Upfront surgery in patients with epithelial ovarian cancer and enlarged supradiaphragmatic lymph nodes associated with comparable to neoadjuvant chemotherapy.

BACKGROUND: There is little data regarding the optimal approach to advanced epithelial ovarian cancer (EOC) with isolated extra-peritoneal disease in the cardiophrenic lymph nodes. This study assessed whether the prognosis and surgical outcomes are affected by the treatment approach among these patients. MATERIAL AND METHODS: This retrospective cohort study included patients with advanced EOC, who were treated 2012-2020. Computed tomography scans were reviewed for disease extent and the presence of enlarged supradiaphragmatic nodes (SDLN). Demographic, clinical and oncologic data were recorded. Characteristics and outcomes of patients with and without enlarged SDLN were evaluated, and outcomes of patients with enlarged SDLN who underwent upfront surgery and neoadjuvant chemotherapy were compared. RESULTS: Among 71 women, 47 (66%) had enlarged supradiaphragmatic lymph nodes. Groups had similar baseline characteristics. Among 47 women who had enlarged SDLN. There was no significant difference in progression free survival among patients who had upfront cytoreduction compared to those who received neoadjuvant chemotherapy. Only one asymptomatic chest recurrence was observed. CONCLUSION: Patients with enlarged SDLN have comparable outcomes with either upfront surgery or neoadjuvant chemotherapy. Moreover, the frequency of chest recurrences in patients presenting with enlarged SDLN is exceedingly low.

Chemotherapy Toxicity in BRCA Mutation Carriers Undergoing First-Line Platinum-Based Chemotherapy.

OBJECTIVE: BRCA mutations are the most frequent mutations causing homologous recombination defects in epithelial ovarian cancers (EOC). Germline mutation carriers are heterozygous for the mutation and harbor one defective allele in all cells. This has been hypothesized to cause increased susceptibility to DNA damage in healthy cells as well as neoplastic ones. Our objective was to assess chemotherapy-associated toxicities in patients with epithelial ovarian cancer with and without a germline BRCA mutation. MATEIALS AND METHODS: A retrospective cohort study of patients with EOC receiving first-line platinum-based chemotherapy at a single center between 2006 and 2016. Indices of chemotoxicity, including blood counts, transfusion requirements, granulocyte colony-stimulating factor (gCSF) prescriptions, episodes of febrile neutropenia, and treatment delays were compared for BRCA mutation carriers and noncarriers. RESULTS: A total of 90 women met the inclusion criteria, including 31 BRCA mutation carriers (34%) and 59 noncarriers (66%). Mean hemoglobin, neutrophil count, and platelet counts during treatment were comparable for the two patient groups. There was a trend toward a higher frequency of hematological events in BRCA mutation carriers (neutropenia <1500 per mL: 6% vs. 0%, p = .12; thrombocytopenia <100,000 per mL: 23% vs. 9%, p = .07), but these differences were not statistically significant. Similarly, no significant differences were found in surrogates of bone marrow toxicity such as blood transfusions, use of gCSF, episodes of febrile neutropenia, or treatment delays. CONCLUSION: BRCA mutation carriers and noncarriers receiving first-line platinum-based chemotherapy for EOC have similar hematologic toxicity profiles. Clinicians treating these patients can be reassured that chemotherapy dosing or schedule do not require adjustment in patients carrying BRCA mutations. IMPLICATIONS FOR PRACTICE: Patients with ovarian cancer carrying BRCA mutations are more likely to have serous tumors and present with higher CA125 levels. Germline BRCA mutation status is not associated with increased frequency of adverse hematologic events among patients with ovarian cancer being treated with first-line platinum-based chemotherapy. Germline BRCA mutations are also not associated with more treatment delays or a lower number of courses completed in this patient population. These findings should reassure practitioners engaged in care for patients with ovarian cancer that BRCA mutation status most likely will not affect chemotherapy dosing or schedule.

