Evidence suggests that premenopausal obesity decreases and postmenopausal obesity increases breast cancer risk. Because it is not well known whether this is subtype dependent, we studied the association between body mass index (BMI) and age at breast cancer diagnosis, or the probability of being diagnosed with a specific breast cancer phenotype, by menopausal status.

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Abstract Purpose: Uterine sarcomas are rare and heterogeneous tumors characterized by an aggressive clinical behavior. Their high rates of recurrence and mortality point to the urgent need for novel targeted therapies and alternative treatment strategies. However, no molecular prognostic or predictive biomarkers are available so far to guide choice and modality of treatment. Experimental Design: We investigated the expression of several druggable targets (phospho-S6S240 ribosomal protein, PTEN, PDGFR-α, ERBB2, and EGFR) in a large cohort of human uterine sarcoma samples (288), including leiomyosarcomas, low-grade and high-grade endometrial stromal sarcomas, undifferentiated uterine sarcomas, and adenosarcomas, together with 15 smooth muscle tumors of uncertain malignant potential (STUMP), 52 benign uterine stromal tumors, and 41 normal uterine tissues. The potential therapeutic value of the most promising target, p-S6S240, was tested in patient-derived xenograft (PDX) leiomyosarcoma models. Results: In uterine sarcomas and STUMPs, S6S240 phosphorylation (reflecting mTOR pathway activation) was associated with higher grade (P = 0.001) and recurrence (P = 0.019), as shown by logistic regression. In addition, p-S6S240 correlated with shorter progression-free survival (P = 0.034). Treatment with a dual PI3K/mTOR inhibitor significantly reduced tumor growth in 4 of 5 leiomyosarcoma PDX models (with tumor shrinkage in 2 models). Remarkably, the 4 responding models showed basal p-S6S240 expression, whereas the nonresponding model was scored as negative, suggesting a role for p-S6S240 in response prediction to PI3K/mTOR inhibition. Conclusions: Dual PI3K/mTOR inhibition represents an effective therapeutic strategy in uterine leiomyosarcoma, and p-S6S240 expression is a potential predictive biomarker for response to treatment. Clin Cancer Res; 23(5); 1274–85. ©2017 AACR.

AimTo prospectively evaluate whole body diffusion-weighted MRI (WB-DWI/MRI) for tumour characterisation, staging and prediction of complete (R0)-resection compared with computed tomography (CT) in patients with suspected ovarian carcinoma.

Gestational trophoblastic diseases include placental pathologies comprising fertilization abnormalities (hydatidiform moles) and malignant lesions (choriocarcinoma, placental site trophoblastic tumor and epithelioid trophoblastic tumor). Due to their low incidence and heterogeneity, their diagnosis, management and treatment are not always optimal. Following the example of other European countries, a national registration system with two reference centers has been set up to guide physicians and patients and to propose individualized management. The centers offer their expertise through a systematic centralised pathology review by a panel of experts. HCG values are plotted in regression curves. In case of gestational trophoblastic neoplasia, an imaging work-up is proposed, from which the FIGO score and stage are derived and will guide the choice of treatment. Belgian centers offer a multidisciplinary approach, in partnership with the referent physician. More information for practitioners and patients is available on a web site: www.mole-chorio-bgog.eu, which also harbours a forum of discussion.

Background. Standard treatment of cervical cancer FIGO stage IB1 is a radical hysterectomy with pelvic lymphadenectomy. As the number of patients with a preserved fertility wish has increased, the need for fertility sparing surgery emerges. In this study we discuss 11 patients with cervical carcinoma stage IB treated with neoadjuvant chemotherapy followed by large cone resection.Methods. In this retrospective study we included 10 patients with FIGO stage IB1 and I patient with IB2 cervical cancer, who first received a pelvic lymphadenectomy followed by neoadjuvant chemotherapy and conization. Paclitaxel-ifosfamide-carboplatin or a combination of paclitaxel-carboplatin was used as neoadjuvant chemotherapy.Results. Complete response after chemotherapy was observed in 64%, partial response in 27% and 9% had progressive disease. All patients with response underwent a conization, with no residual disease on pathology in 80%. Patients with residual disease were treated by radical hysterectomy. In 9 patients fertility sparing surgery could be performed and 6 (67%) got pregnant. Five patients had 7 children and two patients had four missed abortions. Two premature deliveries at 32 and 33 weeks were described, both in the same patient. Recurrence was observed in one patient that was treated with simple hysterectomy followed by radiochemotherapy. Median follow up time is 58 months with all patients alive and no evidence of disease until now.Conclusions. Neoadjuvant chemotherapy followed by conization seems to be a promising new fertility sparing treatment modality in patients with cervical carcinoma stage IB1, but further studies with larger populations should confirm these data. (C) 2015 Elsevier Inc. All rights reserved.

