[235] 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 |
| CK5/6+ | 8 | 19 | 42% | 20% | 67% | 0.35 |
| CK5/6- | 7 | 26 | 27% | 12% | 48% | |
| EGFR+ | 4 | 10 | 40% | 12% | 74% | 0.99 |
| EGFR- | 11 | 32 | 34% | 19% | 53% | |
| Ki-67<10% | 1 | 6 | 17% | 1% | 64% | 0.10 |
Ki-67 10%,<25% | 3 | 11 | 27% | 6% | 61% | |
| Ki-67 25% | 12 | 26 | 46% | 27% | 67% | |
| p53+ overexpression | 8 | 30 | 27% | 12% | 46% | 0.04 |
| p53- overexpression | 8 | 13 | 62% | 32% | 86% | |
| p53 mutant | 12 | 33 | 36% | 20% | 55% | 0.99 |
| p53 wild-type | 4 | 10 | 40% | 12% | 74% |
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.
Category: Breast
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 42, Tuesday Afternoon