The efficacy and reliability of sequential adjuvant anthracycline-based chemotherapy and weekly paclitaxel regimen in human epidermal growth factor receptor 2 negative breast cancer: A retrospective analysis of a multicentre study.

PURPOSE: To analyze the reliability and the effectiveness of chemotherapy and prognostic factors for survival in patients with HER2 (human epidermal growth receptor 2) negative early-stage breast cancer treated with adjuvant sequential anthracycline-based chemotherapy and paclitaxel. METHODS: This analysis retrospectively evaluated the medical records of 756 HER2 negative early-stage breast cancer patients who received adjuvant sequential anthracycline-based chemotherapy and weekly paclitaxel in 15 medical oncology centers in Turkey between 2008-2015. Estrogen receptor (ER), progesterone receptor (PR),HER2,age,tumor size and grade,nodal status,perineural and lymphatic invasion,disease-free survival (DFS) and overall survival (OS) were analyzed. RESULTS: The median patient age was 50 years (22-82). Median follow up period was 46 months (13-82). The rates of recurrence and death detected in this period were 14.8% and 7.4%, respectively. Median OS and PFS were not reached in this period. Five-year DFS and OS rates were 87% and 89%, respectively. Age (OR:0.35,95%Cl 0.12-0.96, p=0.04), PR status (OR:0.44,95%Cl 0.18-1, p=0.05), lymphatic invasion (OR:2.6,95%Cl 0.97-7.4, p=0.05) were independent prognostic factors. Most common grade 3-4 toxicities were fatigue (6.7%), neutropenia (1.7%) and nausea (1.3%). Neutropenic fever developed in 1.8% of the patients and peripheral neuropathy in 16.9%. Dose reduction was necessary for 10% of the patients due to grade 3-4 toxicity, whereas postponement of chemotherapy was necessary for 7% of the patients. CONCLUSIONS: This multicentric retrospective study confirmed that sequential adjuvant therapy with anthracycline-based chemotherapy and paclitaxel for HER2 negative breast cancer is an effective and reliable regimen.

Is Change in Hemoglobin Level a Predictive Biomarker of Tyrosine Kinase Efficacy in Metastatic Renal Cell Carcinoma? A Turkish Oncology Group Study.

BACKGROUND: There are insufficient predictive markers for renal cell carcinoma (RCC). METHODS: A total of 308 metastatic RCC patients were analyzed retrospectively. RESULTS: The increased hemoglobin (Hb) group had significantly higher progression-free survival and overall survival (OS) compared with the decreased Hb group at 11.5 versus 6.35 months (p < .001) and 21.0 versus 11.36 months (p < .001) respectively. The 1- and 3-year OS rates were higher in the Hb increased group, i.e., 84% versus 64% and 52% versus 35% respectively. CONCLUSIONS: The present study showed that increased Hb levels after tyrosine kinase inhibitor therapy could be a predictive marker of RCC.

Evaluation of Prognostic Factors and Adjuvant Chemotherapy in Patients With Small Bowel Adenocarcinoma Who Underwent Curative Resection.

BACKGROUND: Small bowel adenocarcinoma (SBA) is a rare tumor of the gastrointestinal system with poor prognosis. Because these are rarely encountered tumors, the aim of this multicenter study was evaluation of prognostic factors and adjuvant chemotherapy in patients with curatively resected SBA. MATERIALS AND METHODS: A total of 78 patients diagnosed with curatively resected SBA were involved in the retrospective study. Forty-eight patients received 1 of 3 different chemotherapy regimens, whereas 30 patients did not receive any adjuvant treatment. No adjuvant and adjuvant chemotherapy cohorts were matched (1:1) by propensity scores based on the likelihood of receiving chemotherapy or the survival hazard from Cox modeling. Overall survival (OS) was compared with Kaplan-Meier estimates. RESULTS: Median age of 78 patients with curatively resected SBA was 58, and 59% of these were men. According to TNM classification, 8 (10%) of the patients were at stage I, 26 (34%) were at stage II, and 44 (56%) were at stage III. Median follow-up duration was 29 months. Three-year median disease-free survival (DFS) and OS were 62.5% and 67.0%, respectively. In univariate analysis, presence of vascular invasion, perineural invasion, lymph node involvement, and presence of positive surgical margin were significant predictors of poor survival. Multivariate analysis showed that the only adverse prognostic factor independently related with OS was the presence of positive surgical margin (hazard ratio, 0.37; 95% confidence interval, 0.11-1.26; P = .01). Neither DFS nor OS was found to be significantly improved by the adjuvant chemotherapy in both matched and unmatched cohorts. CONCLUSIONS: Only status of surgical margin was determined to be an independent prognostic factor in patients with SBA who underwent curative resection.

