Search

PDF file - 299K

Purpose: Members of the Bcl-2 family act as master regulators of mitochondrial homeostasis and apoptosis. We analyzed whether ERBB2 influences the prognosis of breast cancer by influencing the proapoptotic versus antiapoptotic balance of Bcl-2 family members.Experimental Design: ERBB2-regulated Bcl-2 family members were identified by inducible expression of ERBB2 in MCF-7 breast cancer cells and by correlation analysis with ERBB2 expression in breast carcinomas. The prognostic relevance of ERBB2-regulated and all additional Bcl-2 family members was determined in 782 patients with untreated node-negative breast cancer. The biological relevance of ERBB2-induced inhibition of apoptosis was validated in a murine tumor model allowing conditional ERBB2 expression.Results: ERBB2 caused an antiapoptotic phenotype by upregulation of MCL-1, TEGT, BAG1, BNIP1, and BECN1 as well as downregulation of BAX, BMF, BNIPL, CLU, and BCL2L13. Upregulation of the antiapoptotic MCL-1 [P = 0.001, hazard ratio (HR) 1.5] and BNIP3 (P = 0.024; HR, 1.4) was associated with worse prognosis considering metastasis-free interval, whereas clusterin (P = 0.008; HR, 0.88) and the proapoptotic BCL2L13 (P = 0.019; HR, 0.45) were associated with better prognosis. This indicates that ERBB2 alters the expression of Bcl-2 family members in a way that leads to adverse prognosis. Analysis of apoptosis and tumor remission in a murine tumor model confirmed that the prototypic Bcl-2 family member Bcl-xL could partially substitute for ERBB2 to antagonize tumor remission.Conclusions: Our results support the concept that ERBB2 influences the expression of Bcl-2 family members to induce an antiapoptotic phenotype. Antagonization of antiapoptotic Bcl-2 family members might improve breast cancer therapy, whereby MCL-1 and BNIP3 represent promising targets. Clin Cancer Res; 16(2); 451–60

Purpose: According to current guidelines, molecular tests predicting the outcome of breast cancer patients can be used to assist in making treatment decisions after consideration of conventional markers. We developed and validated a gene expression signature predicting the likelihood of distant recurrence in patients with estrogen receptor (ER)–positive, HER2-negative breast cancer treated with adjuvant endocrine therapy.Experimental Design: RNA levels assessed by quantitative reverse transcriptase PCR in formalin-fixed, paraffin-embedded tumor tissue were used to calculate a risk score (Endopredict, EP) consisting of eight cancer-related and three reference genes. EP was combined with nodal status and tumor size into a comprehensive risk score, EPclin. Both prespecified risk scores including cutoff values to determine a risk group for each patient (low and high) were validated independently in patients from two large randomized phase III trials [Austrian Breast and Colorectal Cancer Study Group (ABCSG)-6: n = 378, ABCSG-8: n = 1,324].Results: In both validation cohorts, continuous EP was an independent predictor of distant recurrence in multivariate analysis (ABCSG-6: P = 0.010, ABCSG-8: P < 0.001). Combining Adjuvant!Online, quantitative ER, Ki67, and treatment with EP yielded a prognostic power significantly superior to the clinicopathologic factors alone [c-indices: 0.764 vs. 0.750, P = 0.024 (ABCSG-6) and 0.726 vs. 0.701, P = 0.003 (ABCSG-8)]. EPclin had c-indices of 0.788 and 0.732 and resulted in 10-year distant recurrence rates of 4% and 4% in EPclin low-risk and 28% and 22% in EPclin high-risk patients in ABCSG-6 (P < 0.001) and ABCSG-8 (P < 0.001), respectively.Conclusions: The multigene EP risk score provided additional prognostic information to the risk of distant recurrence of breast cancer patients, independent from clinicopathologic parameters. The EPclin score outperformed all conventional clinicopathologic risk factors. Clin Cancer Res; 17(18); 6012–20. ©2011 AACR.

