International biathlon season during the COVID-19 pandemic was based on frequent on-site PCR-testing protocol with rapid result management.

The resumption of professional sports during the COVID-19 pandemic has been described in team sports but less in individual sports. The International Biathlon Union implemented a COVID-19 concept for the 2020-2021 season aimed to mitigate the risks of transmission by rules designated for the professional biathlon environment. The "bubble" model was based on regular reverse transcript polymerase chain reaction (PCR) testing with rapid results and efficient result management protocol. The objective of this study was report incidence and transmission of SARS-CoV-2 among professional biathletes and staff undergoing frequent PCR testing and risk reduction measures during the international season 2020-2021. The efficiency of risk mitigation measures was also evaluated based on the incidence data. During the 4-month season, altogether 22,182 SARS-CoV-2 PCR tests were conducted on all individuals participating in international biathlon season (athletes, team staff and organizing committee). Ninety-six (0.4%) PCR tests were positive and 30% of the positive PCR tests were considered "persistent positive" following recovery from a recent COVID-19 infection. No transmission events were detected following contact with "persistent positive" cases during the season. A great majority of the positive PCR tests were recorded during the first days after arrival in the "bubble", often in the first entry test taken by the on-site laboratory. In conclusion, a "bubble model" based on frequent PCR testing and hygiene rules was efficient in keeping the infection rate low. The competition activity including international travel was safe, and most of the infections seemed to originate from outside of the "bubble".

Gene Expression-Based Prediction of Neoadjuvant Chemotherapy Response in Early Breast Cancer: Results of the Prospective Multicenter EXPRESSION Trial.

PURPOSE: Expression-based classifiers to predict pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) are not routinely used in the clinic. We aimed to build and validate a classifier for pCR after NACT. PATIENTS AND METHODS: We performed a prospective multicenter study (EXPRESSION) including 114 patients treated with anthracycline/taxane-based NACT. Pretreatment core needle biopsies from 91 patients were used for gene expression analysis and classifier construction, followed by validation in five external cohorts (n = 619). RESULTS: A 20-gene classifier established in the EXPRESSION cohort using a Youden index-based cut-off point predicted pCR in the validation cohorts with an accuracy, AUC, negative predictive value (NPV), positive predictive value, sensitivity, and specificity of 0.811, 0.768, 0.829, 0.587, 0.216, and 0.962, respectively. Alternatively, aiming for a high NPV by defining the cut-off point for classification based on the complete responder with the lowest predicted probability of pCR in the EXPRESSION cohort led to an NPV of 0.960 upon external validation. With this extreme-low cut-off point, a recommendation to not treat with anthracycline/taxane-based NACT would be possible for 121 of 619 unselected patients (19.5%) and 112 of 322 patients with luminal breast cancer (34.8%). The analysis of the molecular subtypes showed that the identification of patients who do not achieve a pCR by the 20-gene classifier was particularly relevant in luminal breast cancer. CONCLUSIONS: The novel 20-gene classifier reliably identifies patients who do not achieve a pCR in about one third of luminal breast cancers in both the EXPRESSION and combined validation cohorts.

Ki-67 Expression as a Factor Predicting Recurrence of Ductal Carcinoma In Situ of the Breast: A Systematic Review and Meta-Analysis.

BACKGROUND: Ki-67 is a marker of proliferating cells; in this meta-analysis we aimed to examine whether Ki-67 expression can predict recurrence rates of breast ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: This systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eligible articles were sought in MEDLINE up to April 30, 2017. Random effects (DerSimonian-Laird) models were used for the calculation of pooled relative risk (RR) estimates; meta-regression analysis was also performed. Separate analyses were performed according to Ki-67 expression cutoff levels, invasiveness of recurrence, and adjustment of studies. RESULTS: Ten eligible cohort studies were synthesized; a significant association between Ki-67 expression and DCIS recurrence was noted for the Ki-67 cutoff at 10% (RR = 1.66; 95% confidence interval [CI], 1.14-2.42) as well as the Ki-67 cutoff at 14% (RR = 1.67; 95% CI, 1.01-2.77). Subanalysis on unadjusted (RR = 1.48; 95% CI, 1.06-2.07) and adjusted studies (RR = 2.19; 95% CI, 1.42-3.38) replicated the statistically significant findings. Ki-67 expression predicted the risk of invasive (RR = 1.53; 95% CI, 1.14-2.06) and noninvasive (RR = 1.59; 95% CI, 1.19-2.13) recurrence. CONCLUSION: This meta-analysis highlights Ki-67 expression as a predictor of DCIS recurrence; nevertheless, additional adjusted studies, with adequate follow-up periods, stemming from various world regions seem to be needed on this topic.

