Search

BACKGROUND:Src, CDKN1B, and JAK2 play a crucial role in the coordination of cell signaling pathways. In the present study, we aim to investigate the prognostic significance of these biomarkers in HER2-positive metastatic breast cancer (MBC) patients treated with trastuzumab (T). METHODS:Formalin-fixed paraffin-embedded tumor tissue samples from 197 patients with HER2-positive MBC treated with T were retrospectively collected. All tissue samples were centrally assessed for ER, PgR, Ki67, HER2, and PTEN protein expression; EGFR gene amplification; PI3KCA mutational status; and tumor-infiltrating lympocytes density. Src, CDKN1B, and JAK2 mRNA expression was evaluated using quantitative reverse transcription-polymerase chain reaction. RESULTS:Only 133 of the 197 patients (67.5%) were found to be HER2-positive by central assessment. CDKN1B mRNA expression was strongly correlated with Src (rho = 0.71) and JAK2 (rho = 0.54). In HER2-positive patients, low CDKN1B conferred higher risk for progression [hazard ratio (HR) = 1.58, 95% confidence interval (CI) 1.08-2.32, P = .018]. In HER2-negative patients, low Src was associated with longer survival (HR = 0.56, 95% CI 0.32-0.99, P = .045). Upon multivariate analyses, only low CDKN1B and JAK2 mRNA expression remained unfavorable factors for PFS in de novoand relapsed (R)-MBC patients, respectively (HR = 2.36, 95% CI 1.01-5.48, P = .046 and HR = 1.76, 95% CI 1.01-3.06, P = .047, respectively). CONCLUSIONS:Low CDKN1B and JAK2 mRNA expressions were unfavorable prognosticators in a cohort of T-treated MBC patients. Our results suggest that CDKN1B and JAK2, if validated, may serve as prognostic factors potentially implicated in T resistance, which seems to be associated with distinct pathways in de novoand R-MBC.

BACKGROUND:Prevention of bone metastases is a major issue for breast cancer patients, as it would improve quality of life in a population where long survival is anticipated. PATIENTS AND METHODS:Early breast cancer patients, who had been treated with anthracycline-based chemotherapy within two randomized trials, were included in the study. We evaluated, by quantitative reverse transcription–polymerase chain reaction, 819 formalin-fixed paraffin-embedded tumor tissue samples for mRNA expression of RANK, OPG, and RANKL, as well as their ratios, for potential prognostic significance for the development of bone metastases and also for disease-free survival (DFS) and overall survival. RESULTS:Median age was 52.7years, whereas 54.2% of the patients were postmenopausal and 78.3% estrogen receptor/progesterone receptor positive. After a median follow-up of 119.9months, 226 patients (27.6%) had died and 291 patients (35.5%) had disease progression. Low mRNA expression of RANKL was associated with postmenopausal status and greater number of positive lymph nodes (P=.002 and P<.001, respectively). In the univariate analysis, low RANKL mRNA expression was found to be an unfavorable factor for DFS [hazard ratio (HR)=1.33, 95% confidence interval (CI) 1.05-1.68, Wald's P=.018] and bone metastasis–free survival (HR=1.67, 95% CI 1.09-2.56, P=.018), although it did not retain its significance in the multivariate analysis. CONCLUSIONS:Low RANKL mRNA expression in early breast cancer patients is of prognostic significance for increased risk for relapse and bone metastases and might potentially guide clinical decision-making for the use of anti-RANKL agents in the treatment of early breast cancer patients at high risk for metastatic spread, provided that our findings are validated in independent cohorts.

Current evidence indicates that angiogenesis plays an important role in the pathogenesis of several malignancies, including breast cancer. Bevacizumab is a monoclonal antibody that targets the vascular endothelial growth factor (VEGF). Recent clinical data have demonstrated that the addition of bevacizumab to first-line chemotherapy improves the progression-free survival of patients with advanced breast cancer. This review presents an update on the role of bevacizumab, as well as other anti-angiogenic agents in the management of patients with breast carcinoma.