Supplementary Table 4 from The Humoral Immune System Has a Key Prognostic Impact in Node-Negative Breast Cancer

Supplementary Table 2 from The Humoral Immune System Has a Key Prognostic Impact in Node-Negative Breast Cancer

Supplementary Tables 1, 3, 5-6, Figures 1-6 from The Humoral Immune System Has a Key Prognostic Impact in Node-Negative Breast Cancer

Estrogen receptor (ER) expression and proliferative activity are established prognostic factors in breast cancer. In a search for additional prognostic motifs, we analyzed the gene expression patterns of 200 tumors of patients who were not treated by systemic therapy after surgery using a discovery approach. After performing hierarchical cluster analysis, we identified coregulated genes related to the biological process of proliferation, steroid hormone receptor expression, as well as B-cell and T-cell infiltration. We calculated metagenes as a surrogate for all genes contained within a particular cluster and visualized the relative expression in relation to time to metastasis with principal component analysis. Distinct patterns led to the hypothesis of a prognostic role of the immune system in tumors with high expression of proliferation-associated genes. In multivariate Cox regression analysis, the proliferation metagene showed a significant association with metastasis-free survival of the whole discovery cohort [hazard ratio (HR), 2.20; 95% confidence interval (95% CI), 1.40–3.46]. The B-cell metagene showed additional independent prognostic information in carcinomas with high proliferative activity (HR, 0.66; 95% CI, 0.46–0.97). A prognostic influence of the B-cell metagene was independently confirmed by multivariate analysis in a first validation cohort enriched for high-grade tumors (n = 286; HR, 0.78; 95% CI, 0.62–0.98) and a second validation cohort enriched for younger patients (n = 302; HR, 0.83; 95% CI, 0.7–0.97). Thus, we could show in three cohorts of untreated, node-negative breast cancer patients that the humoral immune system plays a pivotal role in metastasis-free survival of carcinomas of the breast. [Cancer Res 2008;68(13):5405–13]

Background: Some countries have implemented stand-alone human papillomavirus (HPV) testing while others consider cotesting for cervical cancer screening. We compared both strategies within a population-based study. Methods: The MARZY cohort study was conducted in Germany. Randomly selected women from population registries aged ≥30 years (n = 5,275) were invited to screening with Pap smear, liquid-based cytology (LBC, ThinPrep), and HPV testing (Hybrid Capture2, HC2). Screen-positive participants [ASC-US+ or high-risk HC2 (hrHC2)] and a random 5% sample of screen-negatives were referred to colposcopy. Post hoc HPV genotyping was conducted by GP5+/6+ PCR-EIA with reverse line blotting. Sensitivity, specificity (adjusted for verification bias), and potential harms, including number of colposcopies needed to detect 1 precancerous lesion (NNC), were calculated. Results: In 2,627 screened women, cytological sensitivities (Pap, LBC: 47%) were lower than HC2 (95%) and PCR (79%) for CIN2+. Cotesting demonstrated higher sensitivities (HC2 cotesting: 99%; PCR cotesting: 84%), but at the cost of lower specificities (92%–95%) compared with HPV stand-alone (HC2: 95%; PCR: 94%) and cytology (97% or 99%). Cotesting versus HPV stand-alone showed equivalent relative sensitivity [HC2: 1.06, 95% confidence interval (CI), 1.00–1.21; PCR: 1.07, 95% CI, 1.00–1.27]. Relative specificity of Pap cotesting with either HPV test was inferior to stand-alone HPV. LBC cotesting demonstrated equivalent specificity (both tests: 0.99, 95% CI, 0.99–1.00). NNC was highest for Pap cotesting. Conclusions: Cotesting offers no benefit in detection over stand-alone HPV testing, resulting in more false positive results and colposcopy referrals. Impact: HPV stand-alone screening offers a better balance of benefits and harms than cotesting. See related commentary by Wentzensen and Clarke, p. 432

