The receptor activator of nuclear factor kappa B (RANK) and its ligand (RANKL) have been shown to promote proliferation of the breast and breast carcinogenesis. The objective of this analysis was to investigate whether tumor-specific RANK and RANKL expression in patients with primary breast cancer is associated with high percentage mammographic density (PMD), which is a known breast cancer risk factor. Immunohistochemical staining of RANK and RANKL was performed in tissue microarrays (TMAs) from primary breast cancer samples of the Bavarian Breast Cancer Cases and Controls (BBCC) study. For RANK and RANKL expression, histochemical scores (H scores) with a cut-off value of > 0 vs 0 were established. PMD was measured in the contralateral, non-diseased breast. Linear regression models with PMD as outcome were calculated using common predictors of PMD (age at breast cancer diagnosis, body mass index (BMI) and parity) and RANK and RANKL H scores. Additionally, Spearman rank correlations (ρ) between PMD and RANK and RANKL H score were performed. In the final cohort of 412 patients, breast cancer-specific RANK and RANKL expression was not associated with PMD (P = 0.68). There was no correlation between PMD and RANK H score (Spearman’s ρ = 0.01, P = 0.87) or RANKL H score (Spearman’s ρ = 0.04, P = 0.41). RANK expression was highest in triple-negative tumors, followed by HER2-positive, luminal B-like and luminal A-like tumors, while no subtype-specific expression of RANKL was found. Results do not provide evidence for an association of RANK and RANKL expression in primary breast cancer with PMD.

PDF file, 133KB, Supplemental Table 6a. Per-Allele Association (SE) of Breast Cancer Susceptibility Variants with Mammographic Percent Density Stratifying by Case Status, BMI, Menopausal Status and PMH Use. Supplemental Table 6b. Per-Allele Associations (SE) of Breast Cancer Susceptibility Variants with Adjusted Mammographic Dense Area Stratifying by Case Status, BMI Menopausal Status and PMH Use. Supplemental Table 6c. Per-Allele Associations (SE) of Breast Cancer Susceptibility Variants with Adjusted Mammographic Non Dense Area Stratifying by Case Status, BMI Menopausal Status and PMH Use.

PDF file, 120KB, Supplemental Table 1. Study Descriptions, Design and Sample Size for 19 DENSNP Studies. Caucasian Women Only. Supplemental Table 2. Source and Timing of Reproductive and Anthropometric Variable Collection. Supplemental Table 3. Description of Mammogram View, Side, Film Digitizer and Density Estimation Software for DENSNP Studies. Supplemental Table 4. Genotyping Platform and SNP Call Rates Performed by Each Study.

Background High mammographic density (MD) is a risk factor for the development of breast cancer (BC). Changes in MD are influenced by multiple factors such as age, BMI, number of full-term pregnancies and lactating periods. To learn more about MD, it is important to establish non-radiation-based, alternative examination methods to mammography such as ultrasound assessments. Methods We analyzed data from 168 patients who underwent standard-of-care mammography and performed additional ultrasound assessment of the breast using a high-frequency (12 MHz) linear probe of the VOLUSON ® 730 Expert system (GE Medical Systems Kretztechnik GmbH & Co OHG, Austria). Gray level bins were calculated from ultrasound images to characterize mammographic density. Percentage mammographic density (PMD) was predicted by gray level bins using various regression models. Results Gray level bins and PMD correlated to a certain extent. Spearman’s ρ ranged from − 0.18 to 0.32. The random forest model turned out to be the most accurate prediction model (cross-validated R 2 , 0.255). Overall, ultrasound images from the VOLUSON ® 730 Expert device in this study showed limited predictive power for PMD when correlated with the corresponding mammograms. Conclusions In our present work, no reliable prediction of PMD using ultrasound imaging could be observed. As previous studies showed a reasonable correlation, predictive power seems to be highly dependent on the device used. Identifying feasible non-radiation imaging methods of the breast and their predictive power remains an important topic and warrants further evaluation. Trial registration 325-19 B (Ethics Committee of the medical faculty at Friedrich Alexander University of Erlangen-Nuremberg, Erlangen, Germany).

