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The brown macroalgae Rugulopteryx okamurae is described as one of the most severe and threatening invasive marine macroalgae in European waters. This study reports the first record of R. okamurae in the Madeira archipelago, which represents a new southern distribution limit of this species in NE Atlantic European waters. Morphological and molecular characters were used to confirm the species' identity, and its potential invasion risk in Madeiran waters was screened using the standard risk assessment tool AS-ISK. Results show that R. okamurae has a medium-high risk of becoming invasive in Madeira Island under present and future climate scenarios. The greater risk of impact involves suppressing local species growth and the modification and degradation of local habitats, including trophic cascade effects. However, environmental and commercial impacts could also occur in case of an explosion of the invasive populations. This new introduction in Madeira coastal waters emphasises the need for regular monitoring of R. okamurae, particularly to assess population dynamics to avoid establishing and further expansions. Finally, we recommend the evaluation of the possible derived impacts affecting rocky coastal communities and adopting the necessary mitigation measures and policies. [ABSTRACT FROM AUTHOR]

Species of the genera Cystoseira, Ericaria, Gongolaria, and Sargassum (family Sargassaceae) are key components of the Mediterranean-Atlantic marine forests, essential for biodiversity and ecosystem functioning. Populations of these foundational species are particularly vulnerable to anthropogenic impacts, likely to be intensified under future scenarios of climate change. The decline and even disappearance of these species have been reported in different areas of the world. At Madeira Island (NE Atlantic), populations of Gongolaria abies-marina, Ericaria selaginoides, Sargassum vulgare, and Sargassum filipendula, the most ecologically relevant species in Macaronesian marine forests, have been suffering a drastic decline during the last decades, especially on the southern coast of the island, where anthropogenic pressure is higher than on the north coast. The lack of sufficient temporal coverage on qualitative and quantitative studies of Sargassaceae communities in Madeira poses a challenge to establish a specific period for this decline. Consulting qualitative studies and historical records, we have set for the first time a timeline that shows an evident decrease in Sargassaceae populations in the last 20 years on Madeira Island. Following this timeline, we pinpoint the start of this decline in the first decade of the 2000s. This can be particularly confirmed for places like Funchal and Reis Magos, with significantly higher historical records. Currently, most benthic communities on shallow subtidal rocky reefs along the south coast are dominated by sea urchins and crustose coralline algae, the so-called sea urchin barrens. However, in some cases, they are entirely covered by a layer of sediment. We discuss the possible factors contributing to these drastic changes, bringing Madeira’s marine forests to a dramatic decline. As many animal species rely on marine forests, the decline of Sargassaceae populations represents an invaluable ecological loss for the coastal ecosystem of the island. [ABSTRACT FROM AUTHOR]

The brown alga Lobophora (Dictyotales, Phaeophyceae) is an important macroalga in the North‐eastern Atlantic archipelagos (i.e., Macaronesia). Notably in the Canaries it can dominate benthic assemblages. While the genus has been the subject of several ecological studies in the Canaries, no study has yet been conducted to assess species‐level diversity of Lobophora in Macaronesia. We reassessed the diversity of Lobophora in Macaronesia, reporting the presence of seven species (L. caboverdeana sp. nov., L. canariensis, L. dagamae sp. nov., L. delicata, L. dispersa, L. littlerorum, and L. schneideri). Lobophora spp. from Macaronesia are morphologically and ecologically distinguishable. In the Canaries, L. schneideri dominates the photophilic assemblages from the intertidal to 20‐30 m depth. Lobophora dagamae sp. nov. grows in less illuminated shallow habitats, and replaces L. schneideri from 30 to ~80 m. Lobophora canariensis also has a wide vertical distribution, from the intertidal to deep waters, while L. delicata, L. dispersa and L. littlerorum grow in shallow waters. The dominance of species with an upright habit versus prostrate or crustose species may be mediated by the pressure of herbivores. Four species have an amphi‐Atlantic distribution: L. littlerorum, L. canariensis, L. delicata, and L. schneideri. Lobophora schneideri and L. delicata are furthermore distributed in the Mediterranean Sea. By sampling a pivotal region in the Atlantic, this study significantly improves our knowledge of Lobophora biogeography in the Atlantic Ocean. Macaronesia constitutes a species–poor region for Lobophora where no diversification events occurred, and a region of overlap between the Greater Caribbean and the Indo‐Pacific. [ABSTRACT FROM AUTHOR]

The patterns of variability in the composition and structure of benthic communities along two depth strata (5 and 10 m) and the presence of sea urchins in structuring the subtidal rocky reefs were quantified in a long-established coastal marine protected area (Garajau MPA) and in two size equivalent and contiguous impacted areas (one highly urbanized and other with high fishing pressure) at Madeira Island (northeast Atlantic). Results suggest i) the MPA could be acting as a refuge for local biodiversity, ii) communities from the highly fished area could be suffering an impoverishment of local biodiversity, and iii) communities from the highly urbanized area would be enriched by the establishment of opportunistic species. These findings support that the level of human-pressure likely plays an important role in the composition of benthic communities in this insular ecosystem, although this was more relevant at the shallower stratum where the key grazer Diadema africanum explained 65% of the variance of benthic assemblages. It is suggested that this MPA small dimension and proximity to human impacted areas are limiting the survival of predators of the D. africanum. [ABSTRACT FROM AUTHOR]

In order to investigate social structure, 11 years of individual photo-identification data of bottlenose dolphin were analysed. We examined the type of association indices between pairs of identified individuals; the patterns of affiliation between individual dolphins and the probabilities of association between individuals over time. Between 2001 and 2012, there were 272 encounters which resulted in the identification of 501 individuals. The discovery curve resulting from the photo-identification analysis indicated an open population with regular recruitment of new individuals. All individuals were found to be associated at an association index of <0.05. A total of 291 individuals recorded from 2004 to 2012 were used to assess the temporal pattern of the social structure. The model fit to the Standardized Lagged Association Rate (SLAR) that best described the studied bottlenose dolphin population was ‘casual acquaintances’, and the analysis of associations over time showed a decreasing SLAR curve that falls until reaching the null rate, confirming random associations. The decline of the SLAR curve after ~500 days (1.4 years) suggests disassociation over that time period which can be explained by demographic events such as mortality or emigration. In an open ocean habitat like Madeira this is not unexpected, as there are neither geographic boundaries nor enclosed environments. This population presented a dynamic and fluctuating social structure, where groups change in size and composition. In future conservation efforts this population should be considered as one large community, where individuals associate, disassociate and reassociate with each other over time. [ABSTRACT FROM AUTHOR]