Clinical outcome of 23 patients with mixed endometrioid and serous endometrial carcinomas (mixed EEC-SC) was compared to that of pure endometrioid (EEC) and pure serous (SC) carcinomas. Hotspot mutation frequencies in KRAS, PIK3CA, PTEN, and TP53 and microsatellite instability (MSI) status were determined in mixed EEC-SC, as well as in their EEC and SC microdissected components separately, and alterations were compared to frequencies in pure EEC and SC. Relapse-free (RFS) and overall survival (OS) differed significantly between mixed EEC-SC and pure EEC and SC, revealing that outcome of mixed EEC-SCs was intermediate to that of pure EEC and pure SC. PTEN mutations were absent in pure SC, but occurred in 20 % of pure EEC, and 13 % of mixed EEC-SC. In contrast, TP53 mutations were more frequent in pure SC (17 %) and mixed EEC-SC (22 %) than in pure EEC (2 %). Mutations in mixed EEC-SC were shared by the two microdissected components in 30 %, whereas in 35 %, some mutations were component-specific. Mutation analysis confirms similarities between the EEC and SC components of mixed EEC-SC with pure EEC and pure SC, respectively. However, PTEN and KRAS mutations were more frequent in the SC component of mixed EEC-SC than in pure SC, while TP53 mutations were more frequent in the EEC component of mixed EEC-SC than in pure EEC. Presence of different clonal mutation pattern between EEC and SC components of mixed EEC-SC raises the possibility of divergent tumor heterogeneity or biclonal origin in some cases.

Methods Fifty-one women suspected for recurrent ovarian cancer underwent 3-Tesla WB-DWI/MRI using 2 b-values (b=0-1000 s/mm2), T2and contrast T1-weighted sequences in addition to CT. WB-DWI/MRI and CT were compared for per-patient detection of recurrence, per-site detection of disease extent including peritoneal, serosal, retroperitoneal, periportal and distant metastases and for detecting disease extent according to institutional operability criteria. Imaging findings were correlated with surgical/pathological findings or imaging follow-up for at least 6 months.

Monochorionic (MC) twin pregnancies are at increased risk of adverse outcome because of the vascular anastomoses that connect the two fetal circulations. MC monoamniotic (MA) twins are at an even higher risk because of their almost universal cord entanglement and possible compression, which can cause an acute transfusion imbalance between the twins. Chorionicity and amnionicity should be determined during the first‐trimester ultrasound examination to identify high‐risk MC and MA twin pregnancies for which a fortnightly follow‐up may improve outcome. Although this can be achieved readily by assessing and counting the membranes that separate the twins, some pitfalls may occur. We present our observations of two monozygotic twin pairs with an intermediate type of monodichorionic and monodiamniotic twin pregnancy. The first was recognized during the first‐trimester scan and the second during the second‐trimester scan. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Background: Invasive lobular breast cancer (ILC) is generally believed to have an increased risk for late relapse compared to invasive ductal breast cancer (IDC). However, the study most often referred to is a chemotherapy trial that mainly included node positive patients. We hypothesize that nodal status may influence the hazard of relapse since time of diagnosis differently in invasive ductal carcinoma (IDC) and ILC.Methods: Primary operable breast cancer patients from our institution diagnosed between 2000 and 2009 were studied. Multivariable analysis and subgroup analyses were performed to assess whether ILC carries a different prognosis compared to IDC. SEER data were used for external validation.Results: In lymph node negative patients, ILC carries a better prognosis regarding distant metastasis free interval (DMFI) (HR 3.242 (1.380-7.614), p = 0.0069) with a trend towards improved breast cancer specific survival (BCSS), over the entire study frame (UZ Leuven data). In lymph node positive patients, both DMFI (HR 0.466 (0.309-0.703), p = 0.0003) and BCSS (HR 0.441 (0.247-0.788), p = 0.0057) are significantly worse for ILC, especially after longer follow-up (>4-5 years) (UZ Leuven data). Similar results were found in the SEER cohort. Results remained identical when excluding screen detected cases (data not shown).Conclusion: The prognostic impact of lobular histology not only depends on time since diagnosis but also on nodal status. The general believe that ILC have compromised late-term outcome compared to IDC seems untrue for the majority (= node negative) of ILCs. (C) 2014 Elsevier Ltd. All rights reserved.

AIMTreatment options are limited in uterine cancer, leading to a poor prognosis. Overexpression of Wilms' tumor gene 1 (WT1), the highest ranked tumor antigen, is attractive for immunotherapy.PATIENTS AND METHODSSix pre-treated patients with uterine cancer received four weekly vaccines of autologous dendritic cells (DCs) electroporated with WT1 mRNA. Safety, feasibility and immunogenicity were assessed. In cases of response, patients received monthly booster vaccines.RESULTSThe technique was feasible. One patient had a local allergic reaction. Three out of four Human Leucocyte Antigen-A2 (HLA-A2)-positive patients showed an oncological response; an enrichment of WT1-specific T-cells was observed in two of them. Two HLA-A2-negative patients did not show an oncological or an immunological response.CONCLUSIONA first series of six patients with uterine cancer treated with WT1 mRNA-electroporated DCs is presented herein. Oncological and immunological responses were observed and are supportive for further research.