Evaluation of prognostic factors and treatment in advanced small bowel adenocarcinoma: report of a multi-institutional experience of Anatolian Society of Medical Oncology (ASMO).

PURPOSE: Small bowel adenocarcinoma (SBA) is a rare tumor of the gastrointestinal system with poor prognosis. Since these are rarely encountered tumors, there are limited numbers of studies investigating systemic treatment in advanced SBA. The purpose of this study was to evaluate the prognostic factors and systemic treatments in patients with advance SBA. METHODS: Seventy-one patients from 18 Centers with advanced SBA were included in the study. Fifty-six patients received one of the four different chemotherapy regimens as first-line therapy and 15 patients were treated with best supportive care (BSC). RESULTS: Of the 71 patients, 42 (59%) were male and 29 (41%) female with a median age of 56 years. Median follow- up duration was 14.3 months. The median progression free survival (PFS) and overall survival (OS) were 7 and 13 months, respectively (N=71). In patients treated with FOLFOX (N=18), FOLFIRI (N=11), cisplatin-5-fluorouracil/ 5-FU (N=17) and gemcitabine alone (N=10), median PFS was 7, 8, 8 and 5 months, respectively, while median OS was 15, 16, 15 and 11 months, respectively. No significant differences between chemotherapy groups were noticed in terms of PFS and OS. Univariate analysis revealed that chemotherapy administration, de novo metastatic disease, ECOG PS 0 and 1, and overall response to therapy were significantly related to improved outcome. Only overall response to treatment was found to be significantly prognostic in multivariate analysis (p=0.001). CONCLUSIONS: In this study, overall response to chemotherapy emerged as the single significant prognostic factor for advanced SBAs. Platin and irinotecan based regimens achieved similar survival outcomes in advanced SBA 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.

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.

Impact of adjuvant treatment modalities on survival outcomes in curatively resected pancreatic and periampullary adenocarcinoma.

BACKGROUND: We examined the impact of adjuvant modalities on resected pancreatic and periampullary adenocarcinoma (PAC). METHODS: A total of 563 patients who were curatively resected for PAC were retrospectively analyzed between 2003 and 2013. RESULTS: Of 563 patients, 472 received adjuvant chemotherapy (CT) alone, chemoradiotherapy (CRT) alone, and chemoradiotherapy plus chemotherapy (CRT-CT) were analyzed. Of the 472 patients, 231 were given CRT-CT, 26 were given CRT, and 215 were given CT. The median recurrence-free survival (RFS) and overall survival (OS) were 12 and 19 months, respectively. When CT and CRT-CT groups were compared, there was no significant difference with respect to both RFS and OS, and also there was no difference in RFS and OS among CRT-CT, CT and CRT groups. To further investigate the impact of radiation on subgroups, patients were stratified according to lymph node status and resection margins. In node-positive patients, both RFS and OS were significantly longer in CRT-CT than CT. In contrast, there was no significant difference between groups when patients with node-negative disease or patients with or without positive surgical margins were considered. CONCLUSIONS: Addition of radiation to CT has a survival benefit in patients with node-positive disease following pancreatic resection.

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.

Predictive Significance of VEGF and HIF-1α Expression in Patients with Metastatic Colorectal Cancer Receiving Chemotherapy Combinations with Bevacizumab.

