Recommendations for cyclin­dependent kinase 4/6 inhibitor treatments in the context of co­morbidity and drug interactions (Review).

Breast cancer is most frequently diagnosed among women aged 65-74 years and the prevalence of comorbidities in elderly patients with breast cancer is 32.2%. In addition, polypharmacy is quite common in these patients. Understanding the interaction between breast cancer treatment modalities and comorbidities is important, particularly in elderly patients, as comorbidities affect the choice of appropriate treatment and are independent risk factors for survival. A total of three oral cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i), palbociclib, ribociclib and abemaciclib, notably prolonged progression-free survival when combined with endocrine therapy (ET), compared with ET alone in patients with advanced breast cancer (ABC). The present review article therefore addressed the safety, tolerability and toxicity of CDK4/6i treatment in ABC management, compiled real-world data on how multiple clinical and pharmacological features may affect the choice of these drugs and provided practical recommendations for clinical approaches. Before starting treatment with CDK4/6i drugs, all ongoing medical conditions should be inventorized and re-graded, and examination should be performed for any additional disease that the patient may not be aware of. It is also important to obtain a detailed history of concomitant drugs, including prescription and over-the-counter drugs, vitamins, supplements and herbal products. In addition, patients should be advised to consult their oncologist before starting any new medication.

Is there any prognostic significance in pleural involvement and/or effusion in patients with ALK-positive NSCLC?

PURPOSE: Anaplastic lymphoma kinase (ALK) mutations occurs in approximately 3-5% of patients with non-small cell lung cancer (NSCLC). Pleural involvement/effusion is common in ALK-positive patients with NSCLC at baseline. The aim of the study was to evaluate the characteristics of ALK-positive patients who have Ple-I/E. METHODS: In this multicenter study, patients with ALK-positive NSCLC who have Ple-I/E were retrospectively analyzed. Clinical and demographic characteristics of the disease, response rates, median progression-free survival (PFS), and overall survival (OS) were evaluated in 362 ALK-positive patients with NSCLC. RESULTS: Of the patients, 198 (54.7%) were male. The median age at the time of diagnosis was 54 (range 21-85) years. All patients' histology was adenocarcinoma (100%). At baseline, 57 (15.7%) patients had Ple-I/E. There was no association between Ple-I/E and gender, lung metastasis, or distant lymphadenopathy (LAP) metastasis. The frequencies of liver, brain, and bone metastases were significantly higher in ALK-positive patients without Ple-I/E compared to those with Ple-I/E (respectively 18.2% vs 4.8%, p = 0.008; 19.1% vs 4.8%, p = 0.001; 20.6% vs 8.9%, p = 0.002). The median PFS was longer in ALK-positive patients who had Ple-I/E (18.7 vs 10.6 months, p = 0.017). Similarly, the median OS was longer in ALK-positive patients who had Ple-I/E (44.6 vs 22.6 months, p = 0.051). CONCLUSION: Brain, liver, and bone metastases were lower in ALK-positive patients with Ple-I/E. Patients presented with Ple-I/E were prone to have better PFS and OS.

Demographic and Clinical Features of Patients with Metastatic Breast Cancer: A Retrospective Multicenter Registry Study of the Turkish Oncology Group.