Infections of the central nervous system may provoke glial and autoimmune responses but a definitive linkage between these infections and the pathogenesis of chronic neurologic disorders is still elusive. There are controversial reports implicating infectious agents in the pathogenetic mechanisms of chronic or long-term neurologic disorders, such as multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease and autistic spectrum disorders, but the specific role of bacterial or viral infections in the pathogenesis of these medical entities has not been fully elucidated. Up till now, the evidence is distant from definite, but certain cases may be attributed to infections in the millieu of multiple toxic events such as trauma, nutritional deficits, immune dysregulation and excitotoxicity in genetically vulnerable indiniduals. There is an ongoing debate concering the direct involvement of various infectious agents in the neurodegenerative and neurobehavioral diseases pathogenesis and/or their contribution to the deterioration of the disease or co-morbidity in these patients. These patients are exceptionally difficult to be treated by using single therapeutic modalities, because their disese is multifocal and treatment is aimed to control signs and symptoms rather than the true causes of the disease and its progressive course. Furthermore, even if these causative links were indetifiable, our therapeutic interventions would come too late due to the irreversible damages at the time of the initiation of treatment. Our aim is to comprehensively review all available data suggesting that infections could be common antecedent events of progressive neurologic degenerative or behavioural diseases.

Patients with malignancies are often in a hypercoagulable status. The pathogenetic mechanisms of thrombotic events in malignancy are multifaceted and consist of release or expression of procoagulants by cancer cells, but also appearance of procoagulant action by normal host cells. Most importantly, current therapeutic modalities for cancer such as high dose chemotherapy and surgery represent a significant additional risk for serious or even fatal thromboembolic events. There is a wide spectrum of clinical manifestations of these events which encompass Trousseau's syndrome, deep venous thrombosis, marantic endocarditis, disseminated intravascular coagulation, thrombotic microangiopathy and arterial thrombosis. Cancer chemotherapy is most commonly associated with deep vein thrombosis but intracranial sinus vein thromboses and thrombotic microangiopathy may also occur. Our purpose is to review the relevant literature linked to the effect of chemotherapy and other cancer-related interventions on thromboembolic incidents.

Aim: A randomized, open label with blind assessment, controlled trial was performed to assess efficacy and adverse-event profile of vitamin E, given as supplementation for prophylaxis against cisplatin-induced peripheral neuropathy (CIPN). Patients and methods: A total of 30 patients scheduled to receive six courses of cumulative cisplatin-based regimens were randomly allocated to treatment and control groups and were then studied by means of neurological examination and electrophysiological study. Patients assigned to group I (n=14) orally received vitamin E at a daily dose of 600 mg/day during chemotherapy and 3 months after its cessation were compared to patients of group II (n=16), who received no vitamin E supplementation and served as controls. The severity of neurotoxicity was summarized by means of a modified Peripheral Neuropathy (PNP) score. Results: The incidence of neurotoxicity differed significantly between groups, occurring in 3/14 (21.4%) of patients assigned to the vitamin E supplementation group and in 11/16 (68.5%) of controls (p=0.026). The relative risk (RR) of developing neurotoxicity was significantly higher in case of controls, RR=2.51, 95% C.I.=1.16–5.47. Mean PNP scores were 4.99±1.33 for patients of group I and 10.47±10.62 for controls, (p=0.023). None of the adverse events or deaths occurred, were judged as likely to be related to the vitamin E supplementation. Conclusion: Vitamin E effectively and safely protects patients with cancer from occurrence of cisplatin neurotoxicity.