Shallow subtidal macroalgal communities in the North-eastern Atlantic archipelagos (Azores, Madeira, Canaries and Cape Verde) were studied in order to identify their spatial organization patterns and the main drivers of change. Fifteen islands and 145 sites across 15º of latitude and 2850 km were sampled. We found high spatial variability across the scales considered (archipelago, island and site). The structure of macroalgal communities differed among archipelagos, except between Madeira and the Canaries, which were similar. Across a latitudinal gradient, macroalgal communities in the Azores were clearly separated from the other archipelagos; communities in Madeira and the Canaries occupied an intermediate position, while those in Cape Verde appeared at the opposite end of the gradient. In the Azores, species with warm-temperate affinities dominated communities. Cape Verde communities were, in contrast, dominated by tropical taxa, whereas in the subtropical Canaries and Madeira there was a mixture of species with colder and warmer affinities. Apart from crustose coralline algae, the Dictyotales were the group with greatest cover; larger and longer-lived species were progressively replaced by short-lived species along a latitudinal gradient from north to south. The perennial speciesZonaria tournefortiidominated the sea-bottom in the Azores, the semi-perennialLophophora variegatain the Canaries, the filamentous algae in Madeira and the ephemeralDictyota dichotomain Cape Verde. We hypothesized that the differences among archipelagos could be explained by synergies between temperature and herbivory, which increased in diversity southwards, especially in Cape Verde. This was supported by the predominance of non-crustose macroalgae in the Azores and of crustose macroalgae in Cape Verde, as would be predicted from the greater herbivore activity. At the scale of islands and sites, the same set of environmental variables drove differences in macroalgal community structure across all the Macaronesian archipelagos. [ABSTRACT FROM AUTHOR]

The population structure of the blue jack mackerel (Trachurus picturatus, Osteichthyes, Carangidae), in the northeast Atlantic is still unknown. To identify any distinct population units, three areas were selected: waters off Madeira, Peniche (mainland Portugal), and the Canary Islands. Knowledge of population structure is an aspect of the population dynamics of a species that is essential to effectively assess the existence of stocks and manage fisheries. In this study, geometric morphometrics and otolith shape analysis were successfully applied for population identification. Multivariate analysis of variance (MANOVA) revealed no body shape differences between males and females in each area studied, and therefore the sexes were combined for the analysis. The results of the discriminant analysis showed that a low misclassification occurred among areas; 78.0% of individuals were correctly classified. MANOVA performed on the otolith normalized elliptic Fourier descriptors revealed significant areal differences, but no difference between sexes. An overall classification success of 73.3% in the canonical discriminant analysis was achieved. These results indicate the usefulness of both otolith and body shape analysis for differentiation of blue jack mackerel stocks from the northeast Atlantic and indicate the existence of at least three distinguishable populations of this species. [ABSTRACT FROM AUTHOR]

Okadaic acid and its analogues are potent phosphatase inhibitors that cause Diarrheic Shellfish Poisoning (DSP) through the ingestion of contaminated shellfish by humans. This group of toxins is transmitted worldwide but the number of poisoning incidents has declined over the last 20 years due to legislation and monitoring programs that were implemented for bivalves. In the summer of 2012 and 2013, we collected a total of 101 samples of 22 different species that were made up of benthic and subtidal organisms such echinoderms, crustaceans, bivalves and gastropods from Madeira, São Miguel Island (Azores archipelago) and the northwestern coast of Morocco. The samples were analyzed by UPLC-MS/MS. Our main objective was to detect new vectors for these biotoxins. We can report nine new vectors for these toxins in the North Atlantic: Astropecten aranciacus, Arbacia lixula, Echinaster sepositus, Holothuria sanctori, Ophidiaster ophidianus, Onchidella celtica, Aplysia depilans, Patella spp., and Stramonita haemostoma. Differences in toxin contents among the species were found. Even though low concentrations were detected, the levels of toxins that were present, especially in edible species, indicate the importance of these types of studies. Routine monitoring should be extended to comprise a wider number of vectors other than for bivalves of okadaic acid and its analogues. [ABSTRACT FROM AUTHOR]

Ciguatera fish poisoning (CFP) is a syndrome caused by the ingestion of fish contaminated with Ciguatoxins (CTXs). These phycotoxins are produced mainly by dinoflagellates that belong to the genus Gambierdiscus that are transformed in more toxic forms in predatory fish guts, and are more present in the Indo-Pacific and Caribbean areas. It is estimated that CFP causes per year more than 10,000 intoxications worldwide. With the rise of water temperature and anthropogenic intervention, it is important to study the prevalence of CFP in more temperate waters. Through inter- and subtidal sampling, 22 species of organisms were collected, in Madeira and Azores archipelagos and in the northwestern Moroccan coast, during September of 2012 and June and July of 2013. A total of 94 samples of 22 different species of bivalves, gastropods, echinoderms and crustaceans where analyzed by Ultra Performance Liquid Chromatography-Mass Spectometry-Ion Trap-Time of Flight (UPLC-MS-IT-TOF) and Ultra Performance Chromatography- Mass Spectrometry (UPLC-MS). Our main aim was to detect new vectors and ascertain if there were some geographical differences. We detected for the first time putative CTXs in echinoderms, in two starfish species—M. glacialis and O. ophidianus. We detected differences regarding uptake values by organisms and geographical location. Toxin amounts were significant, showing the importance and the need for continuity of these studies to gain more knowledge about the prevalence of these toxins, in order to better access human health risk. In addition, we suggest monitoring of these toxins should be extended to other vectors, starfish being a good alternative for protecting and accessing human health risk. [ABSTRACT FROM AUTHOR]

