BRCA genes: BRCA 1 and BRCA 2.

BRCA1 and BRCA2 are the genes related with breast and ovarian cancer. They have function in DNA repair processes and thus they are tumor suppressor genes. There are hundreds of mutations identified in these genes. Functional deficiencies due to these mutations impair DNA repair and cause irregularities in the DNA synthesis. The standard method for the laboratory assessment of these BRCA genes includes comprehensive sequencing and testing of broad genomic rearrangements. Members of the families with BRCA mutations have an increased risk for early onset of breast cancer and ovarian cancer occurring at any age. Surveillance of patients with mutations in BRCA 1/2 is done by yearly mammography and breast MRI and by transvaginal ultrasonography and serum CA-125 levels every 6-12 months for ovarian cancer.

Is adjuvant chemotherapy necessary for Luminal A-like breast cancer?

PURPOSE: Patients with breast cancer with Luminal-A subtype have a better prognosis but poor chemotherapy response. Chemotherapy is controversial in lymph node-positive patients with Luminal-A subtype. In this retrospective study, we aimed to evaluate the efficacy and benefit of chemotherapy in the Luminal A-like subtype of breast cancer. METHODS: Patients diagnosed with breast cancer within 2006 and 2011 were retrospectively evaluated. Patients with pathologically confirmed Luminal A-like breast cancer were analyzed , and were divided in those receiving taxane-based adjuvant chemotherapy and those who did not. RESULTS: A total of 136 patients with Luminal-A type were included in the study. The 10-year cumulative disease-free survival (DFS) was 85.6 vs 96.7% (p=0.230) for the chemotherapy and non-chemotherapy groups, and overall survival (OS) was 88.6 vs 100%, respectively (p=0.242). The 10-year cumulative DFS was 80 vs 98.1% for the taxane-based chemotherapy group and taxane-free chemotherapy group (p=0.501), while the OS was 87.5 vs 95.2%, respectively (p=0.391). There was a positive correlation between relapse status and lymph node involvement in the multivariate analysis (p=0.031). CONCLUSION: Adjuvant chemotherapy in Luminal-A showed no significant difference for DFS and OS. Taxane-based chemotherapy did not demonstrate any benefit for OS and DFS with relatively more advanced stage and lymph node involvement. We believe that adjuvant chemotherapy plays a minor role in a significant proportion of Luminal-A subtype of breast cancer.

The prognostic significance of cyclin D1 expression in patients with triple-negative breast cancer.

PURPOSE: Breast cancer (BC) is the most common cancer and the second leading cause of cancer death among women. While receptor-targeted therapies are used for other subtypes due to the presence of such receptors, studies are still continuing on receptor expression in order to identify new therapeutic targets as the triple-negative breast cancer (TNBC) lacks a target receptor and its prognosis is worse than the other subtypes. Cyclin D1 (CycD1) is a cell cycle regulator protein. It is stated that its overexpression plays a role in carcinogenesis. With the present study, we aimed to evaluate the prognostic significance of immunohistochemical expression of CycD1 in patients with TNBC. METHODS: The study included 56 operated patients with TNBC who were diagnosed between 2006 and 2011 at Izmir Katip Celebi University, Ataturk Research and Training Hospital, Department of Pathology. In tumor paraffin-embedded sections, CycD1 was immunohistochemically (IHC) studied. Demographic and survival data of the patients were obtained from the Department of Medical Oncology follow-up files. ROC curve analysis was used to calculate the cutoff value for CycD1 staining density. Patients were divided into two groups using 11.5 cutoff value for the expression of CycD1, obtained by ROC analysis. Kaplan-Meier analysis was utilized for survival analyses, and log rank test for comparisons between the two groups. RESULTS: Of the patients, 62.5% had CycD1 expression (37.5% had not). In the whole group, the 5-year disease-free survival (DFS) was 51%, and the 5-year overall survival (OS) was 65%. No difference in DFS between the two groups was noticed (p=0.37). The 5-year DFS was 47% in the group with CycD1 expression below 11.5, while it was 57% in the group above the 11.5 value. The difference in OS between the groups was statistically significant (p=0.044). The 5-year OS was 55% in the group with a CycD1 expression below 11.5, while it was 79% in the group above the 11.5 value (p=0.044). CONCLUSION: OS differed significantly between the high and low-CycD1 expression. It was also demonstrated that CycD1 may have prognostic significance in TNBC. Further studies with larger populations are required to confirm the prognostic significance of CycD1.

The maximum standardized uptake value of metastatic site in 18 F-FDG PET/CT predicts molecular subtypes and survival in metastatic breast cancer: An Izmir Oncology Group study.

