Background: Cancer-Testis Antigens (CTAs) are immunogenic molecules that have increased expression in triple negative breast cancers (TNBC), a phenotype that whilst associated with poorer survival, is chemosensitive. We investigated expression of the CTAs MAGE-A, MAGE-C1, and NY-ESO-1 in women with Locally Advanced Breast Cancers (LABC) and TNBC to determine the association between CTA expression, survival and response to chemotherapy. Methods: We reviewed patient charts, treated for either TNBC or LABC between 1997 and 2011. Tissue samples were used for immunohistochemical (IHC) staining for MAGE-A, MAGE-C1 and NY-ESO-1 and compared using Fisher’s exact test. Positive expression was defined as any antigen staining above background.. Clinicopathological features were correlated with IHC results and survival estimated using the Kaplan Meier method. Results: A total of 106 cases were investigated (64 TNBC and 42 LABC). In the TNBC cohort the median age was 58 and TNM stages 1 to 3c. CTA expression occurred in 56, 51 and 43% for MAGE-A, MAGE-C1 and NY-ESO-1 respectively. CTA expression was not associated with overall survival (OS) or time to progression. In the LABC cohort the median age was 54 and consisted of stage IIIb tumors. All breast cancer subtypes were represented. CTA expression occurred in 26, 64 and 21% for MAGE-A, MAGE-C1 and NY-ESO-1 respectively. There was no association between CTA expression and response to chemotherapy. In a univariate analysis MAGE-A expression in the LABC group was associated with poorer OS (median 25 vs 76 months, HR 3.347 95% CI 1.44 to 21.68, p=0.015). However, there were more TN patients and Grade 3 tumors in the MAGE-A positive group. Across the two groups, MAGE-A (51 vs 14% p=0.002) and NY-ESO-1 (37 vs 2% p=0.006) but not MAGE-C1 had significantly higher expression in ER -ve tumors. There was higher expression of MAGE-A (51 vs 25% p=0.025) and NY-ESO-1 (43 vs 10% p=0.002) in Grade 3 tumors. Conclusions: MAGE-A, MAGE-C1 and NY-ESO-1 are highly expressed in TNBC and high-grade subsets of early breast cancer. CTA expression in TNBC was not predictive of survival nor response to chemotherapy in LABC. However, MAGE-A expression was found to be associated with poorer overall survival in LABC.