Estimates of population parameters for the short-finned pilot whale, Globicephala macrorhynchus, are scarce in literature, contributing to an International Union for Conservation of Nature ( IUCN) status of Data Deficient. In this study, photo-identification data collected over 7 yr from Madeira were used to estimate for the first time survivorship, capture probability, and abundance in this species using mark-recapture methodology. The Cormack-Jolly-Seber model estimated that the adult island-associated ( i.e., resident and regular visitor) whales had a constant survival rate of 0.960 (95% CI: 0.853-0.990) and an annual capture probability varying between 0.372 ( CI: 0.178-0.619) and 0.843 ( CI: 0.619-0.947). A parameterization of the Jolly-Seber model estimated that 140 island-associated whales ( CI: 131-151) used the area throughout the course of the study. Based on a closed population model, the most precise (lower CV) annual estimate of the total number of pilot whales using the southern and eastern waters of Madeira (~900 km2) in a 3 mo period covering summer/autumn was 334 animals ( CI: 260-437). No trend was observed. Despite including biases, the approach used in this study provided plausible estimates of population parameters, which can contribute to the regional conservation strategies. [ABSTRACT FROM AUTHOR]

Background: In this study, we examined patients who had non-progressive disease for at least 2 years after diagnosis of inoperable locoregional recurrent or metastatic breast cancer under continuous trastuzumab treatment. Our primary goal was to assess the long-term outcome of patients with durable response to trastuzumab. Methods: 268 patients with HER2-positive inoperable locally recurrent or metastatic breast cancer and non-progressive disease for at least 2 years under trastuzumab treatment were documented retrospectively or prospectively in the HER-OS registry, an online documentation tool, between December 2006 and September 2010 by 71 German oncology centers. The study end point was time to tumor progression. Results: Overall, 47.1% of patients (95% confidence interval (CI): 39.9-54.1%) remained in remission for more than 5 years, while the median time to progression was 4.5 years (95% CI: 4.0-6.6 years). Lower age (<50 years) and good performance status (ECOG 0) at time of trastuzumab treatment initiation as well as complete remission after initial trastuzumab treatment were associated with longer time to progression. Interruption of trastuzumab therapy correlated with shorter time to progression. Conclusions: HER2-positive patients, who initially respond to palliative treatment with trastuzumab, can achieve a long-term tumor remission of several years. [ABSTRACT FROM AUTHOR]

Breast cancer has become curable for the majority of women in Western Europe and North America. Advances have been made in imaging diagnostics as well as the implementation of nationwide screening programmes. Nowadays, we talk about prevention as well as treatment. Pathology has moved from pure morphology (tumour type, grade and stage) to biological characterisation of the tumour. Treatment has changed considerably through a better understanding of the disease; from a local disease predominated by extensive and mutilating surgical techniques to a point where breast cancer has come into its own as a systemic disease with equal “rights” to local as well as systemic treatment. This paradigm shift has led to a multidisciplinary approach of the understanding and treatment of breast cancer. Molecular classification has changed the understanding of breast cancer and will be the basis for an even more individualised treatment. New (biological) agents will help to further tailor treatment to response or resistance. While systemic treatment has been increased in number and duration surgical/local strategies have been reduced to minimum. Evidence-based medicine has helped to improve and standardise treatment of breast cancer. This review summarises the 10th Biedenkopf meeting that was held to review the advances in breast cancer understanding and treatment. [ABSTRACT FROM AUTHOR]

ABSTRACT Pilot whales Globicephala spp. are known to display a hierarchical social pattern, but longitudinal data to infer population structure of short-finned pilot whales Globicephala macrorhynchus are rare., Using data collected between 2003-2011 in the oceanic archipelago of Madeira, the grouping structure of short-finned pilot whales was studied using photo-identification methods and mtDNA sequences and microsatellite markers to test the hypotheses that (1) there is at least one pelagic and one or more island-associated communities, and (2) groups are made of related individuals, with a matrilineal social structure., Pilot whales demonstrated a large degree of variability in site fidelity, including residents (up to 14-year interval), regular visitors and transients. The social and temporal analyses revealed a well-differentiated society with long-lasting relationships (of years). The genetic analyses suggested that individuals of the three residency patterns may not be genetically isolated, and that small groups are made up of related individuals, suggesting some degree of social philopatry, while large groups are probably temporary associations of smaller groups., It is proposed that the pilot whales encountered in Madeira belong to a single population encompassing several clans, possibly three clans of island-associated whales and others of transients, each containing two to three matrilineal pods, each with a mean of 15 individuals (SD=9, range: 4-29). We suggest that the clans interact for mating purposes when they meet., For management decisions, it is considered that the island-associated whales should not be regarded as demographically independent populations, but instead as stable social entities to be included in governmental management plans and requiring periodic evaluation of their status. The high proportion of marked individuals and low rate of mark change encourages further research in this species., Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Elderly breast cancer patients are underrepresented in clinical trials and this leads to a lack of knowledge regarding the tolerance and side effects of modern chemotherapy regimens, especially in dose-dense (dd) or dose-intensified combination. Patients and Methods: In this analysis, data from 4 German, randomized (neo-)adjuvant trials, including anthracycline-based chemotherapy, were evaluated for toxicity, compliance and feasibility. Patients were grouped according to age. Results: Of the 4,775 patients, 73.6% were < 60 years, 15.8% were 60-64 years and 10.6% were > 64 years. The patients' compliance decreased with increasing age, the rate of therapy discontinuations was 10.3%; 16.0% were > 64 years old (p < 0.001). The rate of dose reductions also increased with increasing age in the docetaxel/doxorubicin/cyclophosphamide (TAC) (p overall = 0.02) and 5-fluorouracil/epirubicin-cyclophosphamide (FE120C) (p overall < 0.001) treatment groups. Neutropenia grade 3 + 4 in patients of > 64 years was 77% in FE120C- compared to 55% in TAC-treated patients (with primary granulocyte colony-stimulating factors (G-CSFs)). The incidence of febrile neutropenia (FN) was lowest in the regimens without additional taxanes. FN in patients aged > 64 years was lower in the FE120C- than in TAC- and dd-doxorubicin/docetaxel-treated groups. Conclusion: The range and intensity of toxicity increased with age. Neutropenia did not increase significantly in the dd groups; the highest rate was seen in FE120C-treated patients. FE120C without G-CSFs is not an option in patients older than 64 years. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The major aim of neoadjuvant systemic therapy is to improve prognosis by individualizing treatment. The proven benefits of neoadjuvant systemic therapy include reducing tumor burden, higher breast-conserving surgery, and the possibility of in vivo monitoring of response to treatment. Other goals of neoadjuvant treatment are the detection of new prognostic and predictive biomarkers and the investigation of new drugs and imaging modalities. Although many prospective trials have answered important questions regarding neoadjuvant systemic therapy, several topics remain controversial. [ABSTRACT FROM AUTHOR]