BACKGROUND: There is no suggested molecular indicator for the determination of which patients will benefit from anti-angiogenetic treatment in metastatic colorectal cancers. MATERIALS AND METHODS: In this study, VEGF and HIF-1α expression and their clinical significance were studied in tumor tissues of patients with colorectal cancer receiving bevacizumab-based treatment. VEGF and HIF-1α were assessed by immunohistochemistry in the primary tumors of 53 metastatic colorectal cancer patients receiving chemotherapy in combination with first line bevacizumab. RESULTS: The clinical benefit rate in the low-VEGF expression group was 38%, while it was 62% in the high expression group. While the median progression-free survival (PFS) was 10 months in the high-VEGF expression group, it was 8 months in the low-VEGF expression group (p = 0.009). The median overall survival (OS) was found to be 26 months vs 15 months. Thus, when VEGF was strongly expressed it was in favor of that group and the difference was statistically significant (p = 0.03). High VEGF expression rate was an independent factor that correlated with OS or PFS (p=0.016 and 0.009, respectively). CONCLUSIONS: The data showed that VEGF may have predictive value for determining the treatment of CRC.

Is Late Recurrence a Predictive Clinical Marker for Better Sunitinib Response in Metastatic Renal Cell Carcinoma Patients?

BACKGROUND: We investigated the clinicopathological features in patients with recurrent renal cell carcinoma (RCC) within 5 years or more than 5 years after nephrectomy and determined predictors of overall survival (OS) and progression-free survival (PFS) after disease recurrence in the administration of first-line sunitinib in the treatment of metastatic RCC (mRCC). PATIENTS AND METHODS: In this study we enrolled 86 Turkish patients with mRCC who received sunitinib. Univariate analyses were performed using the log rank test. RESULTS: Fifty-six patients (65%) were diagnosed with disease recurrence within 5 years after radical nephrectomy (early recurrence) and 30 patients (35%) were diagnosed with recurrence more than 5 years after radical nephrectomy (late recurrence). Fuhrman grade was statistically significantly different between the 2 groups (P = .013). The late recurrence patients were significantly associated with the Memorial Sloan Kettering Cancer Center favorable risk group compared with patients with early recurrence (P = .001). There was a statistically significant correlation between recurrence time and the rate of objective remission (ORR) (the late recurrence group vs. the early recurrence group: 43.3% vs. 14.3%, respectively; P = .004). From the time of disease recurrence, the median OS was 42.0 (95% confidence interval [CI], 24.4-59.5) months in the late recurrence group, and 16 (95% CI, 11.5-20.4) months in the early recurrence group (P = .001). Median PFS was 8 (95% CI, 4.05-11.9) months in the early recurrence group, and 20 (95% CI, 14.8-25.1) months in the late recurrence group (P ≤ .001). CONCLUSION: The study demonstrated a potential prognostic value of late recurrence in terms of PFS, OS, and ORR.

Prognostic factors for gemcitabine-refractory patients with advanced pancreatic cancer: a retrospective analysis of a multicentre study (Anatolian Society of Medical Oncology).

AIM OF THE STUDY: Systemic chemotherapy for patients with pancreatic cancer has limited impact on overall survival (OS). Patients eligible for chemotherapy should be selected carefully. The aim of the study was to search for prognostic factors for survival in patients with gemcitabine (Gem)-refractory or with gemcitabine and cisplatin (GemCis)-refractory advanced pancreatic cancer. MATERIAL AND METHODS: We retrospectively evaluated patients with Gem- or GemCis-refractory advanced pancreatic cancer. Sixteen potential prognostic variables were chosen for analysis in this study. Univariate and multivariate analyses were conducted to identify prognostic factors associated with survival. Univariate and multivariate statistical methods were used to determine prognostic factors. RESULTS: Multivariate analysis included the four prognostic significance factors in univariate analysis. Multivariate analysis showed that liver metastasis and second-line chemotherapy were considered independent prognostic factors for survival. CONCLUSIONS: Liver metastasis and second-line chemotherapy were identified as important prognostic factors in advanced pancreatic cancer patients refractory to treatment with Gem or GemCis. This prognostic factors may also facilitate pretreatment prediction of survival and can be used for selecting patients for treatment.

Analyses of multiple factors for determination of "selected patients" who should receive rechallenge treatment in metastatic colorectal cancer: a retrospective study from Turkey.

