Clinical response to primary letrozole therapy in elderly patients with early breast cancer : possible role for p53 as a biomarker

Primary tamoxifen therapy has been widely used to treat elderly women with ER-positive breast cancer in the past. Aromatase inhibitors may be more beneficial than tamoxifen when used as primary endocrine therapy in elderly patients. We aimed to retrospectively evaluate a series of elderly women with ER-positive breast cancer treated with primary letrozole therapy as sole therapy with a minimum of 5 years follow up. To identify possible predictive biomarkers a pilot immunohistochemical analysis was performed to assess the expression of PR, HER2, EGFR, BCL2 and p53. A total of 45 women, aged more than 70 years with a diagnosis of ER-positive breast cancer that was treated with primary letrozole therapy were identified. A case note review was undertaken to obtain clinical information. Formalin fixed paraffin embedded tumour tissue from diagnostic core biopsies was available for all patients. Immunohistochemical analysis was performed to establish the protein expression status of p53, PR, HER2, EGFR and BCL2. The mean age of the 45 patients was 87 years (range 70–101). Clinical benefit was seen in 60% of the patients. Median progression free survival was 53 months (95% CI – 34–72) and the median time to progression was 43 months (95% CI – 22–64). BCL2 was expressed in 45/45 (100%); PR in 38/45 (84%); EGFR in 13/45 (28%); HER2 in 9/45 (20%) and p53 in 5/45 (11%) of tissue samples. Positive expression of p53 was associated with poor progression free survival (p = 0.03) in this pilot study. This study demonstrates that letrozole as sole treatment appears to be a suitable treatment option for elderly patients with ER-positive breast cancer who are not fit for, or decline, surgery. The analysis of p53 in a larger study is warranted in order to assess its role as a biomarker in this patient group

Forest processes from stands to landscapes: exploring model forecast uncertainties using cross-scale model comparison

Forest management practices conducted primarily at the stand scale result in simplified forests with regeneration problems and low structural and biological diversity. Landscape models have been used to help design management strategies to address these problems. However, there remains a great deal of uncertainty that the actual management practices result in the desired sustainable landscape structure. To investigate our ability to meet sustainable forest management goals across scales, we assessed how two models of forest dynamics, a scaled-up individual-tree model and a landscape model, simulate forest dynamics under three types of harvesting regimes: clearcut, gap, and uniform thinning. Althougth 50– 100 year forecasts predicted average successional patterns that differed by less than 20% between models, understory dynamics of the landscape model were simplified relative to the scaled-up tree model, whereas successional patterns of the scaled-up tree model deviated from empirical studies on the driest and wettest landtypes. The scale dependencies of both models revealed important weaknesses when the models were used alone; however, when used together, they could provide a heuristic method that could improve our ability to design sustainable forest management practices

Peak radial growth of diffuse-porous species occurs during periods of lower water availability than for ring-porous and coniferous trees

Climate models project warmer summer temperatures will increase the frequency and heat severity of droughts in temperate forests of Eastern North America. Hotter droughts are increasingly documented to affect tree growth and forest dynamics, with critical impacts on tree mortality, carbon sequestration and timber provision. The growing acknowledgement of the dominant role of drought timing on tree vulnerability to water deficit raises the issue of our limited understanding of radial growth phenology for most temperate tree species. Here, we use well-replicated dendrometer band data sampled frequently during the growing season to assess the growth phenology of 610 trees from 15 temperate species over 6 years. Patterns of diameter growth follow a typical logistic shape, with growth rates reaching a maximum in June, and then decreasing until process termination. On average, we find that diffuse-porous species take 16-18 days less than other wood-structure types to put on 50% of their annual diameter growth. However, their peak growth rate occurs almost a full month later than ring-porous and conifer species (ca. 24 +/- 4 days; mean +/- 95% credible interval). Unlike other species, the growth phenology of diffuse-porous species in our dataset is highly correlated with their spring foliar phenology. We also find that the later window of growth in diffuse-porous species, coinciding with peak evapotranspiration and lower water availability, exposes them to a higher water deficit of 88 +/- 19 mm (mean +/- SE) during their peak growth than ring-porous and coniferous species (15 +/- 35 mm and 30 +/- 30 mm, respectively). Given the high climatic sensitivity of wood formation, our findings highlight the importance of wood porosity as one predictor of species climatic sensitivity to the projected intensification of the drought regime in the coming decades.Peer reviewe

A toolkit modeling approach for sustainable forest management planning: Achieving balance between science and local needs

