The antigenic link between thyroid autoimmunity and breast cancer

The association between breast cancer and benign thyroid disorders, in particular thyroid autoimmunity, has been debated for decades. Autoantibodies to thyroid peroxidase, the hallmark of thyroid autoimmunity, have a higher prevalence among patients with breast cancer compared with the general population. Furthermore a correlation between their positivity and a better prognosis of breast cancer was found in several independent small-scale studies, even if such observation was not confirmed in a subsequent retrospective study conducted on the largest patient cohort to date. The thyroid and mammary glands present several biological similarities, therefore the hypothesis of an immune response to shared thyroid/breast antigens could in part explain the association between thyroid autoimmunity and breast cancer. The sodium iodide symporter is expressed in both glands, however it seems unlikely to be the key common antigen, considering that autoantibodies targeting it are rare. Instead thyroid peroxidase, one of the major thyroid autoantigens, is also expressed in breast tissue and therefore represents the main antigenic link between thyroid autoimmunity and breast cancer. Furthermore lactoperoxidase, an enzyme of the same family that shares structural similarities with thyroid peroxidase, is expressed in neoplastic breast cells and is responsible for the cross-reactivity with some autoantibodies to thyroid peroxidase. Novel strategies for the diagnosis and treatment of breast cancer might take advantage of the antigenic link between thyroid and breast tissues

Mesenchymal chondrosarcoma of the maxilla

We report, to our knowledge, the 10th recorded case of mesenchymal chondrosarcoma (MC) occurring in the maxilla. Our case is the youngest person reported with a tumour in this location. The prognosis for cure is poor with a high incidence of local recurrence as well as metastases. Treatment is based on radical surgery. Radiotherapy and chemotherapy have a adjuvant role but additional experience with this tumour is required to define the most efficacious treatment

60. Factors detremining local control in patients (Pts) with locally advanced breast cancer (Labc) managed with radiotherapy (RT) as the primary locoregional treatment

IntroductionRT plays an important role in the management of LABC, yet clinical outcomes still remain far from satisfactory. The aim of this study was to evaluate retrospectively factors determining local control in a large series of consecutive LABC pts managed with RT as the primary locoregional treatment.Material and methodsThe records of 261 primarily inoperable LABC pts treated between 1991 and 1997 at two institutions: Medical University of Gdansk, Poland and Velindre NHS Trust, Cardiff, UK were analysed. All pts received megavoltage RT to the breast with two tangential fields, and the adjacent lymph node areas were irradiated using customised fields. Due to a large scale of RT doses and fractionation schedules, normalised total dose (NTD) was calculated for all patients using a linear quadratic model. In 241 pts RT constituted the only local treatment and the remaining 20 pts were subsequently subjected to mastectomy. Most pts received chemotherapy and/or endocrine therapy prior or after RT.ResultsWithin the median follow-up of 37 months, locoregional recurrence occurred in 95 of 251 evaluable pts (38%). Three-year and five-year locoregional-free survival rates were 59% and 48%, respectively. At multivariate analysis of variables predicting the risk of locoregional relapse, inflammatory carcinoma (

Epoetin Alfa Improves Anemia and Anemia-Related, Patient-Reported Outcomes in Patients with Breast Cancer Receiving Myelotoxic Chemotherapy: Results of a European, Multicenter, Randomized, Controlled Trial

This study evaluated the effects of epoetin alfa on patient-reported outcomes in patients with breast cancer receiving myelotoxic chemotherapy. Early intervention with epoetin alfa was well tolerated and improved anemia-related patient-reported outcomes

Effect of Patient Age on Management Decisions in Breast Cancer: Consensus from a National Consultation

This qualitative study investigated attitudes, perceptions, and practices of breast cancer specialists with reference to the effect of patient age on management decisions in breast cancer, and attempted to identify national consensus on this issue

Breast-cancer adjuvant therapy with zoledronic acid

Background: Data suggest that the adjuvant use of bisphosphonates reduces rates of recurrence and death in patients with early-stage breast cancer. We conducted a study to determine whether treatment with zoledronic acid, in addition to standard adjuvant therapy, would improve disease outcomes in such patients. Methods: In this open-label phase 3 study, we randomly assigned 3360 patients to receive standard adjuvant systemic therapy either with or without zoledronic acid. The zoledronic acid was administered every 3 to 4 weeks for 6 doses and then every 3 to 6 months to complete 5 years of treatment. The primary end point of the study was disease-free survival. A second interim analysis revealed that a prespecified boundary for lack of benefit had been crossed. Results: At a median follow-up of 59 months, there was no significant between-group difference in the primary end point, with a rate of disease-free survival of 77% in each group (adjusted hazard ratio in the zoledronic acid group, 0.98; 95% confidence interval [CI], 0.85 to 1.13; P=0.79). Disease recurrence or death occurred in 377 patients in the zoledronic acid group and 375 of those in the control group. The numbers of deaths — 243 in the zoledronic acid group and 276 in the control group — were also similar, resulting in rates of overall survival of 85.4% in the zoledronic acid group and 83.1% in the control group (adjusted hazard ratio, 0.85; 95% CI, 0.72 to 1.01; P=0.07). In the zoledronic acid group, there were 17 confirmed cases of osteonecrosis of the jaw (cumulative incidence, 1.1%; 95% CI, 0.6 to 1.7; P<0.001) and 9 suspected cases; there were no cases in the control group. Rates of other adverse effects were similar in the two study groups. Conclusions: These findings do not support the routine use of zoledronic acid in the adjuvant management of breast cancer. (Funded by Novartis Pharmaceuticals and the National Cancer Research Network; AZURE Current Controlled Trials number, ISRCTN79831382.

