Do aromatase inhibitors have adverse effects on cognitive function?

Aromatase inhibitors are an important component of treatment for most postmenopausal women with hormone receptor-positive, early-stage breast cancer. Women taking aromatase inhibitors experience very low levels of circulating estrogen. This might be expected to result in cognitive dysfunction given the important relationship between estrogen and cognition in the basic science literature. Several studies have examined the cognitive effects of aromatase inhibitors, including two within large randomized trials which were adequately powered to detect moderate (but not small) effects. With this caveat, the available data do not support the hypothesis that aromatase inhibitors adversely affect cognitive function or that aromatase inhibitors might have a more adverse effect on cognitive function in comparison with tamoxifen. Further research is needed for confirmation

Prostate screening uptake in Australian BRCA1 and BRCA2 carriers

Men who carry mutations in BRCA1 or BRCA2 are at increased risk for prostate cancer. However the efficacy of prostate screening in this setting is uncertain and limited data exists on the uptake of prostate screening by mutation carriers. This study prospectively evaluated uptake of prostate cancer screening in a multi-institutional cohort of mutation carriers. Subjects were unaffected male BRCA1 and BRCA2 mutation carriers, aged 40–69 years, enrolled in the Kathleen Cuningham Consortium for Research into Familial Breast Cancer (kConFab) and who had completed a mailed, self-report follow-up questionnaire 3 yearly after study entry. Of the 75 male carriers in this study, only 26 (35%) had elected to receive their mutation result. Overall, 51 (68%) did not recall having received a recommendation to have prostate screening because of their family history, but 41 (55%) had undergone a prostate specific antigen (PSA) test and 32 (43%) a digital rectal examination (DRE) in the previous 3 years. Those who were aware of their mutation result were more likely to have received a recommendation for prostate screening (43 vs. 6%, p = 0.0001), and to have had a PSA test (77 vs. 43%, p = 0.005) and a DRE (69 vs. 29%, p = 0.001) in the previous 3 years. The majority of unaffected males enrolled in kConFab with a BRCA1/2 mutation have not sought out their mutation result. However, of those aware of their positive mutation status, most have undergone at least one round of prostate screening in the previous 3 years

Women\u27s preferences for selective estrogen reuptake modulators: an investigation using the time trade off technique

PurposeSelective Estrogen Receptor Modulators (SERMs) reduce the risk of breast cancer for women at increased risk by 38%. However, uptake is extremely low and the reasons for this are not completely understood. The aims of this study were to utilize time trade-off methods to determine the degree of risk reduction required to make taking SERMs worthwhile to women, and the factors associated with requiring greater risk reduction to take SERMs. MethodsWomen at increased risk of breast cancer (N = 107) were recruited from two familial cancer clinics in Australia. Participants completed a questionnaire either online or in pen and paper format. Hierarchical multiple linear regression analysis was used to analyze the data. ResultsOverall, there was considerable heterogeneity in the degree of risk reduction required to make taking SERMs worthwhile. Women with higher perceived breast cancer risk and those with stronger intentions to undergo (or who had undergone) an oophorectomy required a smaller degree of risk reduction to consider taking SERMs worthwhile. ConclusionWomen at increased familial risk appear motivated to consider SERMs for prevention. A tailored approach to communicating about medical prevention is essential. Health professionals could usefully highlight the absolute (rather than relative) probability of side effects and take into account an individual’s perceived (rather than objective) risk of breast cancer

Cognitive function in postmenopausal breast cancer patients one year after completing adjuvant endocrine therapy with letrozole and/or tamoxifen in the BIG 1-98 trial

