Seven-year follow-up assessment of cardiac function in NSABP B-31, a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel (ACP) with ACP plus trastuzumab as adjuvant therapy for patients with node-positive, human epidermal growth factor receptor 2-positive breast cancer

Edward H. Romond, Jong Hyeon Jeong, Priya Rastogi, Sandra M. Swain, Charles E. Geyer, Michael S. Ewer, Vikas Rathi, Louis Fehrenbacher, Adam Brufsky, Catherine A. Azar, Patrick J. Flynn, John L. Zapas, Jonathan Polikoff, Howard M. Gross, David D. Biggs, James N. Atkins, Elizabeth Tan-Chiu, Ping Zheng, Greg Yothers, Eleftherios P. Mamounas & 1 others Norman Wolmark

Research output: Contribution to journalArticle

272 Citations (Scopus)

Abstract

Purpose: Cardiac dysfunction (CD) is a recognized risk associated with the addition of trastuzumab to adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer, especially when the treatment regimen includes anthracyclines. Given the demonstrated efficacy of trastuzumab, ongoing assessment of cardiac safety and identification of risk factors for CD are important for optimal patient care. Patients and Methods: In National Surgical Adjuvant Breast and Bowel Project B-31, a phase III adjuvant trial, 1,830 patients who met eligibility criteria for initiation of trastuzumab were evaluated for CD. Recovery from CD was also assessed. A statistical model was developed to estimate the risk of severe congestive heart failure (CHF). Baseline patient characteristics associated with anthracycline-related decline in cardiac function were also identified. Results: At 7-year follow-up, 37 (4.0%) of 944 patients who received trastuzumab experienced a cardiac event (CE) versus 10 (1.3%) of 743 patients in the control arm. One cardiac-related death has occurred in each arm of the protocol. A Cardiac Risk Score, calculated using patient age and baseline left ventricular ejection fraction (LVEF) by multiple-gated acquisition scan, statistically correlates with the risk of a CE. After stopping trastuzumab, the majority of patients who experienced CD recovered LVEF in the normal range, although some decline from baseline often persists. Only two CEs occurred more than 2 years after initiation of trastuzumab. Conclusion: The late development of CHF after the addition of trastuzumab to paclitaxel after doxorubicin/ cyclophosphamide chemotherapy is uncommon. The risk versus benefit of trastuzumab as given in this regimen remains strongly in favor of trastuzumab.

Original languageEnglish (US)
Pages (from-to)3792-3799
Number of pages8
JournalJournal of Clinical Oncology
Volume30
Issue number31
DOIs
StatePublished - Nov 1 2012

Fingerprint

Paclitaxel
Doxorubicin
Cyclophosphamide
Breast Neoplasms
Therapeutics
Anthracyclines
Stroke Volume
Arm
Heart Failure
human ERBB2 protein
B 31
Trastuzumab
Statistical Models
Adjuvant Chemotherapy
Patient Care
Reference Values
Breast
Safety
Drug Therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Seven-year follow-up assessment of cardiac function in NSABP B-31, a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel (ACP) with ACP plus trastuzumab as adjuvant therapy for patients with node-positive, human epidermal growth factor receptor 2-positive breast cancer. / Romond, Edward H.; Jeong, Jong Hyeon; Rastogi, Priya; Swain, Sandra M.; Geyer, Charles E.; Ewer, Michael S.; Rathi, Vikas; Fehrenbacher, Louis; Brufsky, Adam; Azar, Catherine A.; Flynn, Patrick J.; Zapas, John L.; Polikoff, Jonathan; Gross, Howard M.; Biggs, David D.; Atkins, James N.; Tan-Chiu, Elizabeth; Zheng, Ping; Yothers, Greg; Mamounas, Eleftherios P.; Wolmark, Norman.

In: Journal of Clinical Oncology, Vol. 30, No. 31, 01.11.2012, p. 3792-3799.

