Comparison of survival with somatostatin analog and chemotherapy and prognostic factors for treatment in 165 advanced neuroendocrine tumor patients with Ki-67 20% or less.

The objectives of this study were to compare progression-free survival (PFS) with somatostatin analog (SSA) versus chemotherapy (CTx) in first-line therapy and to determine the patient group in which these treatments were more effective in neuroendocrine tumors (NETs) with a Ki-67 index of 20% or less. Patients who received SSA or CTx and had unresectable locally advanced and metastatic NETs with a Ki-67 index of 20% or less were retrospectively selected from 13 centers in the Turkish database between 2000 and 2015. One hundred and sixty-five patients were enrolled. The median age was 56 years and the male-to-female ratio was 1.09. Seventy-four (45%) patients were of grade 1 NET and 91 (55%) were of grade 2. SSA was given to 104 patients, whereas 61 were treated with CTx. The objective response rate after SSA was 15.4%; another 73.1% had stable disease. The objective response rate after CTx was 36.1%, and 40.9% had stable disease (P=0.008). The median PFS in SSA patients was 21 months (95% confidence interval: 12.4-29.6), and 8 months for CTx (95% confidence interval: 5.5-10.6) (P<0.001). There was no significant difference between PFS of receiving SSA and CTx in pancreatic neuroendocrine tumor (PNET) patients; however, the PFS of receiving SSA was longer in non-PNET patients (P<0.001). SSA was better treatment in advanced NET patients with a Ki-67 index of less than 5%, having a primary resected and a performance status of 0 (P<0.05). SSA may be preferred over CTx in advanced NET patients with low-to-intermediate grade.

The effect of the gastrectomy on survival in patients with metastatic gastric cancer: a study of ASMO.

AIM: To investigate the role of surgical resection of primary tumor on overall survival (OS) in advanced gastric cancer patients at the time of diagnosis. PATIENTS & METHODS: The survival rates of metastatic gastric cancer patients whose gastric primary tumor was resected at time of diagnosis were compared with metastatic gastric cancer patients whose primary tumor was nonresected. RESULTS: The median progression-free survival and OS in operated and nonoperated group were 10 versus 6, 14 versus 9 months, respectively (p < 0.001). In multivariate analysis, gastric resection of primary tumor, Eastern Cooperative Oncology Group performance status, second-line chemotherapy had a significant effect on OS (hazard ratio [HR]: 0.52 [95% CI: 0.38-0.71], HR: 0.57 [95% CI: 0.42-0.78], HR: 1.48 [1.09-2.01]; p ≤ 0.001, p = 0.001 and p = 0.012, respectively). CONCLUSION: Subpopulations of patients with metastatic gastric cancer might benefit from surgical removal of primary tumor.

Predicting the role of the pretreatment neutrophil to lymphocyte ratio in the survival of early triple-negative breast cancer patients.

PURPOSE: Increasing evidence supports an association between systemic inflammation and cancer development and progression. The neutrophil to lymphocyte ratio (NLR) is used as a basic parameter of systemic inflammation in some tumors. The aim of this study was to examine the association between the pretreatment NLR, disease-free survival (DFS), and overall survival (OS) in patients with early triple-negative breast cancer (TNBC). METHODS: We retrospectively studied patients diagnosed with stage I-III TNBC who had completed all phases of primary treatment from 2002 to 2013. The association between the pretreatment NLR and survival was analyzed. The difference among variables was calculated by chi-square test. OS and DFS were assessed using the Kaplan-Meier method. Multivariate Cox proportional hazards models were used to analyze the prognostic impact of clinical parameters. RESULTS: Eighty-five patients were eligible for study inclusion. There were no statistically significant differences among the pretreatment NLR and clinicopathological variables. Patients with an NLR of > 2 had significantly lower DFS (p=0.002) and OS (p=0.03) than patients with an NLR of ≤ 2. Multivariate Cox proportional hazards models showed that a higher pretreatment NLR was independently correlated with poor DFS and OS, with a hazard ratio 5.46 (95% confidence interval [CI] 1.61-18.85, p=0.006) and 2.86 (95% CI 1.04-7.86, p=0.04), respectively. CONCLUSION: Patients with early TNBC and with elevated pretreatment NLR showed poorer DFS and OS than patients without elevated NLR. However, this finding needs to be confirmed in a large prospective study.

