Endometrial Cancer

Results from Oncolytics Biotech's phase I trial of Reolysin, its oncolytic reovirus, show stable disease in 7 of 32 patients with advanced or metastatic solid tumors refractory to standard therapy or for which no curative standard therapy exists. Dr. Timothy Yap of The Institute of Cancer Research, Sutton, UK, presented the study at the 18th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics

Hospitalized oncology patients are at particular risk for acute venous thromboembolism (VTE); however, more often than not, a standard for VTE prophylaxis does not exist, according to Jerelyn Osoria, RN, OCN, of Memorial Sloan-Kettering Cancer Center. Ms. Osoria reported at the Oncology Nursing Society 31st Annual Congress (abstract 113) that an electronic medical orders system and better nursing documentation have helped improve this situation at her institution's Gynecology (GYN) oncology inpatient nursing unit.

The review of the histology slides revealed predominantly decidual tissue with exaggerated placental site and a small focus of trophoblastic tissue composed of cytotrophoblast and syncytiotrophoblast with mild atypia (Figure 1). However, no necrosis or tissue invasion was identified. No villi were seen.

Endometrial cancer is the mostcommon gynecologic malignancyaffecting women in theUnited States. In 1988, the InternationalFederation of Gynecology andObstetrics shifted from a clinical stagingprotocol to one based on surgicalfactors, making surgical staging theaccepted treatment approach to endometrialcancers, with excellentsurvival compared to other gynecologicmalignancies. The manuscript byKirby et al brings to light the controversiessurrounding the surgical evaluationof endometrial cancers. Althoughsurgical staging has been shown to haveboth prognostic and therapeutic benefit,major problems in the United Statescontinue to result in suboptimal treatmentof patients with endometrial cancer.These problems include the lack ofan accepted surgical protocol (in termsof adequacy of lymph node sampling)and incomplete surgical staging secondaryto patient factors or the lack ofreferral to specialty-trained gynecologiconcologists.

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomaldominant cancer susceptibility syndrome associated with inheriteddefects in the DNA mismatch repair system. HNPCC family membersare at high risk for developing colorectal, endometrial, and ovariancancers. Studies of HNPCC families have helped define the importantrole that mismatch repair genes play in the molecular pathogenesis ofendometrial and ovarian cancers. This review will describe some of theimportant clinical and molecular features of HNPCC-related endometrialand ovarian cancer and describe how genetic susceptibility can beidentified in patients with sporadic endometrial and ovarian cancers. Itis important to identify patients with HNPCC, as families of mutationcarriers may benefit from genetic counseling, testing, and intensifiedcancer surveillance.

Kirby et al are correct in theirstatement that continued controversysurrounds the comprehensivesurgical staging of all patientswith clinical stage I endometrialadenocarcinoma. Such is the case becauselymph node metastasis is foundin only 10% of these patients. Theproportion of patients found to havelymph node metastasis is even loweramong those with grade 1 and 2 tumorswith minimal or no invasion. Ahigh proportion of patients with endometrialadenocarcinoma fall intothis group.

Early presentation of endometrial cancer permits effective managementwith excellent clinical outcome. The addition of hysteroscopy todilatation and curettage (D&C) in the evaluation of postmenopausalbleeding adds little to the detection of malignancy. Imaging studies suchas computed tomography, magnetic resonance imaging, and positronemissiontomography may be of use in determining the presence ofextrauterine disease in patients medically unfit for surgical staging.However, these studies are not sufficiently sensitive to replace surgicalstaging and have little role in routine preoperative evaluation. Clinicalstaging alone is clearly inadequate, as 23% of preoperative clinicalstage I/II patients are upstaged with comprehensive surgical staging.Preoperative tumor grade from D&C or office biopsy may be inaccurateand lead to an underestimate of tumor progression if used to determinewhich patients should be surgically staged. Clinical estimationof depth of invasion, with or without frozen section, is inaccurate andmay lead to underestimation of disease status when surgical staging isnot performed. The practice of resecting only clinically suspicious nodesshould be discouraged as it is no substitute for comprehensive surgicalstaging. Comprehensive surgical staging provides proper guidance forpostoperative adjuvant therapy, avoiding needless radiation in 85% ofclinical stage I/II patients. Finally, resection of occult metastasis withsurgical staging may improve survival.