ZusammenfassungDie Implantation spannungsfreier Bänder („tension free vaginal tape“ [TVT]) ist eine minimalinvasive Technik zur Behandlung der Belastungsinkontinenz. Um den Stellenwert und die Besonderheiten der Methode bei älteren Menschen zu evaluieren, wurde eine selektive Literaturrecherche in PubMed mit den Stichworten „urinary incontinence“/„tension free vaginal tape“/„stress incontinence“ AND „elderly“ durchgeführt. Angesichts der demografischen Entwicklung weltweit erweist sich die Harninkontinenz im Alter als zunehmendes medizinisches und sozioökonomisches Problem. Ein TVT kann selbst bei Hochaltrigen unter folgenden Bedingungen ins Auge gefasst werden: grundsätzlich fehlende Kontraindikation gegen einen chirurgischen Eingriff; Vorliegen einer Belastungs- oder Mischinkontinenz (mit hohem Belastungsanteil); Versagen der konservativen Therapie. Unter der Voraussetzung von Operationswunsch und gegebener Operabilität zeigen die Langzeitergebnisse des TVT über 11 Jahre eine persistierende Kontinenzrate von mehr als 80 %. Die Operation ist sicher und effektiv, geht allerdings mit einer erhöhten Rate von postoperativen Harnwegsinfekten und De-Novo-Dranginkontinenz einher.

Purpose On January 1st, 2018, the ÖGZ (Austrian Society of Cytology) revised its cytological nomenclature to make it more similar to the 2015 Bethesda system. Following these changes, the Austrian Society of Gynecology and Obstetrics felt it necessary to revise the approach currently used in Austria to diagnose and treat CIN and to review the procedures to be followed when the quality of cytological specimens is unsatisfactory. It was not possible to adopt the German S3 guideline “Prevention of Cervical Cancer” in its entirety, because the Munich III gynecological cytology nomenclature used in Germany is not used in Austria. This made it necessary to compile a separate scientific opinion for Austria. Methodology The OEGGG worked together with the ÖGZ (Austrian Society for Cytology), AGO Austria (Austrian Working Group for Gynecological Oncology), the AGK (Colposcopy Working Group), and physicians representing gynecologists in private practice. The different scientific associations nominated representatives, who attended the various meetings. After an in-depth analysis of the recent literature, three meetings and numerous votes by telephone, we were able to achieve a consensus about the contents of this guideline. Recommendations The guideline provides recommendations for the diagnosis and treatment of CIN which take account of the gynecological cytology nomenclature used in Austria.

Benigne sowie maligne Raumforderungen der Adnexe konnen die Indikation fur eine Adnexektomie sein. Es sind zwei Zugangswege zur Adnexe moglich, uber eine Laparoskopie oder uber eine Laparotomie, das Vorgehen wird individuell festgelegt. Die operativen und anasthesiologischen Besonderheiten werden in diesem Kapitel vorgestellt.

Die plastische und rekonstruktive Mammachirugie umfasst Augmentations- sowie Reduktionsplastiken und die chirurgische Rekonstruktion nach Mastektomie. Die unterschiedlichen Operationsverfahren werden zusammen mit dem anasthesiologischen Management in diesem Kapitel beschrieben.

Es gibt zwei Indikationen in der Geburtshilfe, die ein operatives Eingreifen rechtfertigen: Gefahr fur die Mutter und Gefahr fur das Kind. Um eine vaginal operative Geburt vornehmen zu konnen, muss der Muttermund vollstandig eroffnet, die Fruchtblase bereits gesprungen sein und der kindliche Kopf sich mindestens in Beckenmitte befinden. Die Vakuumextraktion ist die haufigste vaginal-operative Entbindungsmethode. Das anasthesiologische Management entspricht dem der vaginalen Geburt.

