Early thrombocytopenia predicts longer time­to­treatment discontinuation in trastuzumab emtansine treatment.

Thrombocytopenia is a characteristic adverse event of trastuzumab emtansine (T-DM1), one of the essential treatment options for human epithelial growth factor receptor 2 (HER2)-positive breast cancer. The present study investigated the predictive value of thrombocytopenia for time-to-treatment discontinuation (TTD) in patients receiving T-DM1 for advanced-stage HER2-positive breast cancer. The present observational study enrolled 138 patients who received T-DM1 at six oncology centers from January 2016 to December 2021. Univariate and multivariate Cox regression analyses were performed to determine the factors affecting TTD. The median age of patients was 50 years (range, 26-83). The median number of T-DM1 cycles was 9 (range, 2-58), the overall response rate was 50.0% and the disease control rate was 69.6%. At a median follow-up time of 19.3 months, the median TTD was 9.5 months [95% confidence interval (CI), 7.3-11.7], and the median overall survival was 28.2 months (95% CI, 19.2-37.2). Thrombocytopenia during treatment was observed in 39% of all patients, and 66.7% of these patients experienced early thrombocytopenia (in the first four treatment cycles). Multivariate analysis revealed that the independent factors for TTD were hormone receptor status [hazard ratio (HR), 1.837; 95% CI, 1.249-2.701; P=0.002], Eastern Cooperative Oncology Group performance status score (HR, 3.269; 95% CI, 1.788-5.976; P<0.001) and thrombocytopenia during treatment (HR, 0.297; 95% CI, 0.198-0.446; P<0.001). Patients with early thrombocytopenia had a significantly longer TTD of 17.3 months (95% CI, 11.8-22.8) compared with 7.6 months (95% CI, 5.8-9.4) for patients without early thrombocytopenia (P<0.001). The results of the present study indicated that patients with early thrombocytopenia had improved survival outcomes compared with those without. Thus, maximum benefit from T-DM1 treatment may be achieved by confirming the predictive role of thrombocytopenia in T-DM1 treatment in prospective studies and large-scale cohorts.

The prognostic role of epidermal growth factor receptor mutation in completely resected ampullary adenocarcinoma.

The aim of this study is to make a differential diagnosis and prognosis of the ampullary adenocarcinoma subtypes. We also investigated the role of prognostic markers PD-1 and PD-L1, and epidermal growth factor receptor (EGFR). Local or locally advanced stage ampullary adenocarcinoma patients who had undergone pancreaticoduodenectomy at the time of diagnosis were included. MUC1, MUC2, MUC5AC, CDX2, CK7, CK20, PD-1, and PDL-1 were analysed immunohistochemically, and EGFR was analysed by real-time polymerase chain reaction. According to histopathological and immunohistochemical evaluation, we found 27 patients as pancreatobiliary type and 56 patients as intestinal type adenocarcinoma. The median survival of patients with intestinal and pancreatobiliary type adenocarcinoma was 23 months and 76 months ( p = 0.201), respectively. When the survival of PD1-positive ( n = 23) and PD-L1-positive ( n = 18) patients were compared with the patients with negative staining ( n = 60, n = 65), no significant difference was found. Epidermal growth factor receptor mutation was detected in a total of 6 patients, and 5 of these 6 mutations were shown in intestinal type tumours and one in a pancreatobiliary type tumour. A significant difference was determined in terms of overall survival for the patients with EGFR mutations compared to those without ( p = 0.008). In conclusion, we could reveal the prognostic significance of EGFR mutation, which is also a target molecule.

Prevalence of Gastrointestinal Symptoms and Clinical Outcomes in Hospitalized Coronavirus Disease 2019 Patients: A Single-Center Study from Turkey.