Granulocyte-macrophage colony-stimulating factor (GM-CSF,sargramostim [Leukine]) is a powerful cytokine that is able to stimulatethe generation of dendritic cells. Adjuvant treatment with continuous lowdoseGM-CSF has been shown to prolong survival of stage III/IV melanomapatients. Data on continuous low-dose GM-CSF therapy in tumorsother than prostate cancer are still lacking.

The Lynch syndrome (hereditary nonpolyposis colorectal cancer[HNPCC]), is the most common form of hereditary colorectal cancer(CRC), accounting for 2% to 7% of all CRC cases. The next most commonhereditary CRC syndrome is familial adenomatous polyposis (FAP),which accounts for less than 1% of all CRC. Lynch syndrome is ofcrucial clinical importance due to the fact that it predicts the lifetimerisk for CRC and a litany of extra-CRC cancers (of the endometrium,ovary, stomach, small bowel, hepatobiliary tract, upper uroepithelialtract, and brain) through assessment of a well-orchestrated family history.A Lynch syndrome diagnosis is almost certain when a mutation ina mismatch repair gene-most commonly MSH2, MLH1, or, to a lesserdegree, MSH6-is identified. Once diagnosed, the potential for significantreduction in cancer-related morbidity and mortality through highlytargeted surveillance may be profound. Particularly important iscolonoscopy initiated at an early age (ie, 25 years) and repeated annuallydue to accelerated carcinogenesis. In women, endometrial aspirationbiopsy and transvaginal ultrasound are important given the extraordinarilyhigh risk for endometrial and ovarian carcinoma. Thesecancer control strategies have a major impact on at-risk family membersonce they have been counseled and educated thoroughly aboutLynch syndrome’s natural history and their own hereditary cancer risk.

BETHESDA, Maryland-Convincing evidence indicates that physical activity can significantly reduce the risk of colon and breast cancer, according to a newly released National Cancer Institute (NCI) fact sheet. Moreover, studies also suggest a link between exercise and a reduced risk of cancers of the prostate, lung, and endometrium. However, despite the documented cancer and other health benefits of exercise, "recent studies have shown that more than 60% of Americans do not engage in enough regular physical activity," NCI said. The new publication summarizes the evidence supporting the role of exercise in cancer risk reduction and the possible underlying biological mechanisms

SAN DIEGO-In a cohort of endometrial cancer patients at M.D. Anderson Cancer Center, those who had previously developed breast cancer and used tamoxifen did not have a higher incidence of high-risk histologic subtypes, compared with breast cancer patients not receiving tamoxifen, reported Brian M. Slomovitz, MD, at the Society of Gynecologic Oncologists 35th Annual Meeting (SGO abstract 24).

Four randomized prospective trials have evaluated tamoxifen forchemoprevention of breast cancer. The National Surgical AdjuvantBreast and Bowel Project P-1 trial reported that tamoxifen reduced therisk of invasive breast cancer by 49%. Two smaller European trials, theRoyal Marsden Hospital Chemoprevention Trial and the Italian TamoxifenPrevention Study, demonstrated no decrease in the incidence ofbreast cancer among women using tamoxifen. The International BreastCancer Intervention Study confirmed that tamoxifen can reduce therisk of breast cancer in healthy women. The Multiple Outcomes ofRaloxifene Evaluation trial, which evaluated the use of raloxifene(Evista) to prevent osteoporosis, found that the risk of invasive breastcancer decreased by 76%. A uniform theme in these trials is thattamoxifen reduces the risk of breast cancer among women at high riskfor the disease. Tamoxifen is currently approved for breast cancer riskreduction. However, because of the side effects associated with its use(ie, endometrial cancer and thromboembolism), other agents are beinginvestigated. The Study of Tamoxifen and Raloxifene is designed tocompare the efficacy of tamoxifen and raloxifene in reducing breastcancer risk. Aromatase inhibitors will also be studied in the setting ofchemoprevention for breast cancer.