The decades-long global obesity epidemic has resulted in steady increase in the incidence of obesity-related malignancies. The associated diagnostic and therapeutic implications present a clinical challenge for gynecologic oncology treatment strategies. Recent studies have provided solid evidence for an independent, linear, positive correlation between a pathologically increased body mass index and the probability of developing endometrial or postmenopausal breast cancer. The pathogenesis is complex and the subject of current research. Proposed causes include pathologically increased serum levels of sexual steroids and adiponectin, obesity-induced insulin resistance, and systemic inflammatory processes. The scientific evidence for an association between obesity and other gynecological malignancies is, however, less solid. The clinical relevance of obesity as a risk factor for epithelial ovarian cancer, cervical cancer and vulvar cancer appears to be negligible. Nevertheless, obesity appears to have a negative impact on prognosis and oncologic outcomes for all gynecological cancers. Whether or not this effect can be interpreted as correlative or causal is still a subject of ongoing debate.

Aim: To evaluate pre-treatment serum C-reactive protein (CRP) level as a prognostic parameter in patients with adenocarcinoma of the uterine cervix. Materials and Methods: Pre-treatment CRP levels were analyzed to determine potential associations with clinicopathological parameters and to assess prognostic value in 46 patients with sole adenocarcinoma of the uterine cervix. Results: The mean (±SD) pre-treatment serum CRP level was 5.82 (7.21) mg/l. Serum CRP concentration significantly correlated positively with age at diagnosis (p=0.001), lymphovascular space invasion (p=0.0026), recurrent disease (p=0.0001) and International Federation of Gynecology and Obstetrics (FIGO) stage (p=0.0002). In multivariate Cox regression models with age, FIGO stage, histological grade and lymph node status, elevated CRP and cancer antigen 125 levels were associated with shortened survival (p

The modern sling procedures for treating female stress urinary incontinence encompass numerous methods, materials and manufacturers. On the basis of the current S2e guidelines, the methods used most frequently in the diagnosis of and therapy for stress urinary incontinence in women are critically illustrated. An individualised procedure is necessary for the choice of the surgical method, especially in the presence of accompanying pathologies. This article is intended to help the treating physician to carry out quality-assured diagnostics and therapy for the patient and to offer the best possible urogynaecological management. In addition to the complications and chances of success of the surgical options, the legal aspects of therapy planning are also taken into consideration.Die modernen Schlingenverfahren zur Behandlung der weiblichen Belastungsinkontinenz variieren heute zwischen zahlreichen Verfahren, Materialien und Herstellern. Basierend auf der aktuellen S2e-Leitlinie werden die am häufigsten angewendeten Verfahren bei der Diagnostik und Therapie der Belastungsinkontinenz der Frau kritisch beleuchtet. Bei der Wahl der Operationsmethode ist ein individualisiertes Vorgehen erforderlich, insbesondere, wenn Begleitpathologien vorliegen. Der Beitrag soll den behandelnden Ärzten helfen, die Diagnostik und Therapie der Patientinnen qualitätsgesichert durchzuführen und die bestmögliche urogynäkologische Versorgung anbieten zu können. Dabei werden neben den Komplikationen und Erfolgsaussichten der operativen Möglichkeiten auch juristische Aspekte bei der Therapieplanung berücksichtigt.

