Cardiac effects of adjuvant doxorubicin and radiation therapy in breast cancer patients

Charles L. Shapiro, Patricia Harrigan Hardenbergh, Rebecca Gelman, Dana Blanks, Paul Hauptman, Abram Recht, Daniel F. Hayes, Jay Harris, I. Craig Henderson

Research output: Contribution to journalArticle

Abstract

Purpose: To assess the cardiac effects of two different cumulative doses of adjuvant doxarubicin and radiation therapy (RT) in breast cancer patients. Patients and Methods: Two hundred ninety-nine breast cancer patients were prospectively randomized to receive either five cycles (CA5) or 10 cycles (CA10) of adjuvant treatment with cyclophosphamide (500 mg/m2) and doxorubicin (45 mg/m2) administered by intravenous bolus every 21 days. One hundred twenty-two of these patients also received RT. Estimates of the cardiac RT dose-volume were retrospectively categorized as low, moderate, or high. The risk of major cardiac events (congestive heart failure, acute myocardial infarction) was assessable in 276 patients (92%), with a median follow-up time of 6.0 years (range, 0.5 to 19.4). Results: The estimated risk (95% confidence interval) of cardiac events per 100 patient-years was significantly higher for CA10 than far CA5 [1.7 (1.0 to 2.8) v 0.5 (0.1 to 1.2); P = .02]. The risk of cardiac events in CA5 patients, irrespective of the cardiac RT dose volume, did not differ significantly from rates of cardiac events predicted for the general female population by the Framingham Heart Study. In CA10 patients, the incidence of cardiac events was significantly increased (relative risk ratio, 3.6; P < .00003) compared with the Framingham population, particularly in groups that also received moderate and high dose-volume cardiac RT. Conclusion: Conventional-dose adjuvant doxorubicin as delivered in the CA5 regimen by itself, or in combination with locoregional RT, was not associated with a significant increase in the risk of cardiac events. Higher doses of adjuvant doxorubicin (CA10) were associated with a threefold to fourfold increased risk of cardiac events. This appears to be especially true in patients treated with higher dose- volumes of cardiac RT. Larger studies with longer follow-up periods are needed to confirm these results.

Original languageEnglish (US)
Pages (from-to)3493-3501
Number of pages9
JournalJournal of Clinical Oncology
Volume16
Issue number11
DOIs
StatePublished - Jan 1 1998
Externally publishedYes

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Drug Dose Response Relationship
Radiation Dose-Response Relationship
Combined Modality Therapy
Adjuvant Chemotherapy
Antineoplastic Agents
Doxorubicin
Cyclophosphamide
Radiotherapy
Heart Failure
Myocardial Infarction
Breast Neoplasms
Cardiac Volume
Population

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Shapiro, C. L., Hardenbergh, P. H., Gelman, R., Blanks, D., Hauptman, P., Recht, A., ... Henderson, I. C. (1998). Cardiac effects of adjuvant doxorubicin and radiation therapy in breast cancer patients. Journal of Clinical Oncology, 16(11), 3493-3501. https://doi.org/10.1200/JCO.1998.16.11.3493

Cardiac effects of adjuvant doxorubicin and radiation therapy in breast cancer patients. / Shapiro, Charles L.; Hardenbergh, Patricia Harrigan; Gelman, Rebecca; Blanks, Dana; Hauptman, Paul; Recht, Abram; Hayes, Daniel F.; Harris, Jay; Henderson, I. Craig.

In: Journal of Clinical Oncology, Vol. 16, No. 11, 01.01.1998, p. 3493-3501.

Research output: Contribution to journalArticle

Shapiro, CL, Hardenbergh, PH, Gelman, R, Blanks, D, Hauptman, P, Recht, A, Hayes, DF, Harris, J & Henderson, IC 1998, 'Cardiac effects of adjuvant doxorubicin and radiation therapy in breast cancer patients', Journal of Clinical Oncology, vol. 16, no. 11, pp. 3493-3501. https://doi.org/10.1200/JCO.1998.16.11.3493
Shapiro, Charles L. ; Hardenbergh, Patricia Harrigan ; Gelman, Rebecca ; Blanks, Dana ; Hauptman, Paul ; Recht, Abram ; Hayes, Daniel F. ; Harris, Jay ; Henderson, I. Craig. / Cardiac effects of adjuvant doxorubicin and radiation therapy in breast cancer patients. In: Journal of Clinical Oncology. 1998 ; Vol. 16, No. 11. pp. 3493-3501.
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abstract = "Purpose: To assess the cardiac effects of two different cumulative doses of adjuvant doxarubicin and radiation therapy (RT) in breast cancer patients. Patients and Methods: Two hundred ninety-nine breast cancer patients were prospectively randomized to receive either five cycles (CA5) or 10 cycles (CA10) of adjuvant treatment with cyclophosphamide (500 mg/m2) and doxorubicin (45 mg/m2) administered by intravenous bolus every 21 days. One hundred twenty-two of these patients also received RT. Estimates of the cardiac RT dose-volume were retrospectively categorized as low, moderate, or high. The risk of major cardiac events (congestive heart failure, acute myocardial infarction) was assessable in 276 patients (92{\%}), with a median follow-up time of 6.0 years (range, 0.5 to 19.4). Results: The estimated risk (95{\%} confidence interval) of cardiac events per 100 patient-years was significantly higher for CA10 than far CA5 [1.7 (1.0 to 2.8) v 0.5 (0.1 to 1.2); P = .02]. The risk of cardiac events in CA5 patients, irrespective of the cardiac RT dose volume, did not differ significantly from rates of cardiac events predicted for the general female population by the Framingham Heart Study. In CA10 patients, the incidence of cardiac events was significantly increased (relative risk ratio, 3.6; P < .00003) compared with the Framingham population, particularly in groups that also received moderate and high dose-volume cardiac RT. Conclusion: Conventional-dose adjuvant doxorubicin as delivered in the CA5 regimen by itself, or in combination with locoregional RT, was not associated with a significant increase in the risk of cardiac events. Higher doses of adjuvant doxorubicin (CA10) were associated with a threefold to fourfold increased risk of cardiac events. This appears to be especially true in patients treated with higher dose- volumes of cardiac RT. Larger studies with longer follow-up periods are needed to confirm these results.",
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