The use of neoadjuvant systemic therapy (NST) for the treatment of primary breast cancer has constantly increased, especially in trials of new therapeutic regimens. In the 1980 s, NST was shown to substantially improve breast-conserving surgery rates and was first typically used for patients with inoperable locally advanced or inflammatory breast cancer. Investigators have since also used NST as an in vivo test for chemosensitivity by assessing pathologic complete response. Today, by using pathologic response and other biomarkers as intermediate end points, results from trials of new regimens and therapies that use NST are aimed to precede and anticipate the results from larger adjuvant trials. In 2003, a panel of representatives from various breast cancer clinical research groups was first convened in Biedenkopf to formulate recommendations on the use of NST. The obtained consensus was updated in two subsequent meetings in 2004 and 2006. The most recent conference on recommendations on the use of NST took place in 2010 and forms the basis of this report. [ABSTRACT FROM AUTHOR]

The goals of treatment for metastatic breast cancer (MBC) are to prolong overall survival (OS) while maximizing quality of life, palliating symptoms, and delaying tumor progression. For many years, anthracyclines and taxanes have been the mainstay of treatment for MBC, but these agents are now commonly administered earlier in the course of the disease. A recent meta-analysis revealed adverse effects on OS and overall response rates in patients with MBC receiving first-line anthracycline-based chemotherapy following relapse on adjuvant chemotherapy. Noncrossresistant cytotoxic agents and combinations that combine high clinical activity and acceptable tolerability while being convenient for patients are therefore needed for the first-line treatment of MBC patients. Capecitabine has substantial antitumor activity in the first-line treatment of patients with MBC in prospective, randomized, phase II/III clinical trials as monotherapy and in combination with biologic and novel agents. First-line capecitabine monotherapy has a favorable safety profile, lacking myelosuppression and alopecia, and does not compromise the administration of further lines of chemotherapy. Capecitabine is suitable for long-term administration without the cumulative toxicity that can limit the prolonged use of other chemotherapy agents. Here, we review the available data on capecitabine as a single agent for first-line treatment of patients with human epidermal growth factor receptor 2-negative MBC. [ABSTRACT FROM AUTHOR]

Background: Current prognostic gene signatures for breast cancer mainly reflect proliferation status and have limited value in triple-negative (TNBC) cancers. The identification of prognostic signatures from TNBC cohorts was limited in the past due to small sample sizes. Methodology/Principal Findings: We assembled all currently publically available TNBC gene expression datasets generated on Affymetrix gene chips. Inter-laboratory variation was minimized by filtering methods for both samples and genes. Supervised analysis was performed to identify prognostic signatures from 394 cases which were subsequently tested on an independent validation cohort (n = 261 cases). Conclusions/Significance: Using two distinct false discovery rate thresholds, 25% and <3.5%, a larger (n = 264 probesets) and a smaller (n = 26 probesets) prognostic gene sets were identified and used as prognostic predictors. Most of these genes were positively associated with poor prognosis and correlated to metagenes for inflammation and angiogenesis. No correlation to other previously published prognostic signatures (recurrence score, genomic grade index, 70-gene signature, wound response signature, 7-gene immune response module, stroma derived prognostic predictor, and a medullary like signature) was observed. In multivariate analyses in the validation cohort the two signatures showed hazard ratios of 4.03 (95% confidence interval [CI] 1.71-9.48; P = 0.001) and 4.08 (95% CI 1.79-9.28; P = 0.001), respectively. The 10-year event-free survival was 70% for the good risk and 20% for the high risk group. The 26-gene signatures had modest predictive value (AUC = 0.588) to predict response to neoadjuvant chemotherapy, however, the combination of a B-cell metagene with the prognostic signatures increased its response predictive value. We identified a 264-gene prognostic signature for TNBC which is unrelated to previously known prognostic signatures. [ABSTRACT FROM AUTHOR]

The luminal B subtype represents a group of high proliferating estrogen receptor positive breast cancers which are associated with a poor prognosis. Genes exclusively expressed in this subtype should help to better understand these tumors. In a finding cohort of 171 breast cancers luminal B specific genes were identified displaying strong expression in highly proliferating Ki-67 positive/ ER positive tumors but no expression either in Ki-67 negative/ ER positive or in Ki-67 positive/ ER negative samples. The clinical relevance of the scaffold protein NHERF1 identified by this strategy was assessed in a total of 3,030 breast cancers. NHERF1 expression was associated with the luminal B subtype both in the finding and validation cohort. A positive correlation of NHERF1 expression with tumor size ( P < 0.001), grade ( P < 0.001), and HER2 status ( P = 0.033) was observed. NHERF1 expression was associated with a worse survival in ER positive breast cancer ( P < 0.001) and retained its prognostic value in multivariate analysis. For ER positive samples with low NHERF1 expression a benefit of endocrine therapy was detected ( P = 0.007). In contrast no differences in disease free survival were found for high NHERF1 expressing breast cancers which were either treated with endocrine therapy or no systemic therapy. Our data indicate that NHERF1 expressing breast cancers seem to have a greater risk to develop resistance to endocrine therapy. However, based on previous findings of NHERF1 functioning in PI3K signalling from basic research, these tumors might be appropriate candidates for a targeted therapy of the PI3K/Akt pathway. [ABSTRACT FROM AUTHOR]