Hepatic steatosis is associated with higher incidence of liver metastasis in patients with metastatic breast cancer; an observational clinical study.

PURPOSE: To investigate the relationship between hepatic steatosis (HS) (at the time of diagnosis) and hepatic metastasis (at the time of diagnosis and follow-up) in metastatic breast cancer (BC) patients by using computed tomography (CT). METHODS: A total of 107 metastatic BC patients who had an abdominal CT were retrospectively enrolled in this study. Patients without HS (N=79) were regarded as the control group and those with HS constituted the HS study group (N-28). RESULTS: Hepatic metastases at diagnosis and during follow-up were more common in patients with HS (p=0.018 and p=0.041, respectively) and in the premenopausal group (p<0.001 and p=0.004, respectively), whereas they were similar in patients with and without HS in the postmenopausal group (p=0.655 and p=0.656, respectively). Overall survival rates were similar in patients with and without HS (p=0.606). CONCLUSION: Hepatic metastases at diagnosis and during follow-up were more frequent in patients with HS, especially in premenopausal patients. Survival was similar in both groups.

Results of adjuvant FOLFOX regimens in stage III colorectal cancer patients: retrospective analysis of 667 patients.

OBJECTIVE: The aim of this study was to assess the use of 5-fluorouracil (5-FU), leucovorin and oxaliplatin (FOLFOX) regimens in clinical practice according to their efficacy and toxicity. METHODS: Patients who received oxaliplatin-containing regimens after curative resection for colorectal carcinoma from 10 different oncology centers between May 2004 and December 2009 were included in the study. All patients were treated with FOLFOX regimens. Patients with rectal carcinoma were also treated with chemoradiotherapy with 5-FU after 2 cycles of a FOLFOX regimen. RESULTS: The median age of the patients was 56 years (range 17-78). Of the total 667 patients, 326 were given FOLFOX-4, 232 were given modified FOLFOX-4 and 109 were given FOLFOX-6. The distribution according to disease stage was 33 patients with stage IIIA colorectal cancer, 382 patients with stage IIIB and 252 patients with stage IIIC. The most common adverse events were neutropenia (54%), nausea (36.9%), neuropathy (38.2%) and anemia (33.1%) for all grades. The median follow-up time was 23 months (range 1-79). Three-year disease-free survival and overall survival were 65 and 85.7%, respectively. CONCLUSION: The different oxaliplatin-containing 5-FU-based adjuvant chemotherapy regimens in patients with stage III colorectal cancer seemed to be at least equal in terms of efficacy regardless of the method of 5-FU administration or oxaliplatin dose.

Moxifloxacin-associated neutropenia.

A 32-y-old woman presented with pneumonia. Treatment was started with moxifloxacin. On day 2 of moxifloxacin treatment the patient developed neutropenia. After discontinuing the moxifloxacin, neutrophil counts were normal on day 4. Clinicians should be aware of the possibility of this adverse effect in patients treated with moxifloxacin.

Prognostic factors for recurrence-free survival in patients with HER2-positive early-stage breast cancer treated with adjuvant trastuzumab.

BACKGROUND: The objective of this study was to identify prognostic factors affecting the recurrence-free survival (RFS) in patients who received a 52-week trastuzumab therapy for HER2-positive early stage breast cancer (EBC). PATIENTS AND METHODS: The medical records of all patients with EBC from 10 centers were analyzed. Pathologic and clinical tumor characteristics were evaluated in 424 female patients who received 52 weeks of adjuvant trastuzumab for HER2-positive EBC. Survival was estimated using the Kaplan-Meier method. Univariate analyses of RFS were performed with the log-rank test. Independent prognostic and predictive factors affecting RFS were assessed by Cox regression analysis. RESULTS: Median follow-up time was 33.1 months (range 9.2-75.9 months). 3-year RFS and overall survival were 87 and 97%, respectively. In multivariate analysis, patients aged 70 years or over (p = 0.017, relative risk (RR) 2.7, 95% confidence interval (CI) 1.19-6.13), patients with > 9 positive lymph nodes (p = 0.001, RR 2.52, 95% CI 1.42-4.46), and those with progesterone receptor-negative tumors (p = 0.006, RR 2.33, 95% CI 1.27-4.27) had worse RFS. CONCLUSION: In spite of a 52-week adjuvant trastuzumab treatment, classic poor prognostic factors for invasive EBC remained as such in patients with HER2-positive EBC.