Expression of aurora kinase A is associated with metastasis-free survival in node-negative breast cancer patients.

BACKGROUND: Inhibitors targeting the cell cycle-regulated aurora kinase A (AURKA) are currently being developed. Here, we examine the prognostic impact of AURKA in node-negative breast cancer patients without adjuvant systemic therapy (n = 766). METHODS: AURKA was analyzed using microarray-based gene-expression data from three independent cohorts of node-negative breast cancer patients. In multivariate Cox analyses, the prognostic impact of age, histological grade, tumor size, estrogen receptor (ER), and HER2 were considered. RESULTS: Patients with higher AURKA expression had a shorter metastasis-free survival (MFS) in the Mainz (HR 1.93; 95% CI 1.34 - 2.78; P < 0.001), Rotterdam (HR 1.95; 95% CI 1.45- 2.63; P<0.001) and Transbig (HR 1.52; 95% CI 1.14-2.04; P=0.005) cohorts. AURKA was also associated with MFS in the molecular subtype ER+/HER2- carcinomas (HR 2.10; 95% CI 1.70-2.59; P<0.001), but not in ER-/HER2- nor in HER2+ carcinomas. In the multivariate Cox regression adjusted to age, grade and tumor size, AURKA showed independent prognostic significance in the ER+/HER2- subtype (HR 1.73; 95% CI 1.24-2.42; P=0.001). Prognosis of patients in the highest quartile of AURKA expression was particularly poor. In addition, AURKA correlated with the proliferation metagene (R=0.880; P<0.001), showed a positive association with grade (P<0.001), tumor size (P<0.001) and HER2 (P<0.001), and was inversely associated with ER status (P<0.001). CONCLUSIONS: AURKA is associated with worse prognosis in estrogen receptor positive breast carcinomas. Patients with the highest AURKA expression (>75% percentile) have a particularly bad prognosis and may profit from therapy with AURKA inhibitors.

Immunoglobulin kappa C predicts overall survival in node-negative breast cancer.

BACKGROUND: Biomarkers of the immune system are currently not used as prognostic factors in breast cancer. We analyzed the association of the B cell/plasma cell marker immunoglobulin kappa C (IGKC) and survival of untreated node-negative breast cancer patients. MATERIAL AND METHODS: IGKC expression was evaluated by immunostaining in a cohort of 335 node-negative breast cancer patients with a median follow-up of 152 months. The prognostic significance of IGKC for disease-free survival (DFS) and breast cancer-specific overall survival (OS) was evaluated with Kaplan-Meier survival analysis as well as univariate and multivariate Cox analysis adjusted for age at diagnosis, pT stage, histological grade, estrogen receptor (ER) status, progesterone receptor (PR) status, Ki-67 and human epidermal growth factor receptor 2 (HER-2) status. RESULTS: 160 patients (47.7%) showed strong expression of IGKC. Univariate analysis showed that IGKC was significantly associated with DFS (P = 0.017, hazard ratio [HR] = 0.570, 95% confidence interval [CI] = 0.360-0.903) and OS (P = 0.011, HR = 0.438, 95% CI = 0.233-0.822) in the entire cohort. The significance of IGKC was especially strong in ER negative and in luminal B carcinomas. In multivariate analysis IGKC retained its significance independent of established clinical factors for DFS (P = 0.004, HR = 0.504, 95% CI = 0.315-0.804) as well as for OS (P = 0.002, HR = 0.371, 95% CI = 0.196-0.705). CONCLUSION: Expression of IGKC has an independent protective impact on DFS and OS in node-negative breast cancer.

A comprehensive analysis of human gene expression profiles identifies stromal immunoglobulin κ C as a compatible prognostic marker in human solid tumors.

