Hypoxia-regulated carbonic anhydrase IX expression is associated with poor survival in patients with invasive breast cancer.

Tumour hypoxia is a microenvironmental factor related to poor response to radiation, chemotherapy, genetic instability, selection for resistance to apoptosis, and increased risk of invasion and metastasis. Hypoxia-regulated carbonic anhydrase IX (CA IX) has been studied in various tumour sites and its expression has been correlated with the clinical outcome. The purpose of this study was to investigate the correlation of CA IX expression with outcome in patients with invasive breast cancer. We conducted a retrospective study examining the effects of carbonic anhydrase IX (CA IX) on survival in patients with breast cancer. To facilitate the screening of multiple tissue blocks from each patient, tissue microarrays were prepared containing between two and five representative samples of tumour per patient. Immunohistochemistry was used to examine expression of CA IX in patients with breast cancer. The study includes a cohort of 144 unselected patients with early invasive breast cancer who underwent surgery, and had CA IX expression and follow-up data available for analysis. At the time of analysis, there were 28 deaths and median follow-up of 48 months with 96% of patients having at least 2 years of follow-up. CA IX was negative for 107 patients (17 deaths) and positive for 37 patients (11 deaths). Kaplan-Meier survival curves show that survival was superior in the CA IX-negative group with a 2-year survival of 97% for negatives and 83% for positives (log-rank test P=0.01). Allowing for potential prognostic variables in a Cox regression analysis, CA IX remained a significant independent predictor of survival (P=0.035). This study showed in both univariate and multivariate analysis that survival is significantly inferior in patients with tumour expressing CA IX. Prospective studies are underway to investigate this correlation in clinical trial setting

Neoadjuvant chemotherapy prior to preoperative chemoradiation or radiation in rectal cancer: should we be more cautious?

Neoadjuvant chemotherapy (NACT) is a term originally used to describe the administration of chemotherapy preoperatively before surgery. The original rationale for administering NACT or so-called induction chemotherapy to shrink or downstage a locally advanced tumour, and thereby facilitate more effective local treatment with surgery or radiotherapy, has been extended with the introduction of more effective combinations of chemotherapy to include reducing the risks of metastatic disease. It seems logical that survival could be lengthened, or organ preservation rates increased in resectable tumours by NACT. In rectal cancer NACT is being increasingly used in locally advanced and nonmetastatic unresectable tumours. Randomised studies in advanced colorectal cancer show high response rates to combination cytotoxic therapy. This evidence of efficacy coupled with the introduction of novel molecular targeted therapies (such as Bevacizumab and Cetuximab), and long waiting times for radiotherapy have rekindled an interest in delivering NACT in locally advanced rectal cancer. In contrast, this enthusiasm is currently waning in other sites such as head and neck and nasopharynx cancer where traditionally NACT has been used. So, is NACT in rectal cancer a real advance or just history repeating itself? In this review, we aimed to explore the advantages and disadvantages of the separate approaches of neoadjuvant, concurrent and consolidation chemotherapy in locally advanced rectal cancer, drawing on theoretical principles, preclinical studies and clinical experience both in rectal cancer and other disease sites. Neoadjuvant chemotherapy may improve outcome in terms of disease-free or overall survival in selected groups in some disease sites, but this strategy has not been shown to be associated with better outcomes than postoperative adjuvant chemotherapy. In particular, there is insufficient data in rectal cancer. The evidence for benefit is strongest when NACT is administered before surgical resection. In contrast, the data in favour of NACT before radiation or chemoradiation (CRT) is inconclusive, despite the suggestion that response to induction chemotherapy can predict response to subsequent radiotherapy. The observation that spectacular responses to chemotherapy before radical radiotherapy did not result in improved survival, was noted 25 years ago. However, multiple trials in head and neck cancer, nasopharyngeal cancer, non-small-cell lung cancer, small-cell lung cancer and cervical cancer do not support the routine use of NACT either as an alternative, or as additional benefit to CRT. The addition of NACT does not appear to enhance local control over concurrent CRT or radiotherapy alone. Neoadjuvant chemotherapy before CRT or radiation should be used with caution, and only in the context of clinical trials. The evidence base suggests that concurrent CRT with early positioning of radiotherapy appears the best option for patients with locally advanced rectal cancer and in all disease sites where radiation is the primary local therapy

20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years

The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)-positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment

Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials

Background Neoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with a collaborative meta-analysis of individual patient data from relevant randomised trials. Methods We obtained information about prerandomisation tumour characteristics, clinical tumour response, surgery, recurrence, and mortality for 4756 women in ten randomised trials in early breast cancer that began before 2005 and compared NACT with the same chemotherapy given postoperatively. Primary outcomes were tumour response, extent of local therapy, local and distant recurrence, breast cancer death, and overall mortality. Analyses by intention-to-treat used standard regression (for response and frequency of breast-conserving therapy) and log-rank methods (for recurrence and mortality). Findings Patients entered the trials from 1983 to 2002 and median follow-up was 9 years (IQR 5–14), with the last follow-up in 2013. Most chemotherapy was anthracycline based (3838 [81%] of 4756 women). More than two thirds (1349 [69%] of 1947) of women allocated NACT had a complete or partial clinical response. Patients allocated NACT had an increased frequency of breast-conserving therapy (1504 [65%] of 2320 treated with NACT vs 1135 [49%] of 2318 treated with adjuvant chemotherapy). NACT was associated with more frequent local recurrence than was adjuvant chemotherapy: the 15 year local recurrence was 21·4% for NACT versus 15·9% for adjuvant chemotherapy (5·5% increase [95% CI 2·4–8·6]; rate ratio 1·37 [95% CI 1·17–1·61]; p=0·0001). No significant difference between NACT and adjuvant chemotherapy was noted for distant recurrence (15 year risk 38·2% for NACT vs 38·0% for adjuvant chemotherapy; rate ratio 1·02 [95% CI 0·92–1·14]; p=0·66), breast cancer mortality (34·4% vs 33·7%; 1·06 [0·95–1·18]; p=0·31), or death from any cause (40·9% vs 41·2%; 1·04 [0·94–1·15]; p=0·45). Interpretation Tumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT. Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by NACT should be considered—eg, careful tumour localisation, detailed pathological assessment, and appropriate radiotherapy

Increasing N and P Resorption Efficiency and Proficiency in Northern Deciduous Hardwoods With Decreasing Foliar N and P Concentrations

The objective of this study was to assess the relationships between pre-senescence leaf N and P concentrations, and resorp- tion efficiency and proficiency of eight deciduous hardwood tree species. Trees were sampled on two sites of contrasting fertility/pro- ductivity in southern Quebec. Measured resorption efficiencies ranged from 56 to 71% for N, and from 30 to 78% for P. Linear and exponential models between leaf N and litter N, and between leaf P and litter P were significant. Intercepts of linear models were signifi- cantly different from zero. Resorption efficiency and proficiency increased with a decrease in leaf N and P, and the rate of change of re- sorption efficiency increased with leaf nutrient concentration. Concentrations corresponding to ultimate potential resorption were calculated to be 3.2 mg N g –1 and 0.09 mg P g –1 . Maximum resorption efficiencies were estimated at 70% for N and 80% for P. The concept of ultimate potential resorption in hardwoods is discussed

Interactions between macroclimate, microclimate, and anthropogenic disturbance affect the distribution of aspen near its northern edge in Quebec: Implications for climate change related range expansions

Policy to address the shifting tree species distributions anticipated in coming decades requires a sound understanding of how forests respond to environmental change. Using a combination of remote sensing, geographic information systems (GIS) analysis, and ground-based techniques, we explored the environmental factors associated with the distribution and abundance of trembling aspen (Populus tremuloides Michx.) across regional gradients near its northern range limit in northwestern Quebec, Canada. Although not regionally abundant, aspen is the main deciduous tree species in this conifer-dominated landscape. Regionally, the ~51,200-km2 study area has very few settlements or roads, and little industrial resource extraction. Most of the region is inaccessible to humans except by foot or water travel. We utilized Landsat Thematic Mapper images from 2010 and 2011, and a robust collection of ground reference data developed from aerial photography, supported by field verification (vegetation sampling) where access permitted, to construct a thematic map of 11 land cover classes. The map highlights the spatial distribution of aspen, which represents only 0.3% of the study area. Map validation indicated an overall mapping accuracy of 74%, and the aspen predicted class was determined to be over 77% accurate. The regional-scale distribution of aspen stands ≥ 5 ha within the study area shows two patterns: (1) a shift toward greatest abundance on south-facing aspects with increasing latitude; and (2) a highly clustered pattern with a strong signal of concentration in areas of human activity. These patterns suggest that aspen range expansion due to climate warming will vary with topographic and other microclimatic factors (i.e. be a function of climate change interacting with landscapes) and that anthropogenic activities have the potential to influence future aspen abundance independently of climate. Forest management policies concerned with changing forest composition in these northern landscapes should recognize the potentially important role of human activity in driving the abundance of aspen

Demographics and social values as drivers of change in the Canadian boreal zone

The boreal zone, a vast region with abundant natural resources and related industries, has both provisioning and non-provisioning ecosystem services that draw some people, while warding off others. It is an area that arguably affects many Canadians in different ways and represents a wide range of tangible and intangible values. Changes in demographic patterns over time shed light on the development of the social-ecological landscape of the boreal zone, and elucidate potential changes in the future. Using past and current demographic data, we explore population size, immigration and emigration, and birth and death rates within and outside the boreal zone. We also explore links between demographics, social values, and important factors of change in the boreal zone, and present three contrasting scenarios predicting the state of this zone in 2050. We pay particular attention to the Indigenous population, generational differences, international immigration, and the urban-rural divide. Fertility rates and immigration influence population demographics within and outside the boreal zone, respectively, alluding to potential divergences in social values and between communities located within and outside the boreal zone. The boreal zone is currently comprised of many smaller towns and communities scattered across the landscape, yet it is equally important to consider the influences of larger cities located outside the boreal zone, particularly in terms of governance, population movements, and political power. Considered together, these factors provide insight on social cohesion and connectedness, demand for goods and services, and changes in boreal-centric activities.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author