Seden Kucucuk

Lower Level of MAPK Expression Is Associated with Anthracycline Resistance and Decreased Survival in Patients with Hormone Receptor Negative Breast Cancer

Introduction: Hormone receptor negative breast cancer is encountered in about 30% of all patients with breast cancer and is considered as a prognostically unfavorable subset. The aim of this study is to evaluate the prognostic impact of various molecular markers in patients with receptor negative breast cancer. Methods: Tumor specimens from 140 patients with receptor negative (ER, PR) breast cancer were analyzed for MAPK, Her-2/neu, EGFR and PI3K expression by immunohistochemistry. The prognostic significance of these molecular factors, in addition to various prognostic variables were determined with respect to disease-free and overall survival.Results: Nineteen (13.6%), 45 (32.1%), 16 (11.4%) and 47 (33.5%) patients had positive staining for EGFR, PI3K, Her-2/neu and MAPK, respectively. Twenty-three patients with positive MAPK (16.4%) had a high level of expression (score 4–7) and 24 (17.1%) had a low score (1–3). A lower percentage of MAPK expression was significantly associated with a poorer OS (p = 0.03) and a tendency for shorter DFS (p = 0.08) among those who were positive for MAPK. Anthracycline resistance remained the only independent significant variable for OS by Cox regression analysis (p = 0.001, HR:26.1). In patients with recurrent disease, median survival after initial relapse was 16.8 months. MAPK was determined as the only prognostic factor for this endpoint. Patients with higher level of MAPK staining showed significantly shorter survival following initial recurrence (p = 0.04). Conclusion: MAPK expression is a significant prognostic factor for non-metastatic patients with hormone receptor breast cancer. A lower level of staining is shown to be associated with with antracycline resistance and oveall survival, whereas a higher expression level is correlated with shorter survival following initial relapse, suggesting possible role of different molecular mechanisms pertaining to tumor progression once recurrence occurs. Further translational research is required to elucidate molecular mechanisms of the cross-talk between intracellular signaling and molecular pathways leading to drug resistance in patients with receptor negative breast cancer.

Factors affecting the prognosis of breast cancer patients with brain metastases

The aim of this retrospective analysis was to investigate the factors affecting the prognosis of brain metastases in breast cancer patients to identify subgroups which might benefit from prophylactic treatments in future. Seventy-three early and 13 advanced stage patients with known Erb-2 status were included. In 14% of the early stage patients, the first recurrence site was isolated brain metastasis. None of the anthracycline resistant patients had brain metastases as their first recurrence site. The median interval between diagnosis and brain metastasis was 41.5 months (95% CI, 35.79-47.20) in early stage patients. The median interval between the first extracerebral metastases to the brain metastases was 15.5 months (95% CI, 12.24-18.76) in all patients. High histologic and nuclear grade, large tumor, anthracycline resistance were the factors which significantly affected the early appearance of brain metastases but only advanced age (> or =55 years, P=.035) correlated with isolated brain metastasis. Progression with isolated brain metastases was significantly higher in responsive ErbB-2 positive population (P=.036) and none of other pathological factors was associated with isolated brain metastasis in advanced stage. The median survival after brain metastasis in patients with brain metastasis as first recurrence was longer than the patients with brain metastasis after other organ metastasis (13 months vs 2 months P=.003). The median survival following brain metastases in complete responsive patients was higher than the others (24 months vs 6 months, P=.002). Therefore, response to systemic treatment was more determinative in the development of isolated brain metastases than clinical and pathologic features. ErbB-2 should be emphasized in prophylactic treatment strategies. Prophylactic cranial radiotherapy may be an effective treatment option for metastatic patients with complete responsive disease and with controlled ErbB-2 positive disease.

Serum prolidase I activity and some bone metabolic markers in patients with breast cancer: in relation to menopausal status

OBJECTIVES The purpose of this study was to investigate the diagnostic value of some osteoblastic/osteoclastic biochemical markers and serum prolidase I activity in breast cancer (BC). DESIGN AND METHODS Serum bone gla protein (BGP), prolidase I activity, urinary deoxypyridinoline (Dpy) and calcium excretions were measured, in metastatic and nonmetastatic BC patients, and in 52 healthy women. RESULTS In patients with metastases, bone turnover markers were found to be significantly higher than those in the control group and in patients without metastases. Serum prolidase activity in patients with and without metastases was also significantly higher than those in the control group, but there was no difference between the two patient groups. CONCLUSIONS Bone turnover has been suggested to be accelerated in BC patients with the more pronounced osteolytic activation, especially in metastatic state. Serum prolidase in premenopausal period appears to be valuable in discriminating cancer patients from controls. BGP and to a lesser degree of Dpy, may be useful markers for predicting the metastatic bone involvement, as well as for the more cost effective management of BC patients and monitoring the effects of antiresorptive therapy of malignant osteolysis before any metastasis could be detected by other invasive techniques.