Supplementary Table 2. Associations (95% Confidence Interval (CI) in brackets) between all 77 breast cancer susceptibility variants and percent dense area, dense area, and non-dense area

Supplementary Table 1. Mean (95% Confidence Interval (CI)) mammographic density measurements by covariate distribution

Supplementary Table 3. Associations (95% Confidence Interval (CI) in brackets) between breast cancer susceptibility variants and the mammographic measures with adjustment for case-control status

PDF file, 20KB, Supplemental Table 5a. Associations of Common Breast Cancer Susceptibility Variants with Adjusted Percent Mammographic Density. Supplemental Table 5b. Associations of Common Breast Cancer Susceptibility Variants with Adjusted Mammographic Dense Area. Supplemental Table 5c. Associations of Common Breast Cancer Susceptibility Variants with Adjusted Mammographic Non Dense Area.

PURPOSE:In many diseases, it is possible to classify a heterogeneous group into subgroups relative to tumor biology, genetic variations, or clinical and pathological features. No such classification is available for endometriosis. In our retrospective case-case analysis we defined subgroups of endometriosis patients relative to the type and location of the endometriosis lesion and relative to basic patient characteristics.METHODS:From June 2013 to July 2017, a total of 1576 patients with endometriosis diagnosed at surgery were included in this study. The patients' history and clinical data were documented using a web-based remote data entry system. To build subgroups, all possible combinations of endometriosis locations/types (peritoneal; ovarian endometriosis; deeply infiltrating endometriosis; adenomyosis) were used. Due to the variation in group sizes, they were combined into five substantial larger groups.RESULTS:Age, pregnancy rate, and live birth rate were identified as characteristics that significantly differed between the five patient groups that were defined. No significant differences were noted in relation to body mass index, length of menstrual cycle, age at menarche, reason for presentation, or educational level.CONCLUSION:This study describes basic patient characteristics in relation to common clinical subgroups in a large clinical cohort of endometriosis patients. Epidemiological information about different clinical groups may be helpful in identifying groups with specific clinical courses, potentially suggesting novel approaches to early detection and to surgical and systemic treatment.

Purpose: Mammographic density (MD) is one of the strongest risk factors for breast cancer (BC). However, the influence of MD on the BC prognosis is unclear. The objective of this study was therefore to investigate whether percentage MD (PMD) is associated with a difference in disease-free or overall survival in primary BC patients. Methods: A total of 2525 patients with primary, metastasis-free BC were followed up retrospectively for this analysis. For all patients, PMD was evaluated by two readers using a semi-automated method. The association between PMD and prognosis was evaluated using Cox regression models with disease-free survival (DFS) and overall survival (OS) as the outcome, and the following adjustments: age at diagnosis, year of diagnosis, body mass index, tumor stage, grading, lymph node status, hormone receptor and HER2 status. Results: After median observation periods of 9.5 and 10.0 years, no influence of PMD on DFS (p = 0.46, likelihood ratio test (LRT)) or OS (p = 0.22, LRT), respectively, was found. In the initial unadjusted analysis higher PMD was associated with longer DFS and OS. The effect of PMD on DFS and OS disappeared after adjustment for age and was caused by the underlying age effect. Conclusions: Although MD is one of the strongest independent risk factors for BC, in our collective PMD is not associated with disease-free and overall survival in patients with BC. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Zielsetzung Es wurde die praktische Anwendbarkeit und die Erfolgsraten einer neuen Patientinnen-kontrollierten Pumpentherapie zur pulsatilen Gabe von GnRH zur Ovulationsinduktion untersucht.

Zielsetzung Die Mammographische Dichte (MD) ist einer der stärksten Risikofaktoren für Brustkrebs. Der Einfluss der MD auf die Prognose von Mammakarzinompatientinnen ist hingegen unklar. Das Ziel dieser Studie war es, herauszufinden ob die prozentuale MD (PMD) mit einer Veränderung des krankheitsfreien Überlebens (DFS) oder Gesamtüberlebens (OS) bei Patientinnen mit primärem Mammakarzinom assoziiert ist.

