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      Major clinical research advances in gynecologic cancer in 2011

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          Abstract

          The annual review of 2011 comprised 11 themes of major research achievements in gynecologic oncology including breast cancer. A potential paradigm shift in the management of ovarian cancer was reviewed through comprehensive genomic analyses and a tumor-specific new intraoperative fluorescence imaging technique using folate receptor-α targeted agent, which is expected to improve intraoperative staging and more radical cytoreduction. In addition, updates of bevacizumab and poly (ADP-ribose) polymerase inhibitors, risk-reducing salpingo-oophorectomy, and risk evaluation of pelvic mass were discussed. Regarding cervical cancer, this review covered new findings on human papillomavirus vaccines and human papillomavirus tests as well as the current status of clinical trials on locally advanced cervical cancer. The promising role of sentinel lymph node biopsy in the management of early stage endometrial cancer was followed by two notable clinical researches on: exemestane, an aromatase inhibitor, for the prevention of breast cancer and eribulin, a non-taxane microtubule dynamics inhibitor for the treatment of metastatic breast cancer. Lastly, in premenopausal women with breast cancer, the effect of gonadotropin-releasing hormone analogue on the occurrence of chemotherapy-induced early menopause was discussed.

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          Most cited references118

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          Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial.

          Olaparib is a novel, orally active poly(ADP-ribose) polymerase (PARP) inhibitor that induces synthetic lethality in homozygous BRCA-deficient cells. We aimed to assess the efficacy and safety of olaparib for treatment of advanced ovarian cancer in patients with BRCA1 or BRCA2 mutations. In this international, multicentre, phase 2 study, we enrolled two sequential cohorts of women (aged >or=18 years) with confirmed genetic BRCA1 or BRCA2 mutations, and recurrent, measurable disease. The study was undertaken in 12 centres in Australia, Germany, Spain, Sweden, and the USA. The first cohort (n=33) was given continuous oral olaparib at the maximum tolerated dose of 400 mg twice daily, and the second cohort (n=24) was given continuous oral olaparib at 100 mg twice daily. The primary efficacy endpoint was objective response rate (ORR). This study is registered with ClinicalTrials.gov, number NCT00494442. Patients had been given a median of three (range 1-16) previous chemotherapy regimens. ORR was 11 (33%) of 33 patients (95% CI 20-51) in the cohort assigned to olaparib 400 mg twice daily, and three (13%) of 24 (4-31) in the cohort assigned to 100 mg twice daily. In patients given olaparib 400 mg twice daily, the most frequent causally related adverse events were nausea (grade 1 or 2, 14 [42%]; grade 3 or 4, two [6%]), fatigue (grade 1 or 2, ten [30%]; grade 3 or 4, one [3%]), and anaemia (grade 1 or two, five [15%]; grade 3 or 4, one [3%]). The most frequent causally related adverse events in the cohort given 100 mg twice daily were nausea (grade 1 or 2, seven [29%]; grade 3 or 4, two [8%]) and fatigue (grade 1 or 2, nine [38%]; none grade 3 or 4). Findings from this phase 2 study provide positive proof of concept of the efficacy and tolerability of genetically targeted treatment with olaparib in BRCA-mutated advanced ovarian cancer. AstraZeneca. Copyright 2010 Elsevier Ltd. All rights reserved.
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            Novel anticancer targets: revisiting ERBB2 and discovering ERBB3.

            Aberrant receptor expression or functioning of the epidermal growth factor receptor (Erbb) family plays a crucial part in the development and evolution of cancer. Inhibiting the signalling activity of individual receptors in this family has advanced the treatment of a range of human cancers. In this Review we re-evaluate the role of two important family members, ERBB2 (also known as HER2) and ERBB3 (also known as HER3), and explore the mechanisms of action and preclinical and clinical data for new therapies that target signalling through these pivotal receptors. These new therapies include tyrosine kinase inhibitors, antibody-chemotherapy conjugates, heat-shock protein inhibitors and antibodies that interfere with the formation of ERBB2-ERBB3 dimers.
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              Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study

              (2009)
              Summary Background Hysterectomy and bilateral salpingo-oophorectomy (BSO) is the standard surgery for stage I endometrial cancer. Systematic pelvic lymphadenectomy has been used to establish whether there is extra-uterine disease and as a therapeutic procedure; however, randomised trials need to be done to assess therapeutic efficacy. The ASTEC surgical trial investigated whether pelvic lymphadenectomy could improve survival of women with endometrial cancer. Methods From 85 centres in four countries, 1408 women with histologically proven endometrial carcinoma thought preoperatively to be confined to the corpus were randomly allocated by a minimisation method to standard surgery (hysterectomy and BSO, peritoneal washings, and palpation of para-aortic nodes; n=704) or standard surgery plus lymphadenectomy (n=704). The primary outcome measure was overall survival. To control for postsurgical treatment, women with early-stage disease at intermediate or high risk of recurrence were randomised (independent of lymph-node status) into the ASTEC radiotherapy trial. Analysis was by intention to treat. This study is registered, number ISRCTN 16571884. Findings After a median follow-up of 37 months (IQR 24–58), 191 women (88 standard surgery group, 103 lymphadenectomy group) had died, with a hazard ratio (HR) of 1·16 (95% CI 0·87–1·54; p=0·31) in favour of standard surgery and an absolute difference in 5-year overall survival of 1% (95% CI −4 to 6). 251 women died or had recurrent disease (107 standard surgery group, 144 lymphadenectomy group), with an HR of 1·35 (1·06–1·73; p=0·017) in favour of standard surgery and an absolute difference in 5-year recurrence-free survival of 6% (1–12). With adjustment for baseline characteristics and pathology details, the HR for overall survival was 1·04 (0·74–1·45; p=0·83) and for recurrence-free survival was 1·25 (0·93–1·66; p=0·14). Interpretation Our results show no evidence of benefit in terms of overall or recurrence-free survival for pelvic lymphadenectomy in women with early endometrial cancer. Pelvic lymphadenectomy cannot be recommended as routine procedure for therapeutic purposes outside of clinical trials. Funding Medical Research Council and National Cancer Research Network.
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                Author and article information

                Journal
                J Gynecol Oncol
                JGO
                Journal of Gynecologic Oncology
                Korean Society of Gynecologic Oncology and Colposcopy
                2005-0380
                2005-0399
                January 2012
                09 January 2012
                : 23
                : 1
                : 53-64
                Affiliations
                [1 ]Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.
                [2 ]Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, Korea.
                Author notes
                Correspondence to Jae Weon Kim. Department of Obstetrics and Gynecology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea. Tel: 82-2-2072-3511, Fax: 82-2-762-3599, kjwksh@ 123456snu.ac.kr
                Article
                10.3802/jgo.2012.23.1.53
                3280068
                22355468
                0a62b251-6b7e-4c9f-a6f6-7abac7f07f32
                Copyright © 2012. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 19 December 2011
                : 22 December 2011
                Categories
                Review Article

                Oncology & Radiotherapy
                gynecologic oncology,poly (adp-ribose) polymerase inhibitors,breast cancer,human papillomavirus vaccines,comprehensive genomic analyses

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