This Article Full Text Full Text (PDF) Erratum (v23,p1594) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Perez, E. A. Articles by Jaffe, A. S. Search for Related Content PubMed PubMed Citation Articles by Perez, E. A. Articles by Jaffe, A. S. Social Bookmarking                            What's this?

Effect of Doxorubicin Plus Cyclophosphamide on Left Ventricular Ejection Fraction in Patients With Breast Cancer in the North Central Cancer Treatment Group N9831 Intergroup Adjuvant Trial

From the North Central Cancer Treatment Group; Eastern Cooperative Oncology Group; Cancer and Leukemia Group B; Southwest Oncology Group; Mayo Clinic, Jacksonville, FL; and Mayo Clinic, Rochester, MN

Address reprint requests to Edith A. Perez, MD, Division of Hematology/Oncology, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224; e-mail: perez.edith{at}mayo.edu

PURPOSE: To evaluate changes in left ventricular ejection fraction (LVEF) after four cycles of adjuvant doxorubicin plus cyclophosphamide (AC) in women with human epidermal growth factor receptor 2–positive (node-positive or node-negative) breast cancer enrolled onto the North Central Cancer Treatment Group N9831 Intergroup Adjuvant Trial.

PATIENTS AND METHODS: Patients were randomly assigned to receive standard doxorubicin (60 mg/m²) plus cyclophosphamide (600 mg/m²) every 3 weeks for four cycles followed by (1) weekly paclitaxel for 12 weeks; (2) weekly paclitaxel for 12 weeks, then weekly trastuzumab for 52 weeks; or (3) weekly paclitaxel plus trastuzumab for 12 weeks, then weekly trastuzumab for 40 weeks. LVEF was monitored before and after AC.

RESULTS: Of the 1,576 eligible patients who completed AC, 1,458 had pre- and post-AC LVEF measurements taken using the same methodology (multiple-gated acquisition in 1,153 patients and echocardiogram in 305 patients). Among these 1,458 patients, 745 (51.1%) had 15% decrease in LVEF and LVEF that remained at or above the radiologic lower limit of normal (LLN); 42 patients (2.9%) had 15% decrease in LVEF and LVEF that decreased to or below the LLN; and 37 patients (2.5%) had an LVEF decrease of more than 15%. There was grade 2 LVEF toxicity in 96 (6.6%) of the 1,458 patients.

CONCLUSION: Standard AC chemotherapy is associated with frequent decreases in LVEF, which are noted when measured 3 weeks after completion of the fourth cycle. Patients are being observed to determine the long-term significance of this and the potential impact on subsequent treatment options.

Supported in part by grant No. NIH CA25224, Genentech, and the Breast Cancer Research Foundation.

These data were presented in part at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 3, 2003.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				P. J. Barrett-Lee, J. M. Dixon, C. Farrell, A. Jones, R. Leonard, N. Murray, C. Palmieri, C. J. Plummer, A. Stanley, and M. W. Verrill Expert opinion on the use of anthracyclines in patients with advanced breast cancer at cardiac risk Ann. Onc., May 1, 2009; 20(5): 816 - 827. [Abstract] [Full Text] [PDF]

				D. Rayson, D. Richel, S. Chia, C. Jackisch, S. van der Vegt, and T. Suter Anthracycline-trastuzumab regimens for HER2/neu-overexpressing breast cancer: current experience and future strategies Ann. Onc., September 1, 2008; 19(9): 1530 - 1539. [Abstract] [Full Text] [PDF]

				B. Freidlin, E. L. Korn, R. Gray, and A. Martin Multi-Arm Clinical Trials of New Agents: Some Design Considerations Clin. Cancer Res., July 15, 2008; 14(14): 4368 - 4371. [Abstract] [Full Text] [PDF]

				E. A. Perez, V. J. Suman, N. E. Davidson, G. W. Sledge, P. A. Kaufman, C. A. Hudis, S. Martino, J. R. Gralow, S. R. Dakhil, J. N. Ingle, et al. Cardiac Safety Analysis of Doxorubicin and Cyclophosphamide Followed by Paclitaxel With or Without Trastuzumab in the North Central Cancer Treatment Group N9831 Adjuvant Breast Cancer Trial J. Clin. Oncol., March 10, 2008; 26(8): 1231 - 1238. [Abstract] [Full Text] [PDF]

				B. R.J. H. Bird and S. M. Swain Cardiac Toxicity in Breast Cancer Survivors: Review of Potential Cardiac Problems Clin. Cancer Res., January 1, 2008; 14(1): 14 - 24. [Abstract] [Full Text] [PDF]

