Relationship between topoisomerase 2A RNA expression and recurrence after adjuvant chemotherapy for breast cancer

Joseph A. Sparano, Lori J. Goldstein, Barrett H. Childs, Steven Shak, Diana Brassard, Sunil Badve, Frederick L. Baehner, Roberto Bugarini, Steve Rowley, Edith Perez, Lawrence N. Shulman, Silvana Martino, Nancy E. Davidson, George W. Sledge, Robert Gray

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Purpose: To perform an exploratory analysis of the relationship between gene expression and recurrence in operable hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-normal breast cancer patients treated with adjuvant doxorubicin-containing chemotherapy. Experimental Design: RNA was extracted from archived tumor samples derived from 378 patients with stage I to III HR-positive, HER2-normal breast cancer and analyzed by reverse transcription-PCR for a panel of 374 genes, including the 21-gene recurrence score (RS). Patients were randomized to receive adjuvant doxorubicin plus cyclophosphamide or docetaxel in trial E2197, with no difference in recurrence seen in the treatment arms. All available recurrent cases were selected plus a nonrecurrent cohort. Cox proportional hazard models were used to identify relationships between gene expression and recurrence. Results: TOP2A expression exhibited the strongest association with increased recurrence risk (P = 0.01), and was significantly associated with recurrence (P = 0.008) in a multivariate analysis adjusted for clinicopathologic features. Elevated TOP2A expression above the median was associated with a 2.6-fold increase (95% confidence interval, 1.3-5.2; P = 0.008) in risk of recurrence if the RS was <18, and a 2.0-fold increase (95% confidence interval, 1.2-3.2, P = 0.003) if there was an intermediate RS of 18 to 30. Conclusions: In patients with HR-positive, HER2-normal breast cancer, a population known to have a low incidence of TOP2A gene alterations thought to be predictive of anthracycline benefit, there is a range of TOP2A RNA expression that is strongly associated with recurrence after adjuvant anthracyclines, which provides information complementary to RS, indicating that it merits further evaluation as a prognostic and predictive marker.

Original languageEnglish (US)
Pages (from-to)7693-7700
Number of pages8
JournalClinical Cancer Research
Volume15
Issue number24
DOIs
StatePublished - Dec 15 2009

Fingerprint

Adjuvant Chemotherapy
RNA
Breast Neoplasms
Recurrence
Anthracyclines
docetaxel
Hormones
Doxorubicin
Confidence Intervals
Genes
Gene Expression
Proportional Hazards Models
Cyclophosphamide
Reverse Transcription
Research Design
Multivariate Analysis
Drug Therapy
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Sparano, J. A., Goldstein, L. J., Childs, B. H., Shak, S., Brassard, D., Badve, S., ... Gray, R. (2009). Relationship between topoisomerase 2A RNA expression and recurrence after adjuvant chemotherapy for breast cancer. Clinical Cancer Research, 15(24), 7693-7700. https://doi.org/10.1158/1078-0432.CCR-09-1450

Relationship between topoisomerase 2A RNA expression and recurrence after adjuvant chemotherapy for breast cancer. / Sparano, Joseph A.; Goldstein, Lori J.; Childs, Barrett H.; Shak, Steven; Brassard, Diana; Badve, Sunil; Baehner, Frederick L.; Bugarini, Roberto; Rowley, Steve; Perez, Edith; Shulman, Lawrence N.; Martino, Silvana; Davidson, Nancy E.; Sledge, George W.; Gray, Robert.

In: Clinical Cancer Research, Vol. 15, No. 24, 15.12.2009, p. 7693-7700.

Research output: Contribution to journalArticle

Sparano, JA, Goldstein, LJ, Childs, BH, Shak, S, Brassard, D, Badve, S, Baehner, FL, Bugarini, R, Rowley, S, Perez, E, Shulman, LN, Martino, S, Davidson, NE, Sledge, GW & Gray, R 2009, 'Relationship between topoisomerase 2A RNA expression and recurrence after adjuvant chemotherapy for breast cancer', Clinical Cancer Research, vol. 15, no. 24, pp. 7693-7700. https://doi.org/10.1158/1078-0432.CCR-09-1450
Sparano, Joseph A. ; Goldstein, Lori J. ; Childs, Barrett H. ; Shak, Steven ; Brassard, Diana ; Badve, Sunil ; Baehner, Frederick L. ; Bugarini, Roberto ; Rowley, Steve ; Perez, Edith ; Shulman, Lawrence N. ; Martino, Silvana ; Davidson, Nancy E. ; Sledge, George W. ; Gray, Robert. / Relationship between topoisomerase 2A RNA expression and recurrence after adjuvant chemotherapy for breast cancer. In: Clinical Cancer Research. 2009 ; Vol. 15, No. 24. pp. 7693-7700.
@article{6e2fd5c3a6994fae93d929c084a24ac1,
title = "Relationship between topoisomerase 2A RNA expression and recurrence after adjuvant chemotherapy for breast cancer",
abstract = "Purpose: To perform an exploratory analysis of the relationship between gene expression and recurrence in operable hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-normal breast cancer patients treated with adjuvant doxorubicin-containing chemotherapy. Experimental Design: RNA was extracted from archived tumor samples derived from 378 patients with stage I to III HR-positive, HER2-normal breast cancer and analyzed by reverse transcription-PCR for a panel of 374 genes, including the 21-gene recurrence score (RS). Patients were randomized to receive adjuvant doxorubicin plus cyclophosphamide or docetaxel in trial E2197, with no difference in recurrence seen in the treatment arms. All available recurrent cases were selected plus a nonrecurrent cohort. Cox proportional hazard models were used to identify relationships between gene expression and recurrence. Results: TOP2A expression exhibited the strongest association with increased recurrence risk (P = 0.01), and was significantly associated with recurrence (P = 0.008) in a multivariate analysis adjusted for clinicopathologic features. Elevated TOP2A expression above the median was associated with a 2.6-fold increase (95{\%} confidence interval, 1.3-5.2; P = 0.008) in risk of recurrence if the RS was <18, and a 2.0-fold increase (95{\%} confidence interval, 1.2-3.2, P = 0.003) if there was an intermediate RS of 18 to 30. Conclusions: In patients with HR-positive, HER2-normal breast cancer, a population known to have a low incidence of TOP2A gene alterations thought to be predictive of anthracycline benefit, there is a range of TOP2A RNA expression that is strongly associated with recurrence after adjuvant anthracyclines, which provides information complementary to RS, indicating that it merits further evaluation as a prognostic and predictive marker.",
author = "Sparano, {Joseph A.} and Goldstein, {Lori J.} and Childs, {Barrett H.} and Steven Shak and Diana Brassard and Sunil Badve and Baehner, {Frederick L.} and Roberto Bugarini and Steve Rowley and Edith Perez and Shulman, {Lawrence N.} and Silvana Martino and Davidson, {Nancy E.} and Sledge, {George W.} and Robert Gray",
year = "2009",
month = "12",
day = "15",
doi = "10.1158/1078-0432.CCR-09-1450",
language = "English (US)",
volume = "15",
pages = "7693--7700",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "24",