BACKGROUND: Repeating a prior chemotherapy (rechallenge therapy) is an option for selected patients with metastatic colorectal cancer, but there is very little evidence in the literature for this approach. Thus, we reviewed our registry to evaluate prognostic factors and survival of patients who received irinotecan and oxaliplatin- based regimens as rechallenge third and fourth-line therapy. MATERIALS AND METHODS: Patients who received irinotecan-based or oxaliplatin-base regimen as first-line had been rechallenged with third-line or fourth-line therapy. These patients were selected from the database of Turkish mCRC registry archives between October 2006 and June 2013 and evaluated retrospectively for factors effecting progression free survival (PFS) and overall survival (OS) by the Kaplan-Meir and Cox-regression methods. RESULTS: Thirty-nine patients were enrolled. The median duration of follow-up was 36 months (14-68 months). Thirty-one patients (76%) died during follow-up. In terms of rechallenge treatments, 29 patients had received third-line and 10 patients had received fourth-line. Response rate (RR) was found to be 12.9%, with stable disease in 19 (48.7%) patients. The median PFS was 6 months (95%CI=4.64-7.35 months) and the median OS was 11 months (95%CI=8.31-13.7 months). The factors effecting survival (PFS and OS) were only being PFS after first-line chemotherapy≥12 months (p=0.007, 95% CI=1.75-35.22 and p=0.004, 95%CI=1.44-7.11), both in univariate and multivariate analyses. CONCLUSIONS: This study indicates that rechallenge treatment could be a good option as a third or later line therapy in patients who had ≥12 months PFS on receiving first line therapy.

Factors affecting prognosis in metastatic colorectal cancer patients.

BACKGROUND: Colorectal cancer (CRC) is a major cause of mortality in developed countries, and it is the third most frequent malignancy in Turkey. There are many biological, genetic, molecular, and tissue-derived prognostic factors for CRCs. In this study, we evaluated prognostic factors in patients who were metastatic at diagnosis or progressed to metastatic disease during follow-up. PATIENTS AND METHODS: This study included 116 patients with malignancies either in the colon or rectum. Of these, 65 had metastatic disease at diagnosis, and 51 progressed to metastatic disease during the course of the disease. The parameters evaluated were age, gender, comorbidity, performance status and stage of the disease at the beginning, localization, history of surgery, chemotherapy regimen, response to first-line treatment, K-RAS status, site and number of metastases, expression of tumor predictors (CEA, CA19-9), and survival times. A multivariate analysis conducted with factors that considered statistically significant in the univariate analysis. FINDINGS: Median age was 56 (32-82) years and the male/ female ratio was 80/36. Eleven patients were at stage II, 40 at stage III, and 65 at stage IV at diagnosis. Twenty three patients had tumor in the right colon, 48 in the left colon, and 45 in the rectum. Ninety seven patients were operated, and 27 had surgical metastasectomy. Ninety three patients received targeted therapy. At the end of follow-up, 61 patients had died, and 55 survived. Metastatic period survival times were longer in the adjuvant group, but the difference did not reach the level of statistical significance (adjuvant group: median 29 months, metastatic group: median 22 months; p=0.285). In the adjuvant group before the metastatic first-line therapy, CEA and CA 19-9 levels were significiantly lower compared to the metastatic group (p<0.005). We also found that patients with elevated tumor predictor (CEA, CA 19-9) levels before the first-line therapy had significiantly poorer prognosis and shorter survival time. Survival was significiantly better with the patients who were younger than 65 years of age, had better initial performance status, a history of primary surgery and metastatectomy, and single site of metastasis. Those who benefitted from the first-line therapy were K-RAS wild type and whose tumor markers (CEA, CA 19-9) were not elevated before the first line therapy. CONCLUSIONS: Among the patients with metastatic CRC, those who benefited from first-line therapy, had history of metastasectomy, were K-RAS wild type and had low CA 19-9 levels before the first-line therapy, showed better prognosis independent of other factors.

Efficacy of dose dense doxorubicin and cyclophosphamide followed by paclitaxel versus conventional dose doxorubicin, cyclophosphamide followed by paclitaxel or docetaxel in patients with node-positive breast cancer.