Lymph node ratio (LNR) can predict treatment outcome and prognosis in patients with solid tumors. Aim of the present analysis was to confirm the concept of using LNR for assessing outcome in patients with vulvar cancer after surgery with inguinal lymphadenectomy in a large multicenter project.The AGO-CaRE-1 study multicenter database was used for analysis. LNR was defined as ratio of number of positive lymph nodes (LN) to the number of resected. Previously established LNR risk groups were used to stratify patients. LNR was investigated with respect to clinical parameters. Univariate and multivariable survival analyses were performed to assess the value of LNR in order to predict overall (OS) and progression-free (PFS) survival.In total, 1047 patients treated with surgery including inguinal lymph node resection for squamous cell carcinoma of the vulva were identified from the database. Of these, 370 (35.3%) were found to have positive inguinal LN. In total, 677 (64.7%) had a LNR of 0% (N0), 255 (24.4%) a LNR of0% 20%, and 115 (11%) a LNR of ≥20%. Patients with higher LNR were found to have larger tumor size (P .001), advanced tumor stage (P .001), high tumor grade (P .001), and deep stromal invasion (P .001), more frequently. Three-year PFS rates were 75.7%, 44.2%, and 23.1% and three-year OS rates were 89.7%, 65.4%, and 41.9%, in patients with LNRs 0%,0% 20%, and ≥20%, respectively (P .001, P .001). On multivariable analyses LNR (HR 7.75, 95%-CI 4.01-14.98, P .001), FIGO stage (HR 1.41, 95%-CI 1.18-1.69, P .001), and patient's performance status (HR 1.59, 95%-CI 1.39-1.82, P .001), were associated with PFS. In addition, LNR (HR 12.74, 95%-CI 5.64-28.78, P .001), and performance status (HR 1.72, 95%-CI 1.44-2.07, P .001) were also the only two parameters independently associated with OS. LNR generally showed stronger correlation than number of affected LN when comparing the two different multivariable models.In women with vulvar cancer LNR appears to be a consistent, independent prognostic parameter for both PFS and OS and allows patient stratification into three distinct risk groups. In survival analyses, LNR outperformed nodal status and number of positive nodes.

The working group recommends against contralateral prophylactic mastectomy (CPM) in women with breast cancer without a family history or genetic predisposition with unilateral breast cancer. This is based on the low risk of developing contralateral breast cancer, the lack of a survival benefit, the increased risk of surgical complications, and the lack of benefit on quality of life.

Purpose Therapeutic decisions in breast cancer patients crucially depend on the status of estrogen receptor, progesterone receptor and HER2, obtained by immunohistochemistry (IHC). These are known to be inaccurate sometimes, and we demonstrate how to use gene-expression to increase precision of receptor status. Methods We downloaded data from 3241 breast cancer patients out of 36 clinical studies. For each receptor, we modelled the mRNA expression of the receptor gene and a co-gene by logistic regression. For each patient, predictions from logistic regression were merged with information from IHC on a probabilistic basis to arrive at a fused prediction result. Results We introduce Sankey diagrams to visualize the step by step increase of precision as information is added from gene expression: IHC-estimates are qualified as ‘confirmed’, ‘rejected’ or ‘corrected’. Additionally, we introduce the category ‘inconclusive’ to spot those patients in need for additional assessments so as to increase diagnostic precision and safety. Conclusions We demonstrate a sound mathematical basis for the fusion of information, even if partly contradictive. The concept is extendable to more than three sources of information, as particularly important for OMICS data. The overall number of undecidable cases is reduced as well as those assessed falsely. We outline how decision rules may be extended to also weigh consequences, being different in severity for false-positive and false-negative assessments, respectively. The possible benefit is demonstrated by comparing the disease free survival between patients whose IHC could be confirmed versus those for which it was corrected. Electronic supplementary material The online version of this article (10.1007/s10549-018-4920-x) contains supplementary material, which is available to authorized users.

Objective: To compare the efficacy and safety of mirabegron 50 mg and solifenacin 5 mg in overactive bladder (OAB) patients dissatisfied with previous antimuscarinic treatment due to lack of efficacy. Patients and methods: This randomized, double-blind, phase IIIb, noninferiority study, enrolled male and female patients aged ⩾18 years old, with symptoms of OAB for ⩾3 months, who were dissatisfied with their previous antimuscarinic drug due to lack of efficacy. A total of 1887 patients were randomized to receive mirabegron 50 mg ( n = 943) or solifenacin 5 mg ( n = 944) daily for 12 weeks. The primary efficacy endpoint was change from baseline to end of treatment in mean number of micturitions/24 h. Noninferiority was confirmed if the lower limit of the two-sided 95% confidence interval (CI) for the treatment difference between solifenacin and mirabegron was > −0.20. Secondary efficacy endpoints, which included change from baseline in mean number of incontinence episodes/24 h, urgency incontinence episodes/24 h, urgency episodes (grade 3 or 4)/24 h and nocturia episodes/24 h, were analyzed using analysis of covariance. Results: For the primary endpoint, adjusted mean treatment difference (95% CI) in mean number of micturitions/24 h was −0.18 (−0.42, 0.06) and therefore noninferiority of mirabegron to solifenacin was not demonstrated. Both treatments demonstrated clinically meaningful reductions in efficacy variables and were well tolerated, with a lower incidence of dry mouth with mirabegron. Conclusions: Noninferiority of mirabegron compared with solifenacin for reduction in micturition frequency could not be demonstrated in this population of OAB patients who were dissatisfied with previous antimuscarinic therapy due to lack of efficacy. Both mirabegron and solifenacin improved key OAB symptoms with no statistically significant differences observed between the two treatments. Both drugs were well tolerated.

