TY - JOUR
T1 - Chemotherapy response and recurrence-free survival in Neoadjuvant breast cancer depends on biomarker profiles
T2 - Results from the I-SPY 1 TRIAL (CALGB 150007/150012; ACRIN 6657)
AU - Esserman, Laura J.
AU - Berry, Donald A.
AU - Cheang, Maggie C.U.
AU - Yau, Christina
AU - Perou, Charles M.
AU - Carey, Lisa
AU - De Michele, Angela
AU - Gray, Joe W.
AU - Conway-Dorsey, Kathleen
AU - Lenburg, Marc E.
AU - Buxton, Meredith B.
AU - Davis, Sarah E.
AU - Van't Veer, Laura J.
AU - Hudis, Clifford
AU - Chin, Koei
AU - Wolf, Denise
AU - Krontiras, Helen
AU - Montgomery, Leslie
AU - Tripathy, Debu
AU - Lehman, Constance
AU - Liu, Minetta C.
AU - Olopade, Olufunmilayo I.
AU - Rugo, Hope S.
AU - Carpenter, John T.
AU - Livasy, Chad
AU - Dressler, Lynn
AU - Chhieng, David
AU - Singh, Baljit
AU - Mies, Carolyn
AU - Rabban, Joseph
AU - Chen, Yunni Yi
AU - Giri, Dilip
AU - Au, Alfred
AU - Hylton, Nola
N1 - Funding Information:
Funding National Cancer Institute Specialized Program of Research Excellence in Breast Cancer (CA58207), American College of Radiology Imaging Network (CA079778 & CA080098), Cancer and Leukemia Group B (CA31964 & CA33601), National Cancer Institute Center for Bioinformatics, The Breast Cancer Research Foundation, Bruce and Martha Atwater, The Terry Fox Foundation Postdoctoral Fellowship, and ‘‘Give Breast Cancer the Boot.’’ Disclosures Joe W. Gray (Author #8) declares a consultant/advisory role with New Leaf Ventures, Susan G. Komen for the Cure, and Kroma TiD. He has no other disclosures. Laura J. van’t Veer (Author #13) declares an employment/leadership role and has stock or other ownership interests at Agendia Inc (Chief Research Officer). She has no other disclosures.
PY - 2012/4
Y1 - 2012/4
N2 - Neoadjuvant chemotherapy for breast cancer allows individual tumor response to be assessed depending on molecular subtype, and to judge the impact of response to therapy on recurrence-free survival (RFS). The multicenter I-SPY 1 TRIAL evaluated patients with ≥3 cm tumors by using early imaging and molecular signatures, with outcomes of pathologic complete response (pCR) and RFS. The current analysis was performed using data from patients who had molecular profiles and did not receive trastuzumab. The various molecular classifiers tested were highly correlated. Categorization of breast cancer by molecular signatures enhanced the ability of pCR to predict improvement in RFS compared to the population as a whole. In multivariate analysis, the molecular signatures that added to the ability of HR and HER2 receptors, clinical stage, and pCR in predicting RFS included 70-gene signature, wound healing signature, p53 mutation signature, and PAM50 risk of recurrence. The low risk signatures were associated with significantly better prognosis, and also identified additional patients with a good prognosis within the no pCR group, primarily in the hormone receptor positive, HER-2 negative subgroup. The I-SPY 1 population is enriched for tumors with a poor prognosis but is still heterogeneous in terms of rates of pCR and RFS. The ability of pCR to predict RFS is better by subset than it is for the whole group. Molecular markers improve prediction of RFS by identifying additional patients with excellent prognosis within the no pCR group.
AB - Neoadjuvant chemotherapy for breast cancer allows individual tumor response to be assessed depending on molecular subtype, and to judge the impact of response to therapy on recurrence-free survival (RFS). The multicenter I-SPY 1 TRIAL evaluated patients with ≥3 cm tumors by using early imaging and molecular signatures, with outcomes of pathologic complete response (pCR) and RFS. The current analysis was performed using data from patients who had molecular profiles and did not receive trastuzumab. The various molecular classifiers tested were highly correlated. Categorization of breast cancer by molecular signatures enhanced the ability of pCR to predict improvement in RFS compared to the population as a whole. In multivariate analysis, the molecular signatures that added to the ability of HR and HER2 receptors, clinical stage, and pCR in predicting RFS included 70-gene signature, wound healing signature, p53 mutation signature, and PAM50 risk of recurrence. The low risk signatures were associated with significantly better prognosis, and also identified additional patients with a good prognosis within the no pCR group, primarily in the hormone receptor positive, HER-2 negative subgroup. The I-SPY 1 population is enriched for tumors with a poor prognosis but is still heterogeneous in terms of rates of pCR and RFS. The ability of pCR to predict RFS is better by subset than it is for the whole group. Molecular markers improve prediction of RFS by identifying additional patients with excellent prognosis within the no pCR group.
KW - Breast cancer
KW - Molecular biomarkers
KW - Neoadjuvant chemotherapy
KW - Pathologic complete response
UR - http://www.scopus.com/inward/record.url?scp=84865191389&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84865191389&partnerID=8YFLogxK
U2 - 10.1007/s10549-011-1895-2
DO - 10.1007/s10549-011-1895-2
M3 - Article
C2 - 22198468
AN - SCOPUS:84865191389
SN - 0167-6806
VL - 132
SP - 1049
EP - 1062
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 3
ER -