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.

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.

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.

Clinical outcomes of cyclin-dependent kinase 4-6 (CDK 4-6) inhibitors in patients with male breast cancer: A multicenter study.

BACKGROUND: Since breast cancer is less common in men than in women, data on the use of new therapeutic agents, including cyclin-dependent kinase 4-6 (CDK 4-6) inhibitors, are limited in patients with metastatic hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) male breast cancer. Therefore; we aimed to investigate the treatment responses of metastatic HR+, HER2-male breast cancer patients treated with CDK 4-6 inhibitors in a multicenter real-life cohort. METHODS: Male patients with a diagnosis of HR+ and HER2-metastatic breast cancer, treated with any CDK 4-6 inhibitor, were included in the study. Demographic and clinical characteristics of the patients were recorded. We aimed to determine progression-free survival (PFS) time, response rates and drug related side effects. RESULTS: A total 25 patients from 14 institutions were recruited. The mean age at diagnosis was 57 years. Median follow-up was 19.53 (95% CI: 14.04-25.02) months. The overall response rate was 60%. While the median PFS was 20.6 months in the whole cohort, it wasn't reached in those using CDK 4-6 inhibitors in first line and 10 months in the subsequent lines (p:0.009). No new adverse events were encountered. CONCLUSION: In our study, we found that CDK 4-6 inhibitors are effective and safe options in men with HR+ and HER2-metastatic breast cancer as in women. Our results support the use of CDK 4-6 inhibitor-based combinations in the first-line treatment of HR+ and HER2-metastatic male breast cancer.