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Tung N.,Beth Israel Deaconess Medical Center | Tung N.,Harvard University | Wang Y.,Harvard University | Wang Y.,Beth Israel Deaconess Medical Center | And 22 more authors.
Breast Cancer Research | Year: 2010

Introduction: Most breast cancers that occur in women with germline BRCA1 mutations are estrogen receptor-negative (ER-) and also typically lack expression of progesterone receptor (PR) and HER2 overexpression. We undertook a study to assess the clinical factors that predict for an estrogen receptor positive (ER+) breast cancer in BRCA1 mutation carriers and to characterize the pathologic features of these tumors.Methods: Clinical characteristics of BRCA1 carriers with 58 ER+ and 114 ER- first invasive breast cancers were compared. Pathologic features of BRCA1 ER+ cancers were compared to those of BRCA1 ER- cancers and to age-matched ER+ sporadic cancers.Results: BRCA1 carriers aged ≥ 50 at diagnosis of first invasive breast cancer were more likely to have an ER+ cancer compared to those aged < 50 (57% vs 29%, P = 0.005). ER+ BRCA1 cancers were less likely than ER- BRCA1 cancers to have "BRCA-associated" features such as high mitotic activity, geographic necrosis/fibrotic focus, and pushing margins (RR 0.06, 0.22, 0.24; P < 0.001, 0.02, 0.03 respectively). When compared to sporadic ER+ cancers, ER+ BRCA1 cancers were more often of invasive ductal type (RR 2.4, P = 0.03), with a high mitotic rate (RR 5.0, P = 0.006) and absent or mild lymphocytic infiltrate (RR 10.2, P = 0.04).Conclusions: BRCA1 carriers who are older at first breast cancer diagnosis are more likely to have ER+ tumors than younger BRCA1 carriers. These ER+ cancers appear pathologically "intermediate" between ER- BRCA1 cancers and ER+ sporadic breast cancers raising the possibility that either some ER+ BRCA1 cancers are incidental or that there is a unique mechanism by which these cancers develop. © 2010 Tung et al.; licensee BioMed Central Ltd.

Dizon D.S.,Program in Womens Oncology
Gynecologic Oncology | Year: 2010

Objective: Endometrial carcinoma is the most common malignancy of the female reproductive tract. Most cases are diagnosed at an early stage due to the appearance of symptoms such as postmenopausal bleeding. However, endometrial carcinoma carries a poor prognosis when it recurs after previous definitive treatment or when diagnosed at an advanced stage. Here, treatment options for advanced endometrial carcinoma are evaluated. Methods: Literature review was performed to determine current therapy options, with a focus on the treatment landscape for women with recurrent, advanced, or metastatic disease. Results: Combination chemotherapy is being used more frequently as first-line treatment of advanced disease, consisting of cisplatin/doxorubicin/paclitaxel, if tolerated, or the doublet of carboplatin/paclitaxel. Options following disease progression after first-line treatment are extremely limited, particularly with the increasing use of active agents in the adjuvant setting. Fortunately, several new cytotoxic and biologic therapies appear promising for women who have progressed on first-line treatment. Conclusions: Clinical trials are planned to further explore how to best incorporate novel agents into the current treatment algorithm with the aim to improve the options in both first- and second-line treatments for women with endometrial adenocarcinomas. © 2010 Elsevier Inc. All rights reserved.

Finamore P.S.,Winthrop University | Hunter K.,Cooper University Hospital | Goldstein H.B.,Center for Urogynecology and Pelvic Surgery | Stuckey A.R.,Program in Womens Oncology | And 2 more authors.
Female Pelvic Medicine and Reconstructive Surgery | Year: 2010

Introduction: To determine the attributes and motivation of physicians who pursue fellowship training in the subspecialties of Obstetrics and Gynecology (Ob/Gyn). Methods: We surveyed current fellows and recent graduates from the ABOG recognized subspecialties in Ob/Gyn. Demographics and reasons for pursuing fellowship training were obtained. Significant differences between and among groups were determined using the Mann-Whitney U test and Pearson Χ2 test. Results: Forty-two percent of those sent a survey responded. The majority were between ages 30 to 35 (65.7%), female (60.5%), married (74.5%), and White (68.8%). Over 55% in each subspecialty cited interest in subject area as the primary reason for choosing their fellowship. Conclusion: Interest in subject remains the primary motivation for the majority of physicians choosing subspecialty fellowship training in Ob/ Gyn. There is considerably more variation regarding what physicians' secondary motivation is and these reasons appear to vary according to the particular subspecialty. Copyright © 2010 by Lippincott Williams & Wilkins.

