Women with breast and uterine cancer are more likely to harbor germline mutations than women with breast or uterine cancer alone: A case for expanded gene testing.

OBJECTIVE: We explored the germline mutation spectrum and prevalence among 1650 women with breast and uterine cancer (BUC) who underwent multi-gene hereditary cancer panel testing at a single commercial laboratory. METHODS: The combined frequency of mutations in 23 BC and/or UC genes was compared between BUC cases and control groups with (1) no personal cancer history; (2) BC only; and (3) UC only using logistic regression. RESULTS: Fourteen percent (n = 231) of BUC cases tested positive for mutations in BC and/or UC genes and were significantly more likely to test positive than individuals with BC only (P < 0.001), UC only (P < 0.01), or unaffected controls (P < 0.001). Analysis of gene-specific mutation frequencies revealed that MSH6, CHEK2, BRCA1, BRCA2, ATM, PMS2, PALB2 and MSH2 were most frequently mutated among BUC cases. Compared to BC only, BRCA1, MLH1, MSH2, MSH6, PMS2 and PTEN mutations were more frequent among BUC; however, only ATM mutations were more frequent among BUC compared to UC only. All of the more commonly mutated genes have published management guidelines to guide clinical care. Of patients with a single mutation in a gene with established testing criteria (n = 152), only 81.6% met their respective criteria, and 65.8% met criteria for multiple syndromes. CONCLUSIONS: Women with BUC are more likely to carry hereditary cancer gene mutations than women with breast or uterine cancer alone, potentially warranting expanded genetic testing for these women. Most mutations found via multi-gene panel testing in women with BUC have accompanying published management guidelines and significant implications for clinical care.

Risk factors for the development of uterine cancer in breast cancer survivors: an army of women study.

BACKGROUND: Our study compares breast cancer survivors without a secondary diagnosis of uterine cancer (BC) to breast cancer survivors with a diagnosis of uterine cancer (BUC) to determine clinical characteristics that increase the odds of developing uterine cancer. METHODS: A total of 7,228 breast cancer survivors were surveyed. A case-control study was performed with 173 BUC patients matched by age and race in a 1:5 ratio to 865 BC patients. Multivariable logistic regression examined which factors influence the odds of developing uterine cancer. RESULTS: A total of 5,980 (82.3 %) women did not have a previous hysterectomy at the time of breast cancer diagnosis, of which 173 (2.9 %) subsequently developed uterine cancer. There was no significant difference in body mass index (BMI) (34.4 vs. 34.1, p = 0.388) or age (52.3 vs. 52.3 years, p = 0.999) between the two groups. Increased odds for developing uterine cancer were found in patients with a personal history of hypertension [odds ratio (OR) = 1.62, 95 % confidence interval (CI) 1.45-2.70, p < 0.001], gallbladder disease (OR = 1.30, 95 % CI 1.14-1.55, p = 0.005), and thyroid disease (OR = 1.55, 95 % CI 1.37-1.69, p < 0.001). More than 80 % of women in both groups expressed a desire for a blood test to estimate the risk of uterine cancer (80.4 % BUC vs. 91.2 % BC, p < 0.001). CONCLUSIONS: Hypertension, gallbladder disease, and thyroid disease in breast cancer survivors increase the odds of developing uterine cancer. Breast cancer survivors also express significant interest in potential serum tests to assess the risk of developing uterine cancer.

Clinical significance of inadequate endometrial biopsies prior to hysterectomy.