This multicenter registry study aims to analyze time-related changes in the treatment patterns and outcome of patients with metastatic breast cancer (MBC) over a ten-year period. Correlations between demographic, prognostic variables and survival outcomes were carried out in database aggregates consisting of cohorts based on disease presentation (recurrent vs. de novo) and the diagnosis date of MBC (Cohort I: patient diagnosed between January 2010 and December 2014; and Cohort II: between January 2015 and December 2019). Out of 1382 patients analyzed, 52.3% patients had recurrent disease, with an increased frequency over time (47.9% in Cohort I vs. 56.1% in Cohort II, p < 0.001). In recurrent patients, 38.4% (n = 277) relapsed within two years from initial diagnosis, among which triple-negative BC (TNBC) was the most frequent (51.7%). Median overall survival (OS) was 51.0 (48.0-55.0) months for all patients, which was similar across both cohorts. HER2+ subtype had the highest OS among subgroups (HER2+ vs. HR+ vs. TNBC; 57 vs. 52 vs. 27 months, p < 0.001), and the dnMBC group showed a better outcome than recMBC (53 vs. 47 months, p = 0.013). Despite the lack of CDK inhibitors, luminal A patients receiving endocrine therapy had a favorable outcome (70 months), constituting an appealing approach with limited resources. The only survival improvement during the timeframe was observed in HER2+ dnMBC patients (3-year OS Cohort I: 62% vs. Cohort II: 84.7%, p = 0.009). The incorporation of targeted agents within standard treatment has improved the outcome in HER2+ MBC patients over time. Nevertheless, despite advances in early diagnosis and treatment, the prognosis of patients with TNBC remains poor, highlighting the need for more effective treatment options.

Efficacy of subsequent treatments in patients with hormone-positive advanced breast cancer who had disease progression under CDK 4/6 inhibitor therapy.

BACKGROUND: There is no standard treatment recommended at category 1 level in international guidelines for subsequent therapy after cyclin-dependent kinase 4/6 inhibitor (CDK4/6) based therapy. We aimed to evaluate which subsequent treatment oncologists prefer in patients with disease progression under CDKi. In addition, we aimed to show the effectiveness of systemic treatments after CDKi and whether there is a survival difference between hormonal treatments (monotherapy vs. mTOR-based). METHODS: A total of 609 patients from 53 centers were included in the study. Progression-free-survivals (PFS) of subsequent treatments (chemotherapy (CT, n:434) or endocrine therapy (ET, n:175)) after CDKi were calculated. Patients were evaluated in three groups as those who received CDKi in first-line (group A, n:202), second-line (group B, n: 153) and ≥ 3rd-line (group C, n: 254). PFS was compared according to the use of ET and CT. In addition, ET was compared as monotherapy versus everolimus-based combination therapy. RESULTS: The median duration of CDKi in the ET arms of Group A, B, and C was 17.0, 11.0, and 8.5 months in respectively; it was 9.0, 7.0, and 5.0 months in the CT arm. Median PFS after CDKi was 9.5 (5.0-14.0) months in the ET arm of group A, and 5.3 (3.9-6.8) months in the CT arm (p = 0.073). It was 6.7 (5.8-7.7) months in the ET arm of group B, and 5.7 (4.6-6.7) months in the CT arm (p = 0.311). It was 5.3 (2.5-8.0) months in the ET arm of group C and 4.0 (3.5-4.6) months in the CT arm (p = 0.434). Patients who received ET after CDKi were compared as those who received everolimus-based combination therapy versus those who received monotherapy ET: the median PFS in group A, B, and C was 11.0 vs. 5.9 (p = 0.047), 6.7 vs. 5.0 (p = 0.164), 6.7 vs. 3.9 (p = 0.763) months. CONCLUSION: Physicians preferred CT rather than ET in patients with early progression under CDKi. It has been shown that subsequent ET after CDKi can be as effective as CT. It was also observed that better PFS could be achieved with the subsequent everolimus-based treatments after first-line CDKi compared to monotherapy ET.

Favorable locoregional control in clinically node-negative hormone-receptor positive breast cancer with low 21-gene recurrence scores: a single-institution study with 10-year follow-up.