BACKGROUND: In patients with coronavirus disease 2019, the gastrointestinal symptoms have been reported increasingly in addition to the respiratory system symptoms. The studies show that the prevalence of gastrointestinal system symptoms and how the gastrointestinal system contributes to the severity and prognosis of the disease is still not clear. This study aims to find the prevalence of gastrointestinal symptoms and the correlation between the gastrointestinal symptoms and the clinical results in hospitalized patients diagnosed with coronavirus disease 2019. METHODS: This study retrospectively analyzes patients diagnosed with coronavirus disease 2019 and hospitalized in the pandemic unit between March 2020 and August 2020 and compares their demographic and clinical characteristics, laboratory and radiologic findings, coronavirus disease 2019 treatments received, the clinical course of the disease, and the gastrointestinal symptoms. RESULTS: In our study, we included 322 patients diagnosed with coronavirus disease 2019 and hospitalized; 39 patients (12.1%) were admitted to the hospital with at least one gastrointestinal symptom (nausea and vomiting, diarrhea, abdominal pain, and the loss of taste). Nausea and vomiting are the most common gastrointestinal symptoms with a prevalence of 7.1%, followed by diarrhea with 2.8%, the loss of taste with 2.2%, and abdominal pain with 1.5%. The mean age and D-dimer levels of the patients showing gastrointestinal symptoms were lower than those who did not have any gastrointestinal symptoms. We did not find a significant correlation between the presence of the gastrointestinal symptoms and the severity of the disease, treatment received, risk of acute respiratory distress syndrome and septic shock, admission to the intensive care unit, the need for mechanical ventilation, the mortality rate or the length of hospitalization in the medical floor or the intensive care unit. CONCLUSION: In this study, we observed that 12.1% of coronavirus disease 2019 patients apply to the hospital due to gastrointestinal symptoms. Furthermore, the gastrointestinal symptoms do not seem to affect the severity and the course of the disease, it is important to identify coronavirus disease 2019 patients showing unusual symptoms such as the gastrointestinal symptoms at an early stage to protect healthcare professionals from infection risk.

Tumoral and Parenchymal Morphological Assessment in Liver Metastases of Colorectal Carcinoma: Micrometastasis, Peritumoral Lymphocytes, Tumor Budding and Differentiation are Potential Prognostic Factors.

Introduction: Various potential prognostic histopathologic factors for colorectal carcinoma liver metastasis have been proposed. However, there is still no consensus on pathological reporting of colorectal carcinoma liver metastasis resection materials. The aim of this study was to investigate the relation between selected tumoral and parenchymal histopathologic features and prognostic factors for better characterization and prognostic prediction of the patients with colorectal carcinoma liver metastasis. Methods: Hematoxylin-eosin stained slides from 100 patients who underwent hepatic resection were evaluated. Pathologic characteristics; including number of tumor nodules, largest tumor size, status of surgical margin, tumor distance to closest margin, tumor necrosis, the presence of tumor capsule, tumor differentiation, perineural and lymphovascular invasion, micrometastasis, tumor budding, peritumoral lymphocytic infiltrate and parenchymal features including steatosis, steatohepatitis, lobular inflammation, confluent necrosis, hepatocyte ballooning, portal inflammation were assessed. For 49 patients who were treated with preoperative chemotherapy, tumor regression grade and chemotherapy-related parenchymal changes such as sinusoidal damage, venous obstruction, nodular regenerative hyperplasia, steatosis and steatohepatitis were also evaluated. Results: The presence of lymphovascular invasion (p < 0.001), micrometastasis (p=0.004), absent or mild peritumoral lymphocytic infiltration (p =0.013), high tumor budding score (p=0.033) and moderate/poor differentiation (p=0.022) were significantly associated with shorter overall survival. Lymphovascular invasion (p < 0.001) was an independent predictor of mortality in multivariate analysis. Conclusions: We conclude that tumor differentiation, lymphovascular invasion, micrometastasis, peritumoral lymphocytic reaction and tumor budding score are potential prognostic histopathological features and candidates for inclusion in pathology reports of colorectal carcinoma liver metastasis resections.

Evaluation of hereditary/familial breast cancer patients with multigene targeted next generation sequencing panel and MLPA analysis in Turkey.