OBJECTIVE: To evaluate preoperative clinical risk factors associated with significant uterine histopathologic abnormalities in final hysterectomy specimens in patients with inadequate preoperative endometrial biopsies. STUDY DESIGN: This is an institutional review board-approved, retrospective cohort analysis of 469 consecutive patients who underwent preoperative endometrial biopsies with subsequent hysterectomy from January 1, 2005, to December 31, 2009, at the University of Louisville Medical Center. We analyzed risk factors for inadequate biopsy and for final diagnosis of endometrial pathology (defined as endometrial hyperplasia or uterine cancer). RESULTS: Of the 469 preoperative endometrial biopsies reviewed, 26.2% (123/469) were inadequate (IBx) and 73.8% (346/469) were adequate and benign. IBx on endometrial biopsies was associated with a greater risk of having significant uterine histopathologic abnormalities on final hysterectomy specimens (6.5% vs. 2.3%, RR 2.8 [95% CI 1.1-7.3], p = 0.04). CONCLUSION: Although inadequate endometrial biopsies are a common finding, they can be associated with significant uterine histopathologic abnormalities on final hysterectomy specimens.

Nodal metastasis risk in endometrioid endometrial cancer.

OBJECTIVE: To estimate the risk for nodal metastasis in women with endometrial cancer based on uterine characteristics on pathology. METHODS: From a study of staging for uterine cancer, women were identified as being at low risk for nodal metastasis based on three specific criteria on final pathology reports: 1) less than 50% invasion, 2) tumor size less than 2 cm, and 3) well or moderately differentiated endometrioid histology. If the uterine specimen did not meet all three criteria, it was viewed as high risk for nodal metastasis. RESULTS: Nine hundred seventy-one women were included in this analysis. Approximately 40% (or 389 of 971) of patients in this study were found to be at low risk, with a rate of nodal metastasis of only 0.8% (3 of 389; exact 95% confidence interval [CI] 0.16-2.2). No statistical differences in median age, body mass index, race, performance status, missing clinical data, or open or minimally invasive techniques were found among the patients with and without nodal metastases. Patients with high-risk characteristics of their uterine specimens compared with those with low-risk characteristics have 6.3 times the risk of nodal metastasis (95% CI 1.67-23.8, P=.007). CONCLUSION: Low-risk endometrioid uterine cancer criteria may be used to help guide treatment planning for reoperation in patients with incomplete surgical staging information. LEVEL OF EVIDENCE: II.

Prediction of incomplete screening mammograms based on age and race.

OBJECTIVE: This study examined the age-associated rate of incomplete mammograms requiring additional testing based on Breast Imaging-Reporting and Data System (BIRADS) score. METHODS: A retrospective, observational study design from a tertiary medical center was used to evaluate which explanatory variables significantly predicted whether a woman had an incomplete mammogram. An incomplete mammogram was defined as a BIRADS score of 0 (requiring further imaging), whereas a benign process was defined as a BIRADS score of 1 or 2. Explanatory variables included traditional clinical factors (age, race, and menopausal state). RESULTS: During the study period, 20,269 subjects were evaluated. The majority of the patients were white (n = 12,955; 64.6%) and had a BIRADS score consistent with a benign finding (n = 17,571; 86.6%). Premenopausal state (odds ratio [OR], 1.38; 95% CI, 1.27-1.50), white race (OR, 1.18; 95% CI, 1.08-1.29), and younger age (OR, 1.38; 95% CI, 1.27-1.50) significantly increased the odds a woman had an incomplete study. CONCLUSIONS: In this cross-sectional, single-institution analysis, premenopausal state and white race are associated with an increased rate for incomplete mammograms. Patients should be counseled appropriately before the initiation of screening.

Atypical presentation of abdominal group A streptococcal-necrotizing fasciitis after pessary removal.

Group A streptococcal (GAS) necrotizing fasciitis is a potentially life-threatening infection. We report on a patient with a history of prolonged pessary use with traumatic removal who developed ascending GAS infection in her gynecologic organs that tracked along the round ligament to her anterior abdominal wall.

Preoperative factors predicting survival after secondary cytoreduction for recurrent ovarian cancer.