Endocrine therapy for breast cancer may affect cognition. The purpose of this study was to examine whether cognitive function improves after cessation of adjuvant endocrine therapy. Change in cognitive function was assessed in 100 postmenopausal breast cancer patients in the BIG 1-98 trial, who were randomized to receive 5years of adjuvant tamoxifen or letrozole alone or in sequence. Cognitive function was evaluated by computerized tests during the fifth year of trial treatment (Y5) and 1year after treatment completion (Y6). Cognitive test scores were standardized according to age-specific norms and the change assessed using the Wilcoxon signed-rank test. There was significant improvement in the composite cognitive function score from Y5 to Y6 (median of change=0.22, effect size=0.53, P<0.0001). This improvement was consistent in women taking either tamoxifen or letrozole at Y5 (P=0.0006 and P=0.0002, respectively). For postmenopausal patients who received either adjuvant letrozole or tamoxifen alone or in sequence, cognitive function improved after cessation of treatmen

Nutrient criteria for surface waters under the European Water Framework Directive: current state-of-the-art, challenges and future outlook

The aim of European water policy is to achieve good ecological status in all rivers, lakes, coastal and transitional waters by 2027. Currently, more than half of water bodies are in a degraded condition and nutrient enrichment is one of the main culprits. Therefore, there is a pressing need to establish reliable and comparable nutrient criteria that are consistent with good ecological status. This paper highlights the wide range of nutrient criteria currently in use by Member States of the European Union to support good ecological status and goes on to suggest that inappropriate criteria may be hindering the achievement of good status. Along with a comprehensive overview of nutrient criteria, we provide a critical analysis of the threshold concentrations and approaches by which these are set. We identify four essential issues: (1) Different nutrients (nitrogen and/or phosphorus) are used for different water categories in different countries. (2) The use of different nutrient fractions (total, dissolved inorganic) and statistical summary metrics (e.g., mean, percentiles, seasonal, annual) currently hampers comparability between countries, particularly for rivers, transitional and coastal waters. (3) Wide ranges in nutrient threshold values within shared water body types, in some cases showing more than a 10-fold difference in concentrations. (4) Different approaches used to set threshold nutrient concentrations to define the boundary between “good” and “moderate” ecological status. Expert judgement-based methods resulted in significantly higher (less stringent) good-moderate threshold values compared with data-driven approaches, highlighting the importance of consistent and rigorous approaches to criteria setting. We suggest that further development of nutrient criteria should be based on relationships between ecological status and nutrient concentrations, taking into account the need for comparability between different water categories, water body types within these categories, and countries

iPrevent®: a tailored, web-based, decision support tool for breast cancer risk assessment and management

We aimed to develop a user-centered, web-based, decision support tool for breast cancer risk assessment and personalized risk management. Using a novel model choice algorithm, iPrevent&reg; selects one of two validated breast cancer risk estimation models (IBIS or BOADICEA), based on risk factor data entered by the user. Resulting risk estimates are presented in simple language and graphic formats for easy comprehension. iPrevent&reg; then presents risk-adapted, evidence-based, guideline-endorsed management options. Development was an iterative process with regular feedback from multidisciplinary experts and consumers. To verify iPrevent&reg;, risk factor data for 127 cases derived from the Australian Breast Cancer Family Study were entered into iPrevent&reg;, IBIS (v7.02), and BOADICEA (v3.0). Consistency of the model chosen by iPrevent&reg; (i.e., IBIS or BOADICEA) with the programmed iPrevent&reg; model choice algorithm was assessed. Estimated breast cancer risks from iPrevent&reg; were compared with those attained directly from the chosen risk assessment model (IBIS or BOADICEA). Risk management interventions displayed by iPrevent&reg; were assessed for appropriateness. Risk estimation model choice was 100% consistent with the programmed iPrevent&reg;logic. Discrepant 10-year and residual lifetime risk estimates of &gt;1% were found for 1 and 4 cases, respectively, none was clinically significant (maximal variation 1.4%). Risk management interventions suggested by iPrevent&reg; were 100% appropriate. iPrevent&reg; successfully integrates the IBIS and BOADICEA risk assessment models into a decision support tool that provides evidence-based, risk-adapted risk management advice. This may help to facilitate precision breast cancer prevention discussions between women and their healthcare providers

