Baffin Bay Narwhal Population Distribution and Numbers: Aerial Surveys in the Canadian High Arctic, 2002–04

Aerial surveys of narwhals (Monodon monoceros) were conducted in the Canadian High Arctic during the month of August from 2002 to 2004. The surveys covered the waters of Barrow Strait, Prince Regent Inlet, the Gulf of Boothia, Admiralty Inlet, Eclipse Sound, and the eastern coast of Baffin Island, using systematic sampling methods. Fiords were flown along a single transect down the middle. Near-surface population estimates increased by 1.9 %– 8.7% when corrected for perception bias. The estimates were further increased by a factor of approximately 3, to account for individuals not seen because they were diving when the survey plane flew over (availability bias). These corrections resulted in estimates of 27 656 (SE = 14 939) for the Prince Regent and Gulf of Boothia area, 20 225 (SE = 7285) for the Eclipse Sound area, and 10 073 (SE = 3123) for the East Baffin Island fiord area. The estimate for the Admiralty Inlet area was 5362 (SE = 2681) but is thought to be biased. Surveys could not be done in other known areas of occupation, such as the waters of the Cumberland Peninsula of East Baffin, and channels farther west of the areas surveyed (Peel Sound, Viscount Melville Sound, Smith Sound and Jones Sound, and other channels of the Canadian Arctic archipelago). Despite these probable biases and the incomplete coverage, results of these surveys show that the summering range of narwhals in the Canadian High Arctic is vast. If narwhals are philopatri to their summering areas, as they appear to be, the total population of that range could number more than 60 000 animals. The largest numbers are in the western portion of their summer range, around Somerset Island, and also in the Eclipse Sound area. However, these survey estimates have large variances due to narwhal aggregation in some parts of the surveyed areas.Des levés aériens ont été effectués dans l’Extrême arctique canadien dans le but de répertorier les populations de narvals (Monodon monoceros) et ce, du mois d’août 2002 à août 2004. Les levés, réalisés à l’aide de méthodes d’échantillonnage systémiques, visaient les eaux du détroit de Barrow, de l’inlet Prince-Régent, du golfe de Boothia, de l’inlet de l’Amirauté, du détroit d’Éclipse et de la côte est de l’île de Baffin. Les fiords ont été survolés le long d’un simple transect situé dans le milieu. Les estimations de population près de la surface augmentaient de 1,9 % à 8,7 % une fois redressées pour tenir compte du biais de perception. Par ailleurs, les estimations ont été de nouveau révisées à la hausse moyennant un facteur d’environ 3 afin de tenir compte des individus qui n’ont pas été vus parce qu’ils se mettaient à plonger en présence de l’avion effectuant les levés (biais de disponibilité). Ces redressements ont donné lieu à des estimations de 27 656 (SE = 14 939) pour la région de l’inlet Prince-Régent et du golfe de Boothia, de 20 225 (SE = 7 285) pour la région du détroit d’Éclipse et de 10 073 (SE = 3 123) pour la région du fiord de l’est de l’île de Baffin. Quand à l’inlet de l’Amirauté, l’estimation s’est chiffrée à 5 362 (SE = 2 681), mais l’on croit que cette estimation pourrait être biaisée. Des levés n’ont pas pu être effectués dans d’autres zones d’occupation connues, comme dans les eaux de la péninsule Cumberland dans l’est de Baffin de même que dans les chenaux plus à l’ouest des régions examinées (détroit de Peel, détroit du Vicomte de Melville, détroit de Smith, détroit de Jones et d’autres chenaux de l’archipel Arctique canadien). Malgré la possibilité que les données soient biaisées et que certaines zones n’aient pas été examinées, les résultats de ces levés montrent que la répartition d’été des narvals dans l’Extrême arctique canadien est vaste. Si les narvals sont philopatriques à leurs aires d’été, comme il semblerait être le cas, la population totale de ce parcours pourrait dépasser les 60 000 individus. Les plus grands nombres se trouvent dans la partie ouest de cette répartition, soit près de l’île Somerset et dans la région du détroit d’Éclipse. Cependant, les estimations découlant de ces levés ont de grandes variances en raison du regroupement des narvals dans certaines parties des régions visées par les levés

Chemotherapy-Response Monitoring of Breast Cancer Patients Using Quantitative Ultrasound-Based Intra-Tumour Heterogeneities

© 2017 The Author(s). Anti-cancer therapies including chemotherapy aim to induce tumour cell death. Cell death introduces alterations in cell morphology and tissue micro-structures that cause measurable changes in tissue echogenicity. This study investigated the effectiveness of quantitative ultrasound (QUS) parametric imaging to characterize intra-tumour heterogeneity and monitor the pathological response of breast cancer to chemotherapy in a large cohort of patients (n = 100). Results demonstrated that QUS imaging can non-invasively monitor pathological response and outcome of breast cancer patients to chemotherapy early following treatment initiation. Specifically, QUS biomarkers quantifying spatial heterogeneities in size, concentration and spacing of acoustic scatterers could predict treatment responses of patients with cross-validated accuracies of 82 ± 0.7%, 86 ± 0.7% and 85 ± 0.9% and areas under the receiver operating characteristic (ROC) curve of 0.75 ± 0.1, 0.80 ± 0.1 and 0.89 ± 0.1 at 1, 4 and 8 weeks after the start of treatment, respectively. The patients classified as responders and non-responders using QUS biomarkers demonstrated significantly different survivals, in good agreement with clinical and pathological endpoints. The results form a basis for using early predictive information on survival-linked patient response to facilitate adapting standard anti-cancer treatments on an individual patient basis