Breast cancer, a worldwide leading cause of cancer in women, may occur in familial cases. Germline mutations in BRCA1/2 genes are responsible for 15% of the familial cases. With the power of next generation sequencing (NGS) analysis, it is possible to analyze genes related to hereditary susceptibility to breast cancer and investigate the genetic etiology more thoroughly. In this study, we investigated 30 genes identified frequent pathogenic alleles in Turkish population. The study includes 495 unrelated individuals diagnosed with breast cancer who are selected for genetic testing according to NCCN criteria for hereditary breast cancer. All patients were analyzed by NGS for BRCA1/2 genes. Deletion/duplication investigation by Multiplex ligation-dependent probe amplification (MLPA) and massive sequencing of 30 breast cancer-related genes (Oncorisk Gene Panel) were performed in a stepwise manner. BRCA1/2 variants are the most frequent pathogenic variants which are found in 45 of 495 (9.1%) patients. Four previously unreported, novel, pathogenic variants of BRCA2 gene are identified. In four cases, exonic deletions of BRCA1/2 genes are determined and there is no duplication of these genes. NGS panel investigation involving other moderate-high risk genes contributed genetic diagnosis in an extra 39 out of 419 (9.3%) cases. Our study presents the cost effectiveness of the gene panel approach. We suggest that gene panels should be the first-tier genetic testing for hereditary breast cancer and MLPA analysis of BRCA1/2 genes should be investigated as a complementary method of NGS analysis.

Final Efficacy Results of Neratinib in HER2-positive Hormone Receptor-positive Early-stage Breast Cancer From the Phase III ExteNET Trial.

BACKGROUND: The ExteNET trial demonstrated improved invasive disease-free survival (iDFS) with neratinib, an irreversible pan-HER tyrosine kinase inhibitor, versus placebo in patients with human epidermal growth factor receptor 2-positive (HER2+)/hormone receptor-positive (HR+) early-stage breast cancer (eBC). PATIENTS AND METHODS: ExteNET was a multicenter, randomized, double-blind, phase III trial of 2840 patients with HER2+ eBC after neoadjuvant/adjuvant trastuzumab-based therapy. Patients were stratified by HR status and randomly assigned 1-year oral neratinib 240 mg/day or placebo. The primary endpoint was iDFS. Descriptive analyses were performed in patients with HR+ eBC who initiated treatment ≤ 1 year (HR+/≤ 1-year) and > 1 year (HR+/> 1-year) post-trastuzumab. RESULTS: HR+/≤ 1-year and HR+/> 1-year populations comprised 1334 (neratinib, n = 670; placebo, n = 664) and 297 (neratinib, n = 146; placebo, n = 151) patients, respectively. Absolute iDFS benefits at 5 years were 5.1% in HR+/≤ 1-year (hazard ratio, 0.58; 95% confidence interval [CI], 0.41-0.82) and 1.3% in HR+/>1-year (hazard ratio, 0.74; 95% CI, 0.29-1.84). In HR+/≤ 1-year, neratinib was associated with a numerical improvement in overall survival (OS) at 8 years (absolute benefit, 2.1%; hazard ratio, 0.79; 95% CI, 0.55-1.13). Of 354 patients in the HR+/≤ 1-year group who received neoadjuvant therapy, 295 had residual disease, and results showed absolute benefits of 7.4% at 5-year iDFS (hazard ratio, 0.60; 95% CI, 0.33-1.07) and 9.1% at 8-year OS (hazard ratio, 0.47; 95% CI, 0.23-0.92). There were fewer central nervous system events with neratinib. Adverse events were similar to those previously reported. CONCLUSION: Neratinib significantly improved iDFS in the HER2+/HR+/≤ 1-year population, and a similar trend was observed in patients with residual disease following neoadjuvant treatment. Numerical improvements in central nervous system events and OS were consistent with iDFS benefits and suggest long-term benefit for neratinib in this population.

The prognostic role of thyroid transcription factor-1 in lung adenocarcinoma.

