Explore the vast range of titles available.

Background In the years following pregnancy, breast cancer risk is elevated, particularly for hormone receptor negative (HR-) tumors. Exposure to high maternal circulating estrogens, when the breast is vastly remodeling in structure and morphology, has been associated with HR- tumor risk. Estrogen metabolite profiles in nonpregnant women, notably the ratio of 2:16 hydroxylation (OH) pathway metabolites, are associated with postmenopausal breast cancer development; whether estrogen metabolism during pregnancy influences subsequent HR- breast cancer risk is unknown. Methods We conducted a population-based case–control study in women 19–39 years identified in the Finnish Maternity Cohort Biobank and linked with the Finnish Cancer Registry to identify breast cancer diagnoses within 20 years of pregnancy. Estrogens and metabolites were measured using highly reliable and sensitive LC–MS/MS methods in serum collected during the first and second trimesters of pregnancy. Included were invasive, ER-/PR- breast cancer cases ( n  = 449) and controls ( n  = 449) matched on maternal age at index pregnancy, parity, calendar year of serum collection, gestational week of blood collection, and number of sample freeze/thaw cycles. Associations between the estrogens and breast cancer risk were estimated using odds ratios (ORs) with 95% confidence intervals (CIs) from conditional logistic regression models. Results The median years of follow-up between blood collection and breast cancer diagnosis/control selection was 9 (range 0–19). Ninety-three percent of cases were < 50 years of age at breast cancer diagnosis. Total estrogens were positively associated with ER-/PR- breast cancer (OR associated with a doubling of total estrogens 1.16; 95% CI 1.02–1.32), as were metabolites in the 16-pathway including estriol [OR 1.11; 95% CI 1.01–1.22], 16-epiestriol [OR 1.11; 95% CI 1.01–1.21)], 17-epiestriol [OR 1.06; 95% CI 1.01–1.13], and total 16-hydroxylation pathway metabolites [OR 1.11; 95% CI 1.00–1.24]. There was no clear association with the ratio of 2:16 hydroxylation pathway metabolites. Some associations differed by parity, age at diagnosis, and gestational timing of blood collection, but interactions were not statistically significant. Results were similar when restricted to cases occurring within 15 years since pregnancy. Conclusion This prospective study demonstrated positive associations of estrogen metabolites in pregnancy and risk of mostly premenopausal ER-/PR- breast cancer, but the magnitudes varied by metabolite. No strong or consistent pattern for one metabolic pathway emerged suggesting that total estrogen concentrations during pregnancy are associated with subsequent HR- breast cancer development, regardless of how they are metabolized.

Esophageal adenocarcinoma (EA) is characterized by a strong male predominance. Sex steroid hormones have been hypothesized to underlie this sex disparity, but no population-based study to date has examined this potential association. Using mass spectrometry and ELISA, we quantitated sex steroid hormones and sex hormone binding globulin, respectively, in plasma from males- 172 EA cases and 185 controls-within the Factors Influencing the Barrett/Adenocarcinoma Relationship (FINBAR) Study, a case-control investigation conducted in Northern Ireland and Ireland. Multivariable adjusted logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between circulating hormones and EA. Higher androgen:estrogen ratio metrics were associated with increased odds of EA (e.g., testosterone:estradiol ratio ORQ4 v. Q1 = 2.58, 95%CI = 1.23-5.43; Ptrend = 0.009). All estrogens and androgens were associated with significant decreased odds of EA. When restricted to individuals with minimal to no decrease in body mass index, the size of association for the androgen:estrogen ratio was not greatly altered. This first study of sex steroid hormones and EA provides tentative evidence that androgen:estrogen balance may be a factor related to EA. Replication of these findings in prospective studies is needed to enhance confidence in the causality of this effect.

