Breast Cancer Screening, Mammography, and Other Modalities.

This article is an overview of the modalities available for breast cancer screening. The modalities discussed include digital mammography, digital breast tomosynthesis, breast ultrasonography, magnetic resonance imaging, and clinical breast examination. There is a review of pertinent randomized controlled trials, studies and meta-analyses which contributed to the evolution of screening guidelines. Ultimately, 5 major medical organizations formulated the current screening guidelines in the United States. The lack of consensus in these guidelines represents an ongoing controversy about the optimal timing and method for breast cancer screening in women. For mammography screening, the Breast Imaging Reporting and Data System lexicon is explained which corresponds with recommended clinical management. The presentation and discussion of the data in this article are designed to help the clinician individualize breast cancer screening for each patient.

In vitro chemoresponse in metachronous pairs of ovarian cancers.

BACKGROUND/AIM: An in vitro chemoresponse assay may aid effective therapy selection in epithelial ovarian cancer (EOC). This study explores changes in chemoresponse between paired primary and recurrent EOC tumors. PATIENTS AND METHODS: RESULTS from metachronous tumors were examined in 242 patients. Changes in in vitro chemoresponse, measured by the area under the dose response curve (AUC) between paired tumors were assessed. RESULTS: A significant increase in AUC was identified in most first-line therapies over time. No significant difference was observed in most recurrent therapies. When the elapsed time between occurrences was <17 months, no difference was observed for any recurrent therapies, and half of first-line therapies exhibited significant increases in AUC. When ≥17 months, all 7 therapies showed significant increases. CONCLUSION: These results suggest an increase in chemoresistance over time, which is more pronounced for first-line therapies. This is consistent with clinical observations and suggests the biologic concordance between assay results and response to chemotherapy.

Phase II evaluation of dasatinib in the treatment of recurrent or persistent epithelial ovarian or primary peritoneal carcinoma: a Gynecologic Oncology Group study.

OBJECTIVES: Preclinical data suggest an important role for the sarcoma proto-oncogene tyrosine kinase (SRC) in the oncogenesis of epithelial ovarian cancer (EOC) or primary peritoneal carcinoma (PPC). The Gynecologic Oncology Group (GOG) conducted a Phase II trial to evaluate the efficacy and safety of dasatinib, an oral SRC-family inhibitor in EOC/PPC, and explored biomarkers for possible association with clinical outcome. METHODS: Eligible women had measurable, recurrent or persistent EOC/PPC and had received one or two prior regimens which must have contained a platinum and a taxane. Patients were treated with 100mg orally daily of dasatinib continuously until progression of disease or adverse effects prevented further treatment. Primary endpoints were progression-free survival (PFS)≥6months and response rate. Serial plasma samples were assayed for multiple biomarkers. Circulating free DNA was quantified as were circulating tumor and endothelial cells. RESULTS: Thirty-five (35) patients were enrolled in a two-stage sequential design. Of the 34 eligible and evaluable patients, 20.6% (90% confidence interval: 10.1%, 35.2%) had a PFS≥6months; there were no objective responses. Grade 3-4 toxicities were gastrointestinal (mostly nausea and emesis; n=4), pulmonary (dyspnea and/or pleural effusion; n=4) and pain (n=5), and infrequent instances of anemia, malaise, insomnia, rash, and central nervous system hemorrhage. Lack of clinical activity limited any correlation of biomarkers with outcome. CONCLUSION: Dasatinib has minimal activity as a single-agent in patients with recurrent EOC/PPC.

Phase II trial of trastuzumab in women with advanced or recurrent, HER2-positive endometrial carcinoma: a Gynecologic Oncology Group study.