AIMS: In this study, we investigated the expression of thyroid transcription factor-1 (TTF-1) in lung adenocarcinoma patients' samples and analyzed the association of TTF-1 with clinicopathological parameters, prognosis, and treatment options in patients with lung adenocarcinoma. SUBJECTS AND METHODS: This retrospective study enrolled 200 patients who were histologically confirmed lung adenocarcinoma with Stage I-IV disease, between 2008 and 2015 years. The cytological archive of these hospitals' Pathology Department was searched. The available slides and the clinical information were reviewed and correlated. All analyses were conducted by SPSS version 15.0 statistical software. RESULTS: Sixty-five (32.5%) of the patients showed TTF-1 negativity and 135 (67.5%) of them showed TTF-1 positivity. The median survival for TTF-1 positive and negative patients was 19.6 and 12.2 months, respectively. We did not find any statistical significance in-between the parameters in terms of the survival data. In TTF-1-negative group, the survival time of epidermal growth factor receptor mutation positive (P = 0.049), cytokeratin 7 (CK7) positive (P = 0.009) patients and those who had received curative radiotherapy (P = 0.028) was significantly better as compared to TTF-1-positive group. We also analyzed the relation between TTF-1 and survival outcome or chemotherapy selection in Stage IV disease. We could not identify any correlation between TTF-1 and survival outcome or treatment selection. CONCLUSIONS: This study suggests that TTF-1 is not a favorable prognostic factor in lung adenocarcinoma patients. The prognostic role of CK7 and relationship between TFF-1 expression in lung adenocarcinoma and predictive role of TTF-1 expression for the selection of first-line treatment in Stage IV lung adenocarcinoma should be validated in prospective and randomized studies.

An Evaluation of the Information Sources of Cancer Patients' Relatives. A Prospective Survey.

Patients followed up with a cancer diagnosis must be well-informed about cancer to be able to cope with it. Besides, informing the relatives of the cancer patients who are also experiencing the same process about the diagnosis and follow-up period of cancer is highly important. In the current study, it was aimed to evaluate the information sources about cancer which are referred to by relatives of cancer patients. Three hundred ninety-one cancer patient relatives were included in medical oncology clinic between May 1 and June 30, 2015. A questionnaire was applied to the participants, comprising 12 questions to elicit demographic information and 11 questions about the information sources to which they referred. The study included 183 female and 208 male participants with a mean age of 47.9 ± 13.6 years. While the oncologists were the primary information sources referred to by 87%, the Internet was the second most preferred information source by 72%. The websites most frequently referred were the official websites (70%), the websites of oncology associations (53%), and social networks and forums (32%). The primary factors affecting the Internet preference were age, education level, income level, and place of residence. The Internet was the second most referred information source about cancer by family caregivers following oncologists. Therefore, it is of crucial importance that physicians inform patients and their relatives comprehensively as well as guiding them to correct and reliable information sources.

The prognostic role of thyroid transcription factor-1 in lung adenocarcinoma.

AIMS: In this study, we investigated the expression of thyroid transcription factor-1 (TTF-1) in lung adenocarcinoma patients' samples and analyzed the association of TTF-1 with clinicopathological parameters, prognosis, and treatment options in patients with lung adenocarcinoma. SUBJECTS AND METHODS: This retrospective study enrolled 200 patients who were histologically confirmed lung adenocarcinoma with Stage I-IV disease, between 2008 and 2015 years. The cytological archive of these hospitals' Pathology Department was searched. The available slides and the clinical information were reviewed and correlated. All analyses were conducted by SPSS version 15.0 statistical software. RESULTS: Sixty-five (32.5%) of the patients showed TTF-1 negativity and 135 (67.5%) of them showed TTF-1 positivity. The median survival for TTF-1 positive and negative patients was 19.6 and 12.2 months, respectively. We did not find any statistical significance in-between the parameters in terms of the survival data. In TTF-1-negative group, the survival time of epidermal growth factor receptor mutation positive (P = 0.049), cytokeratin 7 (CK7) positive (P = 0.009) patients and those who had received curative radiotherapy (P = 0.028) was significantly better as compared to TTF-1-positive group. We also analyzed the relation between TTF-1 and survival outcome or chemotherapy selection in Stage IV disease. We could not identify any correlation between TTF-1 and survival outcome or treatment selection. CONCLUSIONS: This study suggests that TTF-1 is not a favorable prognostic factor in lung adenocarcinoma patients. The prognostic role of CK7 and relationship between TFF-1 expression in lung adenocarcinoma and predictive role of TTF-1 expression for the selection of first-line treatment in Stage IV lung adenocarcinoma should be validated in prospective and randomized studies.