A hitchhiker's guide to European lake ecological assessment and intercalibration

The Water Framework Directive is the first international legislation to require European countries to establish comparable ecological assessment schemes for their freshwaters. A key element in harmonising quality classification within and between Europe's river basins is an "Intercalibration" exercise, stipulated by the WFD, to ensure that the good status boundaries in all of the biological assessment methods correspond to similar levels of anthropogenic pressure. In this article, we provide a comprehensive overview of this international comparison, focusing on the assessment schemes developed for freshwater lakes. Out of 82 lake ecological assessment methods reported for the comparison, 62 were successfully intercalibrated and included in the EC Decision on intercalibration, with a high proportion of phytoplankton (18), macrophyte (17) and benthic fauna (13) assessment methods. All the lake assessment methods are reviewed in this article, including the results of intercalibration. Furthermore, the current gaps and way forward to reach consistent management objectives for European lakes are discussed. (C) 2015 The Authors. Published by Elsevier Ltd.Peer reviewe

Breast cancer risk prediction using a polygenic risk score in the familial setting: a prospective study from the Breast Cancer Family Registry and kConFab.

PURPOSE: This study examined the utility of sets of single-nucleotide polymorphisms (SNPs) in familial but non-BRCA-associated breast cancer (BC). METHODS: We derived a polygenic risk score (PRS) based on 24 known BC risk SNPs for 4,365 women from the Breast Cancer Family Registry and Kathleen Cuningham Consortium Foundation for Research into Familial Breast Cancer familial BC cohorts. We compared scores for women based on cancer status at baseline; 2,599 women unaffected at enrollment were followed-up for an average of 7.4 years. Cox proportional hazards regression was used to analyze the association of PRS with BC risk. The BOADICEA risk prediction algorithm was used to measure risk based on family history alone. RESULTS: The mean PRS at baseline was 2.25 (SD, 0.35) for affected women and was 2.17 (SD, 0.35) for unaffected women from combined cohorts (P < 10-6). During follow-up, 205 BC cases occurred. The hazard ratios for continuous PRS (per SD) and upper versus lower quintiles were 1.38 (95% confidence interval: 1.22-1.56) and 3.18 (95% confidence interval: 1.84-5.23) respectively. Based on their PRS-based predicted risk, management for up to 23% of women could be altered. CONCLUSION: Including BC-associated SNPs in risk assessment can provide more accurate risk prediction than family history alone and can influence recommendations for cancer screening and prevention modalities for high-risk women.Genet Med 19 1, 30-35.National Institutes of HealthThis is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/gim.2016.4

Australian clinicians and chemoprevention for women at high familial risk for breast cancer

<p>Abstract</p> <p>Objectives</p> <p>Effective chemoprevention strategies exist for women at high risk for breast cancer, yet uptake is low. Physician recommendation is an important determinant of uptake, but little is known about clinicians' attitudes to chemoprevention.</p> <p>Methods</p> <p>Focus groups were conducted with clinicians at five Family Cancer Centers in three Australian states. Discussions were recorded, transcribed and analyzed thematically.</p> <p>Results</p> <p>Twenty three clinicians, including genetic counselors, clinical geneticists, medical oncologists, breast surgeons and gynaecologic oncologists, participated in six focus groups in 2007. The identified barriers to the discussion of the use of tamoxifen and raloxifene for chemoprevention pertained to issues of evidence (evidence for efficacy not strong enough, side-effects outweigh benefits, oophorectomy superior for mutation carriers), practice (drugs not approved for chemoprevention by regulatory authorities and not government subsidized, chemoprevention not endorsed in national guidelines and not many women ask about it), and perception (clinicians not knowledgeable about chemoprevention and women thought to be opposed to hormonal treatments).</p> <p>Conclusion</p> <p>The study demonstrated limited enthusiasm for discussing breast cancer chemoprevention as a management option for women at high familial risk. Several options for increasing the likelihood of clinicians discussing chemoprevention were identified; maintaining up to date national guidelines on management of these women and education of clinicians about the drugs themselves, the legality of "off-label" prescribing, and the actual costs of chemopreventive medications.</p