TY - JOUR
T1 - Thirty-gene pharmacogenomic test correlates with residual cancer burden after preoperative chemotherapy for breast cancer
AU - Peintinger, Florentia
AU - Anderson, Keith
AU - Mazouni, Chafika
AU - Kuerer, Henry M.
AU - Hatzis, Christos
AU - Lin, Feng
AU - Hortobagyi, Gabriel N.
AU - Symmans, W. Fraser
AU - Pusztai, Lajos
PY - 2007/7/15
Y1 - 2007/7/15
N2 - Purpose: We examined whether the response predicted by a 30-gene pharmacogenomic test correlated with the residual cancer burden (RCB) after preoperative chemotherapy with paclitaxel, 5-fluorouracil, doxorubicin, and cyclophosphamide (T/FAC). Experimental Design: Gene expression profiling was done at diagnosis in 74 patients with stages I to III breast cancer and was used to calculate a pharmacogenomic score and predict response to chemotherapy [pathologic complete response (pCR) or residual disease (RD)]. All patients received 6 months of preoperative T/FAC. Following pathologic review, a RCB score was calculated based on residual tumor and lymph node features. Four RCB classes were assigned; RCB-0 (pCR), RCB-I (near-PCR), RCB-II (moderate RD), and RCB-III (extensive RD). The correlations between the pharmacogenomic score, predicted pathologic response, RCB score, and RCB class were examined. Results: Thirty-three patients were predicted to have pCR, and 40 were predicted to have RD. Observed responses were RCB-0: n = 20 (27%); RCB-I: n = 5 (7%); RCB-II: n = 36 (49%); and RCB-III: n = 13 (16%) patients. Pharmacogenomic and RCB scores were correlated (Pearson's R = -0.501, P < 0.0001). There was no difference between the mean genomic predictor scores for RCB-0/I groups (P = 0.94), but these were different from the mean scores of the RCB-II/III groups (P < 0.001). Among the 25 patients with RCB-0/I response, 19 (76%) were predicted to achieve pCR. The pharmacogenomic test correctly predicted RD in 92% of the patients with RCB-III, which corresponds to chemotherapy-resistant disease. Conclusions: The 30-gene pharmacogenomic test showed good correlation with the extent of residual invasive cancer burden measured as both continuous and categorical variables.
AB - Purpose: We examined whether the response predicted by a 30-gene pharmacogenomic test correlated with the residual cancer burden (RCB) after preoperative chemotherapy with paclitaxel, 5-fluorouracil, doxorubicin, and cyclophosphamide (T/FAC). Experimental Design: Gene expression profiling was done at diagnosis in 74 patients with stages I to III breast cancer and was used to calculate a pharmacogenomic score and predict response to chemotherapy [pathologic complete response (pCR) or residual disease (RD)]. All patients received 6 months of preoperative T/FAC. Following pathologic review, a RCB score was calculated based on residual tumor and lymph node features. Four RCB classes were assigned; RCB-0 (pCR), RCB-I (near-PCR), RCB-II (moderate RD), and RCB-III (extensive RD). The correlations between the pharmacogenomic score, predicted pathologic response, RCB score, and RCB class were examined. Results: Thirty-three patients were predicted to have pCR, and 40 were predicted to have RD. Observed responses were RCB-0: n = 20 (27%); RCB-I: n = 5 (7%); RCB-II: n = 36 (49%); and RCB-III: n = 13 (16%) patients. Pharmacogenomic and RCB scores were correlated (Pearson's R = -0.501, P < 0.0001). There was no difference between the mean genomic predictor scores for RCB-0/I groups (P = 0.94), but these were different from the mean scores of the RCB-II/III groups (P < 0.001). Among the 25 patients with RCB-0/I response, 19 (76%) were predicted to achieve pCR. The pharmacogenomic test correctly predicted RD in 92% of the patients with RCB-III, which corresponds to chemotherapy-resistant disease. Conclusions: The 30-gene pharmacogenomic test showed good correlation with the extent of residual invasive cancer burden measured as both continuous and categorical variables.
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U2 - 10.1158/1078-0432.CCR-06-2600
DO - 10.1158/1078-0432.CCR-06-2600
M3 - Article
C2 - 17634532
AN - SCOPUS:34547098349
SN - 1078-0432
VL - 13
SP - 4078
EP - 4082
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 14
ER -