}

TY - JOUR

T1 - Relationship between topoisomerase 2A RNA expression and recurrence after adjuvant chemotherapy for breast cancer

AU - Sparano, Joseph A.

AU - Goldstein, Lori J.

AU - Childs, Barrett H.

AU - Shak, Steven

AU - Brassard, Diana

AU - Badve, Sunil

AU - Baehner, Frederick L.

AU - Bugarini, Roberto

AU - Rowley, Steve

AU - Perez, Edith

AU - Shulman, Lawrence N.

AU - Martino, Silvana

AU - Davidson, Nancy E.

AU - Sledge, George W.

AU - Gray, Robert

PY - 2009/12/15

Y1 - 2009/12/15

N2 - Purpose: To perform an exploratory analysis of the relationship between gene expression and recurrence in operable hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-normal breast cancer patients treated with adjuvant doxorubicin-containing chemotherapy. Experimental Design: RNA was extracted from archived tumor samples derived from 378 patients with stage I to III HR-positive, HER2-normal breast cancer and analyzed by reverse transcription-PCR for a panel of 374 genes, including the 21-gene recurrence score (RS). Patients were randomized to receive adjuvant doxorubicin plus cyclophosphamide or docetaxel in trial E2197, with no difference in recurrence seen in the treatment arms. All available recurrent cases were selected plus a nonrecurrent cohort. Cox proportional hazard models were used to identify relationships between gene expression and recurrence. Results: TOP2A expression exhibited the strongest association with increased recurrence risk (P = 0.01), and was significantly associated with recurrence (P = 0.008) in a multivariate analysis adjusted for clinicopathologic features. Elevated TOP2A expression above the median was associated with a 2.6-fold increase (95% confidence interval, 1.3-5.2; P = 0.008) in risk of recurrence if the RS was <18, and a 2.0-fold increase (95% confidence interval, 1.2-3.2, P = 0.003) if there was an intermediate RS of 18 to 30. Conclusions: In patients with HR-positive, HER2-normal breast cancer, a population known to have a low incidence of TOP2A gene alterations thought to be predictive of anthracycline benefit, there is a range of TOP2A RNA expression that is strongly associated with recurrence after adjuvant anthracyclines, which provides information complementary to RS, indicating that it merits further evaluation as a prognostic and predictive marker.

AB - Purpose: To perform an exploratory analysis of the relationship between gene expression and recurrence in operable hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-normal breast cancer patients treated with adjuvant doxorubicin-containing chemotherapy. Experimental Design: RNA was extracted from archived tumor samples derived from 378 patients with stage I to III HR-positive, HER2-normal breast cancer and analyzed by reverse transcription-PCR for a panel of 374 genes, including the 21-gene recurrence score (RS). Patients were randomized to receive adjuvant doxorubicin plus cyclophosphamide or docetaxel in trial E2197, with no difference in recurrence seen in the treatment arms. All available recurrent cases were selected plus a nonrecurrent cohort. Cox proportional hazard models were used to identify relationships between gene expression and recurrence. Results: TOP2A expression exhibited the strongest association with increased recurrence risk (P = 0.01), and was significantly associated with recurrence (P = 0.008) in a multivariate analysis adjusted for clinicopathologic features. Elevated TOP2A expression above the median was associated with a 2.6-fold increase (95% confidence interval, 1.3-5.2; P = 0.008) in risk of recurrence if the RS was <18, and a 2.0-fold increase (95% confidence interval, 1.2-3.2, P = 0.003) if there was an intermediate RS of 18 to 30. Conclusions: In patients with HR-positive, HER2-normal breast cancer, a population known to have a low incidence of TOP2A gene alterations thought to be predictive of anthracycline benefit, there is a range of TOP2A RNA expression that is strongly associated with recurrence after adjuvant anthracyclines, which provides information complementary to RS, indicating that it merits further evaluation as a prognostic and predictive marker.

UR - http://www.scopus.com/inward/record.url?scp=73349122284&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=73349122284&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-09-1450

DO - 10.1158/1078-0432.CCR-09-1450

M3 - Article

VL - 15

SP - 7693

EP - 7700

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 24

ER -