Comparative study of receptor discordance between primary and corresponding metastatic lesions in breast cancer.

PURPOSE: It is well-known that tumor phenotype may change during the progression of breast cancer (BC). The purpose in this study was to compare the discordance in estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2) between primary and recurrent/metastatic lesions (RML) and also to evaluate the prognostic significance of change in tumor phenotype on survival in patients with metastatic BC. METHODS: The medical records of 6638 patients with BC from two breast centers treated between 1992 and 2015 were retrospectively analyzed. Of the 6638 patients, 549 cases in whom recurrence was histologically proven by biopsy or by surgical resection were enrolled into this study. RESULTS: Our presentation 13.5% of the patients had metastatic disease. Biopsy on recurrence was obtained from distant metastasis sites in 250 (63.6%) patients or from locoregional soft tissues/lymph-nodes in 143 (36.4%). Receptor discordance in ER, PgR and HER2 expressions between primary and RML were 27.2% (p=0.32), 38.6% (p<0.001) and 14.4% (p=0.007), respectively. Subsequent gain of ER and PgR showed significantly higher overall survival (OS) and post-recurrence survival (PRS) compared to the corresponding concordant-negative patients (119 vs 57 months, p=0.001 and 56 vs 31 months, p=0.03 for ER, 148 vs 58 months, p=0.003 and 64 vs 31 months, p=0.01 for PgR, respectively), hormone receptor (HR) loss was associated with worse OS. Similarly, HER2-loss cases experienced poorer PRS and OS outcomes, compared with those having stable HER2 expression (median 26 vs 60 months, p=0.009 for PRS and median 60 vs 111 months, p=0.06 for OS, respectively). CONCLUSION: This study confirmed the receptor discordance in ER/PgR and HER2 receptor expressions between primary and RML in patients with metastatic BC. As the loss of receptor expression is the most responsible factor for the discordance, treatments of recurrent/metastatic tumors should be individualized on the basis of molecular and genomic properties.

Effect of body mass index on the efficacy of adjuvant tamoxifen in premenopausal patients with hormone receptor-positive breast cancer.

PURPOSE: Obesity has been confirmed to be an adverse prognostic factor in patients who were treated with aromatase inhibitors; however, such relationship has never been thoroughly investigated in patients treated with tamoxifen. The purpose of this study was to examine the effect of body mass index (BMI) on the efficacy of adjuvant tamoxifen in premenopausal patients with hormone receptor-positive breast cancer. METHODS: Newly diagnosed premenopausal and non-metastatic hormone receptor-positive breast cancer patients were enrolled in the study. Patients with BMI ranging between 18.5 and 24.9 kg/m(2) were considered as normal weight patients (Arm A, n = 408), and/patients with a BMI ≥ 25 kg/m(2) were considered as overweight and obese patients (Arm B, n = 418). RESULTS: In both normal weight and overweight patients, the baseline clinicopathologic properties and the treatment history with radiotherapy and chemotherapy were similar and no statistical significant difference could be detected. Tamoxifen in combination with luteinizing hormone-releasing hormone (LHRH) agonist was used in 33% (136/408) of the patients in Arm A and in 22% (91/418) of patients in Arm B (p<0.001). Three-year disease free survival (DFS) rates were 89% and 87% in arm A and arm B, respectively (p=0.39). Three-year overall survival (OS) rates were 99% in arm A and 94% in arm B which appeared to be of significance (p=0.028). In univariate analysis no statistical significant effect of LHRH agonist usage on DFS (p=0.58) and OS (p=0.96) was found. CONCLUSION: Although BMI had no negative effect on recurrence risk, poor OS was observed in overweight and obese premenopausal breast cancer patients with hormone-receptor positive tumors who were treated with tamoxifen.

Evaluation of erectile dysfunction risk factors in young male survivors of colorectal cancer.

PURPOSE: Improved long-term survival of colorectal cancer patients (CRC) treated with surgery and/or chemotherapy ± radiotherapy (RT) has led to increased awareness of long-term side effects, including effecting sexual life, which can ultimately affect the quality of life in these patients. Because the absolute risk factors of erectile dysfunction (ED) have not been defined in CRC patients, the aim of this research was to identify the severity and the absolute risk factors of ED in male CRC survivors. METHODS: The medical records of 61 male survivors of CRC treated with surgery and/or chemotherapy ± RT were retrieved from the medical oncology outpatient clinics during routine follow-up visits in 2011-2012. Patients older than 55 years and those with ED history before diagnosis were excluded. International Index of Erectile Function (IIEF) questionnaire was filled in by the patients. RESULTS: The patient mean age was 47.6±6.7 years (range 18-55) at the time of filling in the questionnaire. According to the International Index of Erectile Function (IIEF) score, 83.6% of the patients had some degree of ED. The risk factors of erectile dysfunction were advancing age (p=0.01), tumor location (p=0.01), type of surgery (p=0.02), presence of stoma (p=0.03)) and RT (p=0.005). Chemotherapy didn't impact ED (p=0.46). Also, there was no significant correlation between smoking status, hypertension, diabetes mellitus, cardiovascular disease, stage of the tumor and ED. Also hormonal disturbances such as serum FSH, LH and testesterone levels did not affect the presence of ED. CONCLUSION: Overall, 83.6% of the male CRC survivors had some degree of ED according to the IIEF. The risk factors of ED were advancing age, tumor location, type of operation, presence of stoma and RT. Clinicians should be aware of these risk factors to offer their patients adequate treatment options and also come up with new treatment strategies necessary to reduce further ED in CRC survivors.