PURPOSE: This study evaluated efficacy of single-agent trastuzumab against advanced or recurrent HER2-positive endometrial carcinoma (EC), and explored predictors for HER2 amplification. PATIENTS AND METHODS: Eligible patients had measurable stage III, IV, or recurrent EC. There was no limit on prior therapy although total prior doxorubicin dose was limited to 320 mg/m(2). Tumors were required to have HER2 overexpression (2+ or 3+ immunohistochemical staining) or HER2 amplification (FISH HER2/CEP 17 ratio >2.0). Trastuzumab was administered intravenously at a dose of 4 mg/kg in week 1, then 2 mg/kg weekly until disease progression. The primary endpoint was tumor response. RESULTS: Of the 286 tumors centrally screened by LabCorp, 33 (11.5%) were HER2-amplified. Three of 8 clear (38%) cell carcinomas and 7 of 25 serous carcinomas (28%) screened exhibited HER2 amplification compared with 7% (2/29) of endometrioid adenocarcinomas. HER2 overexpression was correlated with HER2 amplification (r=0.459; p<0.0001). Thirty-four women were enrolled; 1 was excluded (refused treatment); and 18 had tumors with known HER2 amplification. No major tumor responses were observed. Twelve women experienced stable disease, 18 had increasing disease, and 3 were indeterminate for tumor response. Neither HER2 overexpression nor HER2 amplification appeared to be associated with progression-free survival or overall survival. CONCLUSION: Trastuzumab as a single agent did not demonstrate activity against endometrial carcinomas with HER2 overexpression or HER2 amplification, although full planned accrual of women with HER2 amplified tumors was not achieved due to slow recruitment. Serous and clear cell endometrial carcinomas appear to be more likely to demonstrate HER2 amplification.

A Phase II evaluation of weekly topotecan as a single agent second line therapy in persistent or recurrent carcinoma of the cervix: a Gynecologic Oncology Group study.

PURPOSE: To estimate antitumor activity and toxicity of weekly topotecan hydrochloride in patients with persistent or recurrent cervical carcinoma who failed prior treatment. PATIENTS AND METHODS: Women entered on study had or failed one prior chemotherapy regimen in addition to radiosensitizing chemotherapy, performance status less than 3, and adequate hematologic, renal, hepatic, and neurological function. Topotecan was infused at 3.0 mg/m(2) on days 1, 8, and 15 every 28 days. RESULTS: Twenty-seven patients were enrolled onto this study with 25 evaluable. Twenty-two patients had received radiation and chemotherapy prior to study. A median of two and mean of three courses of chemotherapy was given (range, one to eight courses). The most frequently severe adverse events were grade 3 anemia (28%) and grade 4 (4%) along with grade 3 neutropenia (8%) and grade 4 (8%). Two patients had grade 4 thrombocytopenia. There were no complete or partial responders. Ten patients (40%) had stable disease, twelve (48%) had increasing disease, and response could not be assessed in three (12%). The median progression-free survival was 2.4 months for the patients with increasing disease and 6.2 months (3.5-8.8 months) for those with stable disease. Disease location was equally divided within and outside the irradiated field. The 12 patients with increasing disease were more likely to have disease outside the pelvic radiation field. CONCLUSION: There were no complete or partial responders to weekly topotecan among the 25 patients in this study.

Subcutaneous management of vertical incisions with 3 or more centimeters of subcutaneous fat.

OBJECTIVE: This study was undertaken to determine the most appropriate management of the subcutaneous tissue of midline vertical incisions with 3 cm or more of subcutaneous fat. STUDY DESIGN: Patients undergoing surgery within the Division of Gynecologic Oncology at University of South Florida and East Tennessee State University with 3 cm or more of subcutaneous fat were randomly assigned to 1 of 3 groups: suture approximation of Camper's fascia, closed suction drainage of the subcutaneous space, or no intervention as a control group. Participants were evaluated daily during postoperative hospitalization and at 2 and 6 weeks postoperatively as an outpatient. Demographic information, perioperative data, and wound complications were recorded and then analyzed with chi2, t test, analysis of variance, and logistic regression where appropriate. RESULTS: Two hundred twenty-five patients were enrolled with 222 eligible for evaluation. Wound complications were observed in 34 (15.3%) patients, and 25 of these women also had wound disruption. Overall wound complication and wound disruption rates were not significantly different between groups: suture (12.8%, 7.7%), drain (17.9%, 14.9%), control (15.6%, 11.7%); P = .70 and P = .39, respectively. CONCLUSION: Suture approximation or drainage of the subcutaneous tissues of women with 3 cm or more subcutaneous fat measured in midline vertical incisions resulted in no significant change in the incidence of overall wound complications or superficial wound disruption.

Clinical results and quality of life analysis for the MVAC combination (methotrexate, vinblastine, doxorubicin, and cisplatin) in carcinoma of the uterine cervix: A Gynecologic Oncology Group study.