Impact of adjuvant treatment on outcome in high-risk early-stage endometrial cancer: a retrospective three-center study.

OBJECTIVE: High grade and non-endometrioid endometrial cancers carry a poor prognosis, and the lack of randomized prospective data has led to a wide range of practice regarding adjuvant therapy. The objective of this study was to evaluate the outcomes of different treatment strategies in patients with high-risk, early-stage endometrial cancer. METHODS: Patients with high-grade endometrioid, serous endometrial cancer and carcinosarcoma diagnosed between 2000 and 2012 were identified from databases in three gynecologic oncology divisions, in Toronto and in Israel. Adjuvant treatment practices differed across the centers, creating a heterogeneous cohort. A comparison of stage I patients stratified by adjuvant treatment was undertaken. Log-rank tests and Cox proportional hazards models were employed to compare recurrence and survival across treatment groups. RESULTS: 490patients with high risk endometrial cancer were identified, among them 213 patients with stage I disease. Israeli patients received more chemotherapy (41% vs 10% in stage I disease; P<0.001) than patients in Toronto. Chemotherapy was not associated with improved disease-free, disease-specific or overall survival, nor was it associated with fewer distant recurrences (50% vs 54%). Radiation was also not associated with improved recurrence or survival, nor did it affect the pattern of recurrence. On Cox multivariable analysis, neither radiation treatment nor chemotherapy were significantly associated with outcome (HR for recurrence, 0.72 for pelvic radiation (P=0.46) and 1.99 for chemotherapy (P=0.09); HR for death, 0.67 for pelvic radiation (P=0.29) and 1.03 for chemotherapy (P=0.94)). CONCLUSIONS: In this retrospective analysis, neither adjuvant radiation nor chemotherapy were associated with improved outcome in stage I, high risk endometrial cancer.

Fertility preservation in women with borderline ovarian tumors - how does it impact disease outcome? A cohort study.

INTRODUCTION: Borderline ovarian tumors are typically indolent neoplasms. Since many are diagnosed in younger women, fertility conservation is an important consideration and has been advocated based on retrospective data. The objective of this study was to identify features impacting on recurrence and survival in a series of borderline ovarian tumors, and to assess the safety of a fertility-sparing approach. MATERIAL AND METHODS: A historical cohort study of consecutive borderline ovarian tumors cases treated at a single institution over 30 years (1981-2011). Data on surgical approach (fertility-sparing or otherwise), disease stage, CA125 levels, histological features, adjuvant treatment and follow-up data were collected. Recurrence and survival were assessed using the Kaplan-Meier method and associations with the variables of interest were evaluated using a multivariate Cox proportional hazards model. RESULTS: 213 patients were included. Of 132 women age 40 years and below at diagnosis, 112 (85%) had a fertility-sparing procedure and 60 (46%) had conservation of an involved ovary. Fifty patients (24%) developed recurrences; fertility preservation (hazard ratio = 2.57; 95% confidence interval 1.1-6; p = 0.029) and advanced stage (hazard ratio = 4.15; 95% confidence interval 2.3-7.6; p < 0.001) were independently associated with recurrence on multivariate analysis. Eleven (5%) patients died of their disease. Fertility preservation was not associated with compromised survival. CONCLUSIONS: Borderline ovarian tumors carry a good prognosis overall. Fertility preservation is associated with a higher risk of disease relapse; however, as most relapses are localized and may be salvaged with surgical treatment, overall survival is not compromised.

Malignant Pericardial Effusion in Ovarian Malignancy: A Treatable Oncologic Emergency.

BACKGROUND: Pericardial tamponade is a life-threatening condition that can occur, albeit rarely, in patients with ovarian cancer. Whether or not prolonged survival is possible after such an event is debatable. Our aim was to describe our experience with seven ovarian cancer patients who experienced malignant cardiac tamponade at tumor diagnosis or at recurrence. CASE REPORT: Six patients were treated with pericardiocentesis and one with pericardial fenestration. Survival after tamponade ranged from 3 to 72 weeks. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: We suggest that when pericardial effusion occurs in patients with recurrent ovarian cancer, timely diagnosis and proper management might allow palliation and prolongation of life.