Detection of disseminated tumor cells (DTCs) in bone marrow is an independent prognostic factor in primary breast cancer. Here, we conducted a proof-of-principle study to evaluate whether this tumor cell spread occurs already in patients with ductal carcinoma in situ (DCIS). After preoperative screening by stereotactic core biopsy, 30 consecutive women with DCIS were included. Bone marrow aspirates, taken at the time of primary surgery, were subjected to DTC detection by a standardized immunoassay using the established monoclonal anti-cytokeratin antibodies A45-B/B3 and AE1/AE3. DTCs were detected in 4 of 19 cases of pure DCIS (21.1%) and in four of seven cases of DCIS with microinvasion (57.1%). After a median follow-up time of 22 months, two initially DTC-positive patients suffered from contralateral carcinoma and contralateral DCIS at months 12 and 30, respectively, whereas the remaining patients were relapse free. Thus, hematogenous tumor cell dissemination into bone marrow is an early event in breast cancer development. [ABSTRACT FROM AUTHOR]

Species richness is the most commonly used but controversial biodiversity metric in studies on aspects of community stability such as structural composition or productivity. The apparent ambiguity of theoretical and experimental findings may in part be due to experimental shortcomings and/or heterogeneity of scales and methods in earlier studies. This has led to an urgent call for improved and more realistic experiments. In a series of experiments replicated at a global scale we translocated several hundred marine hard bottom communities to new environments simulating a rapid but moderate environmental change. Subsequently, we measured their rate of compositional change (re-structuring) which in the great majority of cases represented a compositional convergence towards local communities. Re-structuring is driven by mortality of community components (original species) and establishment of new species in the changed environmental context. The rate of this re-structuring was then related to various system properties. We show that availability of free substratum relates negatively while taxon richness relates positively to structural persistence (i.e., no or slow re-structuring). Thus, when faced with environmental change, taxon-rich communities retain their original composition longer than taxon-poor communities. The effect of taxon richness, however, interacts with another aspect of diversity, functional richness. Indeed, taxon richness relates positively to persistence in functionally depauperate communities, but not in functionally diverse communities. The interaction between taxonomic and functional diversity with regard to the behaviour of communities exposed to environmental stress may help understand some of the seemingly contrasting findings of past research. [ABSTRACT FROM AUTHOR]

Breast cancer is a heterogeneous disease of different subtypes on the molecular, histopathological, and clinical level. Genomic profiling techniques have led to several prognostic and predictive gene signatures of breast cancer that may further refine outcome prediction, especially in clinically equivocal situations. In particular, the predictive value of today's most important therapeutic targets, ER and HER2, are strongly influenced by the proliferative status of the tumor. Genomic assays are generally performed in a centralized manner, whereas routine pathological evaluation is mostly done on a decentralized basis, making the comparison of these methods difficult. Thus, there remains considerable uncertainty about the use of the new molecular markers in routine clinical decision making and their role in patient selection or stratification for future clinical trials. To address this concern, a group of representatives from breast cancer research groups in the areas of breast pathology, genomic profiling, and clinical trials critically reviewed all available data. Consensus recommendations are made on the practical use of molecular markers in breast cancer management and their incorporation into future clinical trials. Cancer 2011. © 2010 American Cancer Society. Considerable uncertainty remains on new molecular markers in breast cancer in routine clinical decision making. An expert panel reviewed all available data, making consensus recommendations on the use of molecular markers in breast cancer management and their incorporation into future clinical trials. [ABSTRACT FROM AUTHOR]

Every 2 years, the International Consensus Conference on the Treatment of Primary Breast Cancer takes place in St. Gallen. Given that the concept of the St. Gallen Consensus Conference mainly reflects an international opinion, it appears useful to adapt the results of the vote for everyday therapy in Germany. A German working group comprising 28 breast cancer experts, amongst whom there are 3 members of the international St. Gallen panel, has therefore commented on this year's St. Gallen Consensus Conference (2011) from the German viewpoint. The focus of interest of this year's St. Gallen Conference was tumour biology as the starting point for decisions regarding individual therapy. There was an intensive discussion in relation to the clinical relevance of predictive and prognostic factors and possible consequences for decisions regarding therapy. Therefore, questions concerning the indication for adjuvant chemotherapy focused especially on the significance of the molecular phenotype of the tumour. In addition, important points for discussion were also the value of complete axillary dissection and the use of accelerated complete breast irradiation. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Every 2 years, the International Consensus Conference on the Treatment of Primary Breast Cancer takes place in St. Gallen. Given that the concept of the St. Gallen Consensus Conference mainly reflects an international opinion, it appears useful to adapt the results of the vote for everyday therapy in Germany. A German working group comprising 28 breast cancer experts, amongst whom there are 3 members of the international St. Gallen panel, has therefore commented on this year's St. Gallen Consensus Conference (2011) from the German viewpoint. The focus of interest of this year's St. Gallen Conference was tumour biology as the starting point for decisions regarding individual therapy. There was an intensive discussion in relation to the clinical relevance of predictive and prognostic factors and possible consequences for decisions regarding therapy. Therefore, questions concerning the indication for adjuvant chemotherapy focused especially on the significance of the molecular phenotype of the tumour. In addition, important points for discussion were also the value of complete axillary dissection and the use of accelerated complete breast irradiation. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Pathological complete response (pCR) to neoadjuvant treatment correlates with outcome in breast cancer. We determined whether characteristics of neoadjuvant therapy are associated with pCR. We used multi-level models, which accounted for heterogeneity in pCR across trials and trial arms, to analyze individual patient data from 3332 women included in 7 German neoadjuvant trials with uniform protocols. PCR was associated with an increase in number of chemotherapy cycles (odds ratio [OR] 1.2 for every two additional cycles; P = 0.009), with higher cumulative anthracycline doses (OR 1.6; P = 0.002), higher cumulative taxane doses (OR 1.6; P = 0.009), and with capecitabine containing regimens (OR 1.62; P = 0.022). Association of pCR with increase in number of cycles appeared more pronounced in hormone receptor (HR)-positive tumors (OR 1.35) than in HR-negative tumors (OR 1.04; P for interaction = 0.046). Effect of anthracycline dose was particularly pronounced in HER2-negative tumors (OR 1.61), compared to HER2-positive tumors (OR 0.83; P for interaction = 0.14). Simultaneous trastuzumab treatment in HER2-positive tumors increased odds of pCR 3.2-fold ( P < 0.001). No association of pCR and number of trastuzumab cycles was found (OR 1.20, P = 0.39). Dosing characteristics appear important for successful treatment of breast cancer. Longer treatment, higher cumulative doses of anthracyclines and taxanes, and the addition of capecitabine and trastuzumab are associated with better response. Tailoring according to breast cancer phenotype might be possible: longer treatment in HR-positive tumors, higher cumulative anthracycline doses for HER2-negative tumors, shorter treatment at higher cumulative doses for triple-negative tumors, and limited number of preoperative trastuzumab cycles in HER2-positive tumors. [ABSTRACT FROM AUTHOR]