OBJECTIVES: The Gynecologic Oncology Group (GOG) compared methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) with topotecan and cisplatin (TC) or cisplatin alone (C) in advanced cervical cancer. The primary endpoint was overall survival (OS), with response rate, progression-free survival (PFS), and quality of life (QOL) as secondary objectives. METHODS: Eligible patients were randomly allocated to receive either cisplatin 50 mg/m2 q 3 weeks (C) or cisplatin 50 mg/m2 day 1 and topotecan 0.75 mg/m2 days 1-3 q 3 weeks (TC) or methotrexate 30 mg/m2 days 1, 15, and 22, vinblastine 3 mg/m2 days 2, 15, and 22, doxorubicin 30 mg/m2 day 2, and cisplatin 70 mg/m2 day 2 q 4 weeks (MVAC). QOL was assessed at four time points using the Functional Assessment of Cancer Therapy-Cervix (FACT-Cx), Neurotoxicity Subscale (FACT/GOG-NTX subscale), and Brief Pain Inventory (BPI). RESULTS: One hundred eighty-six patients (C = 60; TC = 63; MVAC = 63) were enrolled before MVAC was closed by the GOG Data Safety Monitoring Board after four treatment-related deaths occurred on that arm. MVAC produced a 22% overall response rate (95% CI: 0.13 to 0.34) and median PFS and OS of 4.4 months and 9.4 months, respectively. Compared with C and TC, there was more hematologic toxicity with MVAC. There were no appreciable differences in QOL scores after controlling for baseline scores. CONCLUSIONS: MVAC's clinical activity tended to be similar to that of TC but with an unacceptable risk of death from sepsis at this dose and schedule. Nevertheless, QOL, as measured by these instruments, was not substantially impaired by this regimen.

Role of imaging in pretreatment evaluation of early invasive cervical cancer: results of the intergroup study American College of Radiology Imaging Network 6651-Gynecologic Oncology Group 183.

PURPOSE: To compare magnetic resonance imaging (MRI) and computed tomography (CT) with each other and to International Federation of Gynecology and Obstetrics (FIGO) clinical staging in the pretreatment evaluation of early invasive cervical cancer, using surgicopathologic findings as the reference standard. PATIENTS AND METHODS: This prospective multicenter clinical study was conducted by the American College of Radiology Imaging Network and the Gynecologic Oncology Group from March 2000 to November 2002; 25 United States health centers enrolled 208 consecutive patients with biopsy-confirmed cervical cancer of FIGO stage > or = IB who were scheduled for surgery based on clinical assessment. Patients underwent FIGO clinical staging, helical CT, and MRI. Surgicopathologic findings constituted the reference standard for statistical analysis. RESULTS: Complete data were available for 172 patients; surgicopathologic findings were consistent with FIGO stages IA to IIA in 76% and stage > or = IIB in 21%. For the detection of advanced stage (> or = IIB), sensitivity was poor for FIGO clinical staging (29%), CT (42%), and MRI (53%); specificity was 99% for FIGO clinical staging, 82% for CT, and 74% for MRI; and negative predictive value was 84% for FIGO clinical staging, 84% for CT, and 85% for MRI. MRI (area under the receiver operating characteristic curve [AUC], 0.88) was significantly better than CT (AUC, 0.73) for detecting cervical tumors (P = .014). For 85% of patients, FIGO clinical staging forms were submitted after MRI and/or CT was performed. CONCLUSION: CT and MRI performed similarly; both had lower staging accuracy than in prior single-institution studies. Accuracy of FIGO clinical staging was higher than previously reported. The temporal data suggest that FIGO clinical staging was influenced by CT and MRI findings.

Utilization of diagnostic studies in the pretreatment evaluation of invasive cervical cancer in the United States: results of intergroup protocol ACRIN 6651/GOG 183.

PURPOSE: To review the current utilization of diagnostic tests prescribed by the International Federation of Gynecology and Obstetrics (FIGO) clinical staging guidelines in the pretreatment work-up of invasive cervical cancer, and to compare the data with those of previous patterns of care studies. PATIENTS AND METHODS: This interdisciplinary American College of Radiology Imaging Network/Gynecologic Oncology Group prospective clinical trial was conducted between March 1, 2000, and November 11, 2002. Twenty-five participating institutions, all from the United States, enrolled a total of 208 patients. Only patients scheduled for surgery with biopsy-confirmed cervical cancer of clinical FIGO stage IB or higher were eligible. The patterns of care data analysis was based on 197 patients who met all inclusion criteria. The conventional FIGO-recommended tests used for pre-enrollment FIGO clinical stage classification were at the discretion of the treating physician; overall frequency of use was tabulated for each test. RESULTS: Use of cystoscopy (8.1%) and sigmoidoscopy or proctoscopy (8.6%) was significantly lower than in 1988 to 1989 (P < .0001 in each instance). Intravenous urography was used in only 1% of patients as compared with 42% in 1988 to 1989 and 91% in 1983. No patient included in the data analysis had barium enema or lymphangiography. Only 26.9% of patients had examination under anesthesia for FIGO clinical staging. CONCLUSION: There is a large discrepancy between the diagnostic tests recommended by FIGO and the actual tests used for cervical cancer staging, suggesting a need to reassess the relevance of the FIGO guidelines to current clinical practice in the United States.