Safety of ovarian conservation and fertility preservation in advanced borderline ovarian tumors.

OBJECTIVE: To assess the impact of a fertility-sparing approach on disease recurrence in women with advanced borderline ovarian tumors. DESIGN: Historic cohort study. SETTING: A tertiary referral center for gynecological oncology patients and a university teaching hospital. PATIENT(S): Consecutive patients with advanced borderline ovarian tumors defined as stage IC and above, treated at a single institution during a span of 30 years. INTERVENTION(S): Data on surgical approach (e.g., fertility sparing, ovarian conserving) as well as histopathology, disease stage, CA-125 level, and use of chemotherapy were collected from the medical records, and their impact on disease recurrence was assessed. MAIN OUTCOME MEASURE(S): Recurrence-free interval. Its association with the type of surgery and with other clinical and pathological features was assessed using the Kaplan Meier and Cox proportional hazards methods. RESULT(S): Fifty-nine patients with advanced disease were identified. Median follow-up was 55.3 months. Mean age at diagnosis was 35 years. Most of the tumors (51, 84.4%) had serous histology. Twenty-seven patients (45.8%) developed recurrences and 6 (10%) died of their disease. Mean time to recurrence was 30.6 months. Of 44 women ≤40 years, 33 (75%) had a fertility-sparing procedure. Fertility preservation was not associated with disease recurrence. A total of 34 pregnancies and 26 live births were documented among 21 patients attempting conception. CONCLUSION(S): Borderline ovarian tumors carry a favorable prognosis, even at an advanced stage. Fertility preservation was not found to be associated with an increased risk of relapse in young patients with advanced disease, and may be reasonably considered.

Treating gynecologic malignancies in elderly patients.

AIM: To determine the relative benefits of full and partial treatment for gynecologic malignancies in elderly patients. METHODS: A retrospective cohort study of all consecutive patients (n=169) aged 79 and older (median age 82 y; range, 79 to 94 y), diagnosed between 1971 and 2007 with various types of gynecologic malignancies (endometrial, 52%; ovarian, 26%; vulvar, 11%; cervical, 5%; other, 6%) was conducted. Stages were I to II (47%), III to IV (35.5%), and unknown (17.5%). Major comorbidities were hypertension (51%), diabetes (17%), cardiac diseases (34%), and other malignancy (12%). Regardless of age or chronic illnesses, patients were grouped on the basis of having been treated optimally (100 patients; 59.2%), defined as the accepted standard for each diagnosis and stage including surgery and adjuvant radiation or chemotherapy as indicated; or suboptimally (69 patients; 40.8%), that is, no or only partial treatment. Kaplan-Meier survival analysis and Cox proportional hazard models, univariate and multivariable were conducted. RESULTS: For all patients with suboptimal treatment, the age-and-stage-adjusted hazard ratio for death was 1.76 (95% CI, 1.203-2.570; P=0.004) compared with optimal treatment. Age-adjusted hazard ratio was 2.15 (95% CI, 1.127-4.114; P=0.02) and 2.3 (95% CI, 1.415-3.779; P=0.001) for ovarian and endometrial cancer patients, respectively. Age-adjusted and stage-adjusted hazard ratio was 2.8 (95% CI, 1.099-5.157; P=0.028) and 1.53 (95% CI, 0.867-2.702; P=0.1420) for ovarian and endometrial cancer patients, respectively. CONCLUSIONS: Optimal treatment in patients with gynecologic malignancies evidently improves survival in elderly patients at any age, and in patients with ovarian cancer at any stage. Regardless of chronological age, the aim should be to deliver optimal treatment.