Research output: Contribution to journalArticle

Romond, EH, Jeong, JH, Rastogi, P, Swain, SM, Geyer, CE, Ewer, MS, Rathi, V, Fehrenbacher, L, Brufsky, A, Azar, CA, Flynn, PJ, Zapas, JL, Polikoff, J, Gross, HM, Biggs, DD, Atkins, JN, Tan-Chiu, E, Zheng, P, Yothers, G, Mamounas, EP & Wolmark, N 2012, 'Seven-year follow-up assessment of cardiac function in NSABP B-31, a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel (ACP) with ACP plus trastuzumab as adjuvant therapy for patients with node-positive, human epidermal growth factor receptor 2-positive breast cancer', Journal of Clinical Oncology, vol. 30, no. 31, pp. 3792-3799. https://doi.org/10.1200/JCO.2011.40.0010
Romond, Edward H. ; Jeong, Jong Hyeon ; Rastogi, Priya ; Swain, Sandra M. ; Geyer, Charles E. ; Ewer, Michael S. ; Rathi, Vikas ; Fehrenbacher, Louis ; Brufsky, Adam ; Azar, Catherine A. ; Flynn, Patrick J. ; Zapas, John L. ; Polikoff, Jonathan ; Gross, Howard M. ; Biggs, David D. ; Atkins, James N. ; Tan-Chiu, Elizabeth ; Zheng, Ping ; Yothers, Greg ; Mamounas, Eleftherios P. ; Wolmark, Norman. / Seven-year follow-up assessment of cardiac function in NSABP B-31, a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel (ACP) with ACP plus trastuzumab as adjuvant therapy for patients with node-positive, human epidermal growth factor receptor 2-positive breast cancer. In: Journal of Clinical Oncology. 2012 ; Vol. 30, No. 31. pp. 3792-3799.
@article{70e1e5d3f96e4537827371e9f6bce5ba,
title = "Seven-year follow-up assessment of cardiac function in NSABP B-31, a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel (ACP) with ACP plus trastuzumab as adjuvant therapy for patients with node-positive, human epidermal growth factor receptor 2-positive breast cancer",
abstract = "Purpose: Cardiac dysfunction (CD) is a recognized risk associated with the addition of trastuzumab to adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer, especially when the treatment regimen includes anthracyclines. Given the demonstrated efficacy of trastuzumab, ongoing assessment of cardiac safety and identification of risk factors for CD are important for optimal patient care. Patients and Methods: In National Surgical Adjuvant Breast and Bowel Project B-31, a phase III adjuvant trial, 1,830 patients who met eligibility criteria for initiation of trastuzumab were evaluated for CD. Recovery from CD was also assessed. A statistical model was developed to estimate the risk of severe congestive heart failure (CHF). Baseline patient characteristics associated with anthracycline-related decline in cardiac function were also identified. Results: At 7-year follow-up, 37 (4.0{\%}) of 944 patients who received trastuzumab experienced a cardiac event (CE) versus 10 (1.3{\%}) of 743 patients in the control arm. One cardiac-related death has occurred in each arm of the protocol. A Cardiac Risk Score, calculated using patient age and baseline left ventricular ejection fraction (LVEF) by multiple-gated acquisition scan, statistically correlates with the risk of a CE. After stopping trastuzumab, the majority of patients who experienced CD recovered LVEF in the normal range, although some decline from baseline often persists. Only two CEs occurred more than 2 years after initiation of trastuzumab. Conclusion: The late development of CHF after the addition of trastuzumab to paclitaxel after doxorubicin/ cyclophosphamide chemotherapy is uncommon. The risk versus benefit of trastuzumab as given in this regimen remains strongly in favor of trastuzumab.",
author = "Romond, {Edward H.} and Jeong, {Jong Hyeon} and Priya Rastogi and Swain, {Sandra M.} and Geyer, {Charles E.} and Ewer, {Michael S.} and Vikas Rathi and Louis Fehrenbacher and Adam Brufsky and Azar, {Catherine A.} and Flynn, {Patrick J.} and Zapas, {John L.} and Jonathan Polikoff and Gross, {Howard M.} and Biggs, {David D.} and Atkins, {James N.} and Elizabeth Tan-Chiu and Ping Zheng and Greg Yothers and Mamounas, {Eleftherios P.} and Norman Wolmark",
year = "2012",
month = "11",
day = "1",
doi = "10.1200/JCO.2011.40.0010",
language = "English (US)",
volume = "30",
pages = "3792--3799",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "31",

}

TY - JOUR

T1 - Seven-year follow-up assessment of cardiac function in NSABP B-31, a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel (ACP) with ACP plus trastuzumab as adjuvant therapy for patients with node-positive, human epidermal growth factor receptor 2-positive breast cancer

AU - Romond, Edward H.

