Risk factors for developing cardiotoxicity of trastuzumab in breast cancer patients: An observational single-centre study.

BACKGROUND: Trastuzumab is a recombinant humanized monoclonal antibody used to treat human epidermal growth factor receptor 2 positive breast cancer, with recognized associated cardiotoxicity. In this retrospective observational study, we investigated associated cardiotoxicity on clinical outcomes using trastuzumab in women referred to our clinic. MATERIALS AND METHODS: The study was made up of 111 women with human epidermal growth factor receptor 2-overexpressing breast cancer who received trastuzumab in the Medical Oncology Department, between 2010 and 2013. RESULTS: A > 10% reduction of the baseline fraction of the left ventricular ejection fraction was observed in 18 (16.21%) women. Two individuals (1.8%) suffered from symptomatic heart failure, seven women showed cardiac symptoms and nine women showed asymptomatic decline of left ventricular ejection fraction. Risk factors for cardiotoxicity in the group included: postmenopausal status (p = 0.01), hypertension (p = 0.002), obesity (p = 0.0001), previously diagnosed coronary artery disease (p = 0.0001) and smoking (p = 0.03). CONCLUSION: The aforementioned factors pose a risk for cardiotoxicity. We found postmenopausal status, hypertension, obesity, previous coronary artery disease and smoking to be associated with an increased risk of cardiac dysfunction in women using trastuzumab. While administering trastuzumab to women who have these conditions, one must be aware of the risk of cardiotoxicity of trastuzumab.

Evaluation of endometrial thickness and bone mineral density based on CYP2D6 polymorphisms in Turkish breast cancer patients receiving tamoxifen treatment.

BACKGROUND: Several previous studies have examined the effect of CYP2D6 gene polymorphism on the efficacy and metabolism of tamoxifen (Tamoxifen Teva, Nolvadex) in the treatment of breast cancer. In the present study, the metabolic profiles associated with various CYP2D6 genotypes were evaluated. METHOD: In the present study 92 Turkish breast cancer patients with early-stage hormone receptor-positive tumors treated with adjuvant tamoxifen (20 mg) were evaluated for CYP2D6 genotype and metabolic profiles. Known side effects of tamoxifen treatment, including endometrial thickening, changes in serum lipid levels and bone density, and hepatosteatosis, were evaluated according to the CYP2D6 polymorphism. RESULT: The distribution of metabolic characteristics in the Turkish population was as follows: 77.1% normal metabolism, 11.5% intermediate metabolism, 5.2% ultrarapid metabolism, and 2.1% poor metabolism. The CYP2D6 genotypes associated with rapid metabolism were CYP2D6 3X*1/*1 duplication (DUP) and CYP2D6 2X*1/*2, while poor metabolism was associated with the genotypes CYP2D6 *3/*4 and CYP2D6 *6/*6. There was no statistically significant relationship between metabolic characteristics and bone density or hepatosteatosis. A statistically significant difference in total cholesterol and triglycerides was detected in lipid profile analysis (p = 0.003, p = 0.02). Assessment of endometrial thickness revealed a significant association of hyperplasia and poor metabolism, and an association between atrophy and ultrarapid metabolism (p = 0.01). CONCLUSION: Significant development of endometrial hyperplasia was identified among individuals with poor tamoxifen metabolism. As a result, tamoxifen may be a significant predictor of endometrial thickening among individuals with poor metabolic characteristics.

Retrospective analysis of neoadjuvant chemotherapy for breast cancer in Turkish patients.

BACKGROUND: Neoadjuvant systemic chemotherapy is the accepted approach for women with locally advanced breast cancer. Anthracycline- and taxane-based regimens have been extensively studied in clinical trials and consequently are widely used. In this study aimed to research the complete response (pCR) rates in different regimens for neoadjuvant setting and determine associated clinical and biological factors. METHODS: This study included 63 patients diagnosed with breast carcinoma among 95 patients that had been treated with neoadjuvant chemotherapy between 2007 and 2010. TNM staging system was used for staging. The histologic response to neoadjuvant chemotherapy was characterized as a pCR when there was no evidence of residual invasive tumor in the breast or axillary lymph nodes. Biologic subclassification using estrogen receptor (ER), progesterone receptor (PR), HER2 were performed. Luminal A was defined as ER+, PR+, HER2-; Luminal B tumor was defined as ER+, PR-, HER2-; ER+, PR-, HER2+; ER-, PR+, HER2-; ER+, PR+, HER2+, HER2 like tumor ER-, PR+, HER2+; and triple negative tumor ER, PR, HER2 negative. RESULTS: Patients median age was 54.14 (min-max: 30-75). Thirty-two patients (50.8%) were premenopausal and 31 (49.2%) were postmenopausal. Staging was performed postoperatively based on the pathology report and appropriated imaging modalities The TNM (tumor, lymph node, metastasis) system was used for clinical and pathological staging. Fifty-seven (90.5%) were invasive ductal carcinomas, 6 (9.5%) were other subtypes. Thirty nine (61.9%) were grade II and 24 (38.1%) were grade III. Seven (11.1%) patients were stage II and 56 (88.9) patients were stage III. The patients were classified for ER, PR receptor and HER2 positivity. Seventeen patients had complete response to chemotherapy. Forty patients (63.5%) were treated with dose dense regimen (cyclophosphamide 600 mg/m2 and doxorubicine 60 mg/m every two weeks than paclitaxel 175 mg/m2 every two weeks with filgrastim support) 40 patients (48%) were treated anthracycline and taxane containing regimens. Thirteen patients (76%) from 17 patients with pCR were treated with the dose dense regimen but without statistical significance (p=0.06). pCR was higher in HER2(-), ER(-), grade III, premenopausal patients. CONCLUSION: pCR rate was higher in the group that treated with dose dense regimen, which should thus be the selected regimen in neoadjuvant setting. Some other factors can predict pCR in Turkish patients, like grade, menopausal status, triple negativity, percentage of ER positivity, and HER2 expression.

Early detection and gemcitabine/cisplatin combination positively effect survival in sarcomatoid carcinoma of the urinary bladder.

BACKGROUND AND OBJECTIVES: This study aimed to present the clinicopathological characteristics and treatment of patients with bladder carcinoma with sarcomatoid differentiation at our institution. METHODS: Between 1995- 2009, 950 patients were followed-up for bladder carcinoma. Among them, 14 patients with sarcomatoid carcinoma were retrospectively reviewed, and their clinical, pathological features and treatment were recorded. RESULTS: Median age of the patients was 65 years (range: 41-86 years), 12 (86%) being male and 2 (14%) female. All the patients presented with hematuria and 11 (88%) had a history of smoking. The tumor growth pattern was solid in 10 patients, papillary in 2, and mixed in 2. In all, 5 of the patients had urothelial carcinoma with sarcomatoid differentiation and 9 were diagnosed with sarcomatoid carcinoma. Five patients underwent radical cystectomy with ileal conduit surgery, 2 patients refused cystectomy, and 8 patients underwent re-TUR. Following diagnosis ,12 of the patients died in mean 10.7 months (range: 1-48 months). CONCLUSION: Urothelial carcinomas with sarcomatoid features are aggressive and are usually at advanced stage at the time of diagnosis. The outcomes of multimodal treatment are not satisfactory. Significant findings of the present study are that early diagnosis positively affect survival and that gemcitabine and cisplatin in combination can positively affect survival.