BACKGROUND: Recent studies have shown a lower likelihood of locoregional recurrences in patients with a low 21-gene recurrence score (RS). In this single-institution study, we investigated whether there are any associations between different cutoff values of 21-gene RS, histopathological factors, and outcome in patients with long-term follow-up. METHODS: The study included 61 patients who had early-stage (I-II) clinically node-negative hormone receptor-positive and HER2-negative breast cancer and were tested with the 21-gene RS assay between February 2010 and February 2013. Demographic, clinicopathological, treatment, and outcome characteristics were analyzed. RESULTS: The median age was 48 years (range, 29-72 years). Patients with high histologic grade (HG), Ki-67 ≥ 25%, or Ki-67 ≥ 30% were more likely to have intermediate/high RS (≥ 18). Based on the 21-gene RS assay, only 19 patients (31%) received adjuvant chemotherapy. At a median follow-up of 112 months, 3 patients developed locoregional recurrences (4.9%), which were treated with endocrine therapy alone. Among patients treated with endocrine treatment alone (n = 42), the following clinicopathological characteristics were not found to be significantly associated with 10-year locoregional recurrence free survival (LRRFS): age < 40 years, age < 50 years, high histological or nuclear grade, high Ki-67-scores (≥ 15%, ≥ 20%, ≥ 25%, ≥ 30%), presence of lymphovascular invasion, luminal-A type, multifocality, lymph node positivity, tumor size more than 2 cm, RS ≥ 18, and RS > 11. However, patients with RS ≥ 16 had significantly poorer 10-year LRRFS compared to those with RS < 16 (75% vs. 100%, respectively; p = 0.039). CONCLUSIONS: The results suggest that patients with clinically node-negative disease and RS ≥ 16 are more likely to benefit from adjuvant chemotherapies. However, those with RS < 16 have an excellent outcome and local control in long-term follow-up with endocrine treatment alone.

Real-world data on efficacy and safety of first-line alectinib treatment in advanced-stage, ALK-positive non-small-cell lung cancer patients: a Turkish Oncology Group study.

Aims: In this multicenter study, the authors aimed to determine the real-life efficacy and safety of first-line alectinib. Materials & methods: This retrospective trial included advanced-stage, ALK-positive non-small-cell lung cancer patients who were treated with first-line alectinib in terms of ALK-tyrosine kinase inhibitors, regardless of previous chemotherapy. The co-primary end points were progression-free survival both for all patients and for the treatment-naive population. The secondary end points were overall response rate, overall survival, rate of CNS progression and safety. Results & conclusion: A total of 274 patients (n = 177 for treatment-naive patients) were enrolled in the study. The median progression-free survival was 26 and 28.8 months for all patients and the treatment-naive group, respectively. The overall response rate, CNS progression rate and 1-year overall survival ratio were 77.9, 12.4 and 77%. Alectinib is a highly effective therapy with a favorable safety profile.

The advancements in cancer treatment, particularly in the last two decades, have been promising. Non-small-cell lung cancer (NSCLC) is one of the most important diseases experiencing these promising developments. ALK positivity, which is caused by the rearrangement of different gene fragments between two chromosomes, affects about 5% of NSCLC patients. This provides a target for next-generation therapies. One of these targeted therapy drugs is alectinib. The authors examined the outcomes of 271 patients with body-disseminated NSCLC who received alectinib as initial targeted therapy. These patients were not chosen to participate in a clinical phase study. They were treated with an approved drug; the study also included 97 patients who had previously received chemotherapy. The median duration of survival without disease worsening was 26 months for all patients receiving alectinib treatment. This value was 28.8 months in 177 patients who had not received any treatment before alectinib. Regardless of disease status, 77% of all patients were found to be alive at the end of the first year. Alectinib treatment resulted in a significant improvement of the disease in approximately four out of five patients. The treatment's side effects were generally tolerable or manageable. Only four patients were reported to have discontinued their medication due to treatment-related side effects. These real-world findings are compatible with previous clinical research. Alectinib is an important first-line treatment option for patients with advanced, ALK-positive NSCLC.

Efficacy and Safety of Trastuzumab Emtansine in Her2 Positive Metastatic Breast Cancer: Real-World Experience.