PURPOSE: The purpose of this study was to analyse the association between the 18F-2-deoxy-2-fluorodeoxyglucose maximum standardized uptake value (SUVmax) of metastatic sites and molecular subtypes and survival in metastatic breast cancer (MBC) patients. METHODS: Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) was performed in 176 MBC patients before any therapeutic intervention. The FDG uptakes of metastatic sites were evaluated using the SUVmax. Histopathological prognostic parameters, such as the tumor size, grade, lymph node involvement, lymphovascular invasion, estrogen (ER), progesterone receptors (PR), HER2 status and Ki67 were determined from the primary breast tumor tissue. The SUVmax of the metastatic sites was assessed in relation to the molecular subtypes and survival in univariate and multivariate analyses. Cox regression analysis was used to evaluate the associations between SUVmax measurements and overall survival (OS). RESULTS: The mean SUVmax of 176 tumors was 8.0. Among the subtypes 49 (28.8%) were luminal A, 51 (28.9%) luminal B, 35 (19.8%) HER2-overexpressing, and 41 (23.2%) triple- negative, and the corresponding means of SUVmax were 5.6, 7.4, 11.4, 11.0, respectively. A cut-off value of ≤8.4 yielded 80% sensitivity and 57.1% specificity with an area under the receiver operating characteristics curve (AUC) of 0.731 for predicting that a tumor was of the luminal A subtype. A cut-off value of SUVmax ≥10.05 yielded 62.9% sensitivity and 67.4% specificity with an AUC of 0.648 for predicting a HER2 overexpressing subtype. A cut-off value of SUVmax ≥9.25 yielded 61% sensitivity and 64.4% specificity with an AUC of 0.660 for predicting a triple-negative subtype. The SUVmax could not effectively differentiate patients with luminal B subtype. Cox regression analysis showed that in patients with MBC, a SUVmax ≤7.55 acted as an independent negative prognostic factor for OS (hazard ratio/HR = 1.552). CONCLUSION: The SUVmax of metastatic sites on pretreatment 18F-FDG PET/CT may be an independent prognostic factor for the diagnosis of molecular phenotypes and survival in MBC patients.

Quality of life in colorectal cancer patients: an Izmir Oncology Group (IZOG) study.

PURPOSE: To investigate the variables of quality of life (QoL) among Turkish patients with colorectal cancer (CRC). METHODS: In this prospective study we investigated the QoL of Turkish CRC patients. Two hundred and twenty two patients with CRC were included. The sociodemographic form and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) were used. RESULTS: The study group consisted of 142 males (64%) and 80 females (36%). The mean patient age was 55.68±11.387 years. The majority of the patients (36.9%) had local disease while advanced-stage disease and locally advanced stage disease had 32.2% and 28.8% of the patients; respectively. The mean QoL score was moderate (62.81± 27.0). The most common complaints were fatigue, economic difficulties and constipation. Gender, education level and disease stage were associated with QoL. Physical, role and social functioning were more adversely affected in female patients. Compared to women, men had significantly more favorable global QoL (p=0.044). Some functional scales were worse in advanced disease compared to other stages.These outcomes were statistically significant in the functional scales of global health (p=0.007), physical (p=0.03), cognitive (p=0.01) and emotional function (p=0.007). Patients with advanced disease had worse outcomes in some symptoms (nausea, vomiting, dyspnea, loss of appetite and financial distress). CONCLUSIONS: Female gender and advanced disease were strongly associated with poorer QoL among Turkish CRC patients.

Comparison of first-line bevacizumab in combination with mFOLFOX6 or XELOX in metastatic colorectal cancer.

PURPOSE: Currently, there are several oxaliplatin combination regimens for first-line therapy of metastatic colorectal cancer (mCRC). In this study, we compared the survival outcomes of mCRC patients treated with bevacizumab in combination with either modified 5-FU/FA/oxaliplatin (mFOL- FOX6) or capecitabine/oxaliplatin (XELOX). METHODS: We designed a two-arm retrospective study of mCRC patients with adenocarcinoma of the colon or rectum who were treated with bevacizumab and either mFOLFOX6 or XELOX and who had complete clinical and treatment data. We analysed their therapeutic responses, adverse events, progression-free survival (PFS), and overall survival (OS), and then determined whether there were any statistically significant differences. RESULTS: A total of 131 patients (85 male; 65% and 46 female; 35%) were evaluated. Fifty-seven patients (43.5%) were treated with bevacizumab and mFOLFOX6 and 74 (56.5%) with bevacizumab and XELOX. The median PFS was 9.1 months (95% CI, 4.9-13.1) and 10 months (95% CI, 4.2-15.9) in the mFOLFOX6 and XELOX arms, respectively (p=0.610). The median OS was 29 months (95% CI, 21.6- 34.3) and 27.5 months (95% CI 20-38) in the mFOLFOX6 and XELOX arms (p=0.812), respectively. The most common reason for treatment withdrawal was disease progression (102 patients; 91%) and the most common grade 3-4 toxicity was neuropathy (≤14%). CONCLUSION: Our results show that XELOX is a safe and effective alternative to mFOLFOX6 when combined with bevacizumab as first-line treatment for mCRC patients.