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.

Paclitaxel plus doxorubicin chemotherapy as second-line therapy in patients with advanced urothelial carcinoma pretreated with platinum plus gemcitabine chemotherapy.

BACKGROUND: We retrospectively evaluated the efficacy and toxicity of paclitaxel plus doxorubicin as a second-line treatment in patients with urothelial carcinoma, who had not responded to a prior platinum plus gemcitabine combination. PATIENTS AND METHODS: All patients received intravenous infusions of paclitaxel (175 mg/m(2)/h) and doxorubicin (50 mg/m(2)/30 min) on day 1. Chemotherapy courses were repeated every 21 days. RESULTS: The median followup duration was 13.5 months (range 2.8-22.4 months). Complete and partial responses were observed in 2 (5.6%) and 10 (27.8%) patients, respectively. Median overall survival was 8.9 months (95% confidence interval (CI): 6.2-11.6). Median time to progression was 3.8 months (95% CI: 2.7-4.8). The most common hematologic toxicities were neutropenia (n = 21, 58.3%), thrombocytopenia (n = 10, 27.8%), and anemia (n = 9, 25%). The most common nonhematologic toxicities consisted of fatigue (n = 15, 41.7%), nausea/vomiting (n = 13, 36.1%), peripheral neuropathy (n = 11, 30.6%), and mucositis (n = 6, 16.7%). Dose reductions by 25-35% were performed in 6 (16.7%) patients because of grade 3/4 toxicity. Anthracycline-related heart failure did not occur. CONCLUSION: 3-weekly courses of cyclic paclitaxel plus doxorubicin were found to be effective and tolerable in patients with urothelial carcinoma, who had not responded to prior platinum- and gemcitabine-based chemotherapy.

PD-L1 expression in immune cells is a favorable prognostic factor for nasopharyngeal carcinoma.

BACKGROUND: Programmed death-ligand 1 (PD-L1) has been determined as a reliable prognostic factor for various malignancies. In this study, we aimed to determine the prognostic effect of PD-L1 expression in tumor-infiltrating immune cells (TIICs) of nasopharyngeal carcinoma (NPC) patients. METHODS: Seventy patients diagnosed with non-metastatic NPC were included in the study. PD-L1 expression on immune cells was analyzed by immunohistochemical method. Patients were categorized into two groups according to the PD-L1 expression level in TIICs (level of PD-L1 staining ≥5% positive vs <5% negative). RESULTS: Median follow-up period was 34 months (range = 1 - 188). 1 and 2 years survival rate were found as 75% and 63% in PD-L1 negative TIICs group (47%), and 85% and 83% in PD-L1 positive TIICs group (53%), respectively. PD-L1 positivity in immune cells (ICs) was detected in 53% of the patients. The survival rate was found better in the PD- L1 positive group compared to the negative group (P = 0.049). DISCUSSION: In conclusion, the survival rate was found significantly better in the PD-L1 positive TIICs group, compared to the negative group.

Good prognostic factor in patients with nonmetastatic nasopharyngeal carcinoma: Programmed death ligand-1 expression in tumor cells.

PURPOSE: Programmed death ligand-1 (PD-L1) is the main ligand for programmed death-1 (PD-1), and is one of the major targets for cancer immunotherapy. Only a few studies are available for the clinical significance of PD-1/PD-L1 in nasopharyngeal carcinoma (NPC). There is a controversial association between PD-L1 expression and survival in NPC. This study aimed at defining any potential association between PD-L1 expression in tumor cells (TCs) and prognosis in NPC. PATIENTS AND METHODS: A total of seventy NPC patients treated between January 2008 and December 2016 were included in the study. PD-L1 expression was assessed by immunohistochemistry (IHC) in tumor specimens. The IHC assay was considered positive if ≥5% of TCs are stained. Clinicopathological variables were documented. Variables included in the analysis were PD-L1 expression, clinicopathological characteristics, and prognosis. RESULTS: The estimated 5-year overall survival (OS) rate was 62%. Nearly 55.7% (n = 39) of the TCs tested positive for PD-L1 expression. No associations were found between the level of PD-L1 in TCs and clinicopathological characteristics. Comparisons between patients with PD-L1-positive tumors and PD-L1-negative tumors revealed that OS was statistically significantly longer in patients with PD-L1-positive tumors as assessed by the univariate Cox regression analysis (hazard ratio [HR], 0.378; 95% confidence interval, 0.158-0.905; P = 0.029) and Kaplan-Meier curves (P = 0.023). CONCLUSION: PD-L1 expression is an important prognostic factor in NPC. PD-L1 expression positively correlates with survival.

