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Background: \ud \ud Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma.\ud \ud Methods: \ud \ud In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries. Eligible patients were aged 18 years or older, had a platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma, had received at least two previous platinum-based chemotherapy regimens, had achieved complete or partial response to their last platinum-based regimen, had a cancer antigen 125 concentration of less than the upper limit of normal, had a performance status of 0–1, and had adequate organ function. Patients were ineligible if they had symptomatic or untreated central nervous system metastases, had received anticancer therapy 14 days or fewer before starting the study, or had received previous treatment with a poly(ADP-ribose) polymerase inhibitor. We randomly allocated patients 2:1 to receive oral rucaparib 600 mg twice daily or placebo in 28 day cycles using a computer-generated sequence (block size of six, stratified by homologous recombination repair gene mutation status, progression-free interval after the penultimate platinum-based regimen, and best response to the most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary outcome was investigator-assessed progression-free survival evaluated with use of an ordered step-down procedure for three nested cohorts: patients with BRCA mutations (carcinoma associated with deleterious germline or somatic BRCA mutations), patients with homologous recombination deficiencies (BRCA mutant or BRCA wild-type and high loss of heterozygosity), and the intention-to-treat population, assessed at screening and every 12 weeks thereafter. This trial is registered with ClinicalTrials.gov, number NCT01968213; enrolment is complete.\ud Findings: \ud \ud Between April 7, 2014, and July 19, 2016, we randomly allocated 564 patients: 375 (66%) to rucaparib and 189 (34%) to placebo. Median progression-free survival in patients with a BRCA-mutant carcinoma was 16·6 months (95% CI 13·4–22·9; 130 [35%] patients) in the rucaparib group versus 5·4 months (3·4–6·7; 66 [35%] patients) in the placebo group (hazard ratio 0·23 [95% CI 0·16–0·34]; p

Background Identification of families at risk for ovarian cancer offers the opportunity to consider prophylactic surgery thus reducing ovarian cancer mortality. So far, identification of potentially affected families in Germany was solely performed via family history and numbers of affected family members with breast or ovarian cancer. However, neither the prevalence of deleterious variants in \(BRCA1/2\) in ovarian cancer in Germany nor the reliability of family history as trigger for genetic counselling has ever been evaluated. Methods Prospective counseling and germline testing of consecutive patients with primary diagnosis or with platinum-sensitive relapse of an invasive epithelial ovarian cancer. Testing included 25 candidate and established risk genes. Among these 25 genes, 16 genes (\(ATM\), \(BRCA1\), \(BRCA2\), \(CDH1\), \(CHEK2\), \(MLH1\), \(MSH2\), \(MSH6\), \(NBN\), \(PMS2\), \(PTEN\), \(PALB2\), \(RAD51C\), \(RAD51D\), \(STK11\), \(TP53\)) were defined as established cancer risk genes. A positive family history was defined as at least one relative with breast cancer or ovarian cancer or breast cancer in personal history. Results In total, we analyzed 523 patients: 281 patients with primary diagnosis of ovarian cancer and 242 patients with relapsed disease. Median age at primary diagnosis was 58 years (range 16–93) and 406 patients (77.6%) had a high-grade serous ovarian cancer. In total, 27.9% of the patients showed at least one deleterious variant in all 25 investigated genes and 26.4% in the defined 16 risk genes. Deleterious variants were most prevalent in the \(BRCA1\) (15.5%), \(BRCA2\) (5.5%), \(RAD51C\) (2.5%) and \(PALB2\) (1.1%) genes. The prevalence of deleterious variants did not differ significantly between patients at primary diagnosis and relapse. The prevalence of deleterious variants in \(BRCA1/2\) (and in all 16 risk genes) in patients