PURPOSE: Although the central role of the immune system for tumor prognosis is generally accepted, a single robust marker is not yet available. EXPERIMENTAL DESIGN: On the basis of receiver operating characteristic analyses, robust markers were identified from a 60-gene B cell-derived metagene and analyzed in gene expression profiles of 1,810 breast cancer; 1,056 non-small cell lung carcinoma (NSCLC); 513 colorectal; and 426 ovarian cancer patients. Protein and RNA levels were examined in paraffin-embedded tissue of 330 breast cancer patients. The cell types were identified with immunohistochemical costaining and confocal fluorescence microscopy. RESULTS: We identified immunoglobulin κ C (IGKC) which as a single marker is similarly predictive and prognostic as the entire B-cell metagene. IGKC was consistently associated with metastasis-free survival across different molecular subtypes in node-negative breast cancer (n = 965) and predicted response to anthracycline-based neoadjuvant chemotherapy (n = 845; P < 0.001). In addition, IGKC gene expression was prognostic in NSCLC and colorectal cancer. No association was observed in ovarian cancer. IGKC protein expression was significantly associated with survival in paraffin-embedded tissues of 330 breast cancer patients. Tumor-infiltrating plasma cells were identified as the source of IGKC expression. CONCLUSION: Our findings provide IGKC as a novel diagnostic marker for risk stratification in human cancer and support concepts to exploit the humoral immune response for anticancer therapy. It could be validated in several independent cohorts and carried out similarly well in RNA from fresh frozen as well as from paraffin tissue and on protein level by immunostaining.

Collaboration between civilian and military healthcare professionals: a better way for planning, preparing, and responding to all hazard domestic events.

Collaboration is used by the US National Security Council as a means to integrate inter-federal government agencies during planning and execution of common goals towards unified, national security. The concept of collaboration has benefits in the healthcare system by building trust, sharing resources, and reducing costs. The current terrorist threats have made collaborative medical training between military and civilian agencies crucial. This review summarizes the long and rich history of collaboration between civilians and the military in various countries and provides support for the continuation and improvement of collaborative efforts. Through collaboration, advances in the treatment of injuries have been realized, deaths have been reduced, and significant strides in the betterment of the Emergency Medical System have been achieved. This review promotes collaborative medical training between military and civilian medical professionals and provides recommendations for the future based on medical collaboration.

Quantifying the vitamin D3 synthesizing potential of UVB lamps at specific distances over time.

The purpose of this study was to quantify the ultraviolet B (UVB) output and in vitro previtamin D(3) synthesis over time from various artificial light sources. Three incandescent lamps, T-Rex Active UVHeat 160 watt spot, T-Rex Active UVHeat 160 watt flood, and ZooMed PowerSun 160 watt flood, and two 1.2 m fluorescent lamps, Sylvania Blacklight 350 BL and ZooMed Reptisun 5.0, were studied. Total UVB irradiance and concentration of previtamin D synthesized using an in vitro ampoule model were quantified initially and at monthly intervals for 1 year. Incandescent lamps were measured at distances of 0.9 and 1.5 m while fluorescent lamps were measured at distances of 30.5 and 45.7 cm at the lamp's center, using both the radiometer and ampoules. Fluorescent lamp irradiance was also measured at the lamp's ends. Data were analyzed as a repeated measures split-plot in time using SAS with all mean differences determined using Least Squares Means. Incandescent lamp irradiance differences were seen at various distances. The UVHeat lamps had consistently higher previtamin D(3) production and irradiance readings compared with the PowerSun lamp. Reptisun 5.0 was consistently higher in UVB irradiance over Sylvania BL 350 at both 30.5 and 45.7 cm. However, there were no differences when comparing conversion of 7-dehydrocholesterol to previtamin D(3). Irradiance differences were detected between the centers and ends of the fluorescent lamps. Until UVB requirements for vitamin D(3) synthesis in animals are determined, it is impossible to state that one light is superior to another.

Primary Leiomyosarcoma of the Male Breast.

We describe herein the third case of primary leiomyosarcoma of the breast in a 62-year-old man. Preoperative clinical examination and cytology findings indicated a leiomyosarcoma of the breast. A modified radical mastectomy was performed. Immunohistochemical analysis subsequently confirmed a diagnosis of leiomyosarcoma. After a follow-up period of 24 months, the patient is still in good health with no evidence of locoregional recurrence or distant metastasis.

Quality of life and adjuvant tamoxifen treatment in breast cancer patients.

