Confirmation of double-peaked time distribution of mortality among Asian breast cancer patients in a population-based study

INTRODUCTION: Double-peaked time distributions of the mortality hazard function have been reported for breast cancer patients from Western populations treated with mastectomy alone. These are thought to reflect accelerated tumour growth at micrometastatic sites mediated by angiogenesis after primary tumour removal as well as tumor dormancy. Similar data are not available for Asian populations. We sought to investigate whether differences exist in the pattern of mortality hazard function between Western breast cancer patients and their Asian counterparts in Singapore, which may suggest underlying differences in tumor biology between the two populations. METHODS: We performed a retrospective cohort study of female unilateral breast cancer patients diagnosed in Singapore between October 1994 and June 1999. Data regarding patient demographics, tumour characteristics and death were available. Overall survival curves were calculated using the Kaplan-Meier method. The hazard rate was calculated as the conditional probability of dying in a time interval, given that the patient was alive at the beginning of the interval. The life table method was used to calculate the yearly hazard rates. RESULTS: In the 2,105 women identified, 956 patients (45.4%) had mastectomy alone. Demographic characteristics were as follows: 86.5% were Chinese, 45.2% were postmenopausal, 38.9% were hormone receptor positive, 54.6% were node negative and 44.1% had high histological grade. We observed a double-peaked mortality hazard pattern, with a first peak in mortality achieving its maximum between years 2 and 4 after mastectomy, and a second large peak in mortality during year 9. Analyses by subgroups revealed a similar pattern regardless of T stage, or node or menopausal status. This pattern was also noted in high-grade tumors but not in those that were well to moderately differentiated. The double-peaked pattern observed in Singaporean women was quantitatively and qualitatively similar to those reported in Western series. CONCLUSION: Our study confirms the existence of a double-peaked process in Asian patients, and it gives further support to the tumour dormancy hypothesis after mastectomy

An early peak of relapse after surgery for breast cancer

There is great interest among oncologists concerning what we might learn by examining the pattern of relapse after breast cancer surgery. What you see depends upon how hard you look. Up to now, investigators have examined the hazard ratio for relapse every 6–12 months. In a research paper, published in this issue of Breast Cancer Research, the Milan group have looked at the hazard ratio every three months and have found, for the first time, a distinct, very early peak of relapse in a group of premenopausal, node-positive patients not given chemotherapy or hormone therapy. What is now needed is for other groups to repeat this observation and, if found, to examine the characteristics of the tumours producing this phenomenon in order to develop hypotheses about its cause and possible treatments

Qualidade do eucalipto clone h13 em sistemas integrados de produção de leite

Um dos grandes desafios nacionais, atualmente, é transformar áreas degradadas em áreas produtivas com a introdução de árvores em sistemas agropecuários como a integração lavoura pecuária floresta (iLPF) ou sistemas agrossilvipastoris. A presença de árvores em sistemas agropecuários pode proporcionar vários benefícios como a melhoria nos índices de conforto térmico animal, aumento na oferta de forragem ao longo do ano, redução da erosão, otimização do uso da energia solar e da ciclagem de nutrientes. Entretanto, ainda existem poucas informações em relação à qualidade do fuste em sistemas iLPF, que são fundamentais para acessar o mercado de madeira serrada, que propicia maior valor agregado e maiores taxas de retorno aos produtores. Com isso, objetivou-se avaliar a qualidade do fuste, fitossanidade e as características das árvores do clone de híbrido Eucaliptus grandis x Eucalyptus urophylla (clone H13) em sistema iLPF. O experimento foi instalado em blocos casualizados, com quatro repetições e dois tratamentos (1) R3: arranjo em renques triplos com espaçamento 3 x 2 entre árvores e 15 m entre renques de árvores (2) R2: renques duplos com espaçamento 3 x 2 m entre árvores e 50 m entre renques de árvores. O experimento está localizado no campo experimental da Embrapa Agrossilvipastoril, localizada no município de Sinop- MT, situado na região de transição dos biomas Cerrado e Floresta Amazônia. As avaliações da qualidade das árvores de eucalipto em sistema integrado foram realizadas aos 36 meses do plantio, durante a estação seca do ano, mediante observação visual qualidade do fuste (tortuosidade, bifurcações e posição da mesma), fitossanidade (pragas e doenças) e as características (copa, galhos e tronco quebrados, mortalidade, inclinação, e multibrotação das copas) das árvores. A qualidade do fuste encontra-se, em algum grau, comprometida em 68% e 74%, respectivamente, nos arranjos R2 e R3, sendo 55% e 65% da tortuosidade localizado na região apical da planta. No R2, 88% das árvores apresentou a fitossanidade comprometida por bovinos, sendo que 57% atingindo o lenho em mais de 5 cm. O arranjo R3 possui os mesmos danos, causados por bovinos, em 94% das árvores onde 53% são os mais severos com mais de 5cm do lenho exposto. Das características avaliadas, houve maior ocorrência em mortalidade das árvores no R3 com 65% e no R2 com 42%. O arranjo R2 mostrou-se mais vulnerável à quebra de copa com 13% e galhos também com 13%, quando comparado com o arranjo R3 que teve somente 5% das copas quebradas e 3% dos galhos

