Cancer testis antigen (CTAg) expression in early-stage triple negative (TN) breast cancer.

Abstract

e21100 Background: There are limited treatment options for TN breast cancer, as there is no role for hormone therapy or trastuzumab. Expression of CTAgs is confined to testis and cancer cells, making them ideal targets for specific vaccine treatment. We examined the expression of 4 CTAgs (MAGE-A3, NY-ESO-1, MAGE-A1, and MAGE-C1) in TN breast cancer to evaluate their potential as targets for vaccine treatment. We also investigated the association between CTAg expression and histopathologic prognostic factors. Methods: 39 patients with histologically confirmed early-stage TN breast cancer resected at Austin Hospital and The Northern Hospital from January 1, 2001 to February 28, 2009 were included. Immunohistochemical staining was performed on tissue microarrays of formalin-fixed paraffin-embedded tissues, with human testis as the positive control. We examined the proportion of tumours expressing CTAgs, percent of tumour area stained, and intensity of staining (semi-quantitative). Associations between CTAg expression and histopathologic prognostic factors were tested using Fisher's exact tests. Results: 82% (32/39; 95% CI 0.69 – 0.95) of tumours expressed one or more CTAg; MAGE-A3 was expressed in 59% (23/39; 95% CI 0.43 – 0.75), NY-ESO-1 in 51% (20/39; 95% CI 0.35 – 0.68), MAGE-A1 in 33% (13/39; 95% CI 0.18 – 0.49), and MAGE-C1 in 33% (13/39; 95% CI 0.18 – 0.49). There was co-expression of ≥2 CTAgs in 59% (23/39; 95% CI 0.43 – 0.75) of tumours. Staining of >50% of tumour area was observed most frequently in tumours expressing MAGE-A3 and NY-ESO-1 (30% and 20% of tumours, respectively); these CTAgs also had higher staining intensity. There was a positive association between CTAg expression and tumour grade (p = 0.02), but no association with T stage, nodal involvement, multifocal tumour, lymphovascular invasion or necrosis. Conclusions: We found that CTAg expression is very common in early-stage TN breast cancer. There was a positive association between CTAg expression and tumour grade. Staining of >50% of tumour area and higher staining intensity was most frequently observed in tumours expressing MAGE-A3 and NY-ESO-1. Development of vaccines against these CTAgs may have potential in TN breast cancer. No significant financial relationships to disclose.