Pooling of microarray datasets seems to be a reasonable approach to increase sample size when a heterogeneous disease like breast cancer is concerned. Different methods for the adaption of datasets have been used in the literature. We have analyzed influences of these strategies using a pool of 3,030 Affymetrix U133A microarrays from breast cancer samples. We present data on the resulting concordance with biochemical assays of well known parameters and highlight critical pitfalls. We further propose a method for the inference of cutoff values directly from the data without prior knowledge of the true result. The cutoffs derived by this method displayed high specificity and sensitivity. Markers with a bimodal distribution like ER, PgR, and HER2 discriminate different biological subtypes of disease with distinct clinical courses. In contrast, markers displaying a continuous distribution like proliferation markers as Ki67 rather describe the composition of the mixture of cells in the tumor. [ABSTRACT FROM AUTHOR]

Background: Proteomic analysis has become an effective tool in breast cancer research. In this study, we applied the new gel-free tandem mass tag (TMT) reference method for the first time in breast cancer. Materials and Methods: Proteomic analysis was used to compare 10 estrogen receptor (ER)-positive and 10 ER-negative samples. The results of the proteomic approach were validated by Western blot, immunohistochemistry and gene expression analysis. Results: 17 proteins with significant differences in expression were identified. 13 proteins were overexpressed in ER-negative tumors and 4 were overexpressed in ER-positive samples. All these proteins were characterized by relatively high cellular abundance. Conclusions: Our results demonstrate that the gel-free TMT approach allows the quantification of differences in protein expression levels. Further improvement of the sensitivity by subfractionation of the tissue should allow also the identification of low-abundance proteins and might lead to the use of this method in breast cancer research. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Guidelines for the locoregional treatment of primary breast cancer were last published by the US National Institutes of Health in 1991. Since then, new surgical and radiotherapeutic techniques have been developed, clinical trials have provided new evidence, and intriguing long-term effects have emerged from global metadatabases. A revision of these guidelines is therefore necessary and timely. To address this concern, in October 2008, a group of opinion leaders from Austria, Denmark, France, Germany, Italy, the Netherlands, the United Kingdom, and the United States who have worked and published in the field of locoregional treatment met and collectively prepared and approved the described set of recommendations for the use of surgery and radiotherapy in primary breast cancer outside of clinical trials. [ABSTRACT FROM AUTHOR]

The article presents the recommendations by an international panel of oncologists, radiologists, pathologists, surgeons and epidemiologists from Europe and the U.S. on the locoregional treatment of primary breast cancer. It highlights the importance of core needle biopsy as an accurate method of breast cancer diagnosis, as well as appropriate breast-conserving therapies for breast cancer. It also emphasizes on the need for strict monitoring of the quality standards of locoregional treatment.

Sphingolipids are bioactive lipids implicated in apoptosis, cell survival and proliferation. We analyzed the prognostic value of enzymes from sphingolipid metabolism in breast cancer. Differences in expression of ceramide galactosyl transferase (UGT8), ceramide kinase (CERK), and Ganglioside GD3-Synthase (ST8SIA1) in breast cancer cells were investigated by using microarray data of 1,581 tumor samples. UGT8, CERK, and ST8SIA1 were associated with poor pathohistological grading ( P < 0.001). High CERK expression was correlated with ErbB2 status ( P = 0.006). Among ER positive breast cancers a significant worse prognosis for patients with tumors showing low ST8SIA1 and UGT8 expression was observed. In the ER negative subgroup those samples with high CERK expression displayed a worse prognosis. In a multivariate analysis only ST8SIA1 and tumor size remained significant. Our experiments reveal that expression of enzymes from the sphingolipid metabolism has prognostic implications in breast cancer. [ABSTRACT FROM AUTHOR]

A German working group of 23 breast cancer experts discussed the results from the vote at this year’s St. Gallen Consensus Conference on Primary Therapy for Early Breast Cancer (March 11–14, 2009) and came up with some concrete recommendations for day-to-day therapeutic decisions in Germany. Due the fact that the concept of the St. Gallen Consensus Conference merely allows for a minimal consensus, the objective of the working group was to provide practice-related recommendations for day-to-day clinical decisions in Germany. One area of emphasis at St. Gallen was tumor biology as a starting point for reaching individual therapeutic decisions. Intensive discussion was necessary with respect to the clinical relevance of predictive and prognostic factors. A new addition to the area of systemic therapy was a first-ever discussion of the adjuvant administration of bisphosponates and the fact that therapy with trastuzumab in HER2 overexpressing breast cancer has been defined as the standard for neoadjuvant therapy. The value of taxanes as a component of (neo)adjuvant chemotherapy as well as the value of aromatase inhibitors for the endocrine adjuvant treatment of postmenopausal patients were affirmed. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Multidrug resistance (MDR) has been linked to sphingolipid metabolism and preclinical data ascribe glucosylceramide synthase (GCS) a major role for MDR especially in breast cancer cells but no profound data are available on the expression of this potential therapeutic target in clinical breast cancer specimens. We analyzed microarray data of GCS expression in a large cohort of 1,681 breast tumors. Expression of GCS was associated with a positive estrogen receptor (ER) status, lower histological grading, low Ki67 levels and ErbB2 negativity ( P < 0.001 for all). In univariate analysis there was a benefit for disease free survival for patients with tumors displaying low levels of GCS expression but this significance was lost in multivariate Cox regression. Our results suggest ER positive tumors may be the most promising candidates for a potential therapeutic application of GCS inhibitors. [ABSTRACT FROM AUTHOR]