BACKGROUND: Adding taxanes to adjuvant antracycline and cyclophosphamide (AC) in combination may provide significant improvement in node-positive and high risk node-negative breast cancer (BC) patients. However, the optimal dose and the role of dose-dense (DD) chemotherapy have yet to be determined. The aim of this study was to compare the efficacy of a DD paclitaxel (P)-AC combination with conventional weekly P-AC or docetaxel D-AC combinations in patients with node-positive breast cancer. MATERIALS AND METHODS: Newly diagnosed 280 node-positive BC patients diagnosed from 1998 to 2013 in three clinics were retrospectively analyzed. Demographic and medical data were collected from the medical charts. Patients were categorized to 3 groups according to treatment arms: arm A, ddAC-P; arm B, weekly P and AC combination; and arm C; T and AC combination. Adjuvant trastuzumab was added for HER2-positive patients. Kaplan-Meier survival analysis was carried out for disease free survival (DFS) and overall survival (OS). The log-rank test was used to examine the statistical significance of the differences observed between the groups. Two-sided P values <0.05 were considered statistically significant. RESULTS: Of the total of 280 patients, 101 were in arm A, 114 in arm B and 65 in arm C.The median ages were 49, 50 and 46, respectively (p=0.11). Median follow-up was 39 (3-193) months. Stage, lymphovascular and perineural invasion, receptor patern, and menopausal status were similar in the 3 treatment arms, but HER2 positivity was significantly lower in arm A, compared to arms B and C (25.7%, 53.1%, 41.5% in arms A, B and C, respectively; p<0.001). Also grade 3 tumors were significantly less frequent in treatment arm A compared to arm B and C (27.3%, 56.8% and 49.2% , respectively, p=0.01). Afterunivariate and multivariate analysis were performed, 3-year DFS rates were 89%, 81%, and 75%, respectively (p=0.12) and three year OS rates were 96.6%, 89%, and 75% (p=0.62). CONCLUSIONS: In this study, no significant difference was found between adjuvant dose dense and conventional taxane treatment regimens.

[Prevalence of Encephalitozoon intestinalis and Enterocytozoon bieneusi in cancer patients under chemotherapy]. / Kemoterapi alan kanserli hastalarda Encephalitozoon intestinalis ve Enterocytozoon bieneusi prevalansi

Microsporidia species are obligate intracellular parasites and constitute one of the most important opportunistic pathogens that can cause severe infections especially in immunocompromised patients. Enterocytozoon bieneusi and Encephalitozoon intestinalis are the most common species among 14 microsporidia species identified as human pathogens. The aim of this study was to investigate the prevalence of E.intestinalis and E.bieneusi in cancer patients under chemotherapy by immunofluorescent antibody and conventional staining methods. A total of 123 stool samples obtained from 93 patients (58 male, 35 female) with cancer who were followed in oncology and hematology clinics of our hospital and 30 healthy volunteers (13 male, 17 female) were included in the study. Fifty-one (55%) of the patients had complain of diarrhea. The presence of E.intestinalis and E.bieneusi were investigated by a commercial immunofluorescence antibody test using monoclonal antibodies (IFA-MAbs; Bordier Affinity Products, Switzerland) in all of the samples, and 50 of the samples were also investigated by modified trichrome, acid-fast trichrome and calcofluor staining methods. A total of 65 (69.9%) patients were found positive with IFA-MAbs method, including 43 (46.2%) E.intestinalis, 9 (9.7%) E.bieneusi and 13 (14%) mixed infections. In the control group, 5 (16.7%) subjects were positive with IFA-MAbs method, including 2 (6.7%) E.intestinalis, 1 (3.3%) E.bieneusi and 2 (6.7%) mixed infections. The difference between the positivity rate of the patient and control groups was statistically significant (p< 0.05). Of the patients with diarrhea, 68.6% (35/51) were infected with microsporidia, and the difference between cases with and without (48.6%) diarrhea was statistically significant (p< 0.05). When 50 samples in which all of the methods could be performed were evaluated, the frequency of microsporidia were detected as follows; 66% (n= 33) with IFA-MAbs, 34% (n= 17) with modified trichrome staining, 24% (n= 12) with acid-fast trichrome staining and 42% (n= 21) with calcofluor staining methods. Our data indicated that the use of IFA-MAbs method along with the conventional staining methods in diagnosis of microsporidia will increase the sensitivity. As a conclusion, the prevalence of E.intestinalis and E.bieneusi in cancer patients under chemotherapy was detected quite high (69.9%) in our study, it would be appropriate to screen these patients regularly in terms of microsporidian pathogens.

