Background: Breast cancer accounts about one million from total annual ten million new diagnosed cases of neoplasia worldwide and is the main cause of death due to cancer in women. Tamoxifen is the most popular selective estrogen receptor modulator used in anti estrogen treatments. Tamoxifen must be converted into its metabolite endoxifen for biologic effects; this conversion process is catalysed by highly polymorphic cytochrome P450 2D6 (CYP2D6). This study surveyed copy number variation of the CYP2D6 gene and its possible correlation with Tamoxifen resistance in breast cancer patients. Methods: This case control study was performed on samples taken from 79 patients with breast cancer who used tamoxifen in Yazd and Tehran Cities, Iran. Real time reactions were conducted for 10 healthy samples using the comparative C t (Cycles threshold) method, each pair of genes being compared and samples with ratios around 1 were taken as control samples. Proliferation reactions were done by Real-Time PCR ABI Prism 7500. All registered data were transformed into SPSS 15 program and analyzed. Results: Efficiency of PCR for both CYP2D6 and ALB genes was 100%. From all 23 drug resistant patients 21.7% had one copy, 47.8% two copies and 30.4% had three copies. Also from all 56 drug sensitive patients, 26.8% had one copy, 51.8% two copies and 21.4% had three copies. The percentage of patients with one and two copies was similar between two groups but patients with three copies were more likely to belong to the drug resistant group more. Odd ratios for one and two copies were 0.759 and 0.853 respectively, indicating possible protective effects while that for three copies was 1.604. Conclusions: Based on our study there is no significant link between CYP2D6 gene copy numbers and tamoxifen resistance in women with breast cancer. But more studies considering other influencing factors appear warranted.
Background This study compared efficacy and safety of TA4415V, a trastuzumab biosimilar, with reference trastuzumab in patients with human epidermal growth factor receptor 2–positive (HER2-positive) early-stage breast cancer treated in the neoadjuvant setting in Iran. Methods Patients were randomly assigned to receive neoadjuvant TA4415V or reference trastuzumab concurrently with docetaxel (TH phase) for 4 cycles after treatment with 4 cycles of doxorubicin and cyclophosphamide (AC phase). Chemotherapy was followed by surgery. The primary endpoint was the comparison of pathologic complete response (pCR) rate in the per-protocol population. Secondary endpoints included comparisons of overall response rate (ORR), breast-conserving surgery (BCS), safety, and immunogenicity. Results Ninety-two participants were analyzed in the per-protocol population (TA4415V, n = 48; reference trastuzumab, n = 44). The pCR rates were 37.50% and 34.09% with TA4415V and reference drug, respectively. The 95% CI of the estimated treatment outcome difference (− 0·03 [95% CI − 0.23 to 0.16]) was within the non-inferiority margin. No statistically significant difference was observed between the groups for other efficacy variables in the ITT population: ORR (89.13% vs. 83.33%; p = 0.72) and BCS (20.37% vs. 12.96%; p = 0.42) in the TA4415V and reference drug group, respectively. At least one grade 3 or 4 adverse events occurred in 27 (50%) patients in the TA4415V group versus 29 (53.70%) in the reference trastuzumab group (p = 0.70). The decrease in left ventricular ejection fraction (LVEF), as an adverse event of special interest (AESI) for trastuzumab, was compared between treatment groups in TH phase. Results demonstrated an LVEF decrease in 7 (12.96%) and 9 (16.67%) patients in TA4415V and reference trastuzumab groups, respectively (p = 0.59). Anti-drug antibodies (ADA) were not detected in any samples of groups. Conclusions Non-inferiority for efficacy was demonstrated between TA4415V and Herceptin based on the ratio of pCR rates in HER2-positive early breast cancer patients. In addition, ORR and BCS, as secondary endpoints, were not significantly different. Safety profile and immunogenicity were also comparable between the two groups.
Background Blastic plasmacytoid dendritic cell neoplasm represents a rare type of hematologic malignancy that often manifests itself through various skin lesions. It commonly affects the elderly male population. Lymph nodes, peripheral blood, and bone marrow involvement are the typical findings that justify its aggressive nature and dismal prognosis. On histopathological assessment, malignant cells share some similarities with blastic cells from the myeloid lineage that make immunohistochemistry staining mandatory for blastic plasmacytoid dendritic cell neoplasm diagnosis. Case presentation A 35-year-old Asian man presented with cervical lymphadenopathy followed by an erythematous lesion on his left upper back. At first, the lesion was misdiagnosed as an infectious disease and made the patient receive two ineffective courses of azithromycin and clarithromycin. Six months later, besides persistent skin manifestations, he felt a cervical mass, which was misdiagnosed as follicular center cell lymphoma. Tumor recurrence following the chemoradiation questioned the diagnosis, and further pathologic assessments confirmed blastic plasmacytoid dendritic cell neoplasm. The second recurrence occurred 3 months after chemotherapy. Eventually, he received a bone marrow transplant after complete remission. However, the patient expired 3 months after transplant owing to the third recurrence and gastrointestinal graft versus host disease complications. Conclusions Early clinical suspicion and true pathologic diagnosis play a crucial role in patients’ prognosis. Moreover, allogenic bone marrow transplant should be performed with more caution in aggressive forms of blastic plasmacytoid dendritic cell neoplasm because of transplant side effects and high risk of cancer recurrence.
Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine cancer that primarily affects the elderly, Caucasians, and the immunocompromised. We present a rare case of an immunocompetent young Iranian (non-Caucasian) female with a small nodule on her left arm. The lesion was initially misdiagnosed as an infected cyst and was treated with antibiotics for 20 days before being surgically removed. Unfortunately, the lump regrew rapidly 2 weeks later, when she had a biopsy, which revealed stage III MCC. She was then treated with adjuvant chemoradiotherapy after a thorough surgical resection of the tumor. Despite the fact that she was in remission after completing chemotherapy courses, she developed neutropenic fever, sepsis and died from septic shock. This case emphasizes the necessity of early clinical diagnosis of MCC and obtaining a biopsy with histopathologic evaluation of rapidly evolving skin lesions suggestive of malignancy.
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