The case for HER2/neu as a therapeutic target for gynecologic malignancies

Evaluation of: Guzzo F, Bellone S, Buza N et al. HER2/neu as a potential target for immunotherapy in gynecological carcinosarcomas. Int. J. Gynecol. Pathol. 31, 211-221 (2012). Trastuzumab (Herceptin(®)) is a human monoclonal antibody that is US FDA-approved for the treatment of HER2/neu-overexpressing breast cancer and metastatic gastric cancer. HER2/neu expression has also been observed in other malignancies, notably in subsets of endometrial and ovarian cancers, raising the possibility that trastuzumab may be a viable treatment option in these settings. The current paper reveals that HER2/neu may also be expressed in gynecologic carcinosarcomas, which are rare but aggressive tumors with a high rate of resistance to chemotherapy. Cell lines derived from ovarian carcinosarcomas expressed HER2/neu and were sensitive to trastuzumab ADCC. By contrast, cell lines derived from uterine carcinosarcomas were HER2/neu-negative and insensitive to trastuzumab ADCC. These observations indicate that at least a subset of gynecologic carcinosarcoma patients may benefit from trastuzumab treatment. However, trastuzumab monotherapy typically has relatively low response rates, which in part may be related to impaired NK cell function in patients with advanced disease. Accordingly, treatments that boost NK cell activity may improve response rates to trastuzumab treatment, not only for gynecologic carcinosarcomas, but also for other HER2/neu-positive malignancies.