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Cited by 699Breast Cancer Treatment StudiesGene expression and cancer classificationCancer Treatment and Pharmacology

A Genomic Predictor of Response and Survival Following Taxane-Anthracycline Chemotherapy for Invasive Breast Cancer

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Hatzis, Christos·2011·JAMA
DOI 10.1001/jama.2011.593PMC PMC5638042
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Abstract

CONTEXT: Prediction of high probability of survival from standard cancer treatments is fundamental for individualized cancer treatment strategies. OBJECTIVE: To develop a predictor of response and survival from chemotherapy for newly diagnosed invasive breast cancer. DESIGN, SETTING, AND PATIENTS: Prospective multicenter study conducted from June 2000 to March 2010 at the M. D. Anderson Cancer Center to develop and test genomic predictors for neoadjuvant chemotherapy. Patients were those with newly diagnosed ERBB2 (HER2 or HER2/neu)-negative breast cancer treated with chemotherapy containing sequential taxane and anthracycline-based regimens (then endocrine therapy if estrogen receptor [ER]-positive). Different predictive signatures for resistance and response to preoperative (neoadjuvant) chemotherapy (stratified according to ER status) were developed from gene expression microarrays of newly diagnosed breast cancer (310 patients). Breast cancer treatment sensitivity was then predicted using the combination of signatures for (1) sensitivity to endocrine therapy, (2) chemoresistance, and (3) chemosensitivity, with independent validation (198 patients) and comparison with other reported genomic predictors of chemotherapy response. MAIN OUTCOME MEASURES: Distant relapse-free survival (DRFS) if predicted treatment sensitive and absolute risk reduction ([ARR], difference in DRFS between 2 predicted groups) at median follow-up (3 years). RESULTS: Patients in the independent validation cohort (99% clinical stage II-III) who were predicted to be treatment sensitive (28%) had 56% (95% CI, 31%-78%) probability of excellent pathologic response and DRFS of 92% (95% CI, 85%-100%), with an ARR of 18% (95% CI, 6%-28%). Survival was predicted in ER-positive (30% predicted sensitive; DRFS, 97% [95% CI, 91%-100%]; ARR, 11% [95% CI, 0.1%-21%]) and ER-negative (26% predicted sensitive; DRFS, 83% [95% CI, 68%-100%]; ARR, 26% [95% CI, 4%-48%]) subsets and was significant in multivariate analysis. Other genomic predictors showed paradoxically worse survival for patients predicted to be responsive to chemotherapy. CONCLUSION: A genomic predictor combining ER status, predicted chemoresistance, predicted chemosensitivity, and predicted endocrine sensitivity identified patients with high probability of survival following taxane and anthracycline chemotherapy.

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  • The top 23 differentially expressed genes in CIN-high cells (CIN signature) predicted distant-metastasis-free survival in a meta-analysis and a validation cohort of patients with breast cancer, irrespective of tumor subtype, grade, or lymph node status.

    “The top 23 differentially expressed genes in CIN-high cells (referred to as CIN signature) predicted distant-metastasis-free survival (DMFS) in a meta-analysis16 as well as a validation cohort17 of patients with breast cancer, irrespective of tumor subtype, grade, or lymph node status”

    From Chromosomal instability drives metastasis through a cytosolic DNA response (2018) · cites this paper as [17]

    The Methods describe predictors using 33 and 27 probe sets for early relapse, not a 23-gene CIN signature. The Results report distant-relapse-free survival in an independent validation cohort, but our copy does not say that the CIN signature was tested there or that it predicted survival irrespective of subtype, grade, or lymph-node status. Searches for the CIN signature and those validation claims found no supporting passage; page numbers were unavailable. (LLM, conf=0.76)

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Authors
Hatzis, C.
Affiliations
Nuvera Biosciences (United States) (US)
Corresponding author
Hatzis, Christos
ORCID
Hatzis, Christos
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
2011-05-11
Volume
305
Issue
18
Pages
1873
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.2011.593
PMC
PMC5638042
OpenAlex
W2158501247
Cited by
699
References
1
Citations by year
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FWCI
17.63
Type
journal article
Language
en
Open access
Locations
  • JAMA (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Cancer Institute (CA-41287, CA 16450, U10CA077651, CA 77651, CA-47559, CA 60138, CA-33601, U10CA033601, CA 77597, U10CA077597, R43CA130188, U10CA047559, CA37347, U10CA060138, R01CA106290, U10CA031946, U10CA016450, U10CA041287, CA-31946)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
  • Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
Keywords
invasive breast cancer, neoadjuvant chemotherapy, genomic predictors, chemosensitivity, chemoresistance, endocrine therapy sensitivity, estrogen receptor status, HER2-negative breast cancer, distant recurrence-free survival, gene expression signatures, treatment response prediction, pathological response, absolute risk reduction, precision oncology, gene expression microarrays, predictive biomarkers
MeSH terms
Adult, Algorithms, Antineoplastic Combined Chemotherapy Protocols, Biopsy, Needle, Breast Neoplasms, Bridged-Ring Compounds, Female, Forecasting, Humans, Middle Aged, Neoplasm Recurrence, Local, Predictive Value of Tests, Prognosis, Prospective Studies, Receptors, Estrogen, Risk, Disease-Free Survival, Genes, erbB-2, Antineoplastic Agents, Hormonal, Anthracyclines, Drug Resistance, Neoplasm, Neoadjuvant Therapy, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Genomics, Taxoids, Genes, Neoplasm

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