Effect of treatment delay on survival in patients with cervical cancer: a historical cohort study.

OBJECTIVE: The objective of this study was to evaluate the effect of treatment delay on prognosis in patients with cervical cancer. METHODS: The study group of this historic cohort study comprised 321 patients newly diagnosed with cervical cancer between 1999 and 2010. Time from diagnosis to treatment was analyzed both as a continuous variable and as a categorical variable in 3 groups that differed in waiting time between diagnosis and treatment initiation: 30 days or less (group 1, n = 134), 30 to 45 days (group 2, n = 86), and more than 45 days (group 3, n = 101). Associations between waiting time group, patients' characteristics, and disease outcome were investigated using t tests, analyses of variance and Cox regression analyses, Kaplan-Meier survival analysis, and log-rank (Mantel-Cox) tests. RESULTS: Time from diagnosis to treatment initiation, when analyzed as a continuous variable, was not a significant factor in survival. There were no between-group differences in age, smoking rate, marital status, gravidity, parity, tumor histology, or lymph node involvement. Early-stage disease and small tumor diameter were diagnosed most frequently in group 3. However, there was no significant between-group difference in 3-year survival rates (74.6%, 82.2%, and 80.8% in groups 1, 2, and 3, respectively; P = 0.38). On multivariate analysis, only stage, histology, and lymph node involvement were significant prognostic factors for survival. Before starting treatment, 28 patients underwent ovarian preservation procedures. CONCLUSIONS: Longer waiting time from diagnosis to treatment was not associated with worse survival. Our findings imply that if patients desire fertility or ovarian preservation procedures before starting treatment, it is acceptable to allow time for them.

Use of titanium spiral tacks for long-term oophoropexy before pelvic irradiation.

BACKGROUND: Ovarian transposition before planned pelvic irradiation can preserve ovarian function in young patients with pelvic malignancies. The transposed ovaries are fixed to the posterolateral abdominal wall. We described the use of a titanium spiral tack as a fixation device and compared it with other methods of oophoropexy. METHODS: Medical and surgical records of all consecutive patients who underwent oophoropexy in our institution between 2007 and 2013 were reviewed. Demographic and clinical data were summarized; follicle-stimulating hormone values, recorded; and imaging scans, reviewed. RESULTS: Oophoropexy was performed in 30 patients: 28 with cervical carcinomas and 2 with pelvic sarcomas. The procedure was done through laparoscopy in 13 patients and through laparotomy in 17. Titanium spiral tack was used for ovarian fixation in 14 patients, Vicryl suturing in 14, and in 2 cases the ovaries were pulled up through a retroperitoneal tunnel and fixed to the peritoneum with sutures. Titanium spiral tack fixation took a few seconds to perform. There were no immediate intraoperative or postoperative complications. Ovarian function was preserved in 15 patients (7/14 with spiral tack, 6/14 with sutures, and in both patients with retroperitoneal tunneling). Postoperative imaging results showed that all ovaries retained their extrapelvic location for a median period of 11.6 months (range, 2.3-63 months). CONCLUSIONS: Spiral tack is a simple, reliable method for oophoropexy before pelvic irradiation. Its efficacy is comparable with that of suture fixation, with the added advantage of ultrashort operative time. It is therefore worth considering as an alternative to suturing.

Abdominopelvic cytoreduction rates and recurrence sites in stage IV ovarian cancer: is there a case for thoracic cytoreduction?