OBJECTIVE: We evaluated preoperative data that may predict benefit from secondary cytoreductive surgery (CRS) to assist in selecting therapy for patients with platinum-sensitive recurrent epithelial ovarian cancer. MATERIALS AND METHODS: Inclusion criteria included recurrent epithelial or primary peritoneal carcinoma with an initial disease-free interval more than 6 months after chemotherapy, evidence of disease on imaging studies and indication for surgery being to debulk residual disease. Preoperative CA125 values, computed tomographic findings, and time to progression were evaluated as predictors of survival in addition to postoperative information and perioperative morbidity. RESULTS: Sixty-two patients met the inclusion criteria. In the 35.5% of patients debulked to no visible disease, median survival was significantly longer than in those with less than 1 cm of visible residual disease (5.95 vs 2.73 years, P=0.004), but debulking to less than 1 cm visible disease was not better than those with less than 1 cm residual disease (2.02 years). Mean preoperative CA125 levels were significantly lower in the patients who could be debulked to no visible residual disease compared to less than 1 cm or more than 1 cm residual disease (69.1 vs 290.7 vs 1978.4, P=0.001). Generation of a receiver operating characteristic curve determined that a CA125 cutoff of 250 U/mL best predicted successful cytoreduction to no visible disease. CONCLUSIONS: Only patients cytoreduced to no visible disease achieved a survival advantage, and the only preoperative factor that could predict surgical success regarding prolonging survival was a CA125 less than 250 U/mL. These data can guide physicians and patients in deciding whether or not to undergo secondary cytoreduction for first recurrence of ovarian cancer.

Clinical characteristics of patients with prolonged disease-free survival after primary treatment in advanced ovarian cancer: a brief report.

OBJECTIVE: Optimal cytoreduction and response to chemotherapy have been associated with prolonged disease-free survival (DFS), but there are limited data regarding the clinical characteristics of those patients with optimal 5-year DFS (5YrDFS) outcomes. METHODS: A case-control study was performed on 32 patients who were progression-free and alive at 5 years with advanced ovarian cancer 5YrDFS from 1993 to 2005 for this institutional review board-approved study. Matching controls were identified from the subset of patients who died or experienced disease progression before 5 years. RESULTS: One hundred sixty patients were evaluated. There was no statistical difference between cases and controls in regard to neoadjuvant chemotherapy, grade, race, preoperative cancer antigen-125 level, optimal cytoreduction, operating room time, length of hospital stay, or total chemotherapy cycles in regard to 5YrDFS. If a patient achieved complete response after primary treatment, the likelihood of progression-free survival 5 years or longer is 7 times more likely, (odds ratio = 7.2 [95% confidence interval = 2.3-22.4]; P = 0.0006). CONCLUSION: In this matched case-control analysis, complete response after primary treatment was the only significant factor associated with 5YrDFS. Further study is needed in patient and tumor characteristics to identify those patients who may have poor or favorable outcomes before treatment completion.

Neoadjuvant chemotherapy is associated with prolonged primary treatment intervals in patients with advanced epithelial ovarian cancer.

BACKGROUND: We evaluated the impact of neoadjuvant chemotherapy (NC) relative to primary surgery (PS) to determine if there was a difference in the total time and number of chemotherapy cycles given in patients with advanced epithelial ovarian cancer. METHODS: We identified 263 consecutive women meeting eligibility from 1993 to 2005 for this institutional review board-approved study. Eligible patients in this analysis were those women with advanced disease (stage IIIC-IV) in whom a maximal cytoreductive effort was planned either at PS or after NC. Time to start chemotherapy was defined as follows: (1) NC group: confirmation of diagnosis through biopsy, cytological diagnosis from ascites, and pleural effusion; (2) PS group: confirmation of diagnosis from the date of surgery that confirmed the diagnosis of epithelial ovarian cancer. Total chemotherapy cycles: (1) NC group: NC chemotherapy cycles plus postoperative cycles; (2) PS group: chemotherapy after primary tumor debulking surgery. Clinical information evaluated included chemotherapy type, chemotherapy cycle number, total time to administer frontline chemotherapy, and survival. RESULTS: Median chemotherapy cycles were greater in the NC group compared with the PS group (9 [range, 4-30] vs 6 [range, 3-19]; P < 0.01). The PS group was also more likely to undergo chemotherapy regimens involving platinum and taxane treatment compared with the NC group (79% vs 65%; P = 0.017). Total time undergoing primary chemotherapy from initial diagnosis was greater in the NC group compared with PS (223 vs 151 days; P < 0.01). No significant difference was observed in overall survival and progression-free survival in the 2 groups. CONCLUSIONS: In patients with advanced ovarian cancer, NC followed by abdominal hysterectomy is associated with improved perioperative outcomes including optimal cytoreduction, decreased blood loss, and decreased inpatient hospitalization. In this cohort, NC was also associated with prolonged chemotherapy treatment intervals and increased chemotherapy cycles without improvement in survival.

