NSABP B-41, a Randomized Neoadjuvant Trial: Genes and Signatures Associated with Pathologic Complete Response.

MedStar author(s):
Citation: Clinical Cancer Research. 26(16):4233-4241, 2020 08 15.PMID: 32371537Institution: MedStar HealthDepartment: Associate Dean for Research DevelopmentForm of publication: Journal ArticleMedline article type(s): Journal ArticleSubject headings: *Breast Neoplasms/dt [Drug Therapy] | *Neoplasm Proteins/ge [Genetics] | *Receptor, ErbB-2/ge [Genetics] | *Trastuzumab/ad [Administration & Dosage] | Antineoplastic Combined Chemotherapy Protocols/ad [Administration & Dosage] | Biomarkers, Tumor/ge [Genetics] | Breast Neoplasms/ge [Genetics] | Breast Neoplasms/pa [Pathology] | Cell Proliferation/de [Drug Effects] | Chemotherapy, Adjuvant | DNA Damage/de [Drug Effects] | Epithelial-Mesenchymal Transition/ge [Genetics] | Estrogen Receptor alpha/ge [Genetics] | Female | Gene Expression Regulation, Neoplastic/de [Drug Effects] | Humans | Lapatinib/ad [Administration & Dosage] | Middle Aged | Neoadjuvant Therapy | Prognosis | Trastuzumab/ae [Adverse Effects]Year: 2020ISSN:
  • 1078-0432
Name of journal: Clinical cancer research : an official journal of the American Association for Cancer ResearchAbstract: 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. Copyright (c)2020 American Association for Cancer Research.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.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.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.All authors: Bandos H, Brauer HA, Geyer CE Jr, Goerlitz DS, Harris BT, Lucas PC, Mamounas EP, Rastogi P, Ren Y, Robidoux A, Swain SM, Tang G, Wolmark NOriginally published: Clinical Cancer Research. 2020 May 05Fiscal year: FY2020Fiscal year of original publication: FY2020Digital Object Identifier: ORCID: Date added to catalog: 2020-08-26
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Journal Article MedStar Authors Catalog Article 32371537 Available 32371537

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. Copyright (c)2020 American Association for Cancer Research.

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.

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.

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.

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