The ethical behavior of authors, editors, and journals is increasingly placed in the spotlight, by both the public and the research community. Disclosures and conflict of interest (COI) statements of publishing authors represent one important aspect. We aimed to unravel the current management of disclosures, COI, and funding statements in the subspecialty urogynecology. A bibliometric study was carried out. We included six journals that published urogynecology articles between January and December 2013. All original articles, reviews, and opinion articles were assessed for the presence of disclosure/COI and funding statements. Information given on the official disclosure form was compared with information given in the final article (International Urogynecology Journal). All journals investigated require disclosure and funding statements in their instructions to authors. Of the 434 articles included, almost all contained a disclosure statement (98–100 %). Funding statements were present in 41–100 % of articles, indicating a difference in journal type (50 % on average among urogynecology journals; 75 % on average among general gynecology journals). The main source of funding was “grants” (58 %), followed by “none” (16 %), “industry” (16 %), and lastly “hospital/university” (10 %). Disclosure statements in the article were identical to the official disclosure form in 80 % (IUJ). Disclosure/COI statements were included in almost all urogynecology articles investigated. Their content, however, is sometimes incomplete and should possibly be monitored more closely by journals and authors. Despite universal requirements of journals, the reporting of funding seems inconsistent. This issue in addition to the completeness of disclosures should be given more attention.

Objective To investigate a possible correlation between the volume of the tubal ectopic pregnancy (EP) measured by vaginal-ultrasound (VUS) and methotrexate (MTX) therapy outcome. Study design Data of EP volume measured by one expert-sonographer, viability, clinical symptoms, previous IVF/insemination, follow-up of β-hCG and progesterone levels, and treatment of EP was collected of 100 patients with sonographically diagnosed EP, who attended the Department of Obstetrics and Gynecology of the Medical University Vienna between March 2008 and September 2011. Results The mean volume of EP (mVol.) in the group with successful MTX therapy ( n = 38) was 5.11 ml, 95%CI [2.4; 7.8] with a median 3.2 ml, IQR [5.0], in the group with unsuccessful MTX treatment ( n = 11) it was 15.24 ml, 95%CI [−2.6; 33.1], with a median 4.4 ml, IQR [11.4]. We could observe a trend towards a lower mVol. in the successful MTX group (5.11 ml vs. 15.24 ml). We could not show a significant correlation ( u -test p = 0.208). Conclusion A clear tendency was observed towards a lower mVol. in the successful MTX therapy group, but we could not verify a statistically significant correlation of volume of EP and MTX therapy outcome most likely due to the small sample size. This was the first study investigating the correlation of volume of EP and MTX therapy outcome as principal question.