Limited utility of magnetic resonance imaging in determining the primary site of disease in patients with inconclusive endometrial biopsy.

OBJECTIVE: To evaluate the utility of preoperative magnetic resonance imaging (MRI) in determining whether primary disease site is cervical or endometrial in patients with inconclusive preoperative endometrial biopsy. METHODS: We retrospectively identified all patients who underwent pelvic MRI and who had a preoperative diagnosis of cervical or endometrial cancer at MD Anderson Cancer Center between 1990 and 2006. The subset in which endometrial biopsy did not clarify the primary disease site was analyzed. Magnetic resonance imaging results were compared with postoperative histopathologic findings. RESULTS: A total of 168 patients who underwent MRI who had a preoperative diagnosis of cervical or endometrial cancer were identified. Of these patients, 51 had an inconclusive endometrial biopsy. Magnetic resonance imaging suggested an endometrial primary tumor without cervical invasion in 28 patients, of whom 21 (75%) actually had such a tumor and 7 had an endometrial primary tumor with cervical invasion. Magnetic resonance imaging suggested an endometrial primary tumor with cervical invasion in 3 patients, all of whom had such a tumor. Magnetic resonance imaging suggested a cervical primary tumor in 6 patients, of whom 5 had such a tumor and 1 had an endometrial primary tumor without cervical invasion. Magnetic resonance imaging was inconclusive (did not clarify primary disease site or no lesion visualized) in 14 (27%) of 51 patients, 6 of whom had an endocervical primary tumor or an endometrial tumor with cervical involvement. Overall, preoperative MRI was either inaccurate or unhelpful in 22 (43%) of 51 patients. CONCLUSION: Preoperative MRI in patients with inconclusive endometrial biopsy is inaccurate or unhelpful in nearly half of patients.

Microscopic evaluation of lymph-node-bearing tissue in early-stage cervical cancer: a dual-institution review.

OBJECTIVE: We compared two different methods of microscopic lymph node examination of cervical cancer radical hysterectomy specimens to ascertain which method translates into higher nodal counts and improved detection of nodal metastasis, at M. D. Anderson Cancer Center (MDACC) and the University of North Carolina (UNC). METHODS: We retrospectively reviewed the records of 155 patients with early-stage cervical cancer who underwent open radical hysterectomy and pelvic lymph node dissection from 2000 to 2006. At MDACC lymph nodes were grossly dissected from submitted adipose tissue surgical specimens and then microscopically examined. At UNC, grossly detected lymph nodes and the remaining adipose tissue were microscopically examined. Data regarding clinicopathologic features and lymph node dissection were available for all patients. RESULTS: No differences in stage, grade or histology were noted between the two centers. The median age and body mass index were both higher at MDACC (40 versus 36 years of age; 28 versus 26 mg/m(2); P < 0.05) The median lymph node count was lower at MDACC (16 versus 23; P = 0.001). By multivariate analysis, UNC evaluation was associated with higher total lymph node count (P = 0.001). However, no significant difference was noted between institutions in proportion of patients with nodal metastases (MDACC 20.3%; UNC 13.5%; P = 0.47). CONCLUSION: The UNC method of microscopically examining the entire adipose tissue sample may be associated with higher nodal count at open radical hysterectomy. Higher nodal count, however, may not translate into increased identification of nodal metastases.