OBJECTIVE: We report the rates of optimal abdominopelvic cytoreduction and the sites of recurrence in stage IV ovarian cancer patients, with particular attention to the potential impact of thoracic cytoreduction on treatment results in patients with intra-thoracic spread. METHODS: A historic cohort study of all stage IV ovarian cancer patients diagnosed between 1994 and 2010 and underwent abdominopelvic cytoreductive surgery. Controls were stage IIIc patients. Statistical analyses included χ(2) test, Cox proportional hazards regression models and Kaplan-Meier curves with log-rank tests. RESULTS: Group 1 included 76 stage IV patients, 55% with thoracic spread. Group 2 included 142 stage IIIc patients. Age, histology, primary peritoneal tumor and ascites rates were similar for the two groups. Respective rates of optimal abdominopelvic cytoreduction were 68% vs. 83.5% (p<0.05), median time to progression 5.3 vs. 12.3 months (p<0.01) and overall survival 27.2 vs. 46.1 months (p<0.01). Optimal cytoreduction and survival rates were similar for all group 1 patients regardless of spread location. Sites of recurrence in stage IV were abdomen (59.3%), thorax (6.8%), both (28.8%) or other (5.1%). The four patients with thoracic recurrence alone were all initially diagnosed with malignant pleural effusion. Three of them developed abdominal recurrence within 15‒6 months. CONCLUSIONS: Optimal abdominopelvic cytoreduction was achievable in stage IV patients, although in significantly fewer patients than in stage IIIc. Sites of recurrence were rarely thorax alone, implying that thoracic debulking is likely to change the course of disease in only few patients and thus should be carefully individualized.

Ovarian immature teratoma: treatment and outcome in a single institutional cohort.

OBJECTIVE: The aim of this study was to evaluate clinicopathologic characteristics, treatment outcome and reproductive function in women diagnosed with ovarian immature teratoma. METHODS: Thirty-four women with ovarian immature teratoma stages IA to IIIA were identified and included in this study. Patients were treated at one institution; Princess Margaret Hospital, Toronto, Canada between 1970 and 2005. RESULTS: The median age at diagnosis was 25.0 years (range: 9.8-60.2 years). Twenty seven (79%) presented with stage IA disease, 5 (15%) with stage IC, 1 (3%) with stage 2B, and 1 (3%) with stage IIIA disease. Thirteen (38%) of the tumors were found to be grade 1, 12 (35%) grade 2, and 9 (27%) grade 3. Initial management was surgical for all patients: 22 (65%) unilateral oophorectomy, 7 (20%) cystectomy only, and 5 (15%) bilateral oophorectomy (4 with hysterectomy). Fourteen (41.8%) patients received adjuvant therapy. The median follow up was 4.8 years (range 0.2-24.3 years). Four patients recurred (histological grade 2 or 3) within 22 months (87.1% 2-year progression free survival). Only one clinical stage I patient who received adjuvant chemotherapy developed a recurrence. Three of the patients who recurred died from their disease. Eleven patients reported an attempt to conceive resulting in 11 pregnancies in 6 women (3 post chemotherapy). CONCLUSION: The majority of patients diagnosed with an immature teratoma are cured of their disease. However, grade 2 or 3 tumors are associated with a greater chance of recurrence that can be fatal, predominantly within 2 years of diagnosis.

Role of adjuvant radiotherapy in granulosa cell tumors of the ovary.

PURPOSE: To review the role of adjuvant radiotherapy (RT) in the outcome and recurrence patterns of granulosa cell tumors (GCTs) of the ovary. METHODS AND MATERIALS: The records of all patients with GCTs referred to the Princess Margaret Hospital University Health Network between 1961 and 2006 were retrospectively reviewed. The patient, tumor, and treatment factors were assessed by univariate and multivariate analyses using disease-free survival (DFS) as the endpoint. RESULTS: A total of 103 patients with histologically confirmed GCTs were included in the present study. The mean duration of follow-up was 100 months (range, 1-399). Of the 103 patients, 31 received adjuvant RT. A total of 39 patients developed tumor recurrence. The tumor size, incidence of intraoperative rupture, and presence of concurrent endometrial cancer were not significant risk factors for DFS. The median DFS was 251 months for patients who underwent adjuvant RT compared with 112 months for patients who did not (p=.02). On multivariate analysis, adjuvant RT remained a significant prognostic factor for DFS (p=.004). Of the 103 patients, 12 had died and 44 were lost to follow-up. CONCLUSION: Ovarian GCTs can be indolent, with patients achieving long-term survival. In our series, adjuvant RT resulted in a significantly longer DFS. Ideally, randomized trials with long-term follow-up are needed to define the role of adjuvant RT for ovarian GCTs.