Efficacy of sunitinib in Turkish patients with gastrointestinal stromal tumors; retrospective multicenter experience.

BACKGROUND/AIMS: Sunitinib is a multi-targeted thyrosine kinase receptor inhibitor used in patients with advanced gastrointestinal stromal tumours (GISTs). We evaluated the efficacy and tolerability of sunitinib therapy in Turkish patients with GISTs. METHODOLOGY: Between January 2001 and April 2012, 57 patients who had progressive disease or experienced unacceptable toxicity during imatinib treatment from multiple centers were investigated retrospectively. RESULTS: Thirty-three patients were male and 24 were female. The median age was 55 years (range; 16-84 years). Thirty-eight of the patients received imatinib for longer than 12 months, 13 patients received for 6-12 months, and 6 patients received for less than six months. The clinical benefit of sunitinib was 73.7%. Treatment-related adverse events were reported in 78% of the patients. Adverse events were generally mild to moderate in intensity. The median progression free survival (PFS) and overall survival (OS) of the patients that received sunitinib were 10.8 months and 23.9 months, respectively. The time of imatinib usage and response to sunitinib were independent prognostic factors for PFS and OS. Also, tumor size was an independent prognostic factor for PFS. CONCLUSIONS: Sunitinib is an effective treatment in Turkish patients with GISTs, with a clinical benefit of 73.7% and shows an acceptable tolerability.

Prognostic factors in gastrointestinal stromal tumors: multicenter experience of 333 cases from Turkey.

BACKGROUND/AIMS: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal tract. In an attempt to survey the approximate incidence, clinicopathological characteristics, and immunophenotypic features of GISTs in Turkey, we conducted a clinicopathological and immunohistochemical analysis of GISTs. METHODOLOGY: Three hundred and thirty-three patients with GIST from nine institutions in Turkey were retrospectively evaluated. RESULTS: Between January 2001 and March 2011, a total of 333 patients with GISTs were included; of these, 204 (61.2%) were male and 129 (38.8%) were female. The median age was 55 years (range; 22-102 years). At the median follow-up of 26 months (range; 4-166 months), the 1-, 3- and 5-year OS rates of the 333 patients were 96.9%, 85.8% and 78.5%, respectively. The 5-year DFS rate was 40%. The 5-year OS rate and median OS time for the patients with R0 resection were significantly higher than for patients with metastatic diseases (79.7 vs. 75.7% and not reached vs. 115 months, respectively, p=0.04). CONCLUSION: Although our results should be confirmed by prospective studies, we believe that they contribute to the literature because the study included both resectable and metastatic or unresectable GIST patients and multicenter findings from Turkey.

An important tool in lymphedema management: validation of Turkish version of the lymphedema breast cancer questionnaire.