Published literature indicates that the selective estrogen-receptormodulators (SERMs) tamoxifen and raloxifene (Evista) have favorableeffects on bone density, lipid profiles, and the incidence of secondbreast cancers, and unfavorable effects on the incidence of venousthrombosis and hot flushes. Tamoxifen increases the risk of endometrialcancer, but raloxifene does not. The effects of SERMs on sexualfunction and cognition are unclear. Because the selective antiaromataseagents are relatively new, the long-term effects of these agentson normal tissues are less well established. It appears that the nonsteroidalagents (anastrozole [Arimidex], letrozole [Femara]) and steroidal(exemestane [Aromasin]) antiaromatase agents may have differenteffects on normal tissues. Preliminary data demonstrate that anastrozoleincreases the risk of arthralgias and produces a decrease in bonedensity. In contrast, exemestane appears to favorably affect bonedensity and lipid profile, similar to tamoxifen and raloxifene. Theincidence of contralateral breast cancer is decreased in women onadjuvant anastrozole, but data for the other antiaromatase agents arenot yet available. Hot flushes have been reported with the use ofselective aromatase inhibitors, but their incidence seems to be comparableto what is reported with SERMs. Antiaromatase agents do notappear to cause venous thrombosis. More information about the effectsof the antiaromatase agents on normal tissue will become available asdata from ongoing adjuvant and chemoprevention trials are reported.Clinically, we should be conscious of the differences between antiaromataseagents and SERMs and their impact on women’s health.

In their excellent summary of randomized trials examining the management of cancers of the uterus and ovary, Kim and coauthors highlight a significant and worrisome difference that has developed between the two gynecologic malignancies over the past decade, with regard to the direction of clinical research involving chemotherapy. Although it is recognized that cytotoxic chemotherapy is employed in the majority of women with ovarian cancer at initial diagnosis, whereas such treatment is fortunately only required in a minority of individuals with endometrial cancer, it is unclear why there has been such a major divergence in the drugs and combination regimens currently being evaluated in clinical trials.

Over the past few decades, we have gained a better understanding of the risk factors associated with the recurrence of endometrial cancer. Adjuvant postoperative radiotherapy in an intermediate-risk group of

Flavopiridol [2-(2-chlorophenyl 5 ,7-dihydroxy-8-[cis-(3-hydroxy-1-methyl-4-piperidinyl)-4H-1-benzopyran-4-one, hydrochloride] is a semisynthetic flavone with a novel structure compared with that of polyhydroxylated flavones, such as quercetin and genistein.[1] It is derived from rohitukine, an alkaloid isolated from the stem bark of Dysoxylum binectariferum, a plant indigenous to India.[2] Originally synthesized and supplied by Hoechst India Limited, flavopiridol is provided to the Division of Cancer Treatment and Diagnosis of the National Cancer Institute (NCI) by Aventis Pharmaceuticals, Inc.

Handbook of Gynecologic Oncology, edited by Drs. Barakat, Bevers, Gershenson, and Hoskins, is a first-edition clinical handbook formulated primarily for fellows in gynecologic oncology as well as for interested fellows in medical oncology and radiation oncology. The textbook presents concise summaries of the critical issues in the care of gynecologic cancer patients and would also be of interest to residents preparing for their gynecologic oncology rotations, obstetrician/gynecologists, other physicians who care for gynecologic cancer patients, and practicing gynecologic oncologists.

CHICAGO-Adding paclitaxel (Taxol) and G-CSF support to the standard regimen of doxorubicin and cisplatin (Platinol) improved response rates and increased survival by about 3 months for patients with advanced or recurrent endometrial cancer in a randomized controlled phase III trial conducted by the Gynecologic Oncology Group (GOG) (ASCO abstract 807).