Borderline tumors (BOT) of the ovary account for 10% to 20% of ovarian neoplasms. Like ovarian cancer, BOT encompass several different histological subtypes (serous, mucinous, endometrioid, clear cell, transitional cell and mixed) with serous (SBOT) and mucinous (MBOT) the most common. Current hypotheses suggest low-grade serous carcinoma may develop in a stepwise fashion from SBOT whereas the majority of high grade serous carcinomas develop rapidly presumably from inclusion cysts or ovarian surface epithelium. The pathogenesis of mucinous ovarian tumors is still puzzling. Molecular markers could help to better define relationships between such entities. Trefoil factor-3 (TFF3) is an estrogen-regulated gene associated with prognosis in different types of cancer. It has also been included in a recent marker panel predicting subtypes of ovarian carcinoma. We analyzed the expression of TFF3 by immunohistochemistry in a cohort of 137 BOT and its association with histopathological features. Overall expression rate of TFF3 was 21.9%. None of the BOT with serous and endometrioid histology displayed strong TFF3 expression. On the other hand, TFF3 was highly expressed in 61.4% of MBOT cases and 33.3% of BOT with mixed histology (P

Einleitung: Kolorektale Anastomosen im Rahmen gynäkologischer Debulking-Operationen stellen in Gegenwart ausgeprägter Peritonealkarzinosen eine Herausforderung an den Chirurgen dar. Die Datenlage bezüglich der Komplikationen nach Kolonanastomosen bei Peritonealkarzinose gynäkologischen[zum vollständigen Text gelangen Sie über die oben angegebene URL], 133. Kongress der Deutschen Gesellschaft für Chirurgie

e17549Background: The PARP inhibitor olaparib is approved in the EU for maintenance therapy of BRCA-mutated (BRCAm+) platinum-sensitive relapsed ovarian cancer patients, who are in response to thei...

e17537Background: High-grade serous ovarian cancer (HGSOC) (70%) has poor prognosis. Drivers of HGSOC are p53 mutations, homologous recombination deficiencies and CCNE1-amplification. Olaparib chan...

5538Background: Identification of families at risk for OC including recommendation for prophylactic surgery is the only effective method to reduce OC mortality. In addition, BRCA1/2 mutations are k...

5546 Background: BRCA associated cancers show a distinct pattern of genomic gains and losses that is associated with impaired repair of DNA double-strand breaks via homologous recombination (HR). We investigated whether BRCA1- and BRCA2-like classifiers could predict BRCA1 and BRCA2 mutation status in ovarian cancer. In addition, we explored whether promoter hypermethylation or mutations in other genes involved in DNA repair associate with a BRCA-like profile in ovarian cancer. Methods: The AGO-TR1 cohort study (NCT02222883 ) enrolled 525 consecutive patients with primary (PR) and platinum sensitive relapsed (RE) ovarian cancer to perform paired mutational analysis of germline and tumor tissue. We performed mutation panel sequencing, BRCA1 promoter hypermethylation and low-coverage whole genome sequencing to classify samples as BRCA1-like or BRCA2-like in 298 ovarian cancer samples (PR: n = 159, RE: n = 139). Results: A BRCA-like profile was observed in 58.1% of the samples without germline or somatic mutation in BRCA1/2 (n = 179; BRCA1-like: n = 26, BRCA2-like: n = 23, BRCA1- and 2-like: n = 55). There was no significant difference between PR- and RE-cases (54.5% vs 61.3%). 64 of 70 BRCA1 germline mutation carriers could be identified by the BRCA1-like classifier (sensitivity: 0.91). The BRCA2-like classifier identified BRCA2 germline mutation carrier with a sensitivity of 0.71 (17 of 24). The complementary use of both classifiers led to the detection of 22 of 25 somatic mutations in BRCA1 (16/16) or - 2 (6/9). Remarkably, 12 of 13 tumor samples from germline RAD51C mutation carriers were recognized by the BRCA1-like classifier (sensitivity: 0.92). No correlation of PALB2 mutation status (n = 7) with BRCA-like profile was observed. Of 28 tumor samples with a BRCA1 promoter hypermethylation 26 had a BRCA1-like profile (sensitivity: 0.93). Conclusions: A high number of ovarian cancer cases display a BRCA-like profile. Mutations (germline and somatic) in BRCA1, BRCA2, RAD51C as well as BRCA1 hypermethylation strongly associate with a BRCA-like profile and can explain 146 of 212 cases. Future studies will investigate whether the classifiers identify patients who benefit from HR-deficiency directed approaches beyond the BRCA mutation status. Clinical trial information: NCT02222883.