PURPOSE: This study aimed to perform the psychometric evaluation of the Turkish version of the Lymphedema and Breast Cancer Questionnaire (LBCQ). METHODS: Patients with BCRL (n = 50) received a Turkish version of the following measurement tools: Lymphedema Functioning, Disability, and Health Questionnaire (Lymph-ICF), Disabilities of the Arm, Shoulder and Hand questionnaire (Quick DASH), LBCQ and Upper Extremity Functional Index (UEFI-20). Patients without BCRL (n = 50) completed only the Turkish LBCQ. Psychometric properties were analyzed with internal consistency, test-retest reliability, ROC analysis, criterion, and discriminant validity. RESULTS: The internal consistency of the Turkish LBCQ was strong (Cronbach's α coefficient >0.60). Test-retest reliability was also very strong (intraclass correlation coefficients from 0.79 to 1; p < 0.001). Criterion validity was supported by a moderate correlation of LBCQ with volumetric measurement, skinfold thickness, and questionnaires (Lymph-ICF, UEFI, and Quick DASH) (p < 0.05) via the ROC analysis, the cut-off point was found as "6" in distinguishing individuals with lymphedema and those without. There were significant differences in LBCQ total and subscale scores between participants with and without BCRL (p < 0.05). CONCLUSIONS: This study clinically confirmed the validity, reliability, and applicability of the Turkish LBCQ in the Turkish population. LBCQ will enable the early detection of lymphedema and will save the country financially with early diagnosis.IMPLICATIONS FOR REHABILITATIONThe LBCQ was successfully translated, adapted, and validated into the Turkish language.Turkish version of the LBCQ was found to be reliable and valid to evaluate the signs and symptoms of lymphedema in Turkish women with breast cancer.By using LBCQ, rehabilitation professionals can detect lymphedema at an early stage, reduce the cost of lymphedema treatment and prevent the development of advanced lymphedema in their clinics.

Co-existence of gastrointestinal stromal tumors with other primary neoplasms.

BACKGROUND/AIMS: Gastrointestinal stromal tumors (GISTs) are the most common primary mesenchymal neoplasms of the tubular gastrointestinal tract (GI). Here, we present a series of 32 patients diagnosed with a primary neoplasm in addition to GIST, from six different institutions in Turkey. METHODOLOGY: In total, 200 patients with GIST were evaluated; 32 patients with both GISTs and other primary malignancies were identified. RESULTS: This study included 20 men and 12 women median age 66.5 years (range 43-78). GIST was incidentally found intra-operatively in 12 of the cases. All patients underwent surgery. Detection of the GIST was synchronous in 19 cases, metachronous in 7 cases and preceded the GIST diagnosis in 6 cases. The median time before follow-up evaluation ranged from 4 to 80 months. CONCLUSIONS: To our knowledge, no cases of GISTs co-existing with leiomyosarcoma of the spermatic cord and larynx tumors have been reported previously. The prevalence of malignancies in this subpopulation of GIST patients is significantly higher than the prevalence of malignancies in the healthy Turkish population. The high occurrence rate of additional primary malignancies in GIST patients has focused the attention of clinical oncologists on this problem, and may imply a common genetic mechanism for their etiology.

Malignancies diagnosed during pregnancy and treated with chemotherapy or other modalities (review of 27 cases): multicenter experiences.

BACKGROUND: Cancer is the second leading cause of death in women of reproductive age. The most common tumors diagnosed during pregnancy are breast and cervix cancer, Hodgkin lymphoma and non-Hodgkin lymphoma, leukemias, and malignant melanoma. The aim of therapy in pregnancy is to give optimal treatment to the mother without harm to the fetus. In the first trimester, organogenesis continues, so chemotherapy should not be given because of increasing risk of spontaneous abortion, fetal malformation, and mortality. We evaluated mostly seen tumors during pregnancy and assessed treatment type and outcome of pregnancy after chemotherapy in our population. METHODS: We retrospectively analyzed 27 patients who have been treated during pregnancy or after the delivery because of several malignancies. RESULTS: The tumors associated with pregnancy were breast cancer, hematologic malignancies,gynecologic malignancies, sarcomas, and others. The chemotherapy regimens were given in 17 of 27 patients in the second or third trimester of pregnancy. Four of the patients were diagnosed with cervical cancer, hemangiopericytoma, chronic myeloid leukemia,and breast cancer during the first trimester, so their pregnancies were ended by therapeutic abortion. Although 1 of the 3 fetuses who were exposed to chemotherapy in utero at the second or third trimester was born prematurely and low birth weight was diagnosed in the other 2 fetuses, fetal malformation was not seen in any of them. There were 7 normal and 9 cesarean deliveries. Twenty-three healthy babies survived from 27 pregnancies, of whom 17 babies were exposed to chemotherapeutic agents. CONCLUSIONS: We reported herein 27 patients with malignancies diagnosed during pregnancy; 17 patients received chemotherapy during the gestational period without any fetal or maternal abnormalities. Because of the low incidence of malignancy during pregnancy, our report is noteworthy.