Purpose The comparability between serum, plasma, and urinary measurements of estrogen metabolites via liquid chromatography–tandem mass spectrometry (LC–MS/MS) has not been largely explored, and it is unclear if urinary LC–MS/MS measurements are suitable surrogates of circulating levels. Methods Serum, plasma (EDTA and heparin), and urinary estrogen/estrogen metabolite levels were measured via LC–MS/MS in paired samples from 64 healthy volunteers (18 men, 20 premenopausal women, 26 postmenopausal women). Geometric means and Spearman correlation coefficients were used to compare individual and combined pathway levels of estrogens/estrogen metabolites across biologic matrices by sex/menopausal status. Results Measured concentrations of estrogens/estrogen metabolites across blood matrices were almost identical (percent differences < 4.8%). Parent estrogen concentrations measured in serum and urine were moderately correlated in postmenopausal women (estrone: r  = 0.69, estradiol: r  = 0.69). Correlations were similar comparing unconjugated serum estradiol to urinary estrone ( r  = 0.76) and urinary estradiol ( r  = 0.65) in postmenopausal women but were moderate to low in premenopausal women ( r  = 0.60, 0.40, respectively)/men ( r  = 0.33, 0.53, respectively). Comparing metabolite ratios, proportionally higher concentrations of 16-pathway metabolites were measured in urine versus serum across sex/menopausal status groups (e.g., postmenopausal women: 50.3% 16-pathway metabolites/total in urine versus 35.3% in serum). Conclusions There is strong agreement between estrogen/estrogen metabolites measurements in serum, heparin plasma, and EDTA plasma. Individual estrogen metabolite concentrations were moderately correlated between urine and serum, but were not well correlated when evaluating pathway- or relative estrogen concentrations. Differences between serum and urine are likely explained by differences in metabolism and/or excretion.

Background Among women diagnosed with invasive breast cancer, 30% have a prior diagnosis of benign breast disease (BBD). Thus, it is important to identify factors among BBD patients that elevate invasive cancer risk. In the general population, risk factors differ in their associations by clinical pathologic features; however, whether women with BBD show etiologic heterogeneity in the types of breast cancers they develop remains unknown. Methods Using a nested case-control study of BBD and breast cancer risk conducted in a community healthcare plan (Kaiser Permanente Northwest), we assessed relationships of histologic features in BBD biopsies and patient characteristics with subsequent breast cancer risk and tested for heterogeneity of associations by estrogen receptor (ER) status, tumor grade, and size. The study included 514 invasive breast cancer cases (median follow-up of 9 years post-BBD diagnosis) and 514 matched controls, diagnosed with proliferative or non-proliferative BBD between 1971 and 2006, with follow-up through mid-2015. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained using multivariable polytomous logistic regression models. Results Breast cancers were predominantly ER-positive (86%), well or moderately differentiated (73%), small (74% < 20 mm), and stage I/II (91%). Compared to patients with non-proliferative BBD, proliferative BBD with atypia conferred increased risk for ER-positive cancer (OR = 5.48, 95% CI = 2.14–14.01) with only one ER-negative case, P -heterogeneity = 0.45. The presence of columnar cell lesions (CCLs) at BBD diagnosis was associated with a 1.5-fold increase in the risk of both ER-positive and ER-negative tumors, with a 2-fold increase (95% CI = 1.21–3.58) observed among postmenopausal women (56%), independent of proliferative BBD status with and without atypia. We did not identify statistically significant differences in risk factor associations by tumor grade or size. Conclusion Most tumors that developed after a BBD diagnosis in this cohort were highly treatable low-stage ER-positive tumors. CCL in BBD biopsies may be associated with moderately increased risk, independent of BBD histology, and irrespective of ER status.