Molecular clustering of endometrial carcinoma based on estrogen-induced gene expression.

Identification of biomarkers potentially provides prognostic information that can help guide clinical decision-making. Given the relationship between estrogen exposure and endometrial cancer, especially low grade endometrioid carcinoma, we hypothesized that high expression of genes induced by estrogen would identify low risk endometrioid endometrial cancers. cDNA microarray and qRT-PCR verification were used to identify six genes that are highly induced by estrogen in the endometrium. These estrogen-induced biomarkers were quantified in 72 endometrial carcinomas by qRT-PCR. Unsupervised cluster analysis was performed, with expression data correlated to tumor characteristics. Time to recurrence by cluster was analyzed using the Kaplan-Meier method. A receiver operating characteristic (ROC) curve was generated to determine the potential clinical utility of the biomarker panel to predict prognosis. Expression of all genes was higher in endometrioid carcinomas compared to non-endometrioid carcinomas. Unsupervised cluster analysis revealed two distinct groups based on gene expression. The high expression cluster was characterized by lower age, higher BMI, and low grade endometrioid histology. The low expression cluster had a recurrence rate 4.35 times higher than the high expression cluster. ROC analysis allowed for the prediction of stage and grade with a false negative rate of 4.8% based on level of gene expression in endometrioid tumors. We have therefore identified a panel of estrogen-induced genes that have potential utility in predicting endometrial cancer stage and recurrence risk. This proof-of-concept study demonstrates that biomarker analysis may play a role in clinical decision making for the therapy of women with endometrial cancer.

Uterine smooth muscle tumor of uncertain malignant potential: a retrospective analysis.

OBJECTIVE: This retrospective study was designed to evaluate the clinicopathologic features and outcomes of a cohort of patients diagnosed with uterine smooth muscle tumor of uncertain malignant potential (STUMP) seen at a single institution. METHODS: All patients diagnosed with uterine STUMP and seen between 1990 and 2005 at The University of Texas M. D. Anderson Cancer Center were identified using the institution's databases. Variables of interest included age at diagnosis, recurrence rate, and disease-free and overall survival. RESULTS: Forty-one patients with uterine STUMP were identified and included in the study. The mean age at diagnosis was 43 years (range 25-75 years). The mean follow-up time was 45 months (range 1-171 months). Three patients (7.3%) had a recurrence during the follow-up period. One of the three patients who had recurrent disease was found to have a leiomyosarcoma at the time of recurrence. Recurrence rates were similar for women who underwent myomectomy and those who underwent hysterectomy. All three patients with recurrence were alive and disease-free at a mean follow-up time of 121 months. CONCLUSION: Our results suggest that in this cohort of patients with uterine STUMP the recurrence rate was 7%. Recurrences can be in the form of STUMP or leiomyosarcoma.

Postoperative small bowel obstruction associated with use of hemostatic agents.

A case of early postoperative small bowel obstruction (SBO) after intraoperative use of hemostatic agents during laparoscopic staging for endometrial cancer is reported. A 46-year-old woman underwent a laparoscopic staging procedure for endometrial cancer during which hemostatic agents were used in the management of an iatrogenic injury to the inferior vena cava. The patient returned on postoperative day 6 with SBO and was taken to the operating department. She required a small bowel resection in the specific area where the hemostatic agents were used. Pathology showed extensive fibrotic changes caused by a foreign material that was suggestive of a thrombin-related product. Use of hemostatic agents should be considered as a cause in the differential diagnosis of patients with early postoperative SBO.

Enhanced estrogen-induced proliferation in obese rat endometrium.