Pure dysgerminoma of the ovary 35 years on: a single institutional experience.

OBJECTIVE: The aim of this study was to evaluate clinicopathologic characteristics, long-term outcome and reproductive function in women diagnosed with pure dysgerminoma of the ovary. METHODS: Sixty-five women with stage IA to IIIC pure ovarian dysgerminoma were identified and included in this retrospective study. Patients were treated at one institution between 1970 and 2005. RESULTS: Median age at diagnosis was 22.2 years (range 8.2-64.1 years). 72.3% of patients presented with stage I, 4.6% stage II and 21.5% stage III disease (1.5% stage unknown). Initial management was surgical for all patients: unilateral oophorectomy in 47 patients (72.2%), bilateral oophorectomy +/- hysterectomy in 14 (21.5%) and cystectomy alone in 3 (4.6%). Seventeen patients received chemotherapy (15 adjuvant, 2 for residual disease), 20 received adjuvant radiotherapy and one patient received both. Recurrence occurred in 6 (9.2%) patients (5 stage IA, 1 stage IIA). All recurrences occurred within 19 months of primary diagnosis. All patients were successfully salvaged with radiotherapy (2 patients), chemotherapy (1 patient) or a combination of surgery and chemotherapy (3 patients). Overall, median follow up from time of recurrence was 22.5 years (range 9.3-31.4 years). Median follow-up of all patients was 10.5 years (range 1.1-31.9 years). Fifteen patients reported an attempt to conceive posttreatment resulting in 12 pregnancies and 12 live births in 8 women. CONCLUSION: The long-term outcome of patients with pure ovarian dysgerminoma is excellent. Recurrences occur within 2 years of diagnosis and are treatable. Patients can be treated with fertility-sparing surgery and can expect good reproductive outcomes.

Mutations of the MYH gene do not substantially contribute to the risk of breast cancer.

PURPOSE: To explore whether or not there is an association between the presence of either of the germline mutations in the MutY human homologue (MYH) gene (Y165C and G382D) and the risk of breast cancer. METHODS: 691 breast cancer patients and 812 healthy controls were genotyped for the MYH Y165C and G382D mutations. The frequencies of heterozygotes, homozygotes and compound heterozygotes were compared for the two groups. RESULTS: Four (0.6%) of 691 breast cancer cases carried a MYH Y165C mutant allele, compared to five (0.6%) of the controls (OR 1.1, 95%CI 0.29-4.0, P=0.9). Eight (1.2%) cases carried a MYH G382D mutant allele, compared to eight (1.0%) of the controls (OR 1.2, 95%CI 0.44-3.3, P=0.7). No case or control was homozygous for the variant and none were compound heterozygotes. CONCLUSION: Carriers of the MYH Y165C or G382D mutant alleles do not appear to be at increased risk for breast cancer.

Ovarian cancer risk is associated with a common variant in the promoter sequence of the mismatch repair gene MLH1.

OBJECTIVES: Inherited mutations in the MLH1 gene are associated with a proportion of families with the hereditary non-polyposis colon cancer syndrome (HNPCC). The cardinal features of the syndrome are a predisposition to colon, endometrial and ovarian cancers. Recently, it has been shown that a non-coding polymorphic variant in MLH1 (G>A nt-93) predisposes to colon and endometrial cancer, but with much reduced penetrance. We sought to establish whether or not this polymorphic variant also predisposes to ovarian cancer. METHODS: We genotyped 899 women with invasive ovarian cancer and 931 controls for the G>A nt-93 variant. RESULTS: The presence of the variant was associated with a modest, but highly significant risk of ovarian cancer (OR=1.5; 95% CI 1.3-1.9; p=0.00005). The association was present in cancers of all histologies except clear cell, and in all ethnic groups. CONCLUSIONS: The G>A nt-93 variant of the MLH1 gene is associated with an increased risk of invasive ovarian cancer.