AIM: The aim of this study is to evaluate the efficacy and toxicity of trastuzumab emtansine (T-DM1) in cases with metastatic breast cancer (mBC) in different lines of treatment. METHOD: Retrospective analysis of T-DM1 results of human epidermal growth factor receptor 2 (Her2) positive 414 cases with mBC from 31 centers in Turkey. FINDINGS: Except 2, all of the cases were female with a median age of 47. T-DM1 had been used as second-line therapy in 37.7% of the cases and the median number of T-DM1 cycles was 9. Progression-free survival (PFS) and overall survival (OS) times were different according to the line of treatment. The median OS was found as 43, 41, 46, 23 and 17 months for 1st, 2nd, 3rd, 4th and 5th line, respectively (p = 0.032) while the median PFS was found as 37, 12, 8, 8 and 8 months, respectively (p = 0.0001). Treatment was well tolerated by the patients. The most common grade 3-4 adverse effects were thrombocytopenia (2.7%) and increased serum gamma-glutamyl transferase (2%). DISCUSSION: The best of our knowledge this is the largest real-life experience about the safety and efficacy of T-DM1 use in cases with mBC after progression of Her2 targeted treatment. This study suggests and supports that T-DM1 is more effective in earlier lines of treatment and is a reliable option for mBC.

Three Cases of Breast Metastases from Lung Cancer and Systematic Review of the Literature.

Despite the high prevalence of lung cancer among other primary tumors, metastasis of this particular malignancy in the breast is very rare. We report three new cases of lung cancer with breast metastases and discuss radiological and clinical findings. Radiologically, each case displayed different characteristics. First, one of them had bilateral superficially and deeply located irregular lesions. Second, the patient presented with findings similar to inflammatory breast cancer. The third case had a circumscribed mass, resembling a benign complicated cyst. To guide clinicians for proper patient management, radiologists should be aware of the scope of typical and atypical imaging findings of metastatic involvement of the breast.

GLASS: Global Lorlatinib for ALK(+) and ROS1(+) retrospective Study: real world data of 123 NSCLC patients.

Lorlatinib is a third-generation tyrosine-kinases inhibitor (TKI) targeting ALK/ROS1 fusions. The FDA has approved lorlatinib for TKI-pretreated ALK(+) NSCLC, while its approval for ROS1(+) is still pending. Here we present the largest real-world data of NSCLC patients harboring ALK/ROS1 rearrangements treated with lorlatinib. METHODS: 123 patients were enrolled retrospectively (data cut-off 1/1/2019). Lorlatinib was administered through an early access program for patients with no other available therapy. Outcome and response were defined by each investigator upon RECIST 1.1 criteria. RESULTS: 106 ALK(+) and 17 ROS1(+) patients recruited from 8 different countries. The ALK(+) cohort included 50 % males, 73 % never-smokers and 68 % with brain metastases. Extracranial (EC) and intracranial (IC) response rates (RR) were 60 % and 62 %, with disease control rates (DCR) of 91 % and 88 % respectively. Mean duration of therapy (DoT) was 23.9 ±â€¯1.6 months and median overall survival (mOS) was 89.1 ±â€¯19.6 months. ROS1 cohort enrolled 53 % males, 65 % never-smokers and 65 % had brain metastases. EC and IC RR were 62 % and 67 % with DCR of 92 % and 78 % respectively. Median DoT was 18.1 ±â€¯2.5 months and mOS of 90.3 ±â€¯24.4 months. OS and DoT in both cohorts were not significantly correlated with line of therapy nor other parameters. The most common adverse events of any grade were peripheral edema (48 %), hyperlipidemia (47 %), weight gain (25 %) and fatigue (30 %). CNS adverse events such as cognitive effect of grade 1-2 were reported in 18 % of patients. CONCLUSION: Lorlatinib shows outstanding EC/IC efficacy in ALK/ROS1(+) NSCLC. The observed mOS of 89 ±â€¯19 months in ALK(+) NSCLC supports previous reports, while mOS from of 90 ±â€¯24 months is unprecedented for ROS1(+) NSCLC.