OBJECTIVE: We tested the hypothesis that the proliferative estrogen effect on the endometrium is enhanced in obese vs lean animals. STUDY DESIGN: Using Zucker fa/fa obese rats and lean control, we examined endometrial cell proliferation and the expression patterns of certain estrogen-regulated proproliferative and antiproliferative genes after short-term treatment with estradiol. RESULTS: No significant morphologic/histologic difference was seen between the obese rats and the lean rats. Estrogen-induced proproliferative genes cyclin A and c-Myc messenger RNA expression were significantly higher in the endometrium of obese rats compared with those of the lean control. Expression of the antiproliferative gene p27Kip1 was suppressed by estrogen treatment in both obese and lean rats; however, the decrease was more pronounced in obese rats. Estrogen more strongly induced the antiproliferative genes retinaldehyde dehydrogenases 2 and secreted frizzled-related protein 4 in lean rats but had little or no effect in obese rats. CONCLUSION: Enhancement of estrogen-induced endometrial proproliferative gene expression and suppression of antiproliferative gene expression was seen in the endometrium of obese vs lean animals.

Preoperative pathologic findings associated with residual disease at radical hysterectomy in women with stage IA2 cervical cancer.

OBJECTIVE: To correlate findings on pathologic examination of loop electroexcisional procedure (LEEP) or cone biopsy specimens with residual disease in radical hysterectomy specimens in patients with stage IA2 cervical cancer to determine whether a subset of such patients may be eligible for conservative, fertility-sparing treatment. METHODS: We performed a retrospective chart review of patients diagnosed with stage IA2 cervical cancer who had undergone LEEP or cone biopsy before radical hysterectomy. Surgicopathologic features of LEEP and cone biopsy specimens were correlated with the presence or absence of residual tumor in radical hysterectomy specimens. RESULTS: Forty-two patients met the inclusion criteria. At radical hysterectomy, 22 patients (52%) had no residual tumor, while 20 patients (48%) had residual disease. Margin status was the only statistically significant predictor of the presence or absence of residual disease at radical hysterectomy; positive margins predicted the presence of residual disease (P<0.001). CONCLUSION: Women with stage IA2 cervical cancer and negative margins on LEEP or cone biopsy specimens should be counseled that they may be at low risk for having residual disease in the final radical hysterectomy specimen.

Limited public knowledge of obesity and endometrial cancer risk: what women know.

OBJECTIVE: To estimate if women in the general population are aware of the relationship between obesity and cancer risk, and to identify groups who may benefit from educational programs. METHODS: A self-administered survey was distributed to women in the Houston community. The questions were taken from a bank of validated questions published by the Center for Disease Control, Behavioral Risk Factor Surveillance System, and the Harvard Forums on Health Survey. Demographic information and participant knowledge of obesity-related cancer risk was collected. Logistic regression and Cochran-Armitage tests for trend were use to assess the association between predictor variables and knowledge. RESULTS: One thousand five hundred forty-five women completed the survey; 28% were normal weight (body mass index [BMI] less than 25 kg/m(2)), 24% were overweight (BMI 25-30 kg/m(2)), and 45% were obese (BMI at least 30 kg/m(2)). Fifty-eight percent (95% confidence interval 56-61%) were not aware that obesity increased risk for endometrial cancer. There was no difference in knowledge of endometrial cancer risk associated with any of the demographic characteristics studied. Black women were the most likely to respond that they did not know about the relationship between obesity and cancer. There was no association between personal weight and knowledge of obesity-associated risk. CONCLUSION: There is limited knowledge of the relationship between obesity and cancer risk, particularly among black women. Patient education regarding these risks may increase awareness of the relationship between obesity and endometrial cancer among women.

Radical hysterectomy in obese and morbidly obese women with cervical cancer.