Abstract: Purpose: The current setting tested the hypothesis that advanced age would be strongly associated with increased incidence and severity of chemotherapy-induced peripheral neuropathy (CIPN).Patients and methods: We prospectively studied 35 cancer patients treated with paclitaxel or cisplatin-based regimens for lung or breast cancer. All patients underwent a detailed clinical and electrophysiological evaluation for screening of CIPN at baseline, at the third, the sixth course of chemotherapy and up to 3 months after its cessation. Means of a modified Peripheral Neuropathy (PNP) score summarized the results of the clinical and electrophysiological study.Results: Patients were divided according to their age in two groups (mean age difference, p=0.000) to those younger than 65 years (group I, n=18) and those older or equal than 65 years (group II, n=17). According to the clinical, neurological and electrophysiological variables of each patient, the incidence and severity of CIPN was determined and then compared between groups. The incidence of neurotoxicity was similar (p=0.869) between group I (9/18 patients, 50%) and group II (8/17 patients, 52.9%). Likewise, according to the mean PNP scores, the severity of CIPN was similar between age groups (p=0.897). The between-age-groups comparison of electrophysiological data revealed no significant differences in any of the motor or sensory conduction parameters examined.Conclusion: Our study indicates that elderly cancer patients do not have greater risk of CIPN, whilst advanced age was not associated with worst severity of CIPN.

Abstract

Aims and Background The objective of the study was to assess the efficacy of surgical resection of solitary brain metastasis in patients with non-small-cell lung cancer.Methods and Study Design We report a retrospective analysis of 32 patients with single brain metastasis surgically excised at our hospital. All but one patient underwent postoperative whole brain radiation therapy.Results The median survival of patients was 12.5 months postoperatively (mean, 17 months), and the overall 1-year survival was 53%. Thirteen patients had recurrence of brain metastasis: 6 of 13 underwent reoperation for the recurrent lesion, and 1 of the 6 patients had a third craniotomy. Baseline characteristics, which significantly influenced survival, included age less than 60 years, tumor histology (ie, adenocarcinoma), and treatment of the primary lung cancer. The analysis did not yield any significant differences between treatment modalities.Conclusions Our findings correspond well with those reported in the literature and suggest that surgical resection of single brain metastasis in patients with non-small cell lung cancer can improve survival over conservative management. Furthermore, surgical treatment of the primary tumor and the single brain metastasis, combined or not with radiotherapy and chemotherapy, represents an approach that merits further investigation with more patients and a prospective longitudinal design.

The purpose of this phase II study was to evaluate the clinical efficacy of mitomycin C and vinblastine in patients with anthracycline-resistant metastatic breast cancer. This single-center, non-randomized trial enrolled 39 patients. Eligible patients must have received at least three chemotherapy regimens with epirubicin or CAF and had treatment failure while on chemotherapy or within 6 months of completing therapy. Treatment consisted of mitomycin C at a starting dose of 8 mg/m2on day 1 and vinblastine (8 mg/m2, days 1 and 28). The regimen was repeated every 6 weeks with a 20% dose escalation of both drugs after the first cycle in the absence of grade III hematologic or other toxicity. On an intent-to-treat basis, 38 patients were eligible for assessment; 9 (23.7%, 95% confidence interval 1.92-2.45%) achieved a partial response and 13 (34.2%) had stable disease. The median time to disease progression was 6.21 ±4.26 months (range, 1-15; 95% confidence interval, 4.81-7.61), and the median survival was 10.76±7.6 (range, 1-29; 95% confidence interval 8.0-13.1%). Responsive patients had a significantly better survival than those with stable and progressive disease. Treatment was well tolerated. Anemia and neutropenia (grade I-III) developed in 28.9% and 26.3% of the patients, respectively. One patient with grade III granulocytopenia developed fever and infection that required hospitalization. Moderate neurotoxicity, myalgia, constipation, diarrhea and alopecia were observed. No toxic death occurred. Mitomycin C plus vinblastine is an effective and well-tolerated regimen for anthracycline resistant cancer.

•NF-κB2 and RELB levels were upregulated in CRC and surrounding stroma compared to non-neoplastic tissue and stroma.•RELB protein expression in the tumour had prognostic value for overall survival.•Tumour RELB gene expression in the tumour was associated withTTP and NF-κB2 gene expression was prognostic for survival and TTP.•NFKB2 rs12769316 and rs7897947 were associated with lymph node infiltration and rs12769316 correlated with relapse status.•Rs7897947 G allele was associated with reduced risk for developing CRC.