Recent breast cancer incidence trends according to hormone therapy use: the California Teachers Study cohort

Abstract Introduction Recent, international declines in breast cancer incidence are unprecedented, and the causes remain controversial. Few data sources can address breast cancer incidence trends according to pertinent characteristics like hormone therapy use history. Methods We used the prospective California Teachers Study to evaluate changes in self-reported use of menopausal hormone therapy (HT) between 1995 to 1996 and 2005 to 2006 and age-adjusted breast cancer incidence among 74,647 participants aged 50 years or older. Breast cancer occurrence was determined by linkage with the California Cancer Registry. Results During 517,286 woman years of follow up, 565 in situ and 2,668 invasive breast cancers were diagnosed. In situ breast cancer incidence rates in this population did not change significantly from 2000 to 2002 to 2003 to 2005, whereas rates of invasive breast cancer declined significantly by 26.0% from 528.0 (95% confidence intervals (CI) = 491.1, 564.9) per 100,000 women in 2000 to 2002 to 390.6 (95% CI = 355.6, 425.7) in 2003 to 2005. The decline in invasive breast cancer incidence rates was restricted to estrogen receptor-positive tumors. In 1996 to 1999 and 2000 to 2002 invasive breast cancer incidence was higher for women who reported current HT use especially estrogen-progestin (EP) use at baseline than for never or past users; but by 2003 to 2005 rates were comparable between these groups. For women who were taking EP in 2001 to 2002,75% of whom had stopped use by 2005 to 2006, incidence had declined 30.6% by 2003 to 2005 (P = 0.001); whereas incidence did not change significantly for those who never took HT (P = 0.33). Conclusions Few data resources can examine prospectively individual HT use and breast cancer diagnosis. Stable in situ breast cancer rates imply consistent levels of screening and suggest recent declines in invasive breast cancer to be explained predominantly by changes in HT use

Progesterone receptor gene polymorphisms and risk of endometriosis: results from an international collaborative effort

Objective To investigate the association between self-reported endometriosis and the putative functional promoter +331C/T single nucleotide polymorphism (SNP) and the PROGINS allele. Design Control subjects from ovarian cancer case-control studies participating in the international Ovarian Cancer Association Consortium. The majority of controls are drawn from population-based studies. Setting An international ovarian cancer consortium including studies from the Australia, Europe and the United States, Patients 5,812 White female controls, of whom 348 had endometriosis, from eight ovarian cancer case-control studies. Interventions None. Main Outcome Measures Genotypes for the +331C/T SNP and PROGINS allele and a history of endometriosis. Results The occurrence of endometriosis was reduced in women carrying one or more copies of the +331 T allele (OR=0.65; 95% CI: 0.43–0.98, p=0.042), whereas there was no association between the PROGINS allele and endometriosis (OR=0.94, 95% CI 0.76, 1.16). Conclusions Additional studies of the +331C/T variant are warranted given the current finding and the equivocal results of previous studies. The +331 T allele has been shown to result in a reduced PR-A to PR-B ratio and if the observed association with endometriosis is confirmed it would suggest that this ratio is important for this disease

Theodor Fontane and Francois Mauriac: A portrait of female characters in conflict

This dissertation compares selected novels of Theodor Fontane with those of Francois Mauriac, demonstrating the strong thematic parallels and certain stylistic affinities in the presentation of both authors\u27 female characters and the society in which they function. In one group of works female characters appear as victims, economically and socially dependent upon a rigid patriarchal society, itself on the verge of decline. In the other category, women, like their bourgeois social class, become possessive dominators or potential dominators, who in turn oppress other characters. The first half of this study focuses on the portrayal of female victims in the novels Effi Briest and Therese Desqueyroux, examining the prevailing social order and the victimization of the heroines. The authors\u27 stylistic commonalities as thematic supports are then studied. An investigation of attitudes of the male authors toward their female personae concludes this section. The second half of this work concentrates on the authors\u27 depiction of woman as oppressor in Jenny Treibel and Genitrix. A discussion of minor female characters as potential dominators follows. Here too the novelists\u27 stylistic techniques are compared and contrasted. In spite of obvious differences in tone and narrative stance, both authors transpose the reality upon which they base their prose with the use of poetic language and imagery. These presentations reveal the injustices and insufficiencies of a degenerating social system, existent in both Fontane\u27s and Mauriac\u27s fictive worlds, and raise the question of the role of woman in society. Despite their sympathetic view of women, both men nevertheless demonstrate an ambivalence toward their female characters and inadvertently reinforce the sexist ideologies of their times

“Undetectable, Now What?” HIV Provider Opinions on Barriers to Healthy Aging for Older People Living with HIV in North America

Background: People living with HIV (PLWH) experience age-associated health conditions earlier than their HIV-uninfected peers and have higher rates of co-occurring conditions that impact aging. Thus, HIV providers frequently confront issues related to HIV and aging. Objective: The objective of this project was to understand provider opinions about the care of older PLWH better. Design: This was accomplished using a quantitative survey. Participants: This study involved 681 physicians treating PLWH in North America. MAIN MEASURES: We collaborated with the Emerging Infections Network (EIN) to administer a ninequestion survey covering practice characteristics, attitudes, and perceived barriers in caring for older PLWH. Key Results: Two hundred and ninety-four (43.2%) responses were collected. Providers estimate that 35% (IQR: 25-50) of their HIV-infected patients were >50 years. The majority (72%) agreed it is difficult to care for older PLWH but had confidence in their ability to do so (85%). Most list a lack of time (55.4%) and insufficient multidisciplinary support (58.5%) as limitations to the effective management of older PLWH. Multi-morbidity was overwhelmingly perceived as the most important barrier to healthy aging (62.2%) followed by tobacco/alcohol use (10%), low income/savings (8.2%), polypharmacy (4.8%) and mental illness (4.4%). Loneliness, frailty, and cognitive difficulties were judged to be less important. In conclusion, HIV providers recognized the complexity of caring for older PLWH, and yet were confident they could care for this population. Conclusion: Multi-morbidity was identified as a major barrier to healthy aging, while syndromes such as frailty and cognitive difficulties were deemed less important despite a growing body of evidence that these geriatric syndromes are common in older PLWH