Abstract Background Echocardiography is a cost-efficient method to screen cats for presence of heart disease. Current reference intervals for feline cardiac dimensions do not account for body weight (BW). Objective To study the effect of BW on heart rate (HR), aortic (Ao), left atrial (LA) and ventricular (LV) linear dimensions in cats, and to calculate 95% prediction intervals for these variables in normal adult pure-bred cats. Animals 19 866 pure-bred cats. Methods Clinical data from heart screens conducted between 1999 and 2014 were included. Associations between BW, HR, and cardiac dimensions were assessed using univariate linear models and allometric scaling, including all cats, and only those considered normal, respectively. Prediction intervals were created using 95% confidence intervals obtained from regression curves. Results Associations between BW and echocardiographic dimensions were best described by allometric scaling, and all dimensions increased with increasing BW (all P<0.001). Strongest associations were found between BW and Ao, LV end diastolic, LA dimensions, and thickness of LV free wall. Weak linear associations were found between BW and HR and left atrial to aortic ratio (LA:Ao), for which HR decreased with increasing BW (P<0.001), and LA:Ao increased with increasing BW (P<0.001). Marginal differences were found for prediction formulas and prediction intervals when the dataset included all cats versus only those considered normal. Conclusions and Importance BW had a clinically relevant effect on echocardiographic dimensions in cats, and BW based 95% prediction intervals may help in screening cats for heart disease.

Introduction Benign breast disease (BBD) and high mammographic breast density (MBD) are prevalent and independent risk factors for invasive breast cancer. It has been suggested that temporal changes in MBD may impact future invasive breast cancer risk, but this has not been studied among women with BBD. Methods We undertook a nested case–control study within a cohort of 15,395 women with BBD in Kaiser Permanente Northwest (KPNW; 1970–2012, followed through mid-2015). Cases ( n  = 261) developed invasive breast cancer > 1 year after BBD diagnosis, whereas controls ( n  = 249) did not have breast cancer by the case diagnosis date. Cases and controls were individually matched on BBD diagnosis age and plan membership duration. Standardized %MBD change (per 2 years), categorized as stable/any increase (≥ 0%), minimal decrease of less than 5% or a decrease greater than or equal to 5%, was determined from baseline and follow-up mammograms. Associations between MBD change and breast cancer risk were examined using adjusted unconditional logistic regression. Results Overall, 64.5% ( n  = 329) of BBD patients had non-proliferative and 35.5% ( n  = 181) had proliferative disease with/without atypia. Women with an MBD decrease (≤ − 5%) were less likely to develop breast cancer (Odds Ratio (OR) 0.64; 95% Confidence Interval (CI) 0.38, 1.07) compared with women with minimal decreases. Associations were stronger among women ≥ 50 years at BBD diagnosis (OR 0.48; 95% CI 0.25, 0.92) and with proliferative BBD (OR 0.32; 95% CI 0.11, 0.99). Discussion Assessment of temporal MBD changes may inform risk monitoring among women with BBD, and strategies to actively reduce MBD may help decrease future breast cancer risk.

Background Postmenopausal obesity is associated with increased circulating levels of androgens and estrogens and elevated breast cancer risk. Crown-like structures (CLS; microscopic foci of dying adipocytes surrounded by macrophages) are proposed to represent sites of increased aromatization of androgens to estrogens. Accordingly, we examined relationships between CLS and sex-steroid hormones in breast adipose tissue and serum from postmenopausal breast cancer patients. Methods Formalin-fixed paraffin embedded benign breast tissues collected for research from postmenopausal women ( n  = 83) diagnosed with invasive breast cancer in the Polish Breast Cancer Study (PBCS) were evaluated. Tissues were immunohistochemically stained for CD68 to determine the presence of CLS per unit area of adipose tissue. Relationships were assessed between CD68 density and CLS and previously reported sex-steroid hormones quantified using radioimmunoassays in serum taken at the time of diagnosis and in fresh frozen adipose tissue taken at the time of surgery. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the relationships between hormones (in tertiles) and CLS. Results CLS were observed in 36% of benign breast tissues, with a higher frequency among obese versus lean women (54% versus 17%, p  = 0.03). Detection of CLS was not related to individual hormone levels or breast tumor pathology characteristics. However, detection of CLS was associated with hormone ratios. Compared with women in the highest tertile of estrone:androstenedione ratio in fat, those in the lowest tertile were less likely to have CLS (OR 0.12, 95% CI 0.03–0.59). A similar pattern was observed with estradiol:testosterone ratio in serum and CLS (lowest versus highest tertile, OR 0.18, 95% CI 0.04–0.72). Conclusions CLS were more frequently identified in the breast fat of obese women and were associated with increased ratios of select estrogens:androgens in the blood and tissues, but not with individual hormones. Additional studies on CLS, tissue and blood hormone levels, and breast cancer risk are needed to understand and confirm these findings.