BRCA genes: BRCA 1 and BRCA 2.

BRCA1 and BRCA2 are the genes related with breast and ovarian cancer. They have function in DNA repair processes and thus they are tumor suppressor genes. There are hundreds of mutations identified in these genes. Functional deficiencies due to these mutations impair DNA repair and cause irregularities in the DNA synthesis. The standard method for the laboratory assessment of these BRCA genes includes comprehensive sequencing and testing of broad genomic rearrangements. Members of the families with BRCA mutations have an increased risk for early onset of breast cancer and ovarian cancer occurring at any age. Surveillance of patients with mutations in BRCA 1/2 is done by yearly mammography and breast MRI and by transvaginal ultrasonography and serum CA-125 levels every 6-12 months for ovarian cancer.

Do the derived neutrophil to lymphocyte ratio and the neutrophil to lymphocyte ratio predict prognosis in breast cancer?

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is a strong predictor of mortality in patients with cancer. Similarly, a study in a large series has shown that the newly defined derived NLR (dNLR; neutrophil/leukocyte-lymphocyte ratio) also has prognostic value. The present study retrospectively evaluates the prognostic significance of NLR and dNLR in breast cancer. METHODS: Hematological parameters and clinicopathological data during diagnosis were retrospectively recorded for 1,527 patients diagnosed with breast cancer at Izmir Katip Celebi University Ataturk Research and Training Hospital from January 2006 to December 2011. The cut-off values were determined by calculating the NLR and dNLR of the patients. RESULTS: The cut-off values were determined as 4 and 2 for NLR and dNLR, respectively. The association between NLR and dNLR assessed by Spearman's rank correlation analysis was 0.935 (P < 0.001). There was a significant difference regarding disease free survival (DFS) and overall survival (OS) in patients with NLR <4 and NLR ≥4 (respectively, P < 0.00, P < 0.001). Similarly, there was a significant difference regarding DFS and OS in patients with dNLR <2 and dNLR ≥2 (respectively, P < 0.001, P < 0.001). Furthermore, NLR and dNLR demonstrated a significant association with the American Joint Committee on Cancer (AJCC) staging (P < 0.001). Assessment using the Cox proportional multivariate model showed that high NLR, pN, pT, luminal A-like, luminal B-like (HER2 positive), basal-like, and AJCC staging are independent prognostic factors. DISCUSSION: NLR was shown to be better than dNLR in terms of predicting prognosis in patients with breast cancer. However, large prospective studies are required to further demonstrate the prognostic significance of these two values.

Treatment of metastatic colorectal cancer with or without bevacizumab: can the neutrophil/lymphocyte ratio predict the efficiency of bevacizumab?

BACKGROUND: The purpose of this study was to analyze the predictive value of neutrophil/lymphocyte ratio (NLR) to better clarify which patient groups will benefit the most from particular treatments like bevacizumab. MATERIALS AND METHODS: A total of 245 treatment-naive metastatic colorectal cancern (mCRC) patients were retrospectively enrolled and divided into 2 groups: 145 group A patients were treated with chemotherapy in combination with bevacizumab, and 100 group B patients were treated as above without bevacizumab. RESULTS: Group A patients had better median overall survival (OS) and progression-free survival (PFS) (24.0 and 9.0 months) than group B patients (20 and 6.0 months) (p=0.033; p=0.015). In patients with low NLR, OS and PFS were significantly longer in group A patients (27 vs 18 months, p=0.001; 11 vs 7 months, p=0.017). CONCLUSIONS: We conclude that NLR, a basal cancer related inflammation marker, is associated with the resistance to bevacizumab- based treatments in mCRC patients.