Endometriosis is one of the most common benign gynecological diseases. The extremely heterogeneous complex of symptoms complicates the diagnosis and treatment of this disease. In most patients, there is a latency period of several years between the first occurrence of symptoms and the definitive diagnosis. This paper aims (1) to evaluate standards for the diagnosis and treatment of patients with (symptoms suspicious for) endometriosis in terms of feasibility, and (2) to assess the potential use of data collected by a certified clinical and scientific endometriosis center to answer scientific questions. Standards for outpatient consultations were developed for a special endometriosis outpatient clinic. Between January 2014 and December 2017, a total of 1715 outpatients with a suspicion of endometriosis presented to this special endometriosis outpatient clinic; the diagnosis and treatment of patients was carried out in accordance with the developed standards. Data of this patient cohort obtained from patient records created during outpatient consultations and from a questionnaire recorded in an Oracle-based database was analyzed. The patient cohort was also compared with another patient cohort who had attended different outpatient clinics and had been diagnosed intraoperatively with endometriosis. 41.8% of patients examined during special outpatient consultations had surgery for suspicion or recurrence of endometriosis. Endometriosis was confirmed in 81.5% of cases. Pain symptoms were the main indication for surgery in 70.1% of cases compared to 45.1% of cases in the comparison group. The structured approach used in the special endometriosis outpatient clinic is a key aspect of the care provided by the certified clinical and scientific endometriosis center. It ensures that patients are diagnosed and treated in accordance with guideline recommendations, that diagnosis and treatment comply with certification requirements, and that the collected data can be used to answer scientific questions.