Protective effects of spironolactone against anthracycline-induced cardiomyopathy.

AIMS: The protective effect of beta-blockers, ACE inhibitors, and ARBs on anthracycline cardiotoxicity has already been demonstrated, but the effect of aldosterone antagonism, which inhibits the last step of the renin-angiotensin-aldosterone system (RAAS), was questioned. This study sought to investigate whether spironolactone protects the heart against anthracycline-induced cardiotoxicity. METHODS AND RESULTS: Eighty-three female patients who were diagnosed with breast cancer were included in the study. The study population was randomized into spironolactone and control groups. A dose of 25 mg/day spironolactone was administered to the patients in the spironolactone group. There were 43 patients (mean age 50 ± 11 years) in the spironolactone group and 40 patients (mean age 51 ± 10 years) in the control group. LVEF decreased from 67.0 ± 6.1 to 65.7 ± 7.4 (P = 0.094) in the spironolactone group, and from 67.7 ± 6.3 to 53.6 ± 6.8 in the control group (P < 0.001). When the general linear model was applied, the interaction of LVEF decrease between groups was significantly lower in the spironolactone group than in the control group (P < 0.001). The diastolic functional grade of subjects in the spironolactone group was protected (P = 0.096), whereas it deteriorated in the control group (P < 0.001). CONCLUSION: We showed that spironolactone administration used simultaneously with anthracycline group chemotherapeutics protects both myocardial systolic and diastolic functions. Spironolactone can be used to protect against anthracycline-induced cardiotoxicity. TRIAL REGISTRATION: NCT02053974.

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.

Outcome of 561 non-metastatic triple negative breast cancer patients: multi-center experience from Turkey.

PURPOSE: Triple-negative breast cancers account for 15% of breast carcinomas and, when present as early-stage disease, they are associated with higher rates of recurrence and early distant metastasis risk when compared to hormone receptor positive and human epidermal growth factor receptor (HER-2) positive breast cancers. In this study we aimed to explore the basic clinicopathological characteristics, prognostic factors and recurrence patterns of non-metastatic triple negative breast cancer patients. METHODS: In this study 561 non-metastatic triple-negative breast cancer female patients admitted to 8 different cancer centers in Turkey between 2000 and 2010 were retrospectively evaluated through their medical records, to identify the basic clinico-pathological characteristics, prognostic factors and recurrence patterns. RESULTS: The ratio of triple-negative breast cancer was 12%. The median age of patients was 48 years, of whom 311 (55.4%) were premenopausal. The majority had early-stage breast cancer at the time of diagnosis (16.8% stage I, 48.1% stage II, 35.1 % stage III) and the most commonly identified variant was invasive ductal carcinoma (84.1%). Grade II and III tumors were 27.1 and 48.5%, respectively. Adjuvant chemotherapy was administered to 90.5% of women and adjuvant radiotherapy to 41.2%. Median patient follow up was 28 months (range 3-290). During the follow up period 134 (23.8%) patients developed metastatic disease. In most of these cases, metastatic sites were bone, soft tissue, and lung. Factors affecting disease free survival (DFS) and overall survival (OS) were age (both p<0.001), lymph node involvement (both p<0.001), lymphovascular invasion (LVI) (p<0.001 and p=0.004, respectively), tumor stage (both p<0.001), adjuvant administration of anthracycline-based chemotherapy (both <0.001) and type of surgery (not significant for DFS but p=0.05 for OS). Three-year DFS and OS were 72.0 and 93.0%, respectively. CONCLUSION: Age, lymph node involvement, LVI, stage, and adjuvant chemotherapy were determined as prognostic factors for DFS and OS. The most common recurrence sites were bone, soft tissue and the lung. Further prospective randomised trials are needed to confirm the prognostic and predictive factors identified in this study.