Influence of Cytokeratin 5/6, EGFR, p53 and Ki-67 Index on Pathologic Complete Response Rate to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancers: Preliminary Results from the I-SPY TRIAL (CALGB 150007/150012 and ACRIN 6657)
CA Livasy, LA Carey, A DiMichelle, K Conway, D Cowan, D Little, J Markey, DT Moore, L Dressler, I-SPY Clinical Investigators. Univ of North Carolina, Chapel Hill, NC; Univ of Pennsylvania, Philadelphia, PA; I-SPY Trial Network
Background: The I-SPY trial is a multi-institutional study of locally advanced breast cancers. The primary objective is to identify markers of response to neoadjuvant chemotherapy. Pathologic complete response (pCR) of triple-negative breast cancers (TNBCs) to neoadjuvant chemotherapy is associated with a relatively favorable prognosis. The aim of this study was to identify markers associated with pCR in TNBCs.
Design: Immunohistochemistry (IHC) for HER2, EGFR, p53, and Ki-67 was performed centrally on all core samples at baseline. ER and PR results were obtained from each institution. IHC for cytokeratin 5/6 (CK5/6) was performed on TNBCs. A comprehensive approach using microarray analysis, SSCP and sequencing was used to evaluate tumors for p53 mutations. Post-surgical specimens were reviewed centrally to determine residual cancer burden including pCR rate. P-values were calculated with Fisher's exact test.
Results: 221 patients have enrolled and completed therapy. Accrual of patients is ongoing. A total of 53 TNBCs were identified. TNBCs showed a significantly higher pCR rate, 40% (21/53), compared to ER+/PR+/HER2- tumors, 9% (9/101), p<0.0001. The table below shows pCR rate in TNBCs based upon cytokeratin 5/6, EGFR, Ki-67 and p53 status.
|TNBC result||#pCR||Total||%||Lower 95% CI||Upper 95% CI||p-value|
Conclusions: TNBCs showed a significantly higher pCR rate (40%) compared to ER+/PR+/HER2- tumors (9%). Lack of p53 overexpression in TNBC was associated with higher pCR rate as compared to p53-positive tumors. A similar association was not observed from the results of the p53 mutation analysis. Higher pCR rates were observed in TNBCs showing cytokeratin 5/6 expression and Ki-67 index >25%; however, these associations were not statistically significant. Tumor EGFR status was not associated with pCR rate.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 42, Tuesday Afternoon