Upper vaginectomy for the treatment of vaginal intraepithelial neoplasia.

OBJECTIVE: The purpose of this study was to evaluate the use of upper vaginectomy for the treatment of vaginal intraepithelial neoplasia (VAIN). STUDY DESIGN: We conducted a retrospective review. Between August 1, 1985 and April 30, 2004, 105 patients were identified who had undergone upper vaginectomy for VAIN. RESULTS: Thirty-six patients had previously been treated for VAIN. Mean operative time and estimated blood loss were 55 minutes and 113 mL, respectively. Ten percent had intraoperative complications. Twenty-three (22%) patients had negative findings on final pathologic examination, and invasive cancer was found in 13 (12%) patients. Four patients had postoperative complications. Follow-up was available in 52 patients; 46 (88%) remain without recurrence at a mean follow-up of 25 months. CONCLUSION: In our patients, upper vaginectomy was efficacious for the treatment of VAIN. The procedure led to the diagnosis of occult invasive cancer in 12% of these women.

Sites of bowel resected to achieve optimal ovarian cancer cytoreduction: implications regarding surgical management.

OBJECTIVE: The purpose of this study was to 1) report on the distribution of bowel segments resected in a population of patients who underwent primary optimal cytoreductive surgery for epithelial ovarian cancer, and 2) discuss implications for surgical management regarding resection of these bowel segments. STUDY DESIGN: This was a retrospective study from 1995 to 2003 of 144 ovarian cancer patients who underwent primary optimal cytoreductive operations that included bowel resection. RESULTS: Bowel segments removed and major complications are presented in tabulated form. Eighty-one out of 144 resections were rectosigmoid only. Thirty-six percent had extensive involvement of colon segments separate from the rectosigmoid. Excluding hemorrhage, 9 patients (6%) experienced a major complication. CONCLUSION: The present study does suggest the necessity for a highly individualized approach to the surgical management of epithelial ovarian cancer patients who can be optimally cyto-reduced by resection of multifocal colonic involvement. Further study is needed to better assess the complications, function, and oncologic outcome of the different surgical approaches to these patients.

Diagnosing pulmonary embolism: experience with spiral CT pulmonary angiography in gynecologic oncology.

OBJECTIVES: To review our experience with the diagnosis and prognosis of pulmonary embolism (PE) in gynecologic oncology patients. METHODS: Spiral CT pulmonary angiography (CTPA) studies on gynecologic oncology patients were collected from our radiology database from 6/2001 to 6/2003. Patient charts were retrospectively reviewed. Data were abstracted relative to presenting symptoms, demographics and laboratory and diagnostic evaluations. Patient data were compared using chi-square contingency tables and logistic regression analysis. Survival was studied using the Kaplan-Meier method and the log rank test. The effect of PE on survival was adjusted using a proportional hazards regression model. RESULTS: One-hundred and eleven CTPA studies were performed over 2 years and 25 patients were diagnosed with PE. Both PE (n = 25) and non-PE (n = 86) groups were similar for age, race, BMI and cancer diagnosis. Tachycardia (P = 0.02, OR = 3.03 [95% CI 1.16-7.94]) and leukocytosis (P = 0.04, OR = 2.93[95% CI 1.05-8.18]) were more frequent among PE patients and confirmed as independently prognostic of PE. All other clinical and laboratory findings were similar between patients with and without PE. Overall survival for patients with and without PE was 63% versus 94%, respectively, at 2 years (P = 0.02). CONCLUSION: In a gynecologic oncology patient with high clinical suspicion for PE, our clinical pre-test probability was 23.0%. Two-year mortality rates were 6-fold higher for patients diagnosed with PE. The significant overlap in clinical presentations, multiple risk factors and higher mortality rates encourage the aggressive diagnosis and treatment of PE among this population. Further work is needed to reduce the incidence and mortality rate of PE.

Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group Study.