Membrane proteins of the claudin superfamily are important components of cellular tight and adherens junctions. Although their exact function remains unclear, these proteins may play a role in tissue remodeling, a process which is associated with several diseases including endometriosis. In the present work we analyzed the expression of 13 members of the claudin family in the endometrium and peritoneum by microarray analysis. Real-time polymerase chain reaction and immunohistochemistry in human endometrium and peritoneal endometriotic lesions were performed for validation of the expression of claudin-1, -3, -4, -5 and -7. Diminished expression of claudin-3, -4 and -7 in ectopic endometrium was frequently observed as indicated by all three methods. In contrast to a higher expression of claudin-5 mRNA detected in bulk biopsies of ectopic endometrium, immunohistochemistry revealed no alteration of claudin-5 protein expression in glandular cells of endometriosis samples. The downregulation of various members of the claudin family may contribute to endometrial cell detachment and increase the number of cells invading pelvic organs. [ABSTRACT FROM AUTHOR]

The new web tool Adjuvant Consensus gives the user access to the most recent information on how world leading experts suggest to treat a specific breast cancer with systemic therapy. By entering tumor characteristics, age, and menopausal status, the user can find out what experts and national guidelines suggest for this specific tumor. The basis for the suggested treatment options and guidelines are coming from 2 world leading resources: They reflect the reached expert consensus on the implications of evidence for patient treatment selection at the world leading consensus conference on adjuvant therapy held regularly in St. Gallen, and the ‘Clinical Practice Guidelines in Oncology’ for breast cancer published in the US by the National Cancer Center Network in January 2007. The calculated treatment options include the suggested systemic treatment – chemotherapy, hormonal therapy, and antibody therapy, alone or in combination – and the duration and sequence of therapy. Furthermore, the user can find information on the mode of action and important side effects of the different drugs. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Patients with an early response to neoadjuvant chemotherapy have chemosensitive tumors and a high probability for a pathological complete response at surgery. The relationship between extended chemo- therapy and pathological complete response at surgery was investigated in a clinical trial. Untreated breast cancer patients received two 3-week cycles of docetaxel at 75 mg/rn2, doxorubicin at 50 mg/rn2, and cyclophosphamide at 500 mg/rn2 (TAC). Those whose tumor size decreased by 50% or more by sonographic measurement (ie, reduction in the product of the two largest perpendicular diameters by at least 50%) were classified as responders and randomly assigned to receive four or six more cycles of TAC, for a total of six or eight TAC cycles. The primary aim was to increase the rate of a pathological complete response (defined as no invasive or in situ residual tumor masses in the breast and lymph nodes) from 20% to 26%. Sonographic response rates and rates of breast-conserving surgery and adverse effects were also assessed. All statistical tests were two-sided. Of the 2090 patients in the GeparTrio trial, 1390(66.5%) were randomly assigned as responders after two initial TAC cycles to receive an additional four (n = 704) or six (n = 686) TAC cycles. Rates of pathological complete response were not statistically significantly different between the arms (21.0% with six TAC cycles and 23.5% with eight TAC cycles; difference = 2.5%, 95% confidence interval [Cl] = -1.8% to 6.8%; P= .27). More clinical (48.2% vs 52.9%, difference = 4.7%; 95% Cl = -0.55% to 9.95%; P= .08) and sonographic (22.6% vs 27.6%, difference = 5%; 95% Cl = 0.45% to 9.55%; P= .033) complete responses at surgery were observed with eight TAC cycles than with six TAC cycles. The rate of breast-conserving surgery was similar in both arms (67.5% vs 68.5%, respectively, P= .68). Grade 3 or 4 leukopenia and edema and various grade 1 or 2 adverse events were more frequent in patients receiving eight TAC cycles than in those receiving six cycles. Patients receiving eight TAC cycles had statistically significantly higher sonographic response rates but not pathological complete response rates than those receiving six TAC cycles. However, they also had more toxic effects. So far, eight cycles of TAC cannot be recommended for the whole group of patients responding to two initial cycles of TAC. [ABSTRACT FROM AUTHOR]

Among breast cancer patients, nonresponse to initial neoadjuvant chemotherapy is associated with unfavorable outcome. We compared the response of nonresponding patients who continued the same treat- ment with that of patients who switched to a well-tolerated non-cross-resistant regimen. Previously untreated breast cancer patients received two 3-week cycles of docetaxel at 75 mg/m2, doxorubicin at 50 mg/m2, and cyclophosphamide at 500 mg/m2 per day (TAC). Patients whose tumors did not decrease in size by at least 50% were randomly assigned to four additional cycles of TAC or to four cycles of vinorelbine at 25 mg/m2 and capecitabine at 2000 mg/rn2 (NX). The outcome was sonographic response, defined as a reduction in the product of the two largest perpendicular diameters by at least 50%. A differ- ence of 10% or less in the sonographic response qualified as noninferiority of the NX treatment. Pathological complete response was defined as no invasive or in situ residual tumor masses in the breast and lymph nodes. Toxic effects were assessed. All statistical tests were two-sided. Of 2090 patients enrolled in the GeparTrio study, 622 (29.8%) who did not respond to two initial cycles of TAC were randomly assigned to an additional four cycles of TAC (n = 321) or to four cycles of NX (n = 301). Sonographic response rate was 50.5% for the TAC arm and 51.2% for the NX arm. The difference of 0.7% (95% confidence interval = -7.1% to 8.5%) demonstrated noninferiority of NX (P = .008). Similar numbers of patients in both arms received breast-conserving surgery (184 [57.3%] in the TAC arm vs 180 [59.8%] in the NX arm) and had a pathological complete response (5.3% vs 6.0%). Fewer patients in the NX arm than in the TAC arm had hematologic toxic effects, mucositis, infections, and nail changes, but more had hand-foot syndrome and sensory neuropathy. Pathological complete responses to both regimens were marginal. Among patients who did not respond to the initial neoadjuvant TAC treatment, similar efficacy but better tolerability was observed by switching to NX than continuing with TAC. [ABSTRACT FROM AUTHOR]