Prognostic evaluation of breast cancer patients with evident bone marrow metastasis.

In this study, we aimed to evaluate the clinicopathologic characteristics and prognosis of breast cancer (BC) patients with symptomatic bone marrow metastasis (BMM). Fifty-four BC patients, including patients with and without BMM, were evaluated retrospectively. In particular, the clinicopathologic features and survival of the patients with BMM (n = 27) were assessed and compared with the patients without BMM. All of the patients with BMM also had osseous metastases, and bone was the first site for distant recurrence in the majority of patients in the study group. Anemia was the most frequent symptom at presentation. The median time to BMM was 36.1 months (range 1.6-70.5 months, 95% CI). HER2(+) patients developed BMM earlier than HER2(-) patients (3.2 versus 38.3 months, 95% CI; p = 0.05). Patients with advanced disease at the time of initial BC diagnosis developed BMM earlier than patients with early disease (p = 0.04). Time to development of BMM was significantly shorter in tumors with perinodal infiltration (p = 0.001) and multicentric focus (p = 0.025). Median survival time after the diagnosis of apparent BMM was 6.43 months. Survival after BMM diagnosis in patients with grade III tumors was significantly shorter than in patients with grade I-II tumors (1.43 versus 5.36 months, 95% CI; p < 0.001). Systemic therapy after BMM diagnosis significantly prolonged survival (17.3 versus 0.93 months, 95% CI; p < 0.001). Hormone receptor-positive, high-grade, advanced-stage tumors at the time of initial BC diagnosis were more common in patients with BMM. Invasive lobular histology was also more frequent in patients with BMM. In conclusion, the presence of hormone receptor-positive, multicentric, grade III, advanced-stage tumors may be important risk factors for the development of evident BMM in BC patients. Systemic single-agent chemotherapy can prolong survival in these patients. However, multicenter analyses are required to verify these findings.

The impact of cell proliferation markers and p53 mutation status on prognosis of non-metastatic colon cancer.

BACKGROUND AND OBJECTIVES: We aimed to evaluate the prognostic value of cell cycle proteins and p53 together with clinicopathologic features in non-metastatic resected colon cancer. METHODS: One hundred nine patients who were diagnosed with resected colon cancer between 2006 and 2011 were analyzed retrospectively. Immunohistochemical staining analyses were used to evaluate the expression of cyclins D1 and A, p53 and Ki-67 in tumor tissue. RESULTS: High cyclin D1 and cyclin A expression was more common in stage II than stage III tumors. Disease recurrence was more frequent in tumors with low cyclin D1 expression (P = 0.05). No significant association was observed between p53, Ki-67 or cyclin A expression and the risk of relapse and/or death. Multivariate analysis showed that the strongest predictor for a shorter disease-free survival period was extracapsular nodal invasion (ECNI). CONCLUSIONS: We were not able to establish a strong association between patient prognosis and cyclins D1 and A, p53 or Ki-67 expression. However, a negative correlation between cyclin D1 and cyclin A expression and disease stage as well as more frequent relapses in patients with low expression of cyclin D1 suggested that cyclins may be predictive for early relapse in non-metastatic colon cancer.

Long-term outcomes and prognostic factors of high-risk malignant melanoma patients after surgery and adjuvant high-dose interferon treatment: a single-center experience.

