Tumor escape and progression of HER-2/neu negative breast cancer under immune pressure

• Main Authors: Wang Xiang-Yang, Wang Ena, Graham Laura, Ascierto Maria-Libera, Grimes Margaret M, Idowu Michael O, Payne Kyle K, Kmieciak Maciej, Bear Harry D, Manjili Masoud H
• Format: Article
• Language: English
• Published: BMC 2011-03-01
• Series: Journal of Translational Medicine
• Online Access: http://www.translational-medicine.com/content/9/1/35

<p>Abstract</p> <p>Background</p> <p>Emerging data from pre-clinical and clinical studies suggest that HER-2/neu-specific T cell responses could induce HER-2/neu antigen loss in the tumor cells. These data suggest that patients with HER-2/neu negative breast cancer might have had HER-2/neu positive premalignant lesions in the past that progressed to HER-2/neu negative breast cancer under HER-2/neu-specific immune pressure.</p> <p>Methods</p> <p>We conducted a pilot study in patients with HER-2/neu positive and HER-2/neu negative breast cancers as well as a patient with ductal carcinoma in situ (DCIS). HER-2/neu expression was determined by FISH. HER-2/neu-specific T cell responses were determined by using IFN-γ ELISA. Expression of IFN-γ Rα in the tumors was determined by immunohistochemistry analysis of paraffin-embedded tissues.</p> <p>Results</p> <p>We determined that majority of (10 of 12) patients with HER-2/neu negative breast cancer had HER-2/neu-specific IFN-γ producing T cell responses which was stronger than those in patients with HER-2/neu positive tumors. Such immune responses were associated with nuclear translocation of IFN-γ Rα in their tumor cells. Patient with DCIS also showed HER-2/neu-specific T cell responses.</p> <p>Conclusion</p> <p>These data suggest that conducting retrospective studies in patients with HER-2/neu negative breast cancers and prospective studies in patients with HER-2/neu positive DCIS can determine whether HER-2/neu negative invasive carcinomas arise from HER-2/neu positive DCIS under the immune pressure.</p>