Breast-cancer Adjuvant Therapy With Zoledronic Acid

BACKGROUND: Data suggest that the adjuvant use of bisphosphonates reduces rates of recurrence and death in patients with early-stage breast cancer. We conducted a study to determine whether treatment with zoledronic acid, in addition to standard adjuvant therapy, would improve disease outcomes in such patients. METHODS: In this open-label phase 3 study, we randomly assigned 3360 patients to receive standard adjuvant systemic therapy either with or without zoledronic acid. The zoledronic acid was administered every 3 to 4 weeks for 6 doses and then every 3 to 6 months to complete 5 years of treatment. The primary end point of the study was disease-free survival. A second interim analysis revealed that a prespecified boundary for lack of benefit had been crossed. RESULTS: At a median follow-up of 59 months, there was no significant between-group difference in the primary end point, with a rate of disease-free survival of 77% in each group (adjusted hazard ratio in the zoledronic acid group, 0.98; 95% confidence interval [CI], 0.85 to 1.13; P = 0.79). Disease recurrence or death occurred in 377 patients in the zoledronic acid group and 375 of those in the control group. The numbers of deaths - 243 in the zoledronic acid group and 276 in the control group - were also similar, resulting in rates of overall survival of 85.4% in the zoledronic acid group and 83.1% in the control group (adjusted hazard ratio, 0.85; 95% CI, 0.72 to 1.01; P = 0.07). In the zoledronic acid group, there were 17 confirmed cases of osteonecrosis of the jaw (cumulative incidence, 1.1%; 95% CI, 0.6 to 1.7; P < 0.001) and 9 suspected cases; there were no cases in the control group. Rates of other adverse effects were similar in the two study groups. CONCLUSIONS: These findings do not support the routine use of zoledronic acid in the adjuvant management of breast cancer

ER and HER2 expression are positively correlated in HER2 non-overexpressing breast cancer

PMCID: PMC3446380This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

A survey of orphan enzyme activities

<p>Abstract</p> <p>Background</p> <p>Using computational database searches, we have demonstrated previously that no gene sequences could be found for at least 36% of enzyme activities that have been assigned an Enzyme Commission number. Here we present a follow-up literature-based survey involving a statistically significant sample of such "orphan" activities. The survey was intended to determine whether sequences for these enzyme activities are truly unknown, or whether these sequences are absent from the public sequence databases but can be found in the literature.</p> <p>Results</p> <p>We demonstrate that for ~80% of sampled orphans, the absence of sequence data is bona fide. Our analyses further substantiate the notion that many of these enzyme activities play biologically important roles.</p> <p>Conclusion</p> <p>This survey points toward significant scientific cost of having such a large fraction of characterized enzyme activities disconnected from sequence data. It also suggests that a larger effort, beginning with a comprehensive survey of all putative orphan activities, would resolve nearly 300 artifactual orphans and reconnect a wealth of enzyme research with modern genomics. For these reasons, we propose that a systematic effort to identify the cognate genes of orphan enzymes be undertaken.</p

Computation of significance scores of unweighted Gene Set Enrichment Analyses

<p>Abstract</p> <p>Background</p> <p>Gene Set Enrichment Analysis (GSEA) is a computational method for the statistical evaluation of sorted lists of genes or proteins. Originally GSEA was developed for interpreting microarray gene expression data, but it can be applied to any sorted list of genes. Given the gene list and an arbitrary biological category, GSEA evaluates whether the genes of the considered category are randomly distributed or accumulated on top or bottom of the list. Usually, significance scores (p-values) of GSEA are computed by nonparametric permutation tests, a time consuming procedure that yields only estimates of the p-values.</p> <p>Results</p> <p>We present a novel dynamic programming algorithm for calculating exact significance values of unweighted Gene Set Enrichment Analyses. Our algorithm avoids typical problems of nonparametric permutation tests, as varying findings in different runs caused by the random sampling procedure. Another advantage of the presented dynamic programming algorithm is its runtime and memory efficiency. To test our algorithm, we applied it not only to simulated data sets, but additionally evaluated expression profiles of squamous cell lung cancer tissue and autologous unaffected tissue.</p