				L. W. Jones, M. J. Haykowsky, J. J. Swartz, P. S. Douglas, and J. R. Mackey Early Breast Cancer Therapy and Cardiovascular Injury J. Am. Coll. Cardiol., October 9, 2007; 50(15): 1435 - 1441. [Abstract] [Full Text] [PDF]

				K. S. Courneya, R. J. Segal, J. R. Mackey, K. Gelmon, R. D. Reid, C. M. Friedenreich, A. B. Ladha, C. Proulx, J. K.H. Vallance, K. Lane, et al. Effects of Aerobic and Resistance Exercise in Breast Cancer Patients Receiving Adjuvant Chemotherapy: A Multicenter Randomized Controlled Trial J. Clin. Oncol., October 1, 2007; 25(28): 4396 - 4404. [Abstract] [Full Text] [PDF]

				L. W. Jones, M. Haykowsky, E. N. Pituskin, N. G. Jendzjowsky, C. R. Tomczak, R. G. Haennel, and J. R. Mackey Cardiovascular Reserve and Risk Profile of Postmenopausal Women After Chemoendocrine Therapy for Hormone Receptor Positive Operable Breast Cancer Oncologist, October 1, 2007; 12(10): 1156 - 1164. [Abstract] [Full Text] [PDF]

				J. R. Carver, C. L. Shapiro, A. Ng, L. Jacobs, C. Schwartz, K. S. Virgo, K. L. Hagerty, M. R. Somerfield, D. J. Vaughn, and for the ASCO Cancer Survivorship Expert Panel American Society of Clinical Oncology Clinical Evidence Review on the Ongoing Care of Adult Cancer Survivors: Cardiac and Pulmonary Late Effects J. Clin. Oncol., September 1, 2007; 25(25): 3991 - 4008. [Abstract] [Full Text] [PDF]

				M. C. Pinder, Z. Duan, J. S. Goodwin, G. N. Hortobagyi, and S. H. Giordano Congestive Heart Failure in Older Women Treated With Adjuvant Anthracycline Chemotherapy for Breast Cancer J. Clin. Oncol., September 1, 2007; 25(25): 3808 - 3815. [Abstract] [Full Text] [PDF]

				L. W. Jones, M. Haykowsky, C. J. Peddle, A. A. Joy, E. N. Pituskin, L. M. Tkachuk, K. S. Courneya, D. J. Slamon, and J. R. Mackey Cardiovascular Risk Profile of Patients with HER2/neu-Positive Breast Cancer Treated with Anthracycline-Taxane-Containing Adjuvant Chemotherapy and/or Trastuzumab Cancer Epidemiol. Biomarkers Prev., May 1, 2007; 16(5): 1026 - 1031. [Abstract] [Full Text] [PDF]

				V. Guarneri, D. J. Lenihan, V. Valero, J.-B. Durand, K. Broglio, K. R. Hess, L. B. Michaud, A. M. Gonzalez-Angulo, G. N. Hortobagyi, and F. J. Esteva Long-Term Cardiac Tolerability of Trastuzumab in Metastatic Breast Cancer: The M.D. Anderson Cancer Center Experience J. Clin. Oncol., September 1, 2006; 24(25): 4107 - 4115. [Abstract] [Full Text] [PDF]

				E. A. Perez, V. J. Suman, N. E. Davidson, S. Martino, P. A. Kaufman, W. L. Lingle, P. J. Flynn, J. N. Ingle, D. Visscher, and R. B. Jenkins HER2 Testing by Local, Central, and Reference Laboratories in Specimens From the North Central Cancer Treatment Group N9831 Intergroup Adjuvant Trial J. Clin. Oncol., July 1, 2006; 24(19): 3032 - 3038. [Abstract] [Full Text] [PDF]

				H. Joensuu, P.-L. Kellokumpu-Lehtinen, P. Bono, T. Alanko, V. Kataja, R. Asola, T. Utriainen, R. Kokko, A. Hemminki, M. Tarkkanen, et al. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N. Engl. J. Med., February 23, 2006; 354(8): 809 - 820. [Abstract] [Full Text] [PDF]

				J. J. Doyle, A. I. Neugut, J. S. Jacobson, V. R. Grann, and D. L. Hershman Chemotherapy and Cardiotoxicity in Older Breast Cancer Patients: A Population-Based Study J. Clin. Oncol., December 1, 2005; 23(34): 8597 - 8605. [Abstract] [Full Text] [PDF]

				S. Gluck Adjuvant Chemotherapy for Early Breast Cancer: Optimal Use of Epirubicin Oncologist, November 1, 2005; 10(10): 780 - 791. [Abstract] [Full Text] [PDF]