Hindawi Publishing Corporation Obstetrics and Gynecology International Volume 2011, Article ID 128295, 5 pages doi:10.1155/2011/128295 Review Article erbB2 Overexpression in Uterine Serous Cancer: A Molecular Target for Trastuzumab Therapy Karim S. ElSahwi and Alessandro D. Santin Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, P.O. Box 208063, New Haven, CT 06520-8063, USA Correspondence should be addressed to Alessandro D. Santin, alessandro.santin@yale.edu Received 30 May 2011; Revised 27 June 2011; Accepted 27 June 2011 Academic Editor: Bradley J. Monk Copyright © 2011 K. S. ElSahwi and A. D. Santin. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Endometrial cancer is the most common female genital tract malignancy in the United States. Type I endometrial cancer is usually diagnosed at an early stage, and has a good prognosis. Type II is very aggressive, and is responsible for most uterine cancer relapses and deaths. Uterine serous adenocarcinomas (USC) constitute the majority of Type II variants. They have a higher propensity for lymph node and distant metastases. They are frequently aneuploid and associated with p53 mutations. erbB2 overexpression in USC has been described. The incidence, which is higher in African Americans, ranges from 18–80%. erbB2 overexpression was found to be associated with higher stage, chemoresistance, and worse survival. Trastuzumab a humanized mAb was approved by the FDA for treatment of breast cancers that overexpress erbB2 in combination with standard chemotherapy. Evidence of trastuzumab activity in USC has been reported in vitro, as well as in case reports of advanced and recurrent cases. Promising results were obtained in these heavily pretreated patients either with trastuzumab alone or in combination with chemotherapy. This supports the hypothesis that trastuzumab may very well be an attractive and viable treatment option for advanced stage USC tumors that overexpress the erbB2, and is worthy of further study. 1. Endometrial Cancer Endometrial cancer is the most common female genital tract malignancy in the United States, with an incidence of 40100 new cases and 7470 deaths annually [1]. Type I endometrial cancer, which has an endometrioid histology, is associated with obesity, estrogen excess, and is heralded by endometrial hyperplasia. It is usually diagnosed at an early stage and has a good prognosis. On the other hand, Type II endometrial cancer is a very aggressive variant of the disease and is responsible for about 50% of all uterine cancer relapses and most deaths [2]. 2. Uterine Serous Cancer Uterine serous adenocarcinomas (USC) constitute the ma- jority of Type II variants, and about 10% of all endometrial cancers [3]. USC has a higher propensity for lymphovascular invasion, and intraperitoneal as well as extraabdominal spread, than endometrioid carcinoma. It also has a signif- icantly greater incidence of pelvic and para-aortic lymph node metastases [4]. At the time of presentation, approx- imately 60 to 70 percent of women with USC will have- disease spread outside of the uterus [3]. Overall 1-year-, 2-year-, and 5-year-survival in USC is 84%, 71%, and 54%, respectively. This is compared to a respective overall survival of 94%, 89%, and 80% in endometrioid adenocarcinoma [5]. In a Yale series, there was no survival diﬀerence between stage I patients who had 10–50% of the endometrial carcinoma composed of USC compared with those with more than 50% USC [6]. Surgical staging remains the mainstay of treatment of USC, as the majority of patients with disease clinically con- ﬁned to the uterus will be upstaged (57–70%) Staging entails a hysterectomy, bilateral salpingo-oopherectomy, omentec- tomy, bilateral pelvic lymphadenectomy, para-aortic node