4 tolerated in these patients and, consistent with these results, the single agent use of trastuzumab in a Phase II study of advanced/recurrent endometrial cancer patients by the GOG did not identify any new toxicities or an increased frequency of currently reported toxicities of trastuzumab [35]. In this regard, the major potential toxicities associated with trastuzumab use may include infusion reactions, embryo- fetal toxicity, pulmonary toxicity, and cardiotoxicity. Impor- tantly, the incidence of congestive heart failure and cardiac dysfunction in breast cancer patients have been shown to range from 0.4–3.8% in the major adjuvant trastuzumab trials and to be higher in patients receiving trastuzumab with anthracycline containing chemotherapy regimens [30–33]. The above data support the hypothesis that Herceptin may very well be an attractive and viable treatment option for advanced stage USC tumors that overexpress the erbB2 receptor. This constitutes the merit of a multi-institutional randomized trial due to open soon in the United States (clini- caltrials.gov/ct2/show/NCT01367002). The primary objective of this phase II study is to evaluate whether the addition of trastuzumab (Herceptin) to paclitaxel and carboplatin chemotherapy improves progression free survival (PFS) when compared to paclitaxel and carboplatin alone in stages III-IV and recurrent USC patients overexpressing HER2/neu at 3+ level by IHC or positive by FISH. The secondary objectives of the study include (a) assess objective response rate (ORR), (b) assess overall survival (OS), and (c) assess the safety proﬁle of trastuzumab in USPC patients. The exploratory/correlative objectives of the study include (a) determine peripheral blood natural killer (NK) cell numbers and activity in HER2/neu+ USC patients to provide a basis for assessing the possible therapeutic contributions of immune mechanisms of action of trastuzumab, (b) study HER2/neu extracellular domain (ECD) circulating levels in the plasma of USC patients overexpressing HER2/neu before, during and after treatment to elucidate whether changes in HER2/neu ECD would predict response to trastuzumab, and (c) determine whether CA-125 levels correlate with disease activity in advanced and/or recurrent disease. As predicted in 2003, the Achilles heel of USC may soon be exposed [40]. References [1] A. Jemal, R. Siegel, J. Xu, and E. Ward, “Cancer statistics, 2010,” CA Cancer Journal for Clinicians, vol. 60, no. 5, pp. 277– 300, 2010. [2] P. E. Schwartz, “The management of serous papillary uterine cancer,” Current Opinion in Oncology, vol. 18, no. 5, pp. 494– 499, 2006. [3] B. M. Slomovitz, T. W. Burke, P. J. Eifel et al., “Uterine papillary serous carcinoma (UPSC): a single institution review of 129 cases,” Gynecologic Oncology, vol. 91, no. 3, pp. 463–469, 2003. [4] F. Amant, P. Moerman, P. Neven, D. Timmerman, E. Van Limbergen, and I. Vergote, “Endometrial cancer,” Lancet, vol. 366, no. 9484, pp. 491–505, 2005. [5] W. T. Creasman, F. Odicino, P. Maisonneuve et al., “Carcinoma of the corpus uteri,” Journal of Epidemiology and Biostatistics, vol. 6, no. 1, pp. 47–86, 2001. Obstetrics and Gynecology International [6] M. G. Kelly, D. M. O’Malley, P. Hui et al., “Improved survival in surgical stage I patients with uterine papillary serous car- cinoma (UPSC) treated with adjuvant platinum-based chem- otherapy,” Gynecologic Oncology, vol. 98, no. 3, pp. 353–359, 2005. [7] B. A. Goﬀ, “Uterine papillary serous carcinoma: what have we learned over the past quarter century?” Gynecologic Oncology, vol. 98, no. 3, pp. 341–343, 2005. [8] C. A. Hamilton, W. S. Liou, K. Osann et al., “Impact of ad- juvant therapy on survival of patients with early-stage uterine papillary serous carcinoma,” International Journal of Radiation Oncology Biology Physics, vol. 63, no. 3, pp. 839–844, 2005. [9] J. D. Martin, B. Gilks, and P. Lim, “Papillary serous carci- noma—a less radio-sensitive subtype of endometrial cancer,” Gynecologic Oncology, vol. 98, no. 2, pp. 299–303, 2005. [10] K. M. Alektiar, V. Makker, N. R. Abu-Rustum et al., “Con- current carboplatin/paclitaxel and intravaginal radiation in surgical stage I-II serous endometrial cancer,” Gynecologic Oncology, vol. 112, no. 1, pp. 142–145, 2009. [11] S. Acharya, M. L. Hensley, A. C. Montag, and G. F. Fleming, “Rare uterine cancers,” Lancet Oncology, vol. 6, no. 12, pp. 961–971, 2005, Erratum: Lancet Oncology, vol. 7, no. 2, p. 105, 2005. [12] A. D. Santin, S. Bellone, S. Van Stedum et al., “Ampliﬁcation of c-erbB2 oncogene: a major prognostic indicator in uterine serous papillary carcinoma,” Cancer, vol. 104, no. 7, pp. 1391– 1397, 2005. [13] S. F. Lax, “Molecular genetic pathways in various types of endometrial carcinoma: from a phenotypical to a molecular- based classiﬁcation,” Virchows Archiv, vol. 444, no. 3, pp. 213– 223, 2004. [14] A. D. Santin, S. Bellone, M. Gokden et al., “Overexpression of HER-2/neu in uterine serous papillary cancer,” Clinical Cancer Research, vol. 8, no. 5, pp. 1271–1279, 2002. [15] A. D. Santin, F. Zhan, S. Cane et al., “Gene expression ﬁnger- print of uterine serous papillary carcinoma: identiﬁcation of novel molecular markers for uterine serous cancer diagnosis and therapy,” British Journal of Cancer, vol. 92, no. 8, pp. 1561– 1573, 2005. [16] F. E. Odicino, E. Bignotti, E. Rossi et al., “HER-2/neu overex- pression and ampliﬁcation in uterine serous papillary carcino- ma: comparative analysis of immunohistochemistry, real-time reverse transcription-polymerase chain reaction, and ﬂuores- cence in situ hybridization,” International Journal of Gyneco- logical Cancer, vol. 18, no. 1, pp. 14–21, 2008. [17] T. P. D´ıaz-Montes, H. Ji, A. E. Smith Sehdev et al., “Clinical signiﬁcance of Her-2/neu overexpression in uterine serous carcinoma,” Gynecologic Oncology, vol. 100, no. 1, pp. 139– 144, 2006. [18] A. D. Santin, S. Bellone, E. R. Siegel et al., “Racial diﬀerences in the overexpression of epidermal growth factor type II receptor (HER2/neu): a major prognostic indicator in uterine serous papillary cancer,” American Journal of Obstetrics and Gynecol- ogy, vol. 192, no. 3, pp. 813–818, 2005. [19] A. D. Santin, S. Bellone, S. Van Stedum et al., “Determination of HER2/neu status in uterine serous papillary carcinoma: comparative analysis of immunohistochemistry and ﬂuores- cence in situ hybridization,” Gynecologic Oncology, vol. 98, no. 1, pp. 24–30, 2005. [20] T. A. Grushko, V. L. Filiaci, A. J. Mundt, K. Ridderstra˚le, O. I. Olopade, and G. F. Fleming, “An exploratory analysis of HER- 2 ampliﬁcation and overexpression in advanced endometrial carcinoma: a gynecologic oncology group study,” Gynecologic Oncology, vol. 108, no. 1, pp. 3–9, 2008.