OBJECTIVE: To compare intraoperative and postoperative outcomes, pathologic findings, cancer recurrence, and death rates in normal-weight, overweight, obese, and morbidly obese women undergoing radical hysterectomy and pelvic lymphadenectomy for early-stage cervical cancer. METHODS: A review of patients who underwent radical hysterectomy and pelvic lymphadenectomy for invasive cervical cancer between 1990 and 2006 was performed. On the basis of body mass index (BMI) (calculated as weight [kg]/[height (m)](2)), women were categorized as normal weight (BMI 18.5-24.9), overweight (BMI 25.0-29.9), obese (BMI 30.0-34.9), or morbidly obese (BMI at least 35.0). RESULTS: Four hundred eight women met the inclusion criteria. Of these, 155 (38%) were normal weight, 126 (31%) were overweight, 77 (19%) were obese, and 50 (12%) were morbidly obese. There were no statistically significant differences between these four groups in age, Charlson comorbidity score, smoking history, stage, histologic grade or subtype, tumor size, depth of invasion, transfusion rate, operative time, or intraoperative complications. Higher BMI was significantly correlated with higher estimated operative blood loss (P=.001). There were no statistically significant differences between the groups in pathologic findings, length of postoperative hospital stay, postoperative complications, readmission rate, or proportion of women receiving adjuvant radiotherapy. At a median follow-up time of 64 months, there were no differences between groups in rates of recurrence or death from disease. CONCLUSION: Radical hysterectomy and pelvic lymphadenectomy is feasible for obese and morbidly obese women with cervical cancer. Obesity alone should not be a contraindication to radical hysterectomy in women with cervical cancer.

Genetic polymorphisms and endometrial cancer risk.

For most sporadic cancers, genetic susceptibility results from the additive effect of multiple genetic variants, each of which contributes a modest risk individually. The study of genetic single nucleotide polymorphisms (SNPs) may help explain the differences in individual cancer susceptibility and may assist in identifying novel markers of risk that can be utilized to create more effective and tailored cancer prevention strategies. Genetic polymorphisms in functionally critical genes have been suggested as risk factors for the development of a variety of cancers, including endometrial cancer. Candidate SNPs may be involved in DNA damage repair, steroid metabolism, carcinogen metabolism, cell-cycle control, apoptosis and steroid receptor activation pathways. In this review, recent findings of genetic association studies exploring genetic polymorphisms and their association with endometrial cancer are reported. In addition, the challenges of genetic association studies, such as power and bias, and the need for validation of promising findings are explored.

Efficacy of letrozole in the treatment of recurrent platinum- and taxane-resistant high-grade cancer of the ovary or peritoneum.

OBJECTIVE: To evaluate the efficacy and safety of letrozole in patients with recurrent platinum- and taxane-resistant estrogen receptor-positive (ER+) high-grade cancer of the ovary or peritoneum. METHODS: A single-institution, phase II study was performed in women with recurrent ER+ epithelial carcinoma of the ovary or peritoneum. All patients had measurable disease. Letrozole was administered at a dose of 2.5 mg orally once daily until disease progression or toxicity occurred. RESULTS: Thirty-three patients were enrolled. The median age was 63 years (range, 38 to 83 years). Twenty-three patients (74%) had received three or more prior chemotherapy regimens. The 31 patients evaluable for response received a total of 81 cycles (4 weeks/cycle) of therapy (range, 1 to 14 cycles/patient). The median treatment duration was 8 weeks (range, 4 to 52 weeks). None of the patients had a complete response (CR), 1 (3%) had a partial response (PR), and 7 (23%) had stable disease (SD). The median duration of clinical benefit (SD and PR) was 9 weeks (range, 7 to 46 weeks). The median follow-up for all patients was 25 weeks. All patients were evaluable for toxicity. The most common adverse effects were fatigue (36%) and diaphoresis (21%). No grade 3 or 4 toxicities were reported, and no patients discontinued treatment owing to adverse effects. Eighteen patients (58%) went on to receive additional therapy with other agents. CONCLUSION: In patients with ER-positive, platinum- and taxane-resistant high-grade ovarian and primary peritoneal cancer treated with letrozole, 26% derived a clinical benefit (SD and PR).