Introduction Would adolescent girls in Germany choose a different method of contraception to the combined oral contraceptive if provided with the appropriate information? Is there a need for long-acting contraception among our adolescent girls? How satisfied are female patients with the information they receive at their respective gynaecology practices, and how much do the girls know about different methods of contraception? Materials and Methods In the study “Thinking About Needs in COntraception” (TANCO), not only female patients, but also their respective gynaecologists were surveyed online about current methods of contraception, their satisfaction with these methods, and also their level of knowledge concerning the individual methods of contraception, the situation related to advice about different contraceptive options and their general satisfaction with gynaecological care. This article presents the data from the subset of adolescent girls aged 14 to 19 years (n = 2699) out of the total of 18521 women surveyed. Results The girls surveyed were familiar with at least the name of more than five different methods of contraception (average 5.3). The doctors assumed that the respondents would know only 4.2 different methods. When asked explicitly about how the individual methods of contraception work, clear deficits became evident. This applies not only to the entire population of respondents, but also the users of the respective contraceptive method. In addition, a strong interest in long-acting contraception emerged from the survey, particularly among young women. Discussion The data from the TANCO study reveal a clear discrepancy between the existing contraception almost exclusively in the form of the contraceptive pill and the contraceptive options considered by adolescent girls if they are thoroughly informed. The need for education into alternatives to the pill is high, as is the willingness to use such alternatives after receiving information – much higher than the figures suggested by the gynaecologists. ZUSAMMENFASSUNG Einleitung Würden sich Adoleszentinnen in Deutschland nach entsprechender Aufklärung für eine andere Form der Verhütung als die Einnahme eines oralen kombinierten Kontrazeptivums entscheiden? Besteht ein Bedürfnis nach Langzeitverhütung bei unseren Adoleszentinnen? Wie zufrieden sind die Patientinnen mit der Informationsvermittlung in den betreuenden Frauenarztpraxen und wie viel eigenes Wissen haben die Mädchen über verschiedene Methoden der Verhütung? Material und Methoden In der Studie „Thinking About Needs in COntraception“ (TANCO) wurden neben Patientinnen auch deren betreuende Frauenärzte/innen in einer Online-Umfrage nach aktueller Form der Verhütung, Zufriedenheit hiermit, aber auch über den Wissensstand zu einzelnen Verhütungsmethoden, der Beratungssituation in Bezug auf verschiedene kontrazeptive Optionen und ihre allgemeine ZuGebFra Science |Original Article 999 Oppelt PG et al. Situation of Adolescent... Geburtsh Frauenheilk 2018; 78: 999–1007 friedenheit mit der frauenärztlichen Betreuung befragt. Von den 18521 befragten Frauen werden für diesen Artikel die Daten der Adoleszentinnen zwischen 14 und 19 Jahren (n = 2699) dargestellt. Ergebnisse Zumindest dem Namen nach kannten die Befragten mehr als 5 verschiedene Verhütungsmethoden (im Durchschnitt 5,3). Ärzte gingen davon aus, dass die Befragten nur 4,2 unterschiedliche Methoden kennen. Wird nun explizites Wissen über die Wirkweise einzelner Verhütungsmethoden abgefragt, fallen hier deutliche Defizite auf. Dies betrifft nicht nur das gesamte Kollektiv der Befragten, sondern auch die Verwenderinnen der jeweiligen Verhütung. Weiterhin hat sich in der Befragung ein starkes Interesse gerade junger Frauen an einer Langzeitverhütung gezeigt. Diskussion Die Daten der TANCO-Studie zeigen eine deutliche Diskrepanz zwischen der tatsächlich bestehenden fast ausschließlichen Verhütung mittels Pille und den von Adoleszentinnen in Betracht gezogenen Optionen zur Verhütung, wenn denn ausführliche Aufklärung stattfindet. Der Bedarf nach Aufklärung über Alternativen zur Pille ist hoch und auch die Bereitschaft, diese Alternativen nach erfolgter Aufklärung anzuwenden, liegt deutlich über den von den Frauenärzten angenommenen Prozentsätzen. GebFra Science |Original Article Introduction Numerous methods of reliable contraception are available to women in Germany with a desire for contraception. The rate of women who would like a reliable method of contraception but do not have such access is relatively low; Germany ranks third to last worldwide with respect to this issue [1]. This also applies to the situation of contraceptive use among adolescents in Germany. The data from the survey conducted by the Federal Centre for Health Education (Bundeszentrale für gesundheitliche Aufklärung [BZgA]) into youth sexuality in 2015 reveal that 96% of adolescents claimed to have used contraception when last having sexual intercourse [2]. One reason for this positive trend must certainly be, among other things, the fact that the costs for prescriptiononly contraceptives in Germany are covered by medical insurance until an individual turns 20 years of age, meaning that any potential financial difficulties cannot be the cause for failing to use contraception. Another positive factor is that underage girls may also be prescribed contraception without having to involve or obtain consent from their parents, provided the prescribing gynaecologist assumes that consent would be forthcoming. On searching for information on how much adolescent girls know about individual methods of contraception, no data can be found. The available data are limited to the age as of which adolescents use contraception, and which methods are used. For instance, according to the BZgA data from 2015, where multiple responses were possible, 48% of adolescents used a condom, 70% the pill, and 9% another method when they had last had sexual intercourse. The alternatives to the pill, namely the vaginal ring, the implant, and the three-month injection, accounted for 4% and the coil (without differentiating between hormonal and copper) 2% [2]. Most adolescent girls use a combined oral contraceptive, sometimes along with a condom, as their chosen method of contraception. The reliability and handling of this contraceptive method, in particular, are rated positively by the adolescent girls. Conversely, only one in ten of the adolescent respondents reported problems with taking the pill. First and foremost are compliance problems, which directly affect the contraceptive reliability of the pill. Two-thirds of the girls thus reported that they have once forgotten to take the pill; more than one-third described forgetting to take the pack with them for an overnight stay, meaning they could not take the pill; almost one-third of the girls expressed uncertainty concern1000 ing efficacy in the event of vomiting or diarrhoea. Adverse effects, such as interim bleeding (30%), weight gain (24%), headaches (16%) and decreased sexual desire (15%) were also described by the girls as problems associated with taking the pill [2]. Based on this information, i.e. problems with routine intake and adverse effects, the question arises as to why so few adolescent girls opt for alternative reliable methods to the pill. In a large prospective cohort study conducted in the USA (10000 women aged 14–45 years), namely the Contraceptive CHOICE Project, women received standardised information on every common, reliable method of contraception. Consequently, 67% of the participating women, irrespective of their age, opted for long-acting contraception (after analysing the data from the first 2500 women enrolled). It should be added here that the costs for the chosen contraceptive method were reimbursed [3]. The data from the Contraceptive CHOICE Project give rise to the question whether the decision in favour of a combined oral contraceptive tends to be taken primarily due to limited knowledge of alternative methods of contraception, also in Germany. Would adolescent girls in Germany choose a different method of contraception to the combined oral contraceptive if provided with the appropriate information? Is there a need for long-acting contraception among our adolescent girls? How satisfied are female patients with the information they receive at their respective gynaecology practices, and how much do the girls know about different methods of contraception? Do they even want more information about any of the available contraceptives? And how do the gynaecologists themselves assess their patientsʼ situation? The “Thinking About Needs in COntraception” (TANCO) study was the first to address these questions concerning the situation of contraceptive use in Germany. A total of 18521 female patients were surveyed [4]. Of these, 15% (n = 2699) were adolescents aged between 14 and 19 years. Below, the results are presented and discussed based on the subset of adolescents. Materials and Methods The “Thinking About Needs in COntraception” (TANCO) study was conducted between May and November 2015 by means of an anonymous online survey. Oppelt PG et al. Situation of Adolescent... Geburtsh Frauenheilk 2018; 78: 999–1007