Efficacy of Palbociclib and Endocrine Treatment in Heavily Pretreated Hormone Receptor-positive/HER2-negative Advanced Breast Cancer: Retrospective Multicenter Trial

Background: The synthesis of CDK4/6 inhibitors with endocrine treatment in two series of treatment has been widely accepted as the standard for patients with estrogen receptor-positive metastatic breast cancer. In spite of this, the activity of CDK4/6 inhibitors in patients with metastatic breast cancer who have progressed despite receiving multiple lines of treatment is not well understood. Aims: To report the activity and safety of a CDK4/6 inhibitor (palbociclib) in patients in whom at least three lines of treatment for ER+ metastatic breast cancer had failed. Study Design: Multicenter retrospective observational cohort study. Methods: In this retrospective observational cohort study, we included 43 patients who received palbociclib after at least three lines of systemic treatment for ER+/HER2− metastatic breast cancer. Results: The median progression-free survival in our population was 7 months (25th-75th percentile, 4-10), and the median overall survival was 11 months (25th-75th percentile, 6-19). Although there were some adverse events, palbociclib was generally well tolerated, so dose reduction was needed for only six patients (14%). Conclusion: The efficacy of palbociclib among heavily treated hormone receptor-positive/HER2− patients with advanced breast cancer was acceptable in terms of clinical benefit, and it was generally well tolerated among this population.

Pretreatment PET/CT Standardized Uptake Values Play a Role in Predicting Response to Treatment and Survival in Patients with Small Cell Lung Cancer.

BACKGROUND: We investigated the role of standardized uptake values (SUVs) of the primary tumor in small cell lung cancer (SCLC) patients. PATIENTS AND METHODS: The relationship between SUV and response to treatment was investigated using receiver operating characteristic (ROC) curve analysis, and the efficient cut-off value for detecting response to treatment was determined. The effects of SUV on response to treatment and survival were investigated. RESULTS: 90 patients with a median age of 58 years (range 39-83 years) were included. Median follow-up was 11 months. The suitable cut-off SUV for determination of response was found to be 10 in ROC analysis. The sensitivity and specificity of this value were 85.7% (95% confidence interval (95% CI) 63-96) and 61.8% (95% CI 49-73) (area under the curve 0.783; p = 0.0001), respectively. The overall objective response rate in patients with involvement above the cut-off value was 93.3% compared to 59.1% in those with involvement below the cut-off value (p < 0.0001). In uni- and multivariate analysis, favorable effects of limited-stage disease on response to treatment were established (p < 0.05). The effect of an SUV higher than the cut-off value on progression-free survival was borderline (p = 0.085). CONCLUSION: These data may contribute to identifying prognostic disease characteristics and response to treatment.

Comparison of efficacy and safety of three different chemotherapy regimens delivered with concomitant radiotherapy in inoperable stage III non-small cell lung cancer patients.

Concomitant administration of chemotherapy and radiotherapy is currently recognized as the standard of treatment in locally advanced inoperable non-small cell lung cancer (NSCLC). Our study aimed to compare the efficacy and toxicities of three different chemotherapy regimens delivered concurrently with radiotherapy. We retrospectively reviewed the clinical records of patients who received the PE (cisplatin, 50 mg/m(2), on days 1, 8, 29, and 36 plus etoposide, 50 mg/m(2), on days 1 to 5 and 29 to 33), PD (docetaxel, 20 mg/m(2), on day 1 plus cisplatin, 20 mg/m(2), on day 1, every week), and PC (carboplatin, AUC 2 plus paclitaxel, 45 mg/m(2), on day 1, every week) regimens concurrently with radiotherapy. A total of 227 patients were evaluated in the study. Median follow-up time was 13 months (2-101). There were 27 females (11.9 %) and 200 males (88.1 %) with a median age of 61 (38-82) years. The PD group had higher rates of esophagitis, mucositis, and anemia (p < 0.05). The PC group had higher rates of neuropathy (p = 0.000). The progression-free survival (PFS) time was 10 months for patients in the PC group, 15 months for patients in the PD group, and 21 months for the PE group (p = 0.010). Patients in the PC group had a median overall survival time of 23 months, those in the PD group 27 months, and those in the PE group 36 months (p = 0.098). Combination of cisplatin-etoposide with radiotherapy led to a more favorable outcome compared with the other two regimens. It shows generally manageable toxicity profile and compliance to treatment is noticeable.