Hypothesis: Induced angiogenesis after surgery in premenopausal node-positive breast cancer patients is a major underlying reason why adjuvant chemotherapy works particularly well for those patients

BACKGROUND: We suggest that surgical extirpation of primary breast cancer among other effects accelerates relapse for some premenopausal node-positive patients. These accelerated relapses occur within 10 months of surgery for untreated patients. The mechanism proposed is a stimulation of angiogenesis for distant dormant micrometastases. This has been suggested as one of the mechanisms to explain the mammography paradox for women aged 40–49 years. We could imagine that it also plays a role in adjuvant chemotherapy effectiveness since, perhaps not coincidentally, this is most beneficial for premenopausal node-positive patients. HYPOTHESIS: We speculate that there is a burst of angiogenesis of distant dormant micrometastases after surgery in approximately 20% of premenopausal node-positive patients. We also speculate that this synchronizes them into a temporal highly chemosensitive state and is the underlying reason why adjuvant chemotherapy works particularly well for that patient category. Furthermore, this may explain why cancer in younger patients is more often 'aggressive'. TESTING THE HYPOTHESIS: Stimulation of dormant micrometastases by primary tumor removal is known to occur in animal models. However, we need to determine whether it happens in breast cancer. Transient circulating levels of angioactive molecules and serial high-resolution imaging studies of focal angiogenesis might help. IMPLICATIONS: Short-course cytotoxic chemotherapy after surgery has probably reached its zenith, and other strategies, perhaps antiangiogenic methods, are needed to successfully treat more patients. In addition, the hypothesis predicts that early detection, which is designed to find more patients without involved lymph nodes, may not be a synergistic strategy with adjuvant chemotherapy, which works best with positive lymph node patients

Recurrence dynamics does not depend on the recurrence site

Introduction: The dynamics of breast cancer recurrence and death, indicating a bimodal hazard rate pattern, has been confirmed in various databases. A few explanations have been suggested to help interpret this finding, assuming that each peak is generated by clustering of similar recurrences and different peaks result from distinct categories of recurrence. Methods: The recurrence dynamics was analysed in a series of 1526 patients undergoing conservative surgery at the National Cancer Institute of Milan, Italy, for whom the site of first recurrence was recorded. The study was focused on the first clinically relevant event occurring during the follow up (ie, local recurrence, distant metastasis, contralateral breast cancer, second primary tumour), the dynamics of which was studied by estimating the specific hazard rate.Results The hazard rate for any recurrence (including both local and distant disease relapses) displayed a bimodal pattern with a first surge peaking at about 24 months and a second peak at almost 60 months. The same pattern was observed when the whole recurrence risk was split into the risk of local recurrence and the risk of distant metastasis. However, the hazard rate curves for both contralateral breast tumours and second primary tumours revealed a uniform course at an almost constant level. When patients with distant metastases were grouped by site of recurrence (soft tissue, bone, lung or liver or central nervous system), the corresponding hazard rate curves displayed the typical bimodal pattern with a first peak at about 24 months and a later peak at about 60 months.Conclusions The bimodal dynamics for early stage breast cancer recurrence is again confirmed, providing support to the proposed tumour-dormancy-based model. The recurrence dynamics does not depend on the site of metastasis indicating that the timing of recurrences is generated by factors influencing the metastatic development regardless of the seeded organ. This finding supports the view that the disease course after surgical removal of the primary tumour follows a common pathway with well-defined steps and that the recurrence risk pattern results from inherent features of the metastasis development process, which are apparently attributable to tumour cells