Surgery insight: radical vaginal trachelectomy as a method of fertility preservation for cervical cancer.

Over the past decade, the treatment of cervical cancer has evolved with an increased emphasis on preservation of fertility. There has been a gradual abandonment of radical surgical procedures in favor of more conservative techniques in an effort to decrease morbidity and preserve fertility without compromising overall survival. Radical vaginal trachelectomy (RVT) with laparoscopic pelvic lymphadenectomy is a fertility-preserving procedure that has recently gained worldwide acceptance as a method of surgically treating small invasive cancers of the cervix. Since the original description of RVT by Daniel Dargent in 1994, over 500 cases of utilization of this technique have been reported in the literature, with over 100 live births reported following this procedure. The morbidity associated with RVT is low, with a tumor recurrence rate of 5% and a mortality rate of 3%. The current literature indicates no difference in the rate of recurrence with this technique compared with radical hysterectomy when proper selection criteria are used. Combining RVT with laparoscopic sentinel lymph-node biopsy can further reduce the duration, extent, and complications of surgery.

Outcome of in vitro fertilization treatment in infertile women conservatively treated for endometrial adenocarcinoma.

OBJECTIVE: To evaluate IVF characteristics and outcome of infertile women conservatively treated for well-differentiated endometrial adenocarcinoma. DESIGN: Observational case series study. SETTING: The Department of Gynecology Oncology and IVF unit of Chaim Sheba Medical center, Tel-Hashomer, Israel. PATIENT(S): Eight women referred to IVF treatment because of failure of other fertility treatments after conservative treatment of endometrial adenocarcinoma. All women were selected carefully for conservative treatment at the Department of Gynecology Oncology of the Chaim Sheba Medical Center after a thorough metastatic workup. INTERVENTION(S): In vitro fertilization/intracytoplasmic sperm injection treatment. MAIN OUTCOME MEASURE(S): Serum E(2) levels at hCG administration, endometrial thickness, number of oocytes retrieved, fertilization rate, pregnancy and delivery rate. RESULT(S): All women were nulliparous before IVF treatment, and only one woman was older than 35 years. In four of them, endometrial adenocarcinoma was diagnosed during infertility workup or treatment. A total of 31 IVF cycles were performed. The mean number of oocytes retrieved was 9.4 (95% confidence interval, 5.1-13.6), and fertilization rate was 58.6%. Six women (75%) conceived, and four (50%) delivered six healthy offspring. CONCLUSION(S): In vitro fertilization treatment of infertile women conservatively treated for well-differentiated endometrial adenocarcinoma is highly successful and offers the opportunity to cryopreserve embryos for future use.

Clinical outcome of cystectomy compared with unilateral salpingo-oophorectomy as fertility-sparing treatment of borderline ovarian tumors.

OBJECTIVE: To compare recurrence rates and fertility outcomes of patients with borderline ovarian tumors (BOTs) who underwent unilateral salpingo-oophorectomy with those of patients who underwent cystectomy only. DESIGN: Retrospective study. SETTING: Gynecologic oncology department of a tertiary center. PATIENT(S): Sixty-two patients with BOTs who underwent fertility-preserving surgery. INTERVENTION(S): Unilateral salpingo-oophorectomy (USO, n = 40) or cystectomy only (n = 22). MAIN OUTCOME MEASURE(S): Tumor recurrence rate, incidence of pregnancy. RESULT(S): All 62 patients were alive with no clinical evidence of disease after a mean follow-up of 88 months. There was no statistically significant difference in mean tumor recurrence rates between patients who had undergone cystectomy only and those who had undergone USO (22.7% and 27.5%, respectively). In the cystectomy-treated group, the disease-free interval was shortened (23.6 compared with 41 mo), but the difference was not significant. However, the mean follow-up period for the cystectomy group was significantly shorter than for the USO group. Of the 62 patients, 25 (40.3%) attained 38 pregnancies, resulting in 35 deliveries. CONCLUSION(S): Our results support previous findings that conservative surgery is an acceptable option for women with BOTs who wish to preserve fertility. Cystectomy, like oophorectomy, appears to be an adequate treatment, provided that the patient is willing to undergo careful and prolonged follow-up.