Dr. Grigsby has done a masterful job of summarizing current information on the use of radiation in the management of patients with endometrial carcinoma. In the summary, he offers clear recommendations as to the appropriate management of various subsets of patients-recommendations that are based, at least to some extent, on the data reviewed. Such decision-making based on often incomplete information is necessary in the absence of appropriately designed randomized trials addressing the specific clinical situation. It is important, however, to understand clearly what we actually know and what we deduce from bits and pieces of data.

Dr. Grigsby does an excellent job of summarizing the accepted, stage-by-stage treatment recommendations as well as the controversies surrounding the treatment of endometrial carcinoma. This review is both important and timely, as we have seen the incidence of endometrial cancer increase over the past few years to the point where it is now the most common gynecologic malignancy.

The best clinical outcomes for patients with endometrial cancer seem to be achieved with either surgery alone or a combination of surgery and radiation therapy. Although once administered preoperatively, irradiation is now

The aging of the population is a social phenomenon that will present a challenge to clinical practice in the 21st century. Women constitute a majority of the elderly population as they outlive males by 5 to 7 years. Ovarian,

NEW ORLEANS-Adjuvant tam-oxifen (Nolvadex) is as effective among black women as among white women in reducing the incidence of contralateral breast cancer, according to a retrospective analysis of nine trials from the National Surgical Adjuvant Breast and Bowel Project (NSABP) (B-13 through B-20 and B-22). In addition, increases in endometrial cancer with tamoxifen use are similar for both races.

SAN DIEGO-Preliminary data show that a new outcomes measurement tool developed by the Society of Gynecologic Oncologists (SGO) Outcomes Task Force is a reliable method for demonstrating quality of care to third parties. Lead author Alexander W. Kennedy, MD, of the Department of Gynecology and Obstetrics, Cleveland Clinic Foundation, reported on behalf of the task force at the SGO’s 31st Annual Meeting.

Each year close to 600,000 women undergo a hysterectomy in the United States.[1] Although the number of these

SAN DIEGO-Estrogen replacement therapy (ERT) does not increase the risk of recurrence in patients who have had endometrial cancer and should not be categorically ruled out in these women, according to research presented at the 31st Annual Meeting of the Society of Gynecologic Oncologists (SGO).

Research presented recently at the Society of Gynecologic Oncologists (SGO) annual meeting found that survival rates of African-American women with advanced-stage endometrial cancers are significantly worse than those of Caucasian women.

This clinically oriented text focuses on the diagnosis and management of endometrial adenocarcinoma and endometrial hyperplasia. Due to its clinical orientation, the book does not include information on the molecular basis of endometrial cancer.

Although endometrial cancer is the most common gynecologic malignancy diagnosed in US women, it has not received the same attention from health care professionals and the lay public as has its more lethal counterpart in the female gonad-epithelial ovarian cancer.

Endometrial carcinoma is the most common gynecologic malignancy in the United States. Most cases are diagnosed at an early stage. However, the outcome for women diagnosed with advanced-stage disease remains poor. The etiology of most endometrial carcinomas stems from the effects of excess estrogen, whether this comes from exogenous or endogenous sources. Differences in epidemiology and presentation suggest the existence of two forms of endometrial cancer: those related to and those unrelated to hormonal stimulation. Most women with endometrial cancer present with abnormal uterine bleeding; endometrial sampling is essential to exclude endometrial carcinoma in such patients. Endometrial cancer is surgically staged, and staging usually includes a hysterectomy and bilateral salpingo-oophorectomy. Lymphadenectomy also should be performed in selective cases to better assess disease spread and to evaluate the need for adjuvant therapy. Adjuvant treatment may include the use of radiation, progestins, or cytotoxic chemotherapeutic agents. Several clinical trials are underway to compare these treatment modalities, as well as to determine the optimal combination of active chemotherapeutic agents, such as doxorubicin, platinum agents, and paclitaxel (Taxol). [ONCOLOGY 13(12):1665-1675, 1999]