To assist forest managers in balancing an increasing diversity of resource objectives, we developed a toolkit modeling approach for sustainable forest management (SFM). The approach inserts a meta-modeling strategy into a collaborative modeling framework grounded in adaptive management philosophy that facilitates participation among stakeholders, decision makers, and local domain experts in the meta-model building process. The modeling team works iteratively with each of these groups to define osential questions, identify data resources, and then determine whether available tools can be applied or adapted, or whether new tools can be rapidly created to fit the need. The desired goal of the process is a linked series of domain-specific models (tools) that balances generalized "top-down" models (i.e., scientific models developed without input from the local system) with case-specific customized "bottom-up" models that are driven primarily by local needs. Information flow between models is organized according to vertical (i.e., between scale) and horizontal (i.e., within scale) dimensions. We illustrate our approach within a 2.1 million hectare forest planning district in central Labrador, a forested landscape where social hnd ecological values receive a higher priority than economic values. However, the focus of this paper is on the process of how SFM modeling tools and concepts can be rapidly assembled and applied in new locations, balancing efficient transfer of science with adaptation to local needs. We use the Labrador case study to illustrate strengths and challenges uniquely associated with a meta-modeling approach to integrated modeling as it fits within the broader collaborative modeling framework. Principle advantages of the approach include the scientific rigor introduced by peer-reviewed models, combined with the adaptability of meta-modeling. A key challenge is the limited transparency of scientific models to different participatory groups. This challenge can be overcome by frequent and substantive two-way communication among different groups at appropriate times in the model-building process, combined with strong leadership that includes strategic choices when assembling the modeling team. The toolkit approach holds promise for extending beyond case studies, without compromising the bottom-up flow of needs and information, to inform SFM planning using the best available science

Forest dynamics following spruce budworm outbreaks in the northern and southern mixedwoods of central Quebec

The effects of 20th century spruce budworm (Choristoneura fumiferana (Clem.)) outbreaks on forest dynamics was examined in the southern and northern parts of the mixedwood forest zone in central Quebec, Canada. In each region, three study areas were placed in unmanaged stands that had not burned for more than 200 years. Disturbance impacts and forest succession were evaluated using aerial photographs and dendrochronology. Spruce budworm outbreaks occurred around 1910, 1950, and 1980 in both regions. The 1910 outbreak seemed to have limited impact in both regions, and the 1950 outbreak caused heavy mortality in conifer stands (mostly of balsam fir, Abies balsamea (L.) Mill.) in the southern region. The 1980 outbreak caused major mortality in the northern region, but had little impact in the southern region. Successive spruce budworm outbreaks led to a massive invasion by hardwood species in the last century in the southern region but not in the northern region. The reason for such contrasting dynamics between regions is unknown, but we hypothesize that differences in disturbance intensities, influenced by climate, played a major role. Results from this study emphasize that generalizations about the effect of spruce budworm outbreaks on forest dynamics cannot be derived from observations made during a single outbreak or at a single location

Large-scale synchrony of gap dynamics and the distribution of understory tree species in maple-beech forests

Large-scale synchronous variations in community dynamics are well documented for a vast array of organisms, but are considerably less understood for forest trees. Because of temporal variations in canopy gap dynamics, forest communities—even old-growth ones—are never at equilibrium at the stand scale. This paucity of equilibrium may also be true at the regional scale. Our objectives were to determine (1) if nonequilibrium dynamics caused by temporal variations in the formation of canopy gaps are regionally synchronized, and (2) if spatiotemporal variations in canopy gap formation aVect the relative abundance of tree species in the understory. We examined these questions by analyzing variations in the suppression and release history of Acer saccharum Marsh. and Fagus grandifolia Ehrh. from 481 growth series of understory saplings taken from 34 mature stands. We observed that (1) the proportion of stems in release as a function of time exhibited a U-shaped pattern over the last 35 years, with the lowest levels occurring during 1975–1985, and that (2) the response to this in terms of species composition was that A. saccharum became more abundant at sites that had the highest proportion of stems in release during 1975–1985. We concluded that the understory dynamics, typically thought of as a stand-scale process, may be regionally synchronized

Fine-root production in small experimental gaps in successional mixed boreal forests

The effects of small 10 m x 10 m experimental above-ground gaps on fine-root production for the first two years were studied in three fire-initiated stands of the northwestern mixed broad-leaf-conifer boreal forest of Quebec. The 48-yr-old forest is dominated by Populus tremuloides (Trembling aspen), the 122-yr-old forest by a mixture of P. tremuloides, Abies balsamea (balsam fir) and Picea glauca (white spruce), and the 232-yr-old forest by Thuja occidentalis (eastern white cedar) and A. balsamea, with some P. tremuloides. 40 root-ingrowth bags were installed in different locations in and around each gap (at gap center, 1 to 2 m either side of gap edge and in adjacent control plots). Half of the ingrowth bags were harvested after one year following gap creation, the other half after two years. Roots were sorted into different species grouping. Fine-root production was statistically (P < 0.05) larger in the youngest forest compared to the two older ones after one year, but not after two years. The individual species or groups of species increased, decreased or showed no change in fine-root production in gaps, but overall we did not observe a major shift in species proportion between gap and control plots after two years. Some herbs and also Taxus canadensis seemed to benefit in terms of fine-root growth from such small openings after two years. No statistical differences (P > 0.10) in total fine-root production were found among locations within and outside gaps in either year. However, there was a clear tendency for fine-root production to be smaller in gap center than in the other locations for the two younger successional forests the first year after gap creation. We conclude that small above-ground gaps (i.e. < 100 m2) do not produce a significant and long-lasting below-ground gap in terms of total fine-root production in the successional forests investigated

Mountain maple and balsam fir early response to partial and clear-cut harvesting under aspen stands of northern Quebec

This study is a component of the Sylviculture et am