PURPOSE: On the basis of reported activity of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) or topotecan plus cisplatin in advanced cervix cancer, we undertook a randomized trial comparing these combinations versus cisplatin alone, to determine whether survival is improved with either combination compared with cisplatin alone, and to compare toxicities and quality of life (QOL) among the regimens. PATIENTS AND METHODS: Eligible patients were randomly allocated to receive cisplatin 50 mg/m(2) every 3 weeks (CPT); cisplatin 50 mg/m(2) day 1 plus topotecan 0.75 mg/m(2) days 1 to 3 every 3 weeks (CT); or methotrexate 30 mg/m(2) days 1, 15, and 22, vinblastine 3 mg/m(2) days 2, 15, and 22, doxorubicin 30 mg/m(2) day 2, and cisplatin 70 mg/m(2) day 2 every 4 weeks (MVAC). Survival was the primary end point; response rate and progression-free survival (PFS) were secondary end points. QOL data are reported separately. RESULTS: The MVAC arm was closed by the Data Safety Monitoring Board after four treatment-related deaths occurred among 63 patients, and is not included in this analysis. Two hundred ninety-four patients enrolled onto the remaining regimens: 146 to CPT and 147 to CT. Grade 3 to 4 hematologic toxicity was more common with CT. Patients receiving CT had statistically superior outcomes to those receiving CPT, with median overall survival of 9.4 and 6.5 months (P = .017), median PFS of 4.6 and 2.9 months (P = .014), and response rates of 27% and 13%, respectively. CONCLUSION: This is the first randomized phase III trial to demonstrate a survival advantage for combination chemotherapy over cisplatin alone in advanced cervix cancer.

Accuracy of pelvic examination in the assessment of patients with operable cervical cancer.

OBJECTIVE: The purpose of this study was to determine whether pelvic examination identifies factors that suggest the need for radiotherapy after radical hysterectomy for cervical cancer. STUDY DESIGN: This was an observational study that was conducted from July 1, 2000 through December 31, 2002 that comprised 67 patients with stage 1B-2A cervical cancer who underwent primary surgical treatment. Assessments that were made on pelvic examination were compared with pathologic findings. Data were analyzed with the use of descriptive statistics, calculation of sensitivities, specificities, positive and negative predictive values, and determination of odds ratios. RESULTS: The overall spectrum of small to large tumors (<1-8 cm) and cervices (2.5-8 cm) correlated well with examination (r=0.77-0.88). The accuracy of examination was approximately 50% for tumor diameter (+/-25%), 85% for cervical diameter (+/-25%), 80% for outer-third invasion, 80% for endophytic growth, and 90% for vaginal involvement. The likelihood for adjuvant radiotherapy had a significant association with the number of at-risk examination variables that were present. CONCLUSION: For women who undergo radical hysterectomy for stage 1B to 2A cervical cancer, the presence of multiple high-risk factors that are found on pelvic examination is associated significantly with indications for adjuvant postoperative radiotherapy.

Phase II trial of alternating courses of megestrol acetate and tamoxifen in advanced endometrial carcinoma: a Gynecologic Oncology Group study.

OBJECTIVES: To estimate the objective response rate and toxicity associated with alternating megestrol acetate (MA) and tamoxifen citrate (T) in women with endometrial carcinoma. METHODS: Consenting patients with measurable recurrent or advanced endometrial carcinoma were eligible if they had not received prior cytotoxic or hormonal treatment. MA 80 mg BID x 3 weeks alternating with T 20 mg BID x 3 weeks orally was given. RESULTS: Of 61 patients entered, 56 eligible patients were evaluable for toxicity and response. Fifteen patients responded (12 complete, 3 partial) for an overall response rate of 27% (90% Confidence Interval: 17-38%). In 8 of 15 (53%) responders, response duration exceeded 20 months. The response rate was 38% in patients with histologic grade 1 tumors (n = 16), 24% in those with grade 2 disease (n = 17), and 22% among patients with grade 3 disease (n = 23). Women less than or equal to 60 years (n = 16) appear to have a better response rate than those >60 years (n = 40), 44% versus 20%. The response rate in patients with extra pelvic disease (n = 42) was 31% as compared to 14% in those with strictly pelvic and/or vaginal disease (n = 14). The median progression-free survival (PFS) was 2.7 months and median overall survival was 14.0 months. Two patients experienced a grade 4 thromboembolic event. Additional toxicities included one of each grade 3 gastrointestinal, grade 3 neurologic, and grade 3 genitourinary. CONCLUSION: A regimen of alternating megestrol acetate and tamoxifen is active in treating endometrial cancer and may result in a prolonged complete response (CR) in some patients.