AU - Jeong, Jong Hyeon

AU - Rastogi, Priya

AU - Swain, Sandra M.

AU - Geyer, Charles E.

AU - Ewer, Michael S.

AU - Rathi, Vikas

AU - Fehrenbacher, Louis

AU - Brufsky, Adam

AU - Azar, Catherine A.

AU - Flynn, Patrick J.

AU - Zapas, John L.

AU - Polikoff, Jonathan

AU - Gross, Howard M.

AU - Biggs, David D.

AU - Atkins, James N.

AU - Tan-Chiu, Elizabeth

AU - Zheng, Ping

AU - Yothers, Greg

AU - Mamounas, Eleftherios P.

AU - Wolmark, Norman

PY - 2012/11/1

Y1 - 2012/11/1

N2 - Purpose: Cardiac dysfunction (CD) is a recognized risk associated with the addition of trastuzumab to adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer, especially when the treatment regimen includes anthracyclines. Given the demonstrated efficacy of trastuzumab, ongoing assessment of cardiac safety and identification of risk factors for CD are important for optimal patient care. Patients and Methods: In National Surgical Adjuvant Breast and Bowel Project B-31, a phase III adjuvant trial, 1,830 patients who met eligibility criteria for initiation of trastuzumab were evaluated for CD. Recovery from CD was also assessed. A statistical model was developed to estimate the risk of severe congestive heart failure (CHF). Baseline patient characteristics associated with anthracycline-related decline in cardiac function were also identified. Results: At 7-year follow-up, 37 (4.0%) of 944 patients who received trastuzumab experienced a cardiac event (CE) versus 10 (1.3%) of 743 patients in the control arm. One cardiac-related death has occurred in each arm of the protocol. A Cardiac Risk Score, calculated using patient age and baseline left ventricular ejection fraction (LVEF) by multiple-gated acquisition scan, statistically correlates with the risk of a CE. After stopping trastuzumab, the majority of patients who experienced CD recovered LVEF in the normal range, although some decline from baseline often persists. Only two CEs occurred more than 2 years after initiation of trastuzumab. Conclusion: The late development of CHF after the addition of trastuzumab to paclitaxel after doxorubicin/ cyclophosphamide chemotherapy is uncommon. The risk versus benefit of trastuzumab as given in this regimen remains strongly in favor of trastuzumab.

AB - Purpose: Cardiac dysfunction (CD) is a recognized risk associated with the addition of trastuzumab to adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer, especially when the treatment regimen includes anthracyclines. Given the demonstrated efficacy of trastuzumab, ongoing assessment of cardiac safety and identification of risk factors for CD are important for optimal patient care. Patients and Methods: In National Surgical Adjuvant Breast and Bowel Project B-31, a phase III adjuvant trial, 1,830 patients who met eligibility criteria for initiation of trastuzumab were evaluated for CD. Recovery from CD was also assessed. A statistical model was developed to estimate the risk of severe congestive heart failure (CHF). Baseline patient characteristics associated with anthracycline-related decline in cardiac function were also identified. Results: At 7-year follow-up, 37 (4.0%) of 944 patients who received trastuzumab experienced a cardiac event (CE) versus 10 (1.3%) of 743 patients in the control arm. One cardiac-related death has occurred in each arm of the protocol. A Cardiac Risk Score, calculated using patient age and baseline left ventricular ejection fraction (LVEF) by multiple-gated acquisition scan, statistically correlates with the risk of a CE. After stopping trastuzumab, the majority of patients who experienced CD recovered LVEF in the normal range, although some decline from baseline often persists. Only two CEs occurred more than 2 years after initiation of trastuzumab. Conclusion: The late development of CHF after the addition of trastuzumab to paclitaxel after doxorubicin/ cyclophosphamide chemotherapy is uncommon. The risk versus benefit of trastuzumab as given in this regimen remains strongly in favor of trastuzumab.

UR - http://www.scopus.com/inward/record.url?scp=84869125207&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84869125207&partnerID=8YFLogxK

U2 - 10.1200/JCO.2011.40.0010

DO - 10.1200/JCO.2011.40.0010

M3 - Article

VL - 30

SP - 3792

EP - 3799

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 31

ER -