Evaluation of the concordance between the stage of the disease and Ki-67 proliferation index in gastroenteropancreatic neuroendocrine tumors.

AIM: This study aimed to determine the degree of concordance between TNM staging used in the determination of the prognosis of gastroenteropancreatic neuroendocrine tumor (GEP-NET) patients and the Ki-67 proliferation index value used in the grading of these tumors and investigate the most reliable prognostic parameter among them. MATERIALS AND METHODS: The medical files of the patients with GEP-NET who were diagnosed or followed up in Erciyes University Faculty of Medicine were retrospectively examined and demographic characteristics, survival times, grade of these tumors, histopathologically detected Ki-67 values, and histopathological characteristics were recorded and evaluated statistically. RESULTS: The mean age (53.09±14.6 years; range, 16-85 years) of all (n=141) the patients was estimated. The patient population included 72 (51.1%) female and 69 (48.9%) male patients, with a male/female ratio of 0.95. The most frequently encountered primary sites were the stomach (33.3%), and then in decreasing oder of frequency the pancreas (27%), colon-rectum (15.6%), the small intestine (12.8%), and the appendix (11.3%). The GEP-NET of the patients was in grade 1 (G1) (n: 103; 73%), grade 2 (G2) (n: 24; 17%), and grade 3 (G3) (n: 14; 10%). The GEP-NET of the patients was stage I (n: 66; 46.8%), stage II (n: 14; 9.9%), stage III (n: 12; 8.5%), and stage IV (n: 49; 34.8%). In the statistical analysis, Ki-67 increased in parallel with the stage of the disease (P<0.001). As Ki-67 increased at a rate of 1%, survival rates of the patients decreased 1.027 times (P=0.01). Five-year survival rates of the patients were 88% in G1, 44% in G2, and 24% in G3. Patients in G2 and G3 had a 6.67 and 12.38 times lower chance of survival compared with G1 patients, respectively. Survival rates of stage IV patients were 5.6 times lower relative to stages I and II patients, respectively (P<0.001). The median 5-year survival rates of the patients were 90% in stage I, 100% in stage II, 47% in stage III, and 46% in stage IV. In univariate analysis, age of the patients, grade, stage of the tumor, and lymph node metastases were found to be parameters that affected overall survival, whereas no significant correlation was found between the sex of the patient and the primary organ from which the tumor originated and survival rates. However, in the multivariate analysis, survival rates decreased inversely with age, whereas no significant correlation was found between grade and stage of the tumor and survival rates. CONCLUSION: In conclusion, a decrease in the average survival rate in parallel with an increase in the grade of the tumor was more prominent compared with a decrease in survival rates in accordance with an increase in the stage of the tumor. This indicates that in the prediction of prognosis in patients with GEP-NET, the Ki-67 value can be a more important evaluation factor relative to staging.

Psychological distress and loneliness in caregiver of advanced oncological inpatients.

The objective of this study is to compare and examine the relationships between levels of loneliness, anxiety, depression, and other variables on primary caregivers and cancer inpatients. The study involved 100 Turkish primary caregivers of inpatients with advanced or terminal stages of cancer. Loneliness and anxiety scores were significantly higher for the primary caregivers of inpatients with terminal stage of cancer than primary caregivers of inpatients with advanced stage of cancer. Excluding the cancer stage, loneliness and anxiety were primarily associated with the socio-demographic factors of primary caregivers rather than the characteristics of patients.

Primary Pleomorphic Rhabdomyosarcoma of Thyroid Gland in an Adult Patient: A Case Report.

Thyroid sarcoma is a very rare entity, accounting for less than 1% of all malignant thyroid tumours. Rhabdomyosarcoma (RMS) is a sarcoma subtype, which is more common in children and adolescents. In this case, a 68-year old man, presented with hoarseness and diagnosed with pleomorphic RMS, was explored. No study of primary thyroid pure RMS has been reported in the literature, with the exception of the case reports of differentiated RMS.