Breast cancer incidence, stage, treatment and survival in ethnic groups in South East England

Studies from the US have shown variations in breast cancer incidence, stage distribution, treatment and survival between ethnic groups. Data on 35 631 women diagnosed with breast cancer in South East England between 1998 and 2003 with self-assigned ethnicity information available were analysed. Results are reported for White, Indian, Pakistani, Bangladeshi, Black Caribbean, Black African and Chinese women. Age-standardised breast cancer incidence rate ratios, patterns of stage of disease at diagnosis, treatment, overall and breast cancer-specific survival were examined. All ethnic groups studied had lower age-standardised breast cancer incidence rates than White women, with Bangladeshi women having the lowest rate ratio (0.23, 95% CI: 0.20–0.26). White women were the most likely to have a stage recorded at diagnosis (adjusted proportion 75%), and least likely to be diagnosed with metastatic disease (7%). Black African women were the least likely to have a record of cancer surgery (63%) or hormone therapy (32%), and most likely to receive chemotherapy (38%). After fully adjusting for age, socioeconomic deprivation, stage of disease and treatment received, there was no significant variation in breast cancer-specific survival. However, Black African women had significantly worse overall survival (hazard ratio 1.24, P=0.025). These findings suggest that a strategy of earlier detection should be pursued in Black and South Asian women

Evaluation of the current knowledge limitations in breast cancer research: a gap analysis

BACKGROUND A gap analysis was conducted to determine which areas of breast cancer research, if targeted by researchers and funding bodies, could produce the greatest impact on patients. METHODS Fifty-six Breast Cancer Campaign grant holders and prominent UK breast cancer researchers participated in a gap analysis of current breast cancer research. Before, during and following the meeting, groups in seven key research areas participated in cycles of presentation, literature review and discussion. Summary papers were prepared by each group and collated into this position paper highlighting the research gaps, with recommendations for action. RESULTS Gaps were identified in all seven themes. General barriers to progress were lack of financial and practical resources, and poor collaboration between disciplines. Critical gaps in each theme included: (1) genetics (knowledge of genetic changes, their effects and interactions); (2) initiation of breast cancer (how developmental signalling pathways cause ductal elongation and branching at the cellular level and influence stem cell dynamics, and how their disruption initiates tumour formation); (3) progression of breast cancer (deciphering the intracellular and extracellular regulators of early progression, tumour growth, angiogenesis and metastasis); (4) therapies and targets (understanding who develops advanced disease); (5) disease markers (incorporating intelligent trial design into all studies to ensure new treatments are tested in patient groups stratified using biomarkers); (6) prevention (strategies to prevent oestrogen-receptor negative tumours and the long-term effects of chemoprevention for oestrogen-receptor positive tumours); (7) psychosocial aspects of cancer (the use of appropriate psychosocial interventions, and the personal impact of all stages of the disease among patients from a range of ethnic and demographic backgrounds). CONCLUSION Through recommendations to address these gaps with future research, the long-term benefits to patients will include: better estimation of risk in families with breast cancer and strategies to reduce risk; better prediction of drug response and patient prognosis; improved tailoring of treatments to patient subgroups and development of new therapeutic approaches; earlier initiation of treatment; more effective use of resources for screening populations; and an enhanced experience for people with or at risk of breast cancer and their families. The challenge to funding bodies and researchers in all disciplines is to focus on these gaps and to drive advances in knowledge into improvements in patient care

MiR-34b is associated with clinical outcome in triple-negative breast cancer patients

<p>Abstract</p> <p>Background</p> <p>Breast cancer is the most common malignancy with the highest incidence rates among women worldwide. Triple-negative breast cancer (TNBC) represents the major phenotype of basal-like molecular subtype of breast cancer, characterized by higher incidence in young women and a very poor prognosis. MicroRNAs (miRNAs) are small non-coding RNAs playing significant role in the pathogenesis of many cancers including breast cancer. Therefore, miRNAs are also potential prognostic and/or predictive biomarkers in triple-negative breast cancer patients.</p> <p>Methods</p> <p>Thirty-nine TNBC patients with available formalin-fixed paraffin-embedded (FFPE) tissues were enrolled in the study. MiR-34a, miR-34b, and miR-34c were analyzed using qRT-PCR and correlated to clinico-pathological features of TNBC patients.</p> <p>Results</p> <p>Expression levels of miR-34b significantly correlate with disease free survival (DFS) (<it>p </it>= 0.0020, log-rank test) and overall survival (OS) (<it>p </it>= 0.0008, log-rank test) of TNBC patients. No other significant associations between miR-34a, miR-34b, and miR-34c with available clinical pathological data were observed.</p> <p>Conclusions</p> <p>MiR-34b expression negatively correlates with disease free survival and overall survival in TNBC patients. Thus, miR-34b may present a new promising prognostic biomarker in TNBC patients, but independent validations are necessary.</p