BACKGROUND: Surgical excision constitutes an important part of the treatment of local advanced malignant melanoma. Due to the high recurrence risk, adjuvant high-dose interferon therapy is still the only therapy used in stage IIB and III high-risk melanoma patients. METHODS: One hundred two high-risk malignant melanoma patients who received high-dose interferon-α-2b therapy were evaluated retrospectively. The clinicopathological features, survival times, and prognostic factors of the patients were determined. RESULTS: The median disease-free and overall survival times were 25.2 and 60.8 months, respectively. Our findings revealed that male gender, advanced disease stage, lymph node involvement, lymphatic invasion, the presence of ulceration, and a high Clark level were significant negative prognostic factors. CONCLUSION: In light of the favorable survival results obtained in this study, high-dose interferon treatment as adjuvant therapy for high-risk melanoma is still an efficient treatment and its possible side effects can be prevented by taking the necessary precautions.

Clinicopathologic and demographic evaluation of triple- negative breast cancer patients among a turkish patient population: a single center experience.

BACKGROUND: To evaluate the clinicopathologic and demographic characteristics of triple-negative breast cancer (TNBC) patients and to determine differences from non-triple-negative cases. MATERIALS AND METHODS: A detailed review of the medical records of 882 breast cancer (BC) patients was conducted to obtain information regarding age, menopausal status, height and weight at the time of diagnosis, presence of diabetes or hypertension, and pathologic characteristics of the tumor (tumor size, lymph node status, histologic grade, ER status, PR status, HER2 status, p53 mutation). Body mass index (BMI) was calculated and a value of ≥30 was considered as indicative of obesity. RESULTS: 14.9% (n=132) of the patients had TNBC. There was no difference among the patients in terms of median age, comorbid conditions and menopausal status. The proportion of medullary, tubular and mucinous carcinomas was significantly higher (15.9%) in the triple-negative (TN) group, while invasive lobular histology was more frequent (8.2%) among non-triple negative (NTN) cases (p<0.001). Grade 3 (G3) tumors were more frequent in the triple-negative group (p<0.001). The rate of p53 mutation was 44.3% in TN tumors versus 28.2% in the NTN group (p<0.001). The two groups were similar in terms of LN metastasis. In the NTN group, the rate of patients with BMI ≥30 was 53% among postmenopausal patients, while it was 36% among premenopausal women, and the difference was statistically significant (p<0.001). No significant difference was observed in terms of BMI between postmenopausal and premenopausal patients in the TN group (p=0.08). CONCLUSIONS: TNBC rates and clinicopathologic characteristics of the Turkish patient population were consistent with the data from Europe and America. However, no relationship between obesity and TNBC was observed in our study. The association between TNBC and obesity needs to be evaluated in a larger patient population.

Does immunohistochemistry provide additional prognostic data in gastrointestinal stromal tumors?

BACKGROUND: To investigate the predictive and prognostic effects of clinicopathologic and immunohistochemical (IHC) features in patients with gastrointestinal stromal tumours (GISTs). MATERIALS AND METHODS: Fifty-six patients who were diagnosed with GIST between 2002 and 2012 were retrospectively evaluated. Relationships between clinicopathologic/immunohistochemical factors and prognosis were investigated. RESULTS: Median overall survival (OS) of the whole study group was 74.9 months (42.8-107.1 months), while it was 95.2 months in resectable and 44.7 months in metastatic patients respectively (p=0.007). Epitheliolid tumor morphology was significantly associated with shortened OS as compared to other histologies (p=0.001). SMA(+) tumours were significantly correlated with low (<10/50HPF) mitotic activity (p=0.034). Moreover, SMA(+) patients tended to survive longer and had significantly longer disease-free survival (DFS) times than SMA (-) patients (37.7 months vs 15.9 months; p=0.002). High Ki-67 level (≥30%) was significantly associated with shorter OS (34 vs 95.2 months; 95%CI; p=0.001). CD34 (-) tumours were significantly associated with low proliferative tumours (Ki-67<%10) (p=0.026). Median PFS (progression-free survival) of the patients who received imatinib was 36 months (27.7-44.2 months). CD34 (-) patients had significantly longer PFS times than that of negative tumours; (50.8 vs 29.8 months; p=0.045). S100 and desmin expression did not play any role in predicting the prognosis of GISTs. Multivariate analysis demonstrated that ≥10/50HPF mitotic activity/HPF was the only independent factor for risk of death in GIST patients. CONCLUSIONS: Despite the negative prognostic and predictive effect of high Ki-67 and CD34 expression, mitotic activity remains the strongest prognostic factor in GIST patients. SMA positivity seems to affect GIST prognosis positively. However, large-scale, multicenter studies are required to provide supportive data for these findings.