Review of the current role of targeted therapies as maintenance therapies in first and second line treatment of epithelial ovarian cancer; In the light of completed trials.

Late and recurrent stage ovarian cancer has a high mortality and low response rate to therapy beyond first line treatment. Although first line platinum/taxane based regimens have a satisfactory response rate eventually in most cases disease recurrence is common and second-line treatments are not curative. Delaying progression or recurrence is the main goal of current ongoing clinical studies by means of establishing an effective maintenance regimen with acceptable toxicity profile. Clearly, the persistence of dormant and drug-resistant cells after front-line treatments results in the inability to cure the disease. Over the past several years, the idea of prolongation of therapy for ovarian cancer has garnered clinical attention and academic debate. As a result of a greater understanding of the molecular pathways involved in carcinogenesis and tumor growth, a large number of potential therapeutic targets have been identified and drugs to block receptors, ligands or pathways are being developed. Currently, numerous clinical trials with targeted agents have just been completed or are ongoing involving patients achieving a complete or durable response after first-line and beyond the first line chemotherapy in order to evaluate the efficacy of different therapeutic approaches in terms of progression-free survival and overall survival.

Metastasis-Induced Acute Pancreatitis Successfully Treated with Chemotherapy and Radiotherapy in a Patient with Small Cell Lung Cancer.

Although involvement of pancreas is a common finding in small cell lung cancer (SCLC), metastasis-induced acute pancreatitis (MIAP) is very rare. A 50-year-old female with SCLC who had limited disease and achieved full response after treatment presented with acute pancreatitis during her follow-up. The radiologic studies revealed a small area causing obliteration of the pancreatic duct without mass in the pancreatic neck, and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) confirmed the metastasis of SCLC. The patient was treated successfully with systemic chemotherapy and radiotherapy delivered to pancreatic field. In SCLC, cases of MIAP can be encountered with conventional computed tomography with no mass image, and positron emission tomography and EUS-FNA can be useful for diagnosis of such cases. Aggressive systemic and local treatment can prolong survival, especially in patients with good performance status.

Outcomes of Platinum-Sensitive Small-Cell Lung Cancer Patients Treated With Platinum/Etoposide Rechallenge: A Multi-Institutional Retrospective Analysis.

UNLABELLED: Small-cell lung cancer has a high chemotherapeutic sensitivity but with disappointing outcome results. Patients with "sensitive disease" are those who respond to treatment with a long relapse-free interval (RFI): in these cases rechallenge with first-line chemotherapy might represent a therapeutic opportunity. Our largest retrospective experience confirmed that rechallenge is feasible with interesting outcome results; there are no statistical differences between RFI and outcome. INTRODUCTION: Patients with small-cell lung cancer (SCLC) that progresses after first-line (FL) chemotherapy have a poor prognosis and second-line (SL) chemotherapy has limited efficacy. Patients whose disease relapses/progresses > 90 days after FL platinum-based treatment are considered platinum-sensitive and could be rechallenged with a similar regimen. We conducted a multicenter retrospective analysis to evaluate outcomes of SCLC patients rechallenged with platinum/etoposide. PATIENTS AND METHODS: Records of all SCLC patients treated in 7 institutions between January 2007 and December 2011 were reviewed. The primary end point was overall survival from the time of rechallenge (OS-R); secondary end points were progression-free survival (PFS) and overall survival from the time of diagnosis (OS-D). Survival curves were calculated using the Kaplan-Meier method. RESULTS: Of the 2000 SCLC patients identified, 112 (5.6%) had sensitive disease treated with rechallenge platinum/etoposide; 65% were men with a median age of 64 years. At the time of diagnosis, 44% of patients had limited disease, 82% had an Eastern Cooperative Oncology Group performance status of 0 to 1. A median of 4 cycles of rechallenge was administered. Tumor response was 3% for complete response and 42% for partial response, 19% of patients maintained stable disease, 27% progressive disease, and 9% were not evaluable. Median PFS from the time of rechallenge was 5.5 months (95% confidence interval [CI], 4.4-6.3). Median OS-R and OS-D were 7.9 months (95% CI, 6.9-9.7) and 21.4 months (95% CI, 19.8-24.1), respectively. Subgroup analysis according to relapse-free interval (90-119 vs. 120-149 vs. > 150 days) did not show any statistically significant difference in PFS or OS-R. CONCLUSION: The outcome for SL chemotherapy for SCLC is poor. Rechallenge platinum/etoposide is a reasonable option with potentially better outcomes than standard chemotherapy.