About two-thirds of all breast cancer patients are treated with adjuvant hormonal therapy. Side effects of tamoxifen and their effects on physical, emotional and social functioning have been shown to impair the quality of life. Aim of this paper was to evaluate the side effects and level of influence on the physical, emotional and social functioning caused by tamoxifen treatment. For assessment of quality of life an own questionnaire was designed. Between January 2001 and December 2003, 136 women with breast cancer and adjuvant tamoxifen therapy were included in this study. Data of side effects, physical and mental health and patients' self-evaluation identified detrimental effects on patients' quality of life. Prevalence and severity of symptoms were not influenced by length of tamoxifen treatment. Patients were damaged in their constitution in respect to previous chemotherapy and pre-existing diseases; no influence was found by age or histopathological tumour characteristics. Our survey determines that breast cancer patients experience significant influence on quality of life by the negative impact on the physical, emotional and social functioning caused by tamoxifen treatment. Explicit attention to changes in quality of life should be considered as part of the standard care for women receiving adjuvant tamoxifen treatment.

Diagnosis of breast cancer by tear proteomic pattern.

BACKGROUND: Early detection of breast cancer reduces breast cancer-related mortality. Breast cancer biomarkers offer a promising means of detecting this disease at the earliest and most treatable stages. PATIENTS AND METHODS: The aim of this study was to generate a protein biomarker profile in tear fluid for breast cancer patients. This established biomarker profile was then used to discriminate between cancer patients and healthy controls. Potential biomarkers were screened in tear fluid from 50 women with breast cancer and 50 healthy women, matched for age. Tear fluid was drawn prior to surgery. Surface-enhanced laser desorption-ionisation time-of-flight mass spectrometry was used for protein profiling with two different active surfaces on the protein chips: a cationic exchanger (CM-10) and a reverse-phase surface (H50). The data were analyzed by multivariate statistical techniques and artificial neural networks. RESULTS: A total of 404 peaks were found with different molecular weights at different laser intensities and a statistically significant (p<0.05) panel with 20 biomarkers was generated. Use of the biomarker panel resulted in 71.19% of the samples being correctly classified as cancer samples (42 out of 59) and 70.69% as control samples (41 out of 58), thus overall 70.94% were correctly classified. The diagnostic pattern was able to differentiate cancer patients from healthy women with a specificity and sensitivity of approximately 70% using tear fluid. CONCLUSION: In this study a biomarker panel in tear fluid was successfully generated to allow breast cancer patients to be discriminated from healthy women. The study suggests that the proteomic pattern of tear fluid may be useful in the diagnosis of breast cancer and for high-throughput biomarker discovery.

Surface-enhanced Laser Desorption/Ionisation Time-of-flight Mass Spectrometry to Detect Breast Cancer Markers in Tears and Serum.

BACKGROUND: New biomarkers are needed to improve the early detection of breast cancer. This study describes the use of surface-enhanced laser desorption/ionisation time-of-flight mass spectroscopy (SELDI-TOF-MS) in serum and tear fluid. MATERIALS AND METHODS: Blood and tear fluid of 10 women with breast cancer and 10 healthy age-matched women were screened for potential biomarkers. Blood samples and tear fluid were drawn prior to surgery. SELDI-TOF-MS were used for protein profiling with three different active surfaces of the protein chips. The data were analyzed by multivariate statistical techniques and artificial neural networks. RESULTS: Complex protein and peptide patterns were found on all three surfaces. We identified the main proteins in tear fluid. Statistically significant differences in the protein pattern (p<0.001) were found between breast cancer patients and healthy controls. The diagnostic pattern differentiated cancer patients from controls with a specificity and sensitivity of approximately 90% in serum and tear fluid. CONCLUSION: Protein chip technology facilitates the discovery of new and better biomarkers in breast cancer. It is a promising approach to analyse a large number of patients with high sensitivity and specificity. Analysing tear fluid could show some advantages.

Prognostic effect of epithelial cell adhesion molecule overexpression in untreated node-negative breast cancer.