Best prognostic factor of neuroendocrine tumors: Grade or Stage? A multidisciplinary single-center study.

BACKGROUND/AIMS: Currently, there is no definite consensus about the prognostic factors of neuroendocrine tumors (NETs). We evaluate epidemiology, survival and especially prognostic factors in NETs. MATERIALS AND METHODS: Patients who had a NET and were diagnosed between 2000 and 2014 at a tertiary care center were included. Demographic data, tumor characteristics and survival rates were evaluated, retrospectively. RESULTS: Two-hundred and thirty-three patients (123 male, 110 female; median age, 55 years [16-92 years]) took part in the study. Primary NET sites were the lung (n=56), stomach (n=50), pancreas (n=39), colorectal (n=21), small intestine (n=19), and appendix (n=19). According to the NET classification by the WHO in 2010, 60% (n=140) of patients were grade-1, 15% (n=35) were grade-2, and 25% (n=58) were grade-3. According to TNM staging, 88 patients (37.8%) were stage I, 30 patients (12.8%) were stage II, 22 patients (9.5%) were stage III, and 93 patients (39.9%) were stage IV. Univariate analysis revealed significant associations between gender, age, grade, lymph node metastasis, distant metastasis, stage, and the number of organs impacted by metastases and overall survival. However, with multivariate analysis only age greater than 55 years, advancing grade, and inoperable tumors were significantly associated with shortened survival. Five-year survival was 81% in grade-1, 34% in grade-2, and 9% in grade-3 NETs. CONCLUSION: This study is the most comprehensive study in Turkey that has evaluated NETs using a multidisciplinary approach. Also, we suggest that age, operability and especially grade rather than stage are the most important prognostic factors in NETs.

The relationship between plasma hyaluronan levels and anthracycline-related cardiotoxicity in breast cancer patients.

AIM: Anthracycline-derived antineoplastic agents are used as the main form of treatment in many malignant diseases, including breast cancer and childhood cancers. Cardiotoxicity is one of the most feared life-threatening complications of cancer therapy. In the present study, we aimed to investigate the relationship between plasma hyaluronan (HA) levels and anthracycline-induced cardiotoxicity. MATERIALS AND METHODS: Fifty eight of 73 female patients who were diagnosed with breast cancer and treated with a chemotherapy regimen including anthracycline were enrolled in this study. Anamneses were taken from each patient before and after chemotherapy. Further, physical examinations, electrocardiography, and transthoracic echocardiography were performed, and plasma hyaluronan levels were determined by using ELISA assay for each patient before and after treatment. RESULTS: Following anthracycline-based chemotherapy, the average left ventricular ejection fraction decreased (62.6±3.7% vs. 58.6±4.4%, p<0.001), and diastolic functions significantly deteriorated (p<0.001). However, troponin and hyaluronan levels significantly increased following chemotherapy [Troponin (ng/ml, mean±SD): before 0.01±0.002, after 0.037±0.02, p<0.001], [Plasma HA (ng/ml, mean±SD): before 41.3±5.4, after 70±8.5, p<0.001]. The increase in troponin values correlated with systolic dysfunction (p=0.002), but did not correlate with diastolic dysfunction (p=0.661). Significant correlations were found between systolic/diastolic dysfunction and plasma HA levels (r=0.417, p=0.001; r=0.339, p=0.009, respectively). CONCLUSIONS: Both systolic and diastolic functions were significantly deteriorated after chemotherapy. In addition, plasma levels of HA and troponin increased after treatment. Further, both systolic and diastolic dysfunctions were found to correlate with serum HA levels. All these data suggest that HA might have a function on anthracycline-induced cardiotoxicity.

Is sunitinib-induced hypothyroidism a predictive clinical marker for better response in metastatic renal cell carcinoma patients?