To determine the optimal serum β-hCG cut-off level to predict MTX treatment success in tubal ectopic pregnancy (EP).Data of 240 women, who presented between 2003 and 2011 at the Department of Gynecology and Obstetrics, Medical University of Vienna, with tubal EP and who received MTX as primary treatment, were retrieved from the hospital information system (KIS). 198 patients could be included for final evaluation. Statistical analysis included area under the ROC curve, maximal Euclidean and Youden index, chi-squared and a five-fold cross validation.The serum β-hCG level cut-off value was calculated at 2121mlU/ml with a specificity of 76.54% and sensitivity of 80.56% (AUC 0.789; p0.001). Patients with an initial serum β-hCG level below 2121mlU/ml (n=131) experienced MTX treatment failure in 5.3% (n=7), compared to 43.3% (n=29) of patients with an initial serum β-hCG level equal to or above 2121mlU/ml (n=67). There was no statistically significant correlation between clinical symptoms and the MTX therapy outcome (p=0.580; likelihood quotient p=0.716).The correct decision of therapy in patients with tubal ectopic pregnancy still represents a challenge. In this study we can conclude that, according to our results there is no endpoint of initial serum β-hCG levels, which can be clearly used as cut-off value for the optimal management of tubal EP. However, an initial serum β-hCG level of less than 2121mlU/ml seems to be a good value to expect a successful MTX treatment. Limitations are the retrospective study design and the inability of classifying clinical symptoms like pain as an objective parameter. Wider implications of the findings may include more detailed patient information and more accurate selection of suitable patients for MTX therapy.

Background Advanced gynecologic cancers have a poor prognosis and constitute a major challenge for adequate treatment strategies. By analyzing and targeting molecular alterations, precision cancer medicine (PCM) may be a viable option for the treatment of advanced gynecologic cancers. Methods In this single center, real-world retrospective analysis of our PCM platform, we describe the molecular profiling of 72 patients diagnosed with different types of metastasized BTC. Tumor samples of the patients were examined by a 162-gene next-generation sequencing (NGS) panel, immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and RNA fusion panel. Results In total, we identified 209 molecular aberrations in 72 patients. The ten most frequently alterations were TP53 (n = 42), KRAS (n = 14), PIK3CA (n = 11), PIK3R1 (n = 9), ATR (n = 8), PTEN (n = 8), BRCA1 (n = 6), NF1 (n = 4), NOTCH1 (n = 4), POLE (n = 4) that make up together over half of the molecular alterations (52.6%). BRAF mutations and gene fusions each were observed in two patients. 21 patients were found to have only one mutation and 44 patients had more than one mutation. No mutations were detected in 7 patients. IHC detected expression of p-mTOR and EGFR in 58 and 53 patients, respectively. In over two-thirds (n = 51) of the 72 patients, a targeted therapy was suggested, based on the identified genetic mutations. The most frequently recommended specific treatment was the combination of everolimus with exemestan (n = 19). The median turnaround time from biopsy to discussion in our multidisciplinary tumor board was 20 days. The median turnaround time from biopsy to therapy initiation was 26 days. Conclusions Based on our observations, it seems that PCM might be a feasible treatment approach for advanced gynecologic cancers with limited treatment options. Legal entity responsible for the study Medical University of Vienna. Funding Has not received any funding. Disclosure H. Taghizadeh: Travel / Accommodation / Expenses: Roche. All other authors have declared no conflicts of interest.

Objectives The aim of this study is to evaluate the activity and toxicity of fulvestrant, a pure estrogen receptor antagonist in patients with advanced or recurrent endometrial cancer, expressing estrogen and/or progesterone receptors (ER/PR). Methods Eligible patients with advanced or recurrent endometrial cancer not amenable to curative surgery and/or radiotherapy were treated with fulvestrant at a dose of 250mg by IM injection every 4weeks for at least 12weeks. Therapy was continued until disease progression, death, intolerable side effects or end of study. Response was assessed in patients with at least one target lesion according to WHO-criteria. Results Thirty-five patients were enrolled in this study and received at least one injection of fulvestrant (intention to treat-population, ITT). Twenty six patients received the intended 3 injections of fulvestrant (per protocol population, PP). There was no complete response but 4 partial responses (11.4% ITT) and 8 stable diseases. The median time to progression was 2.3months (ITT). Overall survival was 13.2months (ITT). Treatment was well tolerated. Conclusions Fulvestrant at a dose of 250mg IM every 4weeks has marginal activity and good tolerability in patients with ER and/or PR positive advanced or recurrent endometrial cancer. A loading dose strategy and the use of 500mg/4weeks might improve the efficacy of this treatment.

