Integration of Tumor and Host Factors – Implications for Breast Cancer Prognosis

Breast cancer is the most common cancer among women worldwide, although the mortality rates have decreased in the last decades. Breast cancer is a heterogeneous disease, and treatment resistance is a significant clinical problem in spite of the overall high survival rates. Improved screening programs, novel surgical techniques, and adjuvant treatments have contributed to the improved survival, but more extensive detection of breast cancer and subsequent treatment also imply higher rates of overtreatment. Therefore, it is vitally important to identify new tumor markers or host factors for patients who are at risk of recurrence, as well as patients who would benefit from less treatment. This approach would lead to more personalized breast cancer treatment. The aim of this thesis is to elucidate whether combining host factors, including genetic constitution and lifestyle factors, with tumor characteristics could yield a more comprehensive understanding than either factor alone for the prognosis of breast cancer. In paper I, moderate to high coffee consumption was associated with higher frequency of ER-negative tumors but a lower risk of early breast cancer events among tamoxifen-treated patients with ER-positive tumors. Furthermore, the combinations of low coffee consumption with the germline CYP1A2 rs762551 C-allele and CYP2C8*3, respectively, were associated with a significantly increased risk of early breast cancer events, indicating that integrating genotype and lifestyle factors may impact the prognosis of breast cancer. In paper II, any preoperative or postoperative alcohol consumption was weakly associated with a lower risk of early breast cancer events. This association was modified by axillary lymph node status, in that any alcohol consumption was associated with a significantly lower risk of early breast cancer events among patients with axillary lymph node involvement but not in patients without axillary lymph node involvement. The results do not support recommending that all breast cancer patients abstain from low to moderate alcohol consumption. In paper III, the CYP1A2 rs762551 C-allele was strongly associated with a higher risk of breast cancer events among aromatase inhibitor-treated patients, and the main impact was found within the first five years. In addition, the impact of the CYP1A2 rs762551 C-allele was modified by genotypes of AhR Arg554Lys and CYP19A1 rs4646, and the combined genotypes could further improve the prediction of aromatase inhibitor response. If validated, these genotypes could be used as predictive markers for aromatase inhibitor response. In paper IV, tumor-specific COX-2 expression was associated with significantly less aggressive tumor characteristics and was independently associated with a lower risk of early breast cancer events. The association was modified by a history of oral contraceptive (OC) use, preoperative non-steroidal anti-inflammatory drug (NSAID) use, and tumor size. If the findings were validated in an independent prospective cohort or within a randomized trial, history of OC use and tumor size might need to be considered when designing or evaluating clinical outcomes in a randomized controlled trial of adjuvant NSAIDs or COX-2 selective inhibitors for breast cancer patients. In conclusion, a more comprehensive view of tumor characteristics combined with host factors could be beneficial when assessing breast cancer prognosis and may provide a method for more personalized medicine in the treatment of breast cancer patients

Excessive milk production during breast-feeding prior to breast cancer diagnosis is associated with increased risk for early events

Breast-feeding is a known protective factor against breast cancer. Breast-feeding duration is influenced by hormone levels, milk production, and lifestyle factors. The aims were to investigate how breast-feeding duration and milk production affected tumor characteristics and risk for early breast cancer events in primary breast cancer patients. Between 2002 and 2008, 634 breast cancer patients in Lund, Sweden, took part in an ongoing prospective cohort study. Data were extracted from questionnaires, pathology reports, and patients’ charts from 592 patients without preoperative treatment. Breast-feeding duration ≤12 months of the first child was associated with higher frequency of ER+/PgR+ tumors (P=0.02). Median follow-up time was 4.9 years. Higher risk for early events was observed for breast-feeding duration of first child >12 months (LogRank P=0.001), total breast-feeding duration >12 months (LogRank P=0.008), as well as ‘excessive milk production’ during breast-feeding of the first child (LogRank P=0.001). Patients with ‘almost no milk production’ had no events. In a multivariable model including both ‘excessive milk production’ and breast-feeding duration of the first child >12 months, both were associated with a two-fold risk for early events, adjusted HRs 2.33 (95% CI: 1.25-4.36) and 2.39 (0.97-5.85), respectively, while total breast-feeding duration was not. ‘Excessive milk production’ was associated with a two-fold risk of early distant metastases, adjusted HR 2.59 (1.13-5.94), but not duration. In conclusion, ‘excessive milk production’ during breast-feeding was associated with higher risk for early events independent of tumor characteristics, stressing the need to consider host factors in the evaluation of prognostic markers. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2193-1801-2-298) contains supplementary material, which is available to authorized users