Enhanced cytotoxicity and apoptosis by thymoquinone in combination with zoledronic acid in hormone- and drug-resistant prostate cancer cell lines.

PURPOSE: Thymoquinone (TQ), an active ingredient of black seed oil (Nigella Sativa), has been shown to possess cytotoxic activity against a variety of cancer cell lines. Our purpose was to investigate if the cytotoxic and apoptotic effect of zoledronic acid (ZA) can be enhanced by the addition of the TQ in hormone- and drug-refractory prostate cancer cells PC-3 and DU-145. METHODS: XTT cell proliferation assay was used to assess cytotoxicity; DNA fragmentation and caspase 3/7 activity were also measured. RESULTS: The combination of TQ and ZA resulted in a significant synergistic cytotoxic activity and DNA fragmentation when compared to any single agent alone, in a dose- and time-dependent manner. In addition, TQ and ZA combination increased the caspase 3/7 activity in PC-3 cell line, while this activity could not be demonstrated in DU-145 cell line. CONCLUSION: TQ and ZA had minimal hematological and non-hematological toxicity profile compared to cytotoxic agents. So, this combination may be an alternative approach for patients who are unable to be treated by conventional treatments because of poor performance status.

Capecitabine-related increased mean corpuscular volume of red blood cell may be a predictive marker of treatment response and survival in patients with metastatic colorectal cancer.

PURPOSE: Erythrocyte mean corpuscular volume (MCV) increase has been described in patients treated with capecitabine. In this study, we sought to evaluate the potential association of the erythrocyte MCV increase with tumor response and survival in patients with metastatic colorectal cancer (mCRC) treated with capecitabine. METHODS: A retrospective review of 131 patients with mCRC who were treated with capecitabine for at least 3 months at the Izmir Training and Research Hospital was undertaken. Complete blood count (CBC) including red blood cell indices were recorded at baseline and after 9 weeks from capecitabine treatment. RESULTS: The mean patient age was 57.9 years (range 28- 82). In patients treated with capecitabine, MCV increased significantly at 9 weeks compared with baseline (p=0.000). Median ΔMCV [(post-treatment MCV values) - (baseline MCV values)] level was 9.3 fL. Patients were grouped according to ΔMCV into two groups (> 9.3 or ≥ 9.3) in order to carry out survival analysis and correlation with tumor response. ΔMCV was >9.3 in 65 patients and ≤9.3 in 66 patients. Fifty-six of the 65 patients with ΔMCV levels >9.3 and 37 of the 66 patients with ΔMCV levels ≤9.3 had a clinical benefit (complete response + partial response + stable disease) from capecitabine treatment (p=0.000). The difference between progression-free survival (PFS) and overall survival (OS) of the patients who had ΔMCV>9.3 and those who had ≤9.3 was statistically significant (9.48 and 6.94 months, p=0.001 respectively; and 17.5 and 13.6 months respectively, p=0.018). Univariate analysis suggested that a favorable prognosis for OS and PFS was associated with MCV increase (p=0.000). In multivariate analysis, MCV increase was independently associated with favorable survival outcomes. CONCLUSIONS: Erythrocyte MCV increase may be used as a predictive marker for treatment response, PFS and OS in patients with mCRC treated with capecitabine.

Use of oral antidiabetic drugs (metformin and pioglitazone) in diabetic patients with breast cancer: how does it effect serum Hif-1 alpha and 8Ohdg levels?

OBJECTIVE: The aim was to investigate indicators related to DNA damage and cancer pathogenesis in Type II diabetes cases with breast cancer. It was planned to evaluate the relationship between these markers with oral antidiabetic drugs. RESEARCH DESIGN AND METHODS: Fourty patients and 10 healthy individuals were included in the study. HIF-1α and 8-OHdG are examined in blood samples taken from these individuals with an ELISA Kit. Statistical analysis of data was performed with 95% confidence using Windows package program SPSS 15.0. RESULTS: HIF-1α parameters were found to be meaningfully higher in the patient group than the controls in both pretreatment and posttreatment periods (p<0.05). No significant differences in terms of 8-OHdG between patients and controls. However, posttreatment serum HIF-1α ve 8-OHdG levels was found lower than pretreatment levels in patients receiving metformin, but not with pioglitazone. Conversely, serum 8-OHdG levels decreased significantly in these patients. When patients were evaluated according to the treatment groups (pioglitazone vs. metformin) no significant differences in terms of serum HIF-1? and 8-OHdG levels between treatment groups. CONCLUSIONS: HIF-1α levels decreased significantly in the patient group receiving metformin. However, there was no significant difference in terms of HIF-1α levels in the patients receiving pioglitazone.