TY - JOUR
T1 - PIK3CA-activating mutations and chemotherapy sensitivity in stage II-III breast cancer
AU - Liedtke, Cornelia
AU - Cardone, Luca
AU - Tordai, Attila
AU - Yan, Kai
AU - Gomez, Henry L.
AU - Figureoa, Luis J.B.
AU - Hubbard, Rebekah E.
AU - Valero, Vicente
AU - Souchon, Eduardo A.
AU - Symmans, W. Fraser
AU - Hortobagyi, Gabriel N.
AU - Bardelli, Alberto
AU - Pusztai, Lajos
N1 - Funding Information:
This work was supported by grants to CL from the dfg (Deutsche For-schungsgemeinschaft), Germany; to LP from the National Cancer Institute (NCI) (RO1-CA106290), the Breast Cancer Research Foundation, and the Goodwin Foundation; and to GNH by the NCI (2P30 CA016672 28 [PP-4]) and the Nellie B. Connally Breast Cancer Research Fund. AT is a visiting professor of the Hungarian American Enterprise Scholarship Fund. AB and LC were supported by The Italian Association for Cancer Research (AIRC), the Italian Ministry of University and Research, and the Association for International Cancer Research (AICR-UK) (EU FP6 contracts MCSCs 037297).
PY - 2008/3/27
Y1 - 2008/3/27
N2 - Introduction: In vitro evidence suggests that PIK3CA (phosphatidylinositol 3-kinase, catalytic, alpha polypeptide) activation may be associated with altered chemotherapy sensitivity in cancer.Methods: Tumor DNA from 140 patients with stage II-III breast cancer undergoing neoadjuvant chemotherapy was sequenced for PIK3CA mutations on exons 1, 9, and 20. Mutation status was correlated with clinical/pathological parameters and chemotherapy response as (a) pathological complete response (pCR) versus residual cancer or (b) quantitative residual cancer burden (RCB) scores, including stratification for estrogen receptor (ER) expression status, type of chemotherapy, and by exons.Results: Twenty-three patients (16.4%) harbored a PIK3CA mutation, with 12, 11, and 0 mutations located in exons 9, 20, and 1, respectively. PIK3CA exon 9 mutations were more frequent among node-negative (52% versus 25%; P = 0.012) than node-positive tumors, particularly among ER-positive tumors. pCR rates and RCB scores were similar among patients with the wild-type and mutant PIK3CA genes, even after stratification by ER status, chemotherapy regimen (anthracycline versus anthracycline plus paclitaxel), or exon.Conclusion: PIK3CA mutations are not associated with altered sensitivity to preoperative anthracycline-based or taxane-based chemotherapies in ER-positive and ER-negative breast tumors. In this study, PIK3CA mutation was associated with a decreased rate of node-positive disease, particularly among ER-positive tumors.
AB - Introduction: In vitro evidence suggests that PIK3CA (phosphatidylinositol 3-kinase, catalytic, alpha polypeptide) activation may be associated with altered chemotherapy sensitivity in cancer.Methods: Tumor DNA from 140 patients with stage II-III breast cancer undergoing neoadjuvant chemotherapy was sequenced for PIK3CA mutations on exons 1, 9, and 20. Mutation status was correlated with clinical/pathological parameters and chemotherapy response as (a) pathological complete response (pCR) versus residual cancer or (b) quantitative residual cancer burden (RCB) scores, including stratification for estrogen receptor (ER) expression status, type of chemotherapy, and by exons.Results: Twenty-three patients (16.4%) harbored a PIK3CA mutation, with 12, 11, and 0 mutations located in exons 9, 20, and 1, respectively. PIK3CA exon 9 mutations were more frequent among node-negative (52% versus 25%; P = 0.012) than node-positive tumors, particularly among ER-positive tumors. pCR rates and RCB scores were similar among patients with the wild-type and mutant PIK3CA genes, even after stratification by ER status, chemotherapy regimen (anthracycline versus anthracycline plus paclitaxel), or exon.Conclusion: PIK3CA mutations are not associated with altered sensitivity to preoperative anthracycline-based or taxane-based chemotherapies in ER-positive and ER-negative breast tumors. In this study, PIK3CA mutation was associated with a decreased rate of node-positive disease, particularly among ER-positive tumors.
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U2 - 10.1186/bcr1984
DO - 10.1186/bcr1984
M3 - Article
C2 - 18371219
AN - SCOPUS:48949119513
SN - 1465-5411
VL - 10
JO - Breast Cancer Research
JF - Breast Cancer Research
IS - 2
M1 - R27
ER -