TY - JOUR
T1 - NSABP B-41, a Randomized Neoadjuvant Trial
T2 - Genes and Signatures Associated with Pathologic Complete Response
AU - Swain, Sandra M.
AU - Tang, Gong
AU - Brauer, Heather Ann
AU - Goerlitz, David S.
AU - Lucas, Peter C.
AU - Robidoux, Andre
AU - Harris, Brent T.
AU - Bandos, Hanna
AU - Ren, Yuqi
AU - Geyer, Charles E.
AU - Rastogi, Priya
AU - Mamounas, Eleftherios P.
AU - Wolmark, Norman
N1 - Funding Information:
This study was partially supported by the Alexandr Savchuk Foundation, Breast Cancer Research Foundation, GlaxoSmithKline, NSABP Foundation, and the Genomics & Epigenomics Shared Resource and Histopathology & Tissue Shared Resource at the Georgetown Lombardi Comprehensive Cancer Center (P30CA051008; principal investigator: Weiner from the NCI). The authors thank the patients, investigators, and NSABP Foundation staff for their contributions; Phillips Gilmore Oncology Communications for providing technical assistance; T. Blaise Springfield for assistance with figures, tables, and article submission; and Wendy L. Rea for editorial assistance.
Funding Information:
S.M. Swain is a paid consultant for Athenex, AstraZeneca, Daiichi-Sankyo, Eli Lilly and Company, F. Hoffmann-La Roche/Genentech, Inc., Genomic Health, Inivata Ltd., Pieris Pharmaceuticals, Molecular Templates, Silverback Therapeutics, and Tocagen; reports receiving commercial research grants from F. Hoffman-La
Publisher Copyright:
©2020 American Association for Cancer Research.
PY - 2020/8/15
Y1 - 2020/8/15
N2 - Purpose: In NSABP B-41, pathologic complete response (pCR) was associated with prolonged survival among women with HER2-positive operable breast cancer treated with neoadjuvant chemotherapy and lapatinib, trastuzumab, or the combination. We used a large human breast cancer gene expression panel to select candidate prognostic biomarkers for pCR among women treated with trastuzumab in NSABP B-41. Patients and Methods: Eligible patients had a baseline preadjuvant treatment core biopsy sample, known pCR status, and no withdrawal of consent. We analyzed extracted RNA using the human nCounter Breast Cancer 360 gene expression panel. Gene counts were normalized to housekeeping genes and transformed into logarithmic scale with base 2. To screen for candidate genes and metagene signatures prognostic of pCR, we used univariate logistic regression. Variable selection was done by multivariable logistic regression with lasso regularization. Results: Analyses of data from 130 patients revealed that a composite of gene expression from 19 genes and one gene signature appeared to predict pCR in women with HER2-positive early-stage breast cancer undergoing neoadjuvant chemotherapy with trastuzumab-containing regimens. The identified genes are involved in important pathways such as epithelial–mesenchymal transition, adhesion and migration, estrogen receptor signaling, DNA damage and repair, apoptosis, and proliferation. The AUC from a 10-fold cross-validation on predicting pCR, with these 20 genomic markers in a logistic regression model, was 0.73. Conclusions: The expression level of ERBB2, ESR1, and a few other genomic markers was highly predictive of pCR after trastuzumab-containing regimens. These findings need to be validated and calibrated in future studies.
AB - Purpose: In NSABP B-41, pathologic complete response (pCR) was associated with prolonged survival among women with HER2-positive operable breast cancer treated with neoadjuvant chemotherapy and lapatinib, trastuzumab, or the combination. We used a large human breast cancer gene expression panel to select candidate prognostic biomarkers for pCR among women treated with trastuzumab in NSABP B-41. Patients and Methods: Eligible patients had a baseline preadjuvant treatment core biopsy sample, known pCR status, and no withdrawal of consent. We analyzed extracted RNA using the human nCounter Breast Cancer 360 gene expression panel. Gene counts were normalized to housekeeping genes and transformed into logarithmic scale with base 2. To screen for candidate genes and metagene signatures prognostic of pCR, we used univariate logistic regression. Variable selection was done by multivariable logistic regression with lasso regularization. Results: Analyses of data from 130 patients revealed that a composite of gene expression from 19 genes and one gene signature appeared to predict pCR in women with HER2-positive early-stage breast cancer undergoing neoadjuvant chemotherapy with trastuzumab-containing regimens. The identified genes are involved in important pathways such as epithelial–mesenchymal transition, adhesion and migration, estrogen receptor signaling, DNA damage and repair, apoptosis, and proliferation. The AUC from a 10-fold cross-validation on predicting pCR, with these 20 genomic markers in a logistic regression model, was 0.73. Conclusions: The expression level of ERBB2, ESR1, and a few other genomic markers was highly predictive of pCR after trastuzumab-containing regimens. These findings need to be validated and calibrated in future studies.
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U2 - 10.1158/1078-0432.CCR-20-0152
DO - 10.1158/1078-0432.CCR-20-0152
M3 - Article
C2 - 32371537
AN - SCOPUS:85089787417
VL - 26
SP - 4233
EP - 4241
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 16
ER -