Evaluation of Prognostic Factors and Comparison of Systemic Treatment Modalities in Patients with Recurrent or Metastatic Endometrial Carcinoma

BackgroundPrognostic factors related to survival in patients with inoperable metastatic or recurrent endometrial carcinoma (MREC) have remained unclear due to lack of clinical trials. The management of these patients is also controversial. This study was performed to compare the efficacy and toxicity profiles of two different systemic therapies (chemotherapy vs hormonal therapy) given for the treatment of patients with MREC and to identify the impact of various prognostic factors on the survival.MethodsBetween 1992 and 2004, 44 patients with MREC were admitted to our oncology department. Four cases were excluded from this retrospective study because of lack of data in their charts. Age, presence of other systemic diseases (such as diabetes mellitus, hypertension), histological type, tumor grade, stage, disease-free interval, site of recurrence or metastasis, systemic treatment modality, overall response to treatment, and duration of time to progression were evaluated as prognostic factors. Cox regression analysis was performed for identification of independent prognostic factors and differences between patients characteristics of two treatment groups were calculated by the chi-square or t test.ResultsThe median follow-up was 18 mo (range 3–113). The overall response rates for chemotherapy and hormonal therapy group were 42% and 41%, respectively (p>0.05). The median time to progression was 4 mo for the chemotherapy group and 5 mo for the hormonal therapy group (P>0.05). The median survival after metastasis or recurrence was 11 mo for the chemotherapy group and 16 mo for the hormonal therapy group (p>0.05). In the group of chemotherapy, grade 3–4 hematologic and nonhematologic toxicities were seen in eight and two, patients, respectively. No grade 3–4 toxicities were noted in patients treated with hormonal therapy. In multivariate analysis, only time to progression (p=0.001) and grade (p=0.04) were the independent prognostic factors on survival after metastasis or recurrence.ConclusionHistological differentiation and duration of time to progression are predictive factors for survival after metastasis or recurrence in the whole group. The efficacy of two different groups of treatment in these patients appears to be similar. But the chemotherapy may have some disadvantageous in terms of toxicity. This study supports a future randomized prospective trial of hormonal therapy vs chemotherapy in patients with MREC.

Metaplastic Breast Carcinoma Versus Triple-Negative Breast Cancer: Survival and Response to Treatment.

AbstractMetaplastic breast carcinoma (MBC) differs from classic invasive ductal carcinomas regarding incidence, pathogenesis, and prognosis. The purpose of this study was to compare patients with MBC with clinicopathologic and treatment-matched patients with triple-negative breast carcinoma (TNBC) in terms of response to treatment, progression, and survival.Fifty-four patients with MBC and 51 with TNBC, who were treated at Istanbul University, Institute of Oncology, between 1993 and 2014, were included in the study. After correctly matching the patients with 1 of the 2 groups, they were compared to determine differences in response to treatment, disease progression, clinical course, and survival.At a median follow-up of 28 months, 18 patients (17.1%) died and 27 (25.5%) had disease progression. Metaplastic histology was significantly correlated with worse 3-year progression-free survival (PFS) (51 ± 9% vs. 82 ± 6%, P = 0.013) and overall survival (OS) (68 ± 8% vs. 94 ± 4%, P = 0.009) compared with TNBC histology. Patients who received taxane-based chemotherapy (CT) regimens or adjuvant radiotherapy had significantly better PFS (P = 0.002 and P < 0.001) and OS (P < 0.001 and P < 0.001) compared with others. In the multivariate analysis, MBC (hazard ratio [HR]: 0.09, P < 0.001), presence of neoadjuvant chemotherapy (NACT) (HR: 12.8, P = 0.05), and metastasis development at any time during the clinical course (HR: 38.7, P < 0.001) were significant factors that decreased PFS, whereas metastasis development was the only independent prognostic factor of OS (HR: 23.8, P = 0.009).MBC is significantly correlated with worse PFS and OS compared with TNBC. Patients with MBC are resistant to conventional CT agents, and more efficient treatment regimens are required.

Are CYP17 genotypes a biomarker for ovarian cancer in patients with cancer history in their family

BRCA1 and BRCA2 genes are responsible for 5-10% of breast and ovarian cancer cases. However, the vast majority of ovarian and breast cancer cases do not display the hereditary form of the disease. Estrogen-metabolizing genes may also contribute to the predisposition of breast or ovarian cancer. Polymorphic variants of the estrogen-metabolizing gene, CYP17, have been associated with the risk of hormone-related cancers. In this study we investigated the CYP17 polymorphisms in ovarian cancer patients harboring mutations in the BRCA1 and BRCA2 genes, patients displaying familial characteristics but not carrying mutations and patients with sporadic ovarian cancer. Association between the allele frequencies, the CYP17 genotype and tumor characteristics or clinical parameters was evaluated. Our data suggest evidence for an association between ovarian cancer risk and the CYP17 genotype in the subgroup of patients with familial disease in whom no mutations in the BRCA genes are found. Although there were no statistically significant differences in the genotype distribution between the control group and the subgroup of patients with BRCA mutations, the frequency of the CYP17 A2 allele was significantly higher in the subgroup of patients without BRCA mutations. We found a four- to eightfold higher risk in ovarian cancer patients with family history but without BRCA mutations. Our data indicate that the CYP17 A2 allele polymorphism may confer an increased risk and can provide a biomarker for ovarian cancer patients in whom no mutations in the BRCA genes are observed.