The link between higher uptake of isoflavones and a reduced frequency of menopause-related hot flushes were first described in 1992 based on a lower incidence of hot flushes in countries with high dietary soy intake1. Since then, a number of clinical trials with different sources of isoflavones, including soy and red clover, have been performed, and in almost all studies with an appropriate design the outcome was in favour of isoflavone supplementation2. A detailed risk assessment3 revealed that a number of data in humans do not confirm the alleged adverse effect resulting from possible interaction between isoflavones and the hormone-sensitive tissues of the mammary glands, uterus and thyroid. Safety was demonstrated by long-term intake of 150 mg of isoflavones per day, which lasted at least three years. It was also found that a high intake of isoflavones prevented the occurrence of breast cancer4-7. Clinical findings indicate potential benefits of exposure to isoflavones during breast cancer treatment with tamoxifen or anastrozole.

The therapy of choice for breast cancer patients requiring adjuvant chemo- or radiotherapy is increasingly guided by the principle of weighing the individual effectiveness of the therapy against the associated side effects. This has only been made possible by the discovery and validation of modern biomarkers. In the last decades and in the last few years some biomarkers have been integrated in clinical practice and a number have been included in modern study concepts. The importance of biomarkers lies not merely in their prognostic value indicating the future course of disease but also in their use to predict patient response to therapy. Due to the many subgroups, mathematical models and computer-assisted analysis are increasingly being used to assess the prognostic information obtained from established clinical and histopathological factors. In addition to describing some recent computer programmes this overview will focus on established molecular markers which have already been extensively validated in clinical practice and on new molecular markers identified by genome-wide studies.Die Therapiewahl für die Mammakarzinompatientin in der adjuvanten Situation folgt immer mehr dem Prinzip, die individuelle Therapieeffektivität und die Nebenwirkungen gegeneinander abzuwägen. Die Entdeckung und Validierung moderner Biomarker ermöglicht erst dieses Vorgehen. In den letzten Jahrzehnten und insbesondere in den letzten Jahren konnten einige Biomarker in die klinische Praxis und in moderne Studienkonzepte integriert werden. Nicht nur der Vorhersage der Prognose kommt hierbei eine besondere Bedeutung zu, sondern auch der Vorhersage des Therapieansprechens durch Prädiktivfaktoren. Die Nutzung der prognostischen Information aus etablierten, klinischen und histopathologischen Faktoren erfolgt aufgrund der Vielzahl von Untergruppen mehr und mehr in Form von mathematischen Modellen und computergestützter Auswertung. Neben der Darstellung aktueller Programme soll in dieser Übersichtsarbeit des Weiteren der Fokus auf etablierten, molekularen Markern, die bereits eine umfassende klinische Validierung vorweisen können, und neuen molekularen Markern liegen, die durch genomweite Ansätze identifiziert wurden.

Background: We present a series of skin-sparing mastectomies (SSMs) with skin reduction and immediate breast reconstruction to treat large and ptotic breasts. The technique combines oncological mastectomy with immediate subpectoral implant placement as a single-step procedure. Methods: Data was collected from a prospective database from February 2009 to April 2011. A total of 24 patients with macromastia or pronounced ptosis fulfilled the criteria for skin-saving mastectomy. All operations were carried out as a single-step procedure with adaptation of the contralateral breast by reduction mastopexy. Results: A total of 27 SSMs were performed in 24 patients. The mean implant volume was 265 cm3. Immediate reconstruction of the nipple-areola complex was done in 22 patients. The cosmetic and functional results were assessed in all patients 6 months postoperatively; mean follow-up time was 13 months. Mean patient age was 49 years. The cosmetic result was assessed as “very good” or “good” by 22 patients; 2 patients graded the result as “unsatisfactory”. There was one local recurrence. Conclusion: Our results support the use of this technique as a safe oncoplastic procedure which is well tolerated by patients.