]; P <.001). There was no significant change in global longitudinal strain values before and after treatment (global longitudinal strain avg: -21 +/- 7.1%; P =.8). However, there were significant reductions in strain parameters including circumferential and radial strain, and torsion (-17.2 +/- 3.5 to -13 +/- 2.84; P <.001, 45.1 +/- 8.3 to 35.6 +/- 10; P <.001, and 12.1 +/- 3.5 to 7.7 +/- 2.1; P <.001, respectively). Conclusion: Both the electrical and mechanical functions of the heart can be impaired acutely extending to 3 months after anthracycline chemotherapy. Therefore, cardiotoxicity should be evaluated early both electrically and mechanically after chemotherapy

<it>Strongyloides stercoralis </it>hyperinfection in a patient with rheumatoid arthritis and bronchial asthma: a case report

Abstract Objective Strongyloides stercoralis is a soil-transmitted intestinal nematode that has been estimated to infect at least 60 million people, especially in tropical and subtropical regions. Strongyloides infection has been described in immunosupressed patients with lymphoma, rheumatoid arthritis, diabetes mellitus etc. Our case who has rheumatoid arthritis (RA) and bronchial asthma was treated with low dose steroids and methotrexate. Methods A 68 year old woman has bronchial asthma for 55 years and also diagnosed RA 7 years ago. She received immunusupressive agents including methotrexate and steroids. On admission at hospital, she was on deflazacort 5 mg/day and methotrexate 15 mg/week. On her physical examination, she was afebrile, had rhonchi and mild epigastric tenderness. She had joint deformities at metacarpophalengeal joints and phalanges but no active arthritis finding. Results Oesophagogastroduodenoscopy was performed and it showed hemorrhagic focus at bulbus. Gastric biopsy obtained and showed evidence of S.Stercoralis infection. Stool and sputum parasitological examinations were also all positive for S.stercoralis larvae. Chest radiography result had no pathologic finding. Albendazole 400 mg/day was started for 23 days. After the ivermectin was retrieved, patient was treated with oral ivermectin 200 μg once a day for 3 days. On her outpatient control at 15th day, stool and sputum samples were all negative for parasites. Conclusion S.stercoralis may cause mortal diseases in patients. Immunosupression frequently causes disseminated infections. Many infected patients are completely asymptomatic. Although it is important to detect latent S. stercoralis infections before administering chemotherapy or before the onset of immunosuppression in patients at risk, a specific and sensitive diagnostic test is lacking. In immunosupressed patients, to detect S.stercoralis might help to have the patient survived and constitute the exact therapy.</p