Творческий подход студентов в изучении гистологии

Denna rapport innehåller texter som presenterats vid en konferens arrangerad inom ramen för Nätverk för barnomsorgsforskningi . Syftet med konferensen var att lyfta upp begreppet omsorg, diskutera dess innebörd, rädda det från retorisk förflackning och samtidigt via dess koppling till verksamheter belysa ett vidare sammanhang. När bamforskning diskuteras har jag på senare tid funnit det väsentligt att peka på att den har en kapacitet att kasta ljus över centrala samhällsfrågor. Forskning om barn bör inte bara vara en forskning om en viss grupp i samhället. Den nyare bamdomsforskningen söker tillämpa ett bamperspektiv. Detta innebär att fenomen studeras såsom de framstår från barnens perspektiv och att inverkan av olika sociala reformer, politiska förändringar och produktion av varor på barns liv belyses. Det handlar alltså både om att söka efter barnens perspektiv och att söka efter konsekvenserna för barnen av olika samhälleliga förändringar. Nya fålt som t.ex. barndomshistoria, barndomssociologi och barndomsantropologi har uppstått och begreppet generation har införts för att markera vikten av att anlägga ett generationsperspektiv på frågor som vanligtvis grupperats på annat sätt

Tumor-specific expression of HMG-CoA reductase in a population-based cohort of breast cancer patients

The mevalonate pathway synthetizes cholesterol, steroid hormones, and non-steriod isoprenoids necessary for cell survival. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) is the rate-limiting enzyme of the mevalonate pathway and the target for statin treatment. HMGCR expression in breast tumors has recently been proposed to hold prognostic and treatment-predictive information. This study aimed to investigate whether HMGCR expression in breast cancer patients was associated with patient and tumor characteristics and disease-free survival (DFS)

Lessons Learned: Effective Reading Practices For The Struggling Reader

This study investigated schools who received Reading First (RF) monies to determine if student reading achievement in kindergarten through second grade was a function of the funding earmarked for implementation of the RF practices. The researchers also examined a seven-year reading progress trend to observe changes in Texas Primary Reading Inventory (TPRI) composite means of 37 participating campuses by grade level and by assessment measure from 2006 to 2012. Multiple linear regression and one-way repeated measures outputs were used for evaluating the evidence. A longitudinal progress trend was used over a seven-year period. Both a linear regression and a repeated measure analyses of variance produced significant results that supported the claim that the size of a reading budget had an impact on students’ reading achievement. The linear regression judged the size of budget statistically significant at the .01 alpha level. The repeated measure analyses found differences and significant results among the means of the five TPRI measurements tested in kindergarten through second grade. The five critical elements of reading measured by TPRI included: phonemic awareness, graphophonemics, listening comprehension, accuracy, and reading comprehension. The analyses showed that student achievement was at its highest during the implementation of the RF program years. The analyses also showed a steady decline in reading composite scores after the loss of the funding. The results of the long trend performance examination might infer that the practices that teachers used in kindergarten through second-grade during the RF years were more effective than those used before or thereafter

Språkundervisning i förskolan: Teoretiska principer och empiriska exempel

I artikeln teoretiseras ett undervisningsbegrepp relevant för förskolans verksamhet. Teoretiskt grundas detta begreppsliggörande i såväl ett evolutionärt som i ett pedagogiskt-psykologiskt perspektiv. Några centrala teoretiker vi bygger på är Barnett, Rommetveit, Tomasello och Vygotskij. Vi lokaliserar grunden till undervisning i människors tendens att göra sådant de själva sett/insett synligt också för andra. Institutioner såsom förskolan och skolan förstås här som sätt för samhället att främja bevarandet av ackumulerande erfarenheter hos den växande generationen, något som gör undervisning centralt. Vi ger empiriska exempel på hur språkundervisning kan gestalta sig i dagens förskola; aktiviteter som vi analyserar utifrån de teoretiska begrepp vi introducerar. Några av de begrepp vi skriver fram för att teoretisera undervisning mer allmänt och språkundervisning mer specifikt i förskolan är responsivitet, kommunikativa praktiker, spänningsfältet mellan intersubjektivitet och alteritet, polyfoni och barns skilda erfarenheter, samt lek och lekfullhet. Vikten av att teoretisera undervisning i förskolan utifrån empirisk forskning betonas

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Impact of COVID-19 pandemic on cardiovascular testing in Asia: the IAEA INCAPS-COVID study

BACKGROUND The coronavirus disease-2019 (COVID-19) pandemic significantly affected management of cardiovascular disease around the world. The effect of the pandemic on volume of cardiovascular diagnostic procedures is not known. OBJECTIVES This study sought to evaluate the effects of the early phase of the COVID-19 pandemic on cardiovascular diagnostic procedures and safety practices in Asia. METHODS The International Atomic Energy Agency conducted a worldwide survey to assess changes in cardiovascular procedure volume and safety practices caused by COVID-19. Testing volumes were reported for March 2020 and April 2020 and were compared to those from March 2019. Data from 180 centers across 33 Asian countries were grouped into 4 subregions for comparison. RESULTS Procedure volumes decreased by 47% from March 2019 to March 2020, showing recovery from March 2020 to April 2020 in Eastern Asia, particularly in China. The majority of centers cancelled outpatient activities and increased time per study. Practice changes included implementing physical distancing and restricting visitors. Although COVID testing was not commonly performed, it was conducted in one-third of facilities in Eastern Asia. The most severe reductions in procedure volumes were observed in lower-income countries, where volumes decreased 81% from March 2019 to April 2020. CONCLUSIONS The COVID-19 pandemic in Asia caused significant reductions in cardiovascular diagnostic procedures, particularly in low-income countries. Further studies on effects of COVID-19 on cardiovascular outcomes and changes in care delivery are warranted