Revisiting the technical validation of tumour biomarker assays: how to open a Pandora's box

A tumour biomarker is a characteristic that is objectively measured and evaluated in tumour samples as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. The development of a biomarker contemplates distinct phases, including discovery by hypothesis-generating preclinical or exploratory studies, development and qualification of the assay for the identification of the biomarker in clinical samples, and validation of its clinical significance. Although guidelines for the development and validation of biomarkers are available, their implementation is challenging, owing to the diversity of biomarkers being developed. The term 'validation' undoubtedly has several meanings; however, in the context of biomarker research, a test may be considered valid if it is 'fit for purpose'. In the process of validation of a biomarker assay, a key point is the validation of the methodology. Here we discuss the challenges for the technical validation of immunohistochemical and gene expression assays to detect tumour biomarkers and provide suggestions of pragmatic solutions to address these challenges

Systematic Bias in Genomic Classification Due to Contaminating Non-neoplastic Tissue in Breast Tumor Samples

Abstract Background Genomic tests are available to predict breast cancer recurrence and to guide clinical decision making. These predictors provide recurrence risk scores along with a measure of uncertainty, usually a confidence interval. The confidence interval conveys random error and not systematic bias. Standard tumor sampling methods make this problematic, as it is common to have a substantial proportion (typically 30-50%) of a tumor sample comprised of histologically benign tissue. This "normal" tissue could represent a source of non-random error or systematic bias in genomic classification. Methods To assess the performance characteristics of genomic classification to systematic error from normal contamination, we collected 55 tumor samples and paired tumor-adjacent normal tissue. Using genomic signatures from the tumor and paired normal, we evaluated how increasing normal contamination altered recurrence risk scores for various genomic predictors. Results Simulations of normal tissue contamination caused misclassification of tumors in all predictors evaluated, but different breast cancer predictors showed different types of vulnerability to normal tissue bias. While two predictors had unpredictable direction of bias (either higher or lower risk of relapse resulted from normal contamination), one signature showed predictable direction of normal tissue effects. Due to this predictable direction of effect, this signature (the PAM50) was adjusted for normal tissue contamination and these corrections improved sensitivity and negative predictive value. For all three assays quality control standards and/or appropriate bias adjustment strategies can be used to improve assay reliability. Conclusions Normal tissue sampled concurrently with tumor is an important source of bias in breast genomic predictors. All genomic predictors show some sensitivity to normal tissue contamination and ideal strategies for mitigating this bias vary depending upon the particular genes and computational methods used in the predictor

HIF-1 activation induces doxorubicin resistance in MCF7 3-D spheroids via P-glycoprotein expression: a potential model of the chemo-resistance of invasive micropapillary carcinoma of the breast

BACKGROUND: Invasive micropapillary carcinoma (IMPC) of the breast is a distinct and aggressive variant of luminal type B breast cancer that does not respond to neoadjuvant chemotherapy. It is characterized by small pseudopapillary clusters of cancer cells with inverted cell polarity. To investigate whether hypoxia-inducible factor-1 (HIF-1) activation may be related to the drug resistance described in this tumor, we used MCF7 cancer cells cultured as 3-D spheroids, which morphologically simulate IMPC cell clusters. METHODS: HIF-1 activation was measured by EMSA and ELISA in MCF7 3-D spheroids and MCF7 monolayers. Binding of HIF-1α to MDR-1 gene promoter and modulation of P-glycoprotein (Pgp) expression was evaluated by ChIP assay and FACS analysis, respectively. Intracellular doxorubicin retention was measured by spectrofluorimetric assay and drug cytotoxicity by annexin V-FITC measurement and caspase activity assay. RESULTS: In MCF7 3-D spheroids HIF-1 was activated and recruited to participate to the transcriptional activity of MDR-1 gene, coding for Pgp. In addition, Pgp expression on the surface of cells obtained from 3-D spheroids was increased. MCF7 3-D spheroids accumulate less doxorubicin and are less sensitive to its cytotoxic effects than MCF7 cells cultured as monolayer. Finally, HIF-1α inhibition either by incubating cells with 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (a widely used HIF-1α inhibitor) or by transfecting cells with specific siRNA for HIF-1α significantly decreased the expression of Pgp on the surface of cells and increased the intracellular doxorubicin accumulation in MCF7 3-D spheroids. CONCLUSIONS: MCF7 breast cancer cells cultured as 3-D spheroids are resistant to doxorubicin and this resistance is associated with an increased Pgp expression in the plasma membrane via activation of HIF-1. The same mechanism may be suggested for IMPC drug resistance