Impact of acetylsalicylic Acid on the clinicopathological characteristics and prognosis of patients with invasive breast cancer.

BACKGROUND: The impact of acetylsalicylic acid (ASA) on the clinicopathological characteristics of breast cancer has not yet been elucidated in detail; we therefore aimed to investigate the effects of ASA on the clinicopathological characteristics of patients with breast cancer. PATIENTS AND METHODS: Patients diagnosed with breast cancer were retrospectively analyzed. Breast cancer patients who were taking ASA at the time of breast cancer diagnosis were enrolled as ASA users (n = 84); matching patients with the same age who were not taking ASA were included as control group (n = 890). RESULTS: The median age was 56 (range 34-82) years in both groups. ASA users had a significantly lower incidence of grade II-III tumors compared to non-users (P = 0.02). The other clinicopathological characteristics and treatment histories were similar in both groups. In patients using ASA, the disease-free survival (DFS) rate was 97.3%, 89.4%, and 79.9% and in non-users it was 94.1%, 81.8%, and 70.9% in the 1rst, 3rd, and 5th year, respectively (P = 0.01). In aspirin users, the overall survival rate was 95.0%, 90.6%, and 87.6% and in non-users it was 98.1%, 91.2%, and 85.5% in the 1rst, 3rd, and 5th year, respectively (P = 0.50). CONCLUSION: Using ASA at the time of breast cancer diagnosis was associated with significantly improved DFS in breast cancer patients.

The efficacy of adjuvant trastuzumab in HER-2 positive breast cancer with axillary lymph node metastases according to the treatment duration.

INTRODUCTION: Trastuzumab is the first anti-HER-2 humanized monoclonal antibody. The benefit of adjuvant trastuzumab has been shown in randomized phase III trials. Despite trastuzumab being recommended for 52 weeks in the adjuvant treatment of HER-2 positive breast cancer according to the current breast cancer guidelines, there is still no consensus on the optimal duration of adjuvant trastuzumab. The aim of our study is to investigate the efficacy and safety of adjuvant trastuzumab for 9 weeks and 52 weeks in axillary lymph node positive HER-2 positive breast cancer patients. PATIENTS AND METHODS: A total of 271 HER-2 and axillary node positive breast cancer patients who received trastuzumab in adjuvant treatment between the years 2005 and 2013 were retrospectively analyzed. Patients with axillary node positive HER-2 positive breast cancer who were non-metastatic were enrolled to the study. Patients were allocated to the 9 week trastuzumab group (n = 155) or the 52 week trastuzumab group (n = 116). Kaplan-Meier survival analysis was carried out for disease free survival (DFS) and overall survival (OS). Two-sided p values of <0.05 were considered statistically significant. The most important limitation of our manuscript is the retrospective design. RESULTS: The median follow-up time for this analysis was 34 (4-95) months. Patients' clinical and pathological characteristics were well balanced between the two treatment arms. In the 9 week trastuzumab treatment group, the DFS rate was 96.7%, 84.8% and 74.9% in the first, third and fifth years respectively, whereas in the 52 week trastuzumab treatment group it was 94.3%, 80.0% and 80.0% (P = 0.76). In the 9 week trastuzumab treatment group, the OS rate was 99.3%, 92.2% and 88.3% in the first, third and fifth years respectively, whereas in the 52 week trastuzumab treatment group it was 99.0%, 94.7% and 78.6% (P = 0.99). In both groups, symptomatic heart failure was not reported but asymptomatic left ventricular ejection fraction (LVEF) decline was observed 3 (1.9%) and 18 (15.5%) patients in the 9 week and 52 week trastuzumab treatment groups, respectively (P < 0.001). CONCLUSION: In our study, the efficacy of trastuzumab for 52 weeks and 9 weeks was similar in node-positive HER-2 positive breast cancer. Cardiotoxicity was significantly increased in the 52 week trastuzumab arm compared to the 9 week trastuzumab arm.

Current approaches for prophylactic cranial irradiation in extrapulmonary small cell carcinoma.