BACKGROUND: The main goal of this study was to examine whether the occurrence of hypothyroidism during sunitinib therapy in patients with metastatic renal cell carcinoma (mRCC) is associated with a better outcome. METHODS: The study enrolled 81 patients with pathologically proven mRCC who were treated with sunitinib between March 2008 and June 2013.Thyroid function evaluation comprised (free-thyroxine) FT4 and thyroid-stimulating hormone (TSH) before treatment and at day 1 of each 6-week cycle. Survival analysis was performed using the Kaplan-Meier method, and the differences among the groups were determined using the log-rank test. RESULTS: Hypothyroidism occurred in 30 (37%) of 81 patients within a median 3 months (range 1-18) of treatment initiation. There was a statistically significant correlation between the occurrence of hypothyroidism during treatment and the rate of objective remission (ORR) (hypothyroid patients vs euthyroid patients: 46.7 vs 13.7%, respectively; P = 0.001). Median progression-free survival (PFS) was 10 (95% CI 6.13-13.8) months in the euthyroid patients, and 17 (95% CI 9.33-24.6) months in the hypothyroid patients (P = 0.001). The median overall survival (OS) was 39 (95% CI 25.4-52.5) months in the hypothyroid patients and 20 (95% CI 14.7-25.2) months in the euthyroid patients (P = 0.019). CONCLUSIONS: The occurrence of hypothyroidism during treatment in patients was significantly associated with longer PFS, OS and better ORR in the current study.

Risk factors for brain metastasis as a first site of disease recurrence in patients with HER2 positive early stage breast cancer treated with adjuvant trastuzumab.

PURPOSE: The aim of this study was to determine risk factors for brain metastasis as the first site of disease recurrence in patients with HER2-positive early-stage breast cancer (EBC) who received adjuvant trastuzumab. METHODS: Medical records of 588 female patients who received 52-week adjuvant trastuzumab from 14 centers were evaluated. Cumulative incidence functions for brain metastasis as the first site of disease recurrence and the effect of covariates on brain metastasis were evaluated in a competing risk analysis and competing risks regression, respectively. RESULTS: Median follow-up time was 36 months. Cumulative incidence of brain metastasis at 12 months and 24 months was 0.6% and 2%, respectively. HER2-enriched subtype (ER- and PR-) tumor (p = 0.001, RR: 3.4, 95% CI: 1.33-8.71) and stage 3 disease (p = 0.0032, RR: 9.39, 95% CI: 1.33-8.71) were significant risk factors for development of brain metastasis as the first site of recurrence. CONCLUSIONS: In patients with HER2 positive EBC who received adjuvant trastuzumab, HER2-enriched subtype (ER- and PR-) tumor and stage 3 disease were associated with increased risk of brain metastasis as the first site of disease recurrence.

Myrtucommulone-A treatment decreases pluripotency- and multipotency-associated marker expression in bladder cancer cell line HTB-9.

Cancer and stem cells exhibit similar features, including self-renewal, differentiation and immortality. The expression of stem-cell-related genes in cancer cells is demonstrated to be potentially correlated with cancer cell behaviour, affecting both drug response and tumor recurrence. There is an emerging body of evidence that subpopulations of tumors carry a distinct molecular sign and are selectively resistant to chemotherapy. Therefore, it is important to find novel therapeutic agents that could suppress the stem-like features of cancer cells while inhibiting their proliferation. Myrtucommulone-A (MC-A) is an active compound of a nonprenylated acylphloroglucinol isolated from the leaves of myrtle. Here we have investigated the potential of MC-A in inhibiting the expression of self-renewal regulatory factors and cancer stem cell markers in a bladder cancer cell line HTB-9. We used RT-PCR, immunocytochemistry, flow cytometry and western blotting to examine the expression of pluripotency- and multipotency-associated markers with or without treatment with MC-A. Treatment with MC-A not only decreased cancer cell viability and proliferation but also resulted in a decrease in the expression of pluripotency- and multipotency-associated markers such as NANOG, OCT-4, SOX-2, SSEA-4, TRA-1-60, CD90, CD73 and CD44. MC-A treatment was also observed to decrease the sphere-forming ability of HTB-9 cells. In summary, this study provides valuable information on the presence of stem-cell marker expression in HTB-9 cells and our results imply that MC-A could be utilized to target cancer cells with stem-like characteristics.