Bimodal mortality dynamics for uveal melanoma : a cue for metastasis development traits?

Background: The study estimates mortality dynamics (event-specific hazard rates over a follow-up time interval) for uveal melanoma. Methods: Three thousands six hundred seventy two patients undergoing radical or conservative treatment for unilateral uveal melanoma, whose yearly follow-up data were reported in three published datasets, were analysed. Mortality dynamics was studied by estimating with the life-table method the discrete hazard rate for death. Smoothed curves were obtained by a Kernel-like smoothing procedure and a piecewise exponential regression model. The ratio deaths/patients at risk per year was the main outcome measure. Results: The three explored hazard rate curves display a common bimodal pattern, with a sudden increase peaking at about three years, followed by reduction until the sixth-seventh year and a second surge peaking at about nine years after treatment. Conclusions: The bimodal pattern of mortality indicates that uveal melanoma metastatic development cannot be explained by a continuous growth model. Similar metastasis dynamics have been reported for other tumours, including early breast cancer, for which it supported a paradigm shift to an interrupted growth model, the implications of which are episodes of 'tumour dormancy'. We propose that the concepts of tumour homeostasis, tumour dormancy and enhancement of metastasis growth related to primary tumour removal, convincingly explaining the clinical behaviour of breast cancer, may be used for uveal melanoma as well. To confirm this proposition, a careful analysis of uveal melanoma metastasis dynamics is strongly warranted. \ua9 2014 Demicheli et al.; licensee BioMed Central Ltd

Relation of study quality, concordance, take home message, funding, and impact in studies of influenza vaccines: systematic review

Objective To explore the relation between study concordance, take home message, funding, and dissemination of comparative studies assessing the effects of influenza vaccines

Mejoras en el diseño de resistivímetros

El empleo de corrientes continuas en la prospección geoeléctrica es preferido por diversas razones de orden práctico. Los componentes electrónicos modernos permiten diseñar partes críticas de los resistivímetros en forma relativamente simple. La inyección de corriente a potencias moderadas puede proveerse por medio de conversores, a partir de una fuente primaria compuesta de baterías comunes. Para la medición de potencial el empleo de milivoltímetros electrónicos permite mayores facilidades de operación que los métodos potenciométricos clásicos.The use of direct current in geoelectric prospecting is preferred for several practical reasons. Modem electronic components allow to design critical parts of resistivimeters in a relatively easy manner. Direct current injection can be provided by a DC-DC converter by means of a single ordinary lead battery. For potential measurement, the use of electronic millivoltimeters, provide better operational conditions than the classical potentiometric methods.Asociación Argentina de Geofísicos y Geodesta

Mathematical modeling of the metastatic process

Mathematical modeling in cancer has been growing in popularity and impact since its inception in 1932. The first theoretical mathematical modeling in cancer research was focused on understanding tumor growth laws and has grown to include the competition between healthy and normal tissue, carcinogenesis, therapy and metastasis. It is the latter topic, metastasis, on which we will focus this short review, specifically discussing various computational and mathematical models of different portions of the metastatic process, including: the emergence of the metastatic phenotype, the timing and size distribution of metastases, the factors that influence the dormancy of micrometastases and patterns of spread from a given primary tumor.Comment: 24 pages, 6 figures, Revie