BACKGROUND: Small cell lung cancer (SCLC) patients, who have achieved complete or partial response after chemotherapy, should be followed with prophylactic cranial irradiation (PCI). PCI for extrapulmonary small cell carcinoma (EPSCC) is not routinely recommended. The purpose of this review is to discuss all aspects of PCI in management of EPSCC. SCOPE: The PubMed database and the database of online abstracts of the American Society of Oncology (ASCO), ASCO Genitourinary (GU) Cancers meetings and clinical trials were searched up to 15 October 2013 using the following search keywords: 'SCC or EPSCC of each organ site and prophylactic cranial radiotherapy'. The language of screened abstracts and manuscripts was limited to English. The papers which included the largest case series and data of cases about prophylactic cranial radiotherapy and/or were published in the last 10 years were selected. FINDINGS: Many single center studies showed low incidence of brain metastasis in patients with esophageal small cell carcinoma (SCC). Due to the low incidence of brain metastasis, PCI is not recommended for esophageal SCC. Genitourinary, colorectal, small bowel and appendix cranial metastatic SCCs are extremely rare. Therefore, PCI is not recommended. The frequency of brain metastasis of prostate small cell carcinoma is much higher (16-19%) compared to other counterparts of EPSCC. PCI can be performed in selected cases of prostate SCC. High rates (41%) of brain metastasis develop in head and neck SCC. PCI should be considered for patients with head neck SCC. CONCLUSION: In the literature, the brain metastasis incidence of EPSCC might vary from 1.7% up to 40%. In many patients with ESPCC, PCI is not recommended. However, we have to keep in mind that primary head and neck and prostate SCC are exceptions due to the high incidence of cranial metastasis; PCI should be recommended for these patients on an individual basis.

Clinicopathologic features of gastric cancer in young patients.

BACKGROUND/AIM: Gastric cancer (GC) is considered to be a disease of elderly patients. It has been suggested that GC in young adults has more aggressive clinical and pathologic features than in adults. In this study we aimed to evaluate clinical and pathologic features of GC under age 40 years. PATIENTS AND METHODS: Patients included in this study were those treated and followed up for GC under age 40 years in Ankara Numune Education and Research Hospital from 2002 to 2011. RESULTS: Clinical and pathologic features of 82 patients have been evaluated retrospectively. Of the patients 44 were male (54%) and 38 were (46%) female, and the median age was 35 years (min-max: 18-40 years). The tumor was grade 3 in 77% of the patients, 79% had diffuse type tumor, 64% had lymphovascular invasion, and 76% had perineural invasion. Forty-seven patients (57%) were metastatic at the time of diagnosis. The median follow up was 9 (1-101) months. The median overall survival (OS) was 9 months in metastatic patients and 8-year OS was 64% in nonmetastatic patients. CONCLUSIONS: We observed that young GC patients had more aggressive histopathologic features and more than half was metastatic at the time of diagnosis. We need more studies comparing young and elderly patients to confirm that young patients had more aggressive disease.

Bevacizumab plus irinotecan in recurrent or progressive malign glioma: a multicenter study of the Anatolian Society of Medical Oncology (ASMO).

PURPOSES: The overall prognosis for recurrent malignant glioma (MG) is extremely poor, and treatment options are limited. We evaluated our multicenter retrospective experience for patients with recurrent MG administering bevacizumab and irinotecan in combination therapy. METHODS: A total of 115 patients with grade IV glial tumor (n = 93) and grade III glial tumor (n = 22) were retrospectively evaluated at 14 centers in Turkey. Primary objectives of the study were to evaluate the efficacy and toxicity of the bevacizumab and irinotecan as salvage treatment based on response to therapy, progression-free survival (PFS), 6 months of PFS, overall survival (OS), and 6 months of OS (OS6). RESULTS: Bevacizumab and irinotecan were performed as second line (79.1 %) and third line treatment (20.9 %). Median chemotherapy cycle was 6 (range 1-37), and median follow-up was 6 months (range 1-36 months). Objective response rate was 39.1 %. Six-month PFS and OS6 were 46.3 % and 67.5 %, respectively. Median PFS was 6 months (95 % CI 2.5-9.5) and 6 months (95 % CI 4.9-7.1) in the grade III and IV groups, respectively (p = 0.773). Median OS was 9 months (95 % CI 7.1-10.9) and 8 months (95 % CI 6.6-9.4) in the grade III and IV groups, respectively (p = 0.450). Serious toxicities were observed in 7.8 % of patients. Treatment-related toxic death was observed in 3 patients. There was no treatment related to central nervous system hemorrhage or other serious hemorrhages. CONCLUSIONS: Present study results were consistent with previous studies. In addition, we detected similar outcomes in grade III and IV glial tumors.