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Long-term assessment of cardiac function after dose-dense and -intense sequential doxorubicin (A), paclitaxel (T), and cyclophosphamide (C) as adjuvant therapy for high risk breast cancer

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Abstract

Objectives

This study evaluated the incidence of late cardiotoxicity after dose-dense and -intense adjuvant sequential doxorubicin (A), paclitaxel (T), and cyclophosphamide (C) for breast cancer (BC) with ≥ 4 involved ipsilateral axillary lymph nodes.

Methods

Patients were enrolled from 1994 to 2001 after definitive BC surgery if ≥4 axillary nodes were involved. Planned treatment was A 90 mg/m2 q 14 days × 3, T 250 mg/m2 q 14 days × 3, C 3 g/m2 q 14 days × 3 with filgrastim (G) support. Left ventricular ejection fraction (LVEF) was monitored using equilibrium radionuclide angiography (ERNA) before the initiation of chemotherapy, and after three cycles of each chemotherapeutic agent. At a median follow-up of 7 years, we obtained ERNA scans on 32 patients to evaluate the long-term cardiotoxicity of this regimen.

Results

Eighty-five eligible patients enrolled on the treatment protocol. Clinical heart failure developed in one patient. Seven (8%) patients had LVEF < 50% at the end of therapy. No cardiac-related deaths occurred. Thirty-two (46%) of 69 surviving patients have consented to late cardiac imaging. At a median follow-up of 7 years, the median absolute change in LVEF from baseline was -5.5%; [range (−8%) to (+36%)], and from the end of chemotherapy was −2.0%; [range (−25%) to (+16%)]. Four patients (12%) had a LVEF < 50%; two of these four patients had an LVEF of < 50% at the end of chemotherapy.

Conclusions

Late development of asymptomatic decline in cardiac function may occur after dose-dense and -intense adjuvant therapy, but is uncommon.

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Authors and Affiliations

  1. Department of Internal Medicine, Section of Medical Oncology, Yale University School of Medicine, Yale Cancer Center, 333 Cedar Street, FMP 125, New Haven, CT, 06520-8032, USA

    Maysa M. Abu-Khalaf, Vinni Juneja, Gina G. Chung, Michael P. DiGiovanna, Rebecca Sipples & Meghan McGurk

  2. Division of Biostatistics, Yale University, New Haven, CT, USA

    Daniel Zelterman

  3. Department of Radiation Oncology, UMDNJ-Robert Wood Johnson Medical School, Cancer Institute of New Jersey, New Brunswick, NJ, USA

    Bruce Haffty

  4. Department of Internal Medicine, Section of Medical Oncology, UMDNJ-Robert Wood Johnson Medical School, Cancer Institute of New Jersey, New Brunswick, NJ, USA

    Michael Reiss

  5. Department of Internal Medicine, Section of Cardiology, Yale University School of Medicine, New Haven, CT, USA

    Frans J. Wackers & Forrester A. Lee

  6. Department of Medical Oncology, Division of Medical Sciences, Fox Chase Cancer Center, Philadelphia, PA, USA

    Barbara A. Burtness

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  1. Maysa M. Abu-Khalaf
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  2. Vinni Juneja
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Correspondence to Maysa M. Abu-Khalaf.

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Abu-Khalaf, M.M., Juneja, V., Chung, G.G. et al. Long-term assessment of cardiac function after dose-dense and -intense sequential doxorubicin (A), paclitaxel (T), and cyclophosphamide (C) as adjuvant therapy for high risk breast cancer. Breast Cancer Res Treat 104, 341–349 (2007). https://doi.org/10.1007/s10549-006-9413-7

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