Prevalence of K-Ras mutations in hepatocellular carcinoma: A Turkish Oncology Group pilot study.

Hepatocellular carcinoma (HCC) is the fifth most common male-predominant type of cancer worldwide. There is no effective treatment regimen available for advanced-stage disease and chemotherapy is generally ineffective in these patients. The number of studies on the prevalence of K-Ras mutations in HCC patients is currently limited. A total of 58 patients from 6 comprehensive cancer centers in 4 metropolitan cities of Turkey were enrolled in this study. Each center committed to enroll approximately 10 random patients whose formalin-fixed paraffin-embedded tumor tissues were available for K-Ras, exon 2 genotyping. Two methods were applied based on the availability of adequate amounts of tumor DNA. In the first method, the samples were processed using TheraScreen. The genomic DNA was further used to detect the 7 most frequent somatic mutations (35G>A; 35G>C; 35G>T; 34G>A; 34G>C; 34G>T and 38G>A) in codons 12 and 13 in exon 2 of the K-Ras oncogene by quantitative polymerase chain reaction (PCR). In the second method, the genomic DNA was amplified by PCR using primers specific for K-Ras exon 2 with the GML SeqFinder Sequencing System's KRAS kit. The identified DNA sequence alterations were confirmed by sequencing both DNA strands in two independent experiments with forward and reverse primers. A total of 40 samples had adequate tumor tissue for the mutation analysis. A total of 33 (82.5%) of the investigated samples harbored no mutations in exon 2. All the mutations were identified via a direct sequencing technique, whereas none were identified by TheraScreen. In conclusion, in our patients, HCC exhibited a remarkably low (<20%) K-Ras mutation rate. Patients harboring K-Ras wild-type tumors may be good candidates for treatment with epidermal growth factor inhibitors, such as cetuximab.

Clinical outcome of Turkish metastatic breast cancer patients with currently available treatment modalities--single center experience.

BACKGROUND: Breast cancer is the most common malignancy and the second leading cause of cancer-related death among women in the developed countries. Despite advances in screening, improved local therapies and adjuvant systemic treatments, median survival of metastatic breast cancer patients (MBC) is in the range of 2-3 years at most. We aimed to investigate whether the prognostic factors and therapeutic responses of our Turkish patients are similar to those in the literature. MATERIALS AND METHODS: We reviewed the medical records of MBC patients who had been treated in our institution between 1999-2009 and analyzed their clinicopathological features and survival outcomes retrospectively. RESULTS: A hundred and sixty patients were included. Median age was 47 (23-82), median follow up was 24 (2-186) months. At the time of diagnosis 59% of patients were under the age of 50 and 46% were postmenopausal. The majority (37%) had multiple sites of metastases. Forty percent received endocrine therapy and 40% chemotherapy as first line metastatic treatment. Thirty (20%) patients were treated with molecular targeting agents like trastuzumab, lapatinib and sunitinib, frequently combined with a chemotherapy agent. Five-year overall survival (OS) was 32% and median OS was 38 months for the whole group. Five year progression free survival (PFS) was 10% and median PFS was 10 months. Menopausal status, hormone receptor expression and disease free status had a significant impact on overall survival in the multivariate analysis (p 0.018, p 0.018 and p:0.003, respectively). CONCLUSIONS: All our patients were treated with the modern oncologic therapies recommended by the international guidelines. From our data, MBC patients live up to 3-4 years, indicating that further improvement beyond that requires development of new treatment modalities. The survival outcomes of our patients were consistent with the data reported in the literature.