NSABP B-41, a Randomized Neoadjuvant Trial: Genes and Signatures Associated with Pathologic Complete Response.
NSABP B-41, a Randomized Neoadjuvant Trial: Genes and Signatures Associated with Pathologic Complete Response.
- 2020
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.
English
1078-0432
10.1158/1078-0432.CCR-20-0152 [doi] 1078-0432.CCR-20-0152 [pii]
*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]
MedStar Health
Associate Dean for Research Development
Journal Article
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.
English
1078-0432
10.1158/1078-0432.CCR-20-0152 [doi] 1078-0432.CCR-20-0152 [pii]
*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]
MedStar Health
Associate Dean for Research Development
Journal Article