Predictive and prognostic factors in locally advanced breast cancer: effect of intratumoral FOXP3+ Tregs.

This study aimed to investigate the prognostic and predictive effect of FOXP3+ Tregs together with clinicopathologic factors in locally advanced breast cancer (LABC) patients. The medical records of 101 LABC patients who received neoadjuvant chemotherapy (NAC) between 2005 and 2012 were evaluated retrospectively. The density of intratumoral FOXP3+ lymphocytes in paraffin-embedded tissues was assessed by immunohistochemical analyses in appropriate cases. The relationship with clinicopathologic features, prognosis and chemotherapy response was investigated. HR(-) and HER2(+) tumors tended to have higher pre-chemotherapy Tregs than HR(+) tumors, and significantly higher pathologic complete response (PCR) rates were observed in these patients. Treg decline after NAC was associated with better pathological response rates. Lower intratumoral infiltration of FOXP3+ Tregs after NAC (<3.4/HPF) was significantly associated with higher PCR rates for breast, and close to the significance limit for total (or both for breast and axillary) PCR rates (PCR for breast: 25 vs. 2.9 % for low vs. high Treg, p = 0.001; PCR for breast + axillary tissue: 13.9 vs. 0 %, p = 0.05). Despite better PCR rates, patients with high intratumoral Treg infiltrates (≥11.5/HPF) before chemotherapy had significantly shorter overall survival than patients with low Treg infiltrates (<11.5/HPF). Cox multivariate regression analyses demonstrated that the density of Treg infiltration before chemotherapy was the strongest predictor for survival. This study established the predictive and prognostic effect of intratumoral FOXP3+ Tregs in LABC patients. To predict clinical outcome, evaluation of FOXP3+ Tregs in tumoral tissues before and after NAC should be considered for these high-risk patients.

Cisplatin plus gemcitabine for treatment of breast cancer patients with brain metastases; a preferential option for triple negative patients?

BACKGROUND: To assess the efficacy and tolerability of Cisplatin plus Gemcitabine combination in patients with brain metastases (BM) from breast cancer (BC). MATERIALS AND METHODS: Eighteen BC patients with BM who were treated with Cisplatin plus Gemcitabine regimen between 2003-2011 were evaluated. RESULTS: A median of 6 cycles of this regimen were received, in fifteen patients (83.3%) as first-line chemotherapy, in 2 as second- line and in 1 as third-line after diagnosis of BM. Dose reduction was performed in 11 (61.1%) patients; major reasons were neutropenia and leukopenia. Grade III neutropenia and Grade II trombocytopenia rates were 33.3% and 16.7% respectively. Overall response rate (ORR; complete+partial response rate) was 33.4% (n=6) for the entire study population; triple negative patients achieved an 66.6% ORR while hormone receptor (HR) positive patients had 25% and HER2 positive patients 12.5%. Median progression-free survival was 5.6 months (2.4-8.8 months, 95%CI) and longer in patients with triple negative breast cancer (TNBC) (median 7.4 months, 95%CI, 2.4-12.3 months) than the patients with other subtypes (median 5 months for HER2 positive and 3.6 months for HR positive patients). Median PFS of the patients with TNBC who received this regimen as first-line was 9.2 months (5.2-13.2 months, 95%CI). CONCLUSIONS: Cisplatin plus Gemcitabine may be a treatment option for patients with BM from breast cancer. Longer PFS and higher response rates are results that support the usage of this regimen especially for the triple negative subtype. However, further prospective and randomized trials are clearly required to provide more exact information.