Breast density, as estimated by mammography, is a strong risk factor for breast cancer in pre- and postmenopausal women, but the determinants of breast density have not yet been established. The aim of this study was to assess if urinary estrogens or gut microbiota alterations are associated with mammographic density in postmenopausal women. Among 54 cancer-free, postmenopausal controls in the Breast and Colon Health study, we classified low- versus high-density women with Breast Imaging Reporting and Data System (BI-RADS, 5th edition) mammographic screening data, then assessed associations with urinary estrogens and estrogen metabolites (determined by liquid chromatography/tandem mass spectrometry), and fecal microbiota alpha and beta diversity (using Illumina sequencing of 16S rRNA amplicons). Multiple logistic regression revealed no significant association between breast density and fecal microbiota metrics (PD_tree P-value = 0.82; un-weighted and weighted UniFrac P = 0.92 and 0.83, respectively, both by MiRKAT). In contrast, total urinary estrogens (and all 15 estrogens/estrogen metabolites) were strongly and inversely associated with breast density (P = 0.01) after adjustment for age and body mass index. Mammographic density was not associated with the gut microbiota, but it was inversely associated with urinary estrogen levels. The finding of an inverse association between urinary estrogens and breast density in cancer-free women adds to the growing breast cancer literature on understanding the relationship between endogenous estrogens and mammographic density.

The Multiple Detector Stage is an ancillary detector setup for the Materials Imaging and Dynamics instrument at the European X-Ray Free-Electron Laser Facility. It is developed to improve the current capabilities concerning X-ray detection and make entirely new experiments possible. A unique feature of the MID instrument is the large flexibility in positioning of the AGIPD detector relative to the sample. This enables a large variety of instrument configurations ranging from small-angle to wide-angle X-ray scattering setups. A recurrent request from the users, which is currently not enabled, is the option of simultaneously recording both wide- and the small angle scattering by using two area detectors. The aim of developing MDS is to provide this missing capability at MID so that SAXS and WAXS experiments can be performed in parallel. The MDS will not be installed permanently at the instrument but only on request to provide as much flexibility as possible. In this article, the background and status of the MDS project is described in detail.

Background Models that accurately predict risk of breast cancer are needed to help younger women make decisions about when to begin screening. Premenopausal concentrations of circulating anti-Müllerian hormone (AMH), a biomarker of ovarian reserve, and testosterone have been positively associated with breast cancer risk in prospective studies. We assessed whether adding AMH and/or testosterone to the Gail model improves its prediction performance for women aged 35–50. Methods In a nested case-control study including ten prospective cohorts (1762 invasive cases/1890 matched controls) with pre-diagnostic serum/plasma samples, we estimated relative risks (RR) for the biomarkers and Gail risk factors using conditional logistic regression and random-effects meta-analysis. Absolute risk models were developed using these RR estimates, attributable risk fractions calculated using the distributions of the risk factors in the cases from the consortium, and population-based incidence and mortality rates. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminatory accuracy of the models with and without biomarkers. Results The AUC for invasive breast cancer including only the Gail risk factor variables was 55.3 (95% CI 53.4, 57.1). The AUC increased moderately with the addition of AMH (AUC 57.6, 95% CI 55.7, 59.5), testosterone (AUC 56.2, 95% CI 54.4, 58.1), or both (AUC 58.1, 95% CI 56.2, 59.9). The largest AUC improvement (4.0) was among women without a family history of breast cancer. Conclusions AMH and testosterone moderately increase the discriminatory accuracy of the Gail model among women aged 35–50. We observed the largest AUC increase for women without a family history of breast cancer, the group that would benefit most from improved risk prediction because early screening is already recommended for women with a family history.