“Undetectable, Now What?” HIV Provider Opinions on Barriers to Healthy Aging for Older People Living with HIV in North America

Background: People living with HIV (PLWH) experience age-associated health conditions earlier than their HIV-uninfected peers and have higher rates of co-occurring conditions that impact aging. Thus, HIV providers frequently confront issues related to HIV and aging. Objective: The objective of this project was to understand provider opinions about the care of older PLWH better. Design: This was accomplished using a quantitative survey. Participants: This study involved 681 physicians treating PLWH in North America. MAIN MEASURES: We collaborated with the Emerging Infections Network (EIN) to administer a ninequestion survey covering practice characteristics, attitudes, and perceived barriers in caring for older PLWH. Key Results: Two hundred and ninety-four (43.2%) responses were collected. Providers estimate that 35% (IQR: 25-50) of their HIV-infected patients were >50 years. The majority (72%) agreed it is difficult to care for older PLWH but had confidence in their ability to do so (85%). Most list a lack of time (55.4%) and insufficient multidisciplinary support (58.5%) as limitations to the effective management of older PLWH. Multi-morbidity was overwhelmingly perceived as the most important barrier to healthy aging (62.2%) followed by tobacco/alcohol use (10%), low income/savings (8.2%), polypharmacy (4.8%) and mental illness (4.4%). Loneliness, frailty, and cognitive difficulties were judged to be less important. In conclusion, HIV providers recognized the complexity of caring for older PLWH, and yet were confident they could care for this population. Conclusion: Multi-morbidity was identified as a major barrier to healthy aging, while syndromes such as frailty and cognitive difficulties were deemed less important despite a growing body of evidence that these geriatric syndromes are common in older PLWH

Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer

Contains fulltext : 118378.pdf (publisher's version ) (Open Access)HNF1B is overexpressed in clear cell epithelial ovarian cancer, and we observed epigenetic silencing in serous epithelial ovarian cancer, leading us to hypothesize that variation in this gene differentially associates with epithelial ovarian cancer risk according to histological subtype. Here we comprehensively map variation in HNF1B with respect to epithelial ovarian cancer risk and analyse DNA methylation and expression profiles across histological subtypes. Different single-nucleotide polymorphisms associate with invasive serous (rs7405776 odds ratio (OR)=1.13, P=3.1 x 10(-10)) and clear cell (rs11651755 OR=0.77, P=1.6 x 10(-8)) epithelial ovarian cancer. Risk alleles for the serous subtype associate with higher HNF1B-promoter methylation in these tumours. Unmethylated, expressed HNF1B, primarily present in clear cell tumours, coincides with a CpG island methylator phenotype affecting numerous other promoters throughout the genome. Different variants in HNF1B associate with risk of serous and clear cell epithelial ovarian cancer; DNA methylation and expression patterns are also notably distinct between these subtypes. These findings underscore distinct mechanisms driving different epithelial ovarian cancer histological subtypes

Effects of Dietary Fructose Restriction on Liver Fat, De Novo Lipogenesis, and Insulin Kinetics in Children With Obesity

Background & aimsConsumption of sugar is associated with obesity, type 2 diabetes mellitus, nonalcoholic fatty liver disease, and cardiovascular disease. The conversion of fructose to fat in liver (de novo lipogenesis [DNL]) may be a modifiable pathogenetic pathway. We determined the effect of 9 days of isocaloric fructose restriction on DNL, liver fat, visceral fat (VAT), subcutaneous fat, and insulin kinetics in obese Latino and African American children with habitual high sugar consumption (fructose intake >50 g/d).MethodsChildren (9-18 years old; n = 41) had all meals provided for 9 days with the same energy and macronutrient composition as their standard diet, but with starch substituted for sugar, yielding a final fructose content of 4% of total kilocalories. Metabolic assessments were performed before and after fructose restriction. Liver fat, VAT, and subcutaneous fat were determined by magnetic resonance spectroscopy and imaging. The fractional DNL area under the curve value was measured using stable isotope tracers and gas chromatography/mass spectrometry. Insulin kinetics were calculated from oral glucose tolerance tests. Paired analyses compared change from day 0 to day 10 within each child.ResultsCompared with baseline, on day 10, liver fat decreased from a median of 7.2% (interquartile range [IQR], 2.5%-14.8%) to 3.8% (IQR, 1.7%-15.5%) (P < .001) and VAT decreased from 123 cm3 (IQR, 85-145 cm3) to 110 cm3 (IQR, 84-134 cm3) (P < .001). The DNL area under the curve decreased from 68% (IQR, 46%-83%) to 26% (IQR, 16%-37%) (P < .001). Insulin kinetics improved (P < .001). These changes occurred irrespective of baseline liver fat.ConclusionsShort-term (9 days) isocaloric fructose restriction decreased liver fat, VAT, and DNL, and improved insulin kinetics in children with obesity. These findings support efforts to reduce sugar consumption. ClinicalTrials.gov Number: NCT01200043