Infectious urinary tract morbidity with prolonged bladder catheterization after radical hysterectomy.

OBJECTIVE: This study was undertaken to determine the incidence of catheter-associated infection after radical hysterectomy and to evaluate the role of prophylactic antibiotics in these patients. STUDY DESIGN: A 4-year retrospective review of 102 women undergoing radical hysterectomy for cervical or endometrial cancer was performed. Clinical data were abstracted and analyzed with chi(2) and t tests. RESULTS: Catheter-associated infection was observed in 11% (12 of 102) and was not altered by the administration of prophylactic antibiotics (11.1% vs 11.8%, P=.95). Of the 12 women who had infection, 11 were treated as outpatients, and 1 patient required admission for pyelonephritis. Patient age, comorbid medical conditions, class of radical hysterectomy, perioperative complications, operative time, blood loss, catheter type, duration of catheterization, and length of hospitalization had no effect on the development of catheter-associated infection. CONCLUSION: The incidence of catheter-associated infection in women requiring prolonged catheterization after radical hysterectomy is relatively low. Withholding prophylactic antibiotics from these patients is a reasonable clinical option.

The role of topotecan in the treatment of advanced cervical cancer.

Improvements in the early detection of cervical cancer have markedly reduced associated mortality rates over the past few decades; however, in patients diagnosed with cervical cancer the rates have remained unchanged for 25 years. Hysterectomy, alone or with radiotherapy, is effective in early-stage disease, with a high cure rate, but the treatment of advanced and recurrent cervical cancer (usually with radiotherapy and cisplatin) is suboptimal, with 5-year survival rates of 50.9 and 16.5% for patients with regional involvement or distant disease, respectively. There is therefore an unmet need for more effective treatments for patients with advanced disease, and a number of new chemotherapy agents and treatment strategies have been investigated in this setting. Promising results have been reported in phase II trials of the topoisomerase inhibitor I, topotecan. Response rates of up to 19% have been reported in patients treated with topotecan as a single agent and response rates of up to 54% have been achieved when this agent is used in combination chemotherapy regimens. Toxicity levels are similar to those observed in patients with relapsed ovarian cancer and are not significantly different from levels with other chemotherapy agents. This paper reviews the current management of advanced cervical cancer and summarizes the available data on the use of topotecan in this setting.

Activation and overexpression of centrosome kinase BTAK/Aurora-A in human ovarian cancer.

Previous studies have demonstrated amplification of the centrosome serine/threonine kinase BTAK/Aurora-A in 10-25% of ovarian cancers. However, alterations of BTAK/Aurora-A at kinase and protein levels and its role in ovarian cancer progression have not been well documented. In this study, we examined the kinase activity and protein levels of BTAK/Aurora-A in 92 patients with primary ovarian tumors. In vitro kinase analyses revealed elevated BTAK/Aurora-A kinase activity in 44 cases (48%). Increased BTAK/Aurora-A protein levels were detected in 52 (57%) specimens. High protein levels of BTAK/Aurora-A correlated well with elevated kinase activity. Activation and overexpression of BTAK/Aurora-A were more frequently detected in early stage/low-grade ovarian tumors, although there was no statistic significance at the kinase level between early stage/low-grade and late stage/high-grade tumors. Moreover, BTAK/Aurora-A was preferentially expressed in noninvasive tumors, as revealed by immunohistochemical staining, suggesting that alterations of BTAK/Aurora-A could be an early event in human ovarian oncogenesis. To our knowledge, this is the first demonstration of recurrent activation and overexpression of BTAK/Aurora-A in human ovarian cancer, which may play a critical role in development of this malignancy.

Update on the treatment of cervical and uterine carcinoma: focus on topotecan.

Carcinomas of the uterine cervix and corpus are significant causes of morbidity and mortality among women in the U.S. and are expected to contribute 10,700 deaths in 2002. Despite the widespread use of cytologic screening and improvements in early diagnosis, mortality rates have changed little over the past 25 years, and the management of cervical and uterine cancers remains a significant unmet medical need. Currently available modalities, including radiotherapy and cisplatin-based chemotherapy, provide suboptimal control of disease, and there are no effective treatments for recurrent disease. The antitumor activity and tolerability of a number of novel agents, including topoisomerase I inhibitors, vinca alkaloids, taxanes, and gemcitabine, have been of considerable interest in treatment of these cancers. This review discusses current trends in the treatment of cervical and endometrial carcinomas, focusing on the potential role of topotecan in the treatment of non-ovarian gynecologic malignancies.