PURPOSE: Epithelial cell adhesion molecule (Ep-CAM) recently received increased attention not only as a prognostic factor in breast cancer but also as a potential target for immunotherapy. We examined Ep-CAM expression in 402 consecutive node-negative breast cancer patients with long-term follow-up not treated in the adjuvant setting. EXPERIMENTAL DESIGN: Ep-CAM expression was evaluated by immunostaining. Its prognostic effect was estimated relative to overexpression/amplification of HER-2, histologic grade, tumor size, age, and hormone receptor expression. RESULTS: Ep-CAM status was positive in 106 (26.4%) patients. In multivariate analysis, Ep-CAM status was associated with disease-free survival independent of age, pT stage, histologic grade, estrogen receptor (ER), progesterone receptor (PR), as well as HER2 status (P = 0.028; hazard ratio, 1.60; 95% confidence interval, 1.05-2.44). Recently, so-called triple-negative (HER-2, ER, and PR) breast cancer has received increased attention. We noticed a similar association of Ep-CAM with disease-free survival in the triple-negative group as for the entire cohort. CONCLUSION: In this study of untreated breast cancer patients, Ep-CAM overexpression was associated with poor survival in the entire cohort and in the subgroup of triple-negative breast cancer. This suggests that Ep-CAM may be a well-suited target for specific therapies particularly in HER-2-, ER-, and PR-negative tumors.

Influence of resection volume on locoregional recurrence of breast cancer after breast-conserving surgery.

BACKGROUND: The goals of breast-conserving surgery are to provide the survival equivalent of mastectomy, a cosmetically acceptable breast and a low rate of locoregional recurrence in the treated breast. This retrospective study investigated the impact of the resection volume on locoregional recurrence after breast-conserving therapy in patients with early-stage invasive breast cancer. PATIENTS AND METHODS: Retrospective data from 185 women who were treated for operable breast tumours by breast-conserving surgery between 1995-1999 at the Martin-Luther-University in Halle/Germany were included in our study. Extent of total resection volume (TRV), tumour volume (V) and difference volume (DV) was compared for the influence on locoregional recurrence. RESULTS: Our data showed no significant correlation between the risk of locoregional recurrence and the extent of resection volume. Predictors of an increased risk of locoregional recurrence after breast-conserving surgery were large primary tumour, grading, lymphatic vascular invasion, hormone receptor status and lack of radiotherapy or hormonal therapy. CONCLUSION: According to the accuracy of locoregional disease control and maintenance of the breast's shape, our results support conservative surgery in early-stage breast cancer followed by radiotherapy and adjuvant systemic therapy.

Prognostic impact of haemoglobin levels in breast cancer.

BACKGROUND: Many patients with solid tumours suffer from anaemia, as a consequence of the disease itself or its treatment. Anaemia affects the quality of life and can have a negative impact on overall survival. The aim of the current study was to analyse the impact of haemoglobin levels on the prognosis of patients with primary breast cancer. PATIENTS AND METHODS: Retrospective data from 249 women treated for operable breast tumours were included in our study. Haemoglobin (Hb) levels independently of anticancer therapy were compared for the prognostic influence on disease-free and overall survival. RESULTS: A significant correlation between higher minimum Hb level during chemotherapy and the disease-free and overall survival was found. Pre-treatment haemoglobin levels had no prognostic influence on the disease-free and overall survival. CONCLUSION: The present data showed that anaemia during adjuvant chemotherapy to be a negative prognostic indicator for survival of patients with breast cancer.

Reproduction beyond cancer: a message of hope for young women.

OBJECTIVE: Aggressive chemotherapy and radiotherapy or radical oncological surgery in young women with cancer has greatly enhanced these patients' life expectancy, but these treatments often cause infertility or premature ovarian failure due to a massive destruction of the ovarian reserve. The objective of this review is to discuss the effect of the various cancer treatments on fertility and present the various fertility sparing operations and fertility preservation strategies. METHOD: An extensive survey of the most up-to-date literature was performed. RESULTS: This review discusses the impact of current cancer treatment on fertility potential and the various surgical and assisted-reproduction innovations available today for the most common cancers in young women. Although the ability to retain reproductive potential is becoming a major quality-of-life factor in an increasing number of young female cancer survivors, they are still being poorly counseled with regard to the negative impact of the treatment on their fertility and on their options for fertility preservation. CONCLUSION: As the emerging discipline of fertility preservation is steadily attracting increasing interest, developments in the near future promise to be very exciting. However, in everyday routine work, better interdisciplinary cooperation between gynecological and pediatric oncologists, surgeons, immunologists, and endocrinologists is necessary so that individualized options for fertility preservation can be offered in advance of surgical procedures or cancer treatments.