Purpose Uterine serous carcinoma is a rare, aggressive variant of endometrial cancer. Trastuzumab is a humanized monoclonal antibody that targets human epidermal growth factor receptor 2 (HER2)/neu, a receptor overexpressed in 30% of uterine serous carcinoma. This multicenter, randomized phase II trial compared carboplatin-paclitaxel with and without trastuzumab in patients with advanced or recurrent uterine serous carcinoma who overexpress HER2/neu. Methods Eligible patients had primary stage III or IV or recurrent HER2/neu-positive disease. Participants were randomly assigned to receive carboplatin-paclitaxel (control arm) for six cycles with or without intravenous trastuzumab (experimental arm) until progression or unacceptable toxicity. The primary end point was progression-free survival, which was assessed for differences between treatment arms via one-sided log-rank tests. Results From August 2011 to March 2017, 61 patients were randomly assigned. Forty progression-free survival-related events occurred among 58 evaluable participants. Among all patients, median progression-free survival was 8.0 months (control) versus 12.6 months (experimental; P = .005; hazard ratio [HR], 0.44; 90% CI, 0.26 to 0.76). Similarly, median progression-free survival was 9.3 (control) versus 17.9 (experimental) months among 41 patients with stage III or IV disease undergoing primary treatment ( P = .013; HR, 0.40; 90% CI, 0.20 to 0.80) and 6.0 (control) versus 9.2 months (experimental), respectively, among 17 patients with recurrent disease ( P = .003; HR, 0.14; 90% CI, 0.04 to 0.53). Toxicity was not different between treatment arms, and no unexpected safety signals emerged. Conclusion Addition of trastuzumab to carboplatin-paclitaxel was well tolerated and increased progression-free survival. These encouraging results deserve further investigation to determine their impact on overall survival in patients with advanced or recurrent uterine serous carcinoma who overexpress HER2/neu.

Purpose: Uterine-serous-carcinoma (USC) is an aggressive variant of endometrial cancer. On the basis of preliminary results of a multicenter, randomized phase II trial, trastuzumab (T), a humanized-mAb targeting Her2/Neu, in combination with carboplatin/ paclitaxel (C/P), is recognized as an alternative in treating advanced/ recurrent HER2/Neu-positive USC. We report the updated survival analysis of NCT01367002.Patients and Methods: Eligible patients had stage III to IV or recurrent disease. Participants were randomized 1:1 to receive C/P for six cycles AE T followed by maintenance T until progression or toxicity. Progression-free survival (PFS) was the primary endpoint; overall survival (OS) and toxicity were secondary endpoints.Results: Sixty-one patients were randomized. After a medianfollow-up of 25.9 months, 43 progressions and 38 deaths occurred among 58 evaluable patients. Updated median-PFS continued to favor the T-arm, with medians of 8.0 months versus 12.9 months in the control and T-arms (HR ¼ 0.46; 90% CI, 0.28-0.76; P ¼ 0.005). Median-PFS was 9.3 months versus 17.7 months among 41 patients with stage III to IV disease undergoing primary treatment (HR ¼ 0.44; 90% CI, 0.23-0.83; P ¼ 0.015), and 7.0 months versus 9.2 months among 17 patients with recurrent disease (HR ¼ 0.12; 90% CI, 0.03-0.48; P ¼ 0.004). OS was higher in the T compared with the control arm, with medians of 29.6 months versus 24.4 months (HR ¼ 0.58; 90% CI, 0.34-0.99; P ¼ 0.046). The benefit was most notable in those with stage III to IV disease, with survival median not reached in the T-arm versus 24.4 months in the control arm (HR ¼ 0.49; 90% CI, 0.25-0.97; P ¼ 0.041). Toxicity was not different between arms.Conclusions: Addition of T to C/P increased PFS and OS in women with advanced/recurrent HER2/Neu-positive USC, with the greatest benefit seen for the treatment of stage III to IV disease.

Objective Impaired glucose tolerance and diabetes are risk factors for the development of uterine cancer. Although greater progression free survival among diabetic patients with ovarian and breast cancer using metformin have been reported, no studies have assessed the association of metformin use with survival in women with endometrial cancer (EC). Methods We conducted a single-institution retrospective cohort study of all patients treated for uterine cancer from January 1999 through December 2009. Demographic, medical, social, and survival data were abstracted from medical records and the national death registry. Overall survival (OS) was estimated using Kaplan-Meier methods. Cox models were utilized for multivariate analysis. All statistical tests were two-sided. Results Of 985 patients, 114 (12%) had diabetes and were treated with metformin, 136 (14%) were diabetic but did not use metformin, and 735 (74%) had not been diagnosed with diabetes. Greater OS was observed in diabetics with non-endometrioid EC who used metformin than in diabetic cases not using metformin and non-endometrioid EC cases without diabetes (log rank test (p=0.02)). This association remained significant (hazard ratio = 0.54, 95% CI: 0.30–0.97, p<0.04) after adjusting for age, clinical stage, grade, chemotherapy treatment, radiation treatment and presence of hyperlipidemia in multivariate analysis. No association between metformin use and OS in diabetics with endometrioid histology was observed. Conclusion Diabetic EC patients with non-endometrioid tumors who used metformin had lower risk of death than women with EC who did not use metformin. These data suggest that metformin might be useful as adjuvant therapy for non-endometrioid EC.

Introduction Identification of sexual dysfunction may help physicians diagnose problems such as diabetes, pituitary tumors, atherosclerosis, and depression. Sexual concerns are common among patients; however, there is evidence to suggest that these concerns are not appropriately investigated by clinicians. Aim To examine the impact of physician gender on sexual history taking. Methods One hundred and thirty-one study questionnaires were sent to OB/Gyns, family practitioners, internists, pediatricians, and surgeons. Physicians were asked to rank their discomfort during interviews with patients of different ages, races, marital status, sexual preference, religious beliefs, and academic achievement, and they were asked to rank their perception of patient discomfort. Main Outcome Measures A cross-sectional descriptive analysis was generated, Fisher's exact test was performed utilizing SPSS software, and confidence intervals were developed utilizing SAS software. Results Of the 78 questionnaires (59%) returned, 69 (88%) reported taking sexual histories. Characteristics identified by physicians as causing discomfort included patient's age younger than 18 and greater than 65, patient's academic achievement below college level, and patient's divorced or single marital status. Moreover, there was a statistically significant difference (P &lt; 0.05) between male and female physicians reporting their discomfort when interviewing males (19% and 50%, respectively) and females (35% and 12%, respectively). Conclusion Although a high percentage of practitioners report taking a sexual history, physicians reported and perceived greatest discomfort when interviewing opposite gender patients as well as patients of very young and old ages. It is clear that not only is there a need for physician education on the topic of sexual history taking, but also consideration of the impact of physician and patient gender.