Martin L.P.,Chase Medical | Sill M.,Roswell Park Cancer Institute | Shahin M.S.,Hanjani Institute for Gynecologic Oncology | Powell M.,University of Washington | And 6 more authors.
Gynecologic Oncology | Year: 2014

Objective This open-label, multi-institutional phase II trial evaluated activity and safety of rilotumumab (AMG 102), a monoclonal antibody that targets HGF (hepatocyte growth factor), the ligand for the MET receptor, in women with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancer. Patients and methods Women were eligible for treatment with rilotumumab if they had measurable disease, a performance status of 0, 1 or 2, previously received platinum-based therapy with a progression-free interval of < 12 months or a second recurrence, and adequate bone marrow and organ function. Patients received rilotumumab 20 mg/kg IV every 14 days until evidence of unacceptable toxicity or disease progression. The study utilized co-dual primary endpoints of tumor response and six-month PFS to assess the efficacy of rilotumumab. Secondary endpoints included the frequency and severity of adverse events and the duration of progression-free and overall survival. Results Thirty-one women enrolled and received rilotumumab. All were eligible for analysis. One patient achieved a complete response (3.2%; 90% CI 0.2-14%), and two women had 6-month PFS (6.5%; 90% CI 1.1-19%). Most adverse events were grade 1 or 2, with no grade 4 adverse events. Grade 3 adverse events were gastrointestinal (4), metabolic (3) anemia (3), a thromboembolic event (1), ventricular tachycardia (1), hypotension during infusion (1) and fatigue (1). The study was stopped after the first stage of accrual. Conclusion Rilotumumab was well-tolerated, but had limited activity. The level of activity does not warrant further evaluation of rilotumumab as a single agent in patients with ovarian cancer.

Kristjansdottir K.,Program in Womens Oncology | Kim K.,Program in Womens Oncology | Choi J.S.,Sungkyunkwan University | Horan T.C.,Program in Womens Oncology | And 3 more authors.
Gynecologic Oncology | Year: 2012

Objective: Chemotherapy options for advanced endometrial cancer are limited and newer therapeutic agents are urgently needed. This study describes the therapeutic potential of 7 Methyl-indole ethyl isothiocyanate (7Me-IEITC) in endometrial cancer cell lines. Methods: 7Me-IEITC was synthesized in our laboratory. The cell viability of 7Me-IEITC treated ECC-1 and KLE endometrial cancer cell was determined by MTS assay. Morphology and apoptosis were further confirmed by DAPI-staining and TUNEL assay. The measurement of reactive oxygen species (ROS), mitochondrial transmembrane depolarization potential (ΔΨm) and cell cycle phase was determined by FACS analysis. Expression of proteins involved in apoptosis, survival and cell-cycle progression was analyzed by Western blotting. Results: 7Me-IEITC reduced the viability of the ECC-1 and KLE cancer cell-lines (IC 50 ~ 2.5-10 μM) in a dose dependent fashion. 7Me-IEITC treatment caused mitochondrial transmembrane potential reduction, elevated the production of ROS, leading to activation of apoptosis in endometrial cancer KLE and ECC-1 cells. 7Me-IEITC treatment activated Bad, suppressed Bcl2 phosphorylation followed by PARP-1 deactivation and caspase 3 and 7 activation. 7Me-IEITC treatment arrested the progression of KLE cells in S-phase and caused CDC25 and cyclin-D1 downregulation. Pre-treatment with ascorbic acid abrogated 7Me-IEITC induced apoptosis in ECC-1 and KLE cells, suggesting that 7Me-IEITC mediated cytotoxicity is primarily through ROS production. Conclusion: 7Me-IEITC demonstrated promising cytotoxic effects in endometrial cancer cell line model. © 2012 Elsevier Inc. All rights reserved.

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