Background: Malignant transformation of thyroid tissue in struma ovarii and metastasis are uncommon. Benign thyroid tissue may spread to the peritoneal cavity in rare cases, and pathologic examination of the peritoneal implants shows multiple nodules of varying sizes of mature thyroid tissue similar to struma ovarii. This condition is termed “peritoneal strumosis”. It is very rare and therefore, both the criteria for diagnosis and its management are under discussion. The recommended treatment of metastatic struma ovarii should contain, in addition to local resection of the extraovarian tumor, total thyroidectomy in conjunction with radioiodine scanning and radioiodine ablation. Case report: A 38 year-old woman had presented with benign struma ovarii 12 years previously. She was referred to our department because of a right ovarian tumor. After confirming the diagnoses of metastatic recurrent benign struma ovarii, we performed debulking surgery with the aim of resecting all tumor masses. The uterus, left adnexa, and pelvic peritoneum were surgically extracted “en bloc”. No macroscopic tumor was left post-operatively. The first post operative 123 I scintography with15 MBq iodine-123 one month post-operatively showed a small but suspicious focus in the front left perivesical pelvic area. In the ventral visual presentation multiple discrete foci, located in right perivesical, supravesical and in the ventral upper abdomen, were seen. We then referred the patient for thyroidectomy and radioiodine ablation. The following periodic follow-ups of the patient did not show any signs of recurrence or progression of the disease. Conclusion: Patient with benign metastatic struma ovarii (also known as Highly differentiated follicular carcinoma of ovarian origin - HDFCO) may affectively be treated with local resection of the extraovarian tumor and subsequent thyroidectomy followed by radioactive iodine ablation.

Mammacarcinom ist in erster Linie eine Erkrankung der älteren Frauen und das Erkrankungsrisiko steigt mit dem Alter. In einer alternden Bevölkerung ist Brustkrebs ein wichtiges öffentliches Gesundheitsproblem. Ältere Frauen sind, wie die meisten Studien zum Brustkrebs-Screenings und der -therapie zeigten, in den Screeningprogramm unterrepräsentiert oder haben das Screening-Angebot nicht konsequent genutzt. Aufgrund dessen wird das Mammacarcinom älterer Frauen oft zu spät diagnostiziert. Um die Ursachen für die Zurückhaltung in der älteren Bevölkerung gegenüber des Screenings zu identifizieren, prüften wir mittels eines standardisierten Fragebogens die Kenntnisse zu epidemiologischen Basisdaten des Brustkrebes und die Einstellung zum Brustkrebs-Screening sowie allgemeine gesundheitsrelevante Verhaltensweisen von 200 Frauen in Deutschland und in Ägypten. Anschließend wurden die verschiedenen Altersgruppen miteinander verglichen. Die Ergebnisse dieser Untersuchung zeigten Unterschiede zwischen beiden Altersgruppen in beiden Ländern in Bezug auf das Wissen über Brustkrebs und das Brustkrebs-Screening. Alte Frauen in Ägypten und Deutschland schätzen das Risiko im Alter an Brustkrebs zu erkranken und die Bedeutung der Behandlung falsch ein und glaubten weniger an eine bessere Lebensqualität nach der Behandlung. In Deutschland besuchte die Mehrheit der Frauen ihren Gynäkologen jährlich, aber die Teilnahme am Brustkrebs-Screening-Programm sank mit dem steigenden Alter. Frauen in Ägypten unterziehen sich einem Brustkrebs-Screening nur auf eigene Initiative hin. 12% der jungen Frauen hatten mindestens eine Mammographie aber keine in der älteren Gruppe. Nach einer informativen Konfrontation mit den epidemiologischen Daten wollten lediglich 30% der ägyptischen Frauen ihre Haltung hinsichtlich der Teilnahme am Screening ändern. Hingegen zeigte die Gruppe der älteren Frauen in Deutschland deutlich mehr Bereitschaft am Screening teilzunehmen. Schlussfolgerung: Die älteren Frauen müssen stärker im Fokus der Bemühungen stehen. Sie müssen besser informiert und ermutigt werden, am Screening-Programm für Brustkrebs teilzunehmen.