Combination of adjuvant chemotherapy and radiotherapy is associated with improved survival at early stage type II endometrial cancer and carcinosarcoma

The aim of this study was to describe the impact of postoperative adjuvant treatment modalities and identify risk factors associated with recurrence and survival rates in women diagnosed with early stage type II endometrial cancer and carcinosarcoma.

Correlation of clinical and MRI staging in cervical carcinoma treated with radiation therapy: a single-center experience.

PURPOSE To correlate clinical and MRI findings in patients with cervical carcinoma treated with radiation therapy (RT). MATERIALS AND METHODS Forty-two patients with pretreatment IB-IVA cervical carcinoma were included in this retrospective study. Pre- and post-treatment MRI findings of the patients were reevaluated and compared with clinical staging. Six-month, one-year, and two-year follow-up imaging by MR was performed for 36, 20, and 7 patients, respectively. The correlation between clinical and MRI findings was assessed by a Spearmans rho (rank correlation) test. Univariate analyses were performed to identify the prognostic significance of the tumor volume and lymph node status. RESULTS Pre-treatment correlations between MRI and clinical findings for diagnoses without parametrial invasion, with parametrial invasion, and with pelvic sidewall invasion were 71.0%, 64.7%, and 15.8%, respectively. According to the Spearmans rho (rank correlation) test, the parametrial invasion correlation was poor (r = 0.410, P < 0.01). The correlation of clinical and MRI findings at 6 months was 88.9% (r = 0.674, P < 0.0001). CONCLUSION In advanced cervical cancer, the correlation of clinical and MRI staging prior to neoadjuvant RT was low despite a high correspondence in the assessment of local response after RT.

Effectiveness of brachytherapy in the treatment of lip cancer : A retrospective study at the Istanbul university oncology institute

Stage T1 through T3 lip cancers can be treated primarily by brachytherapy (BRTX), with or without external radiotherapy (ERT), with adequate safety margins and good results. In this study, the outcomes of BRTX were reviewed for patients treated at the Brachytherapy Department of the Istanbul University Oncology Institute (IUOE). The medical records of 41 patients registered at IUOE with a diagnosis of lip cancer between 1988 and 2003 were reviewed. The median follow-up time was 88 months (24–160 mo). Among these patients, 21 patients with a primary tumor, 14 with tumors arising postoperatively, and 6 with postoperative recurrence of tumor were treated using BRTX. A total of 33 patients (80%) received BRTX alone and 8 (20%) received BRTX and ERT. The 10-year local control rate was 100%, 93%, and 67% for patients treated with BRTX alone, BRTX and surgery, and those treated for postoperative recurrence, respectively (P < .02). For patients treated with BRTX only and BRTX plus surgery, specific disease-free survival was 95% and 94%, respectively, and overall survival was 93% and 100%, respectively; these differences were not statistically significant. One patient with a postoperative recurrence who had been treated with BRTX died as a result of lip cancer. No patients developed any ulcerations, intra-oral complications, or mandibular necrosis. In the BRTX only group, 83% had excellent or good cosmetic results. In the surgery group, 62% had a contour deformity. In lip cancer management, BRTX results were comparable for local control, survival, and minimal late effects in normal tissue. This is in accordance with current reports in the medical literature. Satisfactory results were observed in patients with stage T1 and T2 lesions who had been treated with BRTX only and in patients with stage T3 lesions who had been treated with BRTX plus ERT, without a need for additional treatment modalities.

Effect of the childhood trauma on the adjustment to cancer in the patients with breast cancer

BackgroundEarly identification of patients coping poorly is important for compliance with treatment and control of distress. This study aims to investigate the effect of the childhood trauma experience on the type of reaction and adjustment that the person exhibits to the cancer among the patients with breast cancer.MethodsThis cross-sectional study enrolled 310 patients with breast cancer. The effect of the childhood trauma and the psychological condition on the adjustment to cancer was investigated by assessing the adjustment to cancer, the experiences of childhood trauma and psychological status of the subjects using mental adjustment to cancer scale (MAC), childhood trauma questionnaire (CTQ28), Beck Depression Inventory (BDI) and Beck anxiety inventory (BAI).ResultsMajority of the subjects (77.4%) showed positive adjustment to cancer. Fighting spirit (63.9%) was the most commonly seen mechanism of adjustment to cancer. Of the subjects, 54.5% suffered at least one of the childhood trauma types. Among the patients, 47.1% had depression and 58.4% had anxiety. In the multivariate logistic regression analysis, emotional neglect and depression, respectively, have an effect on both positive and negative adjustment to cancer.ConclusionsOur study demonstrated that childhood trauma, especially emotional neglect, affects coping and adjustment among the patients with breast cancer. It is necessary to determine the childhood experiences to ensure the development of psychosocial interventions that will increase the adjustment and quality of life after the diagnosis of the cancer.