The risk of endometrial cancer in women with BRCA1 and BRCA2 mutations. A prospective study.

OBJECTIVE: To evaluate the risk of endometrial cancer in women who carry a deleterious mutation in the BRCA1 or BRCA2 genes. PATIENTS AND METHODS: Women known to carry a BRCA1 or BRCA2 mutation, aged 45 to 70, were identified from an international registry and were followed prospectively. A total of 857 women completed a baseline questionnaire and one or more follow-up questionnaires. Study subjects were followed until diagnosis of endometrial cancer, ovarian cancer, death or the date of completion of the last questionnaire. The expected number of endometrial cancers was calculated using age and country-specific incidence rates. RESULTS: After an average follow-up period of 3.3 years, six women were diagnosed with endometrial cancer, compared to 1.13 cancers expected (SIR=5.3, p=0.0011). Four of these six patients used tamoxifen in the past. The risk among women who were never exposed to tamoxifen treatment was not significantly elevated (SIR=2.7, p=0.17), but among the 226 participants who had used tamoxifen (220 as treatment and six for the primary prevention of breast cancer) the relative risk for endometrial cancer was 11.6 (p=0.0004). CONCLUSION: The main contributor to the increased risk of endometrial cancer among BRCA carriers is tamoxifen treatment for a previous breast cancer. The risk and benefits of prophylactic hysterectomy should be discussed with women with a BRCA mutation considering tamoxifen therapy.

Endometrial cancer risk is associated with variants of the mismatch repair genes MLH1 and MSH2.

Women with germ-line mutations in the mismatch repair genes (responsible for hereditary nonpolyposis colorectal cancer) face an increased risk of colonic and endometrial cancer. However, these germ-line mutations are rare and are responsible for fewer than 1% of endometrial cancers. Therefore, we examined whether or not common variants of the hereditary nonpolyposis colorectal cancer-associated genes might also be associated with an increased risk of endometrial cancer. Three single-nucleotide polymorphisms were selected in the MLH1 and MSH2 mismatch repair genes. All the various 672 women with endometrial cancer and 880 controls were genotyped. Each of these three single-nucleotide polymorphisms was associated with an increased risk of endometrial cancer. Carriers of the MLH1 nt-93 A allele were at a 1.5-fold increased risk of developing endometrial cancer compared with controls [95% confidence interval (95% CI), 1.2-2.0; P = 0.001]. The risk was higher for homozygote carriers [odds ratio (OR), 1.9; 95% CI, 1.2-3.2; P = 0.009]. For carriers of the MSH2 rs2303428 C allele, the OR was 1.4 (95% CI, 1.0-1.9; P = 0.05), and for carriers of the MSH2 rs2059520 G allele, the OR was 1.3 (95% CI, 1.0-1.7; P = 0.03). More than 9% of endometrial cancer cases carried a variant allele in both MLH1 and MSH2. For these women, the risk of endometrial cancer was particularly high (OR, 2.1; 95% CI, 1.2-3.6; P = 0.005). For patients younger than 50 years at diagnosis who carried both variants, the risk was even higher (OR, 3.4; 95% CI, 1.7-6.6; P = 0.0005). In summary, two common variant alleles of the MLH1 and MSH2 genes make a substantial contribution to endometrial cancer incidence in Ontario.