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Disturbance and productivity are often cited as the main factors determining temporal and spatial patterns in species distribution and the diversity of communities. A field experiment was conducted to test the role of these factors in the structuring of early successional fouling communities in a nutrient limited system at the south coast of Madeira Island. Macro-benthic sessile communities, established on artificial settlement substrata, were manipulated and surveyed over a 9-week period. We applied mechanical disturbances of four different frequencies crossed with three levels of inorganic nutrient enrichment. Fertilization enhanced community diversity by favouring the establishment and growth of macroalgae. Disturbance reduced diversity by eliminating species – but only at the highest nutrient level. This is explained by a multiple-stressor model; species most sensitive to nutrient deficiency (only present in the highest enrichment treatment) were simultaneously the most sensitive to disturbance. [ABSTRACT FROM AUTHOR]

Background. The metalloproteinases (MMPs) are a family of proteolytic enzymes involved in tissue remodeling and cell migration. Endometrial tissue remodeling proceeds during the menstrual cycle and requires a temporary and spatially balanced expression of several different MMPs. Various members of the MMPs also seem to play an important role in the invasion process of endometriosis; however, so far only a limited number of studies have focused on membrane-associated MMPs. Methods. The present study investigated the expression of membrane-type 5 metalloproteinase (MT5-MMP) in the human endometrium and endometriotic lesions by microarray hybridization, real-time polymerase chain reaction (PCR) and immunofluorescence. Results. Both the gene chip expression analyses as well as PCR indicated expression of MT5-MMP in normal human endometrium and strongly elevated transcript levels in most peritoneal endometriosis lesions analyzed. Moreover we detected enhanced MT5-MMP expression in the eutopic endometrium from patients suffering from endometriosis, further supporting a role of MT5-MMP in the formation of endometriosis. Immunohistochemical analysis was used to determine the intracellular localization and tissue distribution of MT5-MMP. While the MT5-MMP antigen expression could be clearly attributed to the membrane of epithelial cells, a highly complex differential immunohistochemical staining of MT5-MMP in the various compartments of endometrial tissue was observed. The strongest staining was seen in luminal epithelial cells, whereas endometrial glands frequently showed partial expression of MT5-MMP. Conclusion. Our microarray analysis and real-time PCR of MT5-MMP transcripts may point to an elevated tissue remodeling and cell migration in endometrium from endometriosis patients as implied by the function of related MMPs. [ABSTRACT FROM AUTHOR]

The uterus is composed of different smooth muscle layers that serve various functions. First, menstrual debris is expulsed at the time of the menses. Second, sperm is transported in the preovulatory phase to maximize fertility, and third, the human embryo is placed in an adequate setting during implantation. Endometriosis is a gynecologic disorder leading to severe pain symptoms such as severe pain during menstruation (dysmenorrhea), chronic pelvic pain, pain during sexual intercourse (dyspareunia), and abnormal uterine bleeding. Besides, endometriosis is often associated with female infertility and exhibits a massive impairment in the physiology of uterine contractility that can be documented by the in vivo examination method of hysterosalpingoscintigraphy (HSSG). In addition, endometriosis is associated in 80–90% of subjects with adenomyosis and our data clearly indicate that sperm transport is disturbed by hyperperistalsis when at least one focus of adenomyosis can be detected via magnetic resonance imaging (MRI) and turns into dysperistalsis (a complete failure in sperm transport capacity) when diffuse adenomyosis affecting all myometrial uterine muscle layers is detected. Hence, dysperistalsis is significantly associated with reduced spontaneous pregnancy rates. We therefore recommend MRI and HSSG in every sterility workup. [ABSTRACT FROM AUTHOR]

The primary goal of most protocols of past and present mammary cancer clinical trials is the reduction of breast cancer incidence. The assumption that the selective estrogen receptor modulator (SERM) tamoxifen could prevent mammary cancer resulted from the experience obtained in palliative and adjuvant treatments. Several prevention clinical trials involve this SERM, e.g. P1, IBIS I, Royal Marsden Hospital Tamoxifen Prevention Trial, Italian Randomized Trial Among Hysterectomized Women. Second-generation trials tested other types of substances, such as aromatase inhibitors which were included in the IBIS II trial. Other trials investigate alternative SERMs, such as raloxifene, arzoxifene and lasofoxifene, as well as endocrine substances, such as gonadotropinreleasing hormone agonists and enzyme inhibitors (e.g. Cox-2 cyclooxigenases). [ABSTRACT FROM AUTHOR]

During the use of long-cycle regimens of monophasic oral contraceptives, the total number of bleeding and cycle-dependent complaints is considerably lower than during conventional treatment with oral contraceptives. Despite an initially higher rate of irregular bleeding, the majority of women prefer the long-cycle treatment since it may improve quality of life. As this regimen provides an enhanced ovarian suppression, it may prevent pregnancies, especially in noncompliant women or patients who are concomitantly treated with drugs that may impair the efficacy of oral contraceptives. Postponement or suppression of withdrawal bleeding also reduces menses-associated disorders such as menorrhagia and dysmenorrhea, and has beneficial effects in patients with hemorrhagic diathesis, endometriosis, uterine leiomyomas and polycystic ovary syndrome. Long-term studies are necessary to assess the impact of long-term use of extended regimens of oral contraceptives on safety, for example, the risk of cancer and cardiovascular disease, and on fertility after discontinuation of treatment. [ABSTRACT FROM AUTHOR]

The increasing understanding of the pathophysiological background of breast cancer is associated with new molecular techniques, improved risk assessment, targeted therapy and individualized treatment. Gene expression profiling may provide predictive and prognostic gene signatures which could help characterize tumors and enable more tailored therapies. Beyond this, gene expression profiling allows us to better understand tumor development and can help identify new molecular markers which should be investigated in terms of specific clinical objectives. There is also an increasing trend towards translational research in large clinical trials which gives new insight into pathophysiology and the prediction of response according to specific therapeutic approaches. Even if the detection of new molecular markers gives rise to new hypotheses, most studies lack a prospective setting, and thus the use of identified markers or specific gene signatures in clinical routine is still limited. [ABSTRACT FROM AUTHOR]