Risk of heart failure in breast cancer patients after anthracycline and trastuzumab treatment: A retrospective cohort study

Erin J.Aiello Bowles, Robert Wellman, Heather Spencer Feigelson, Adedayo A. Onitilo, Andrew N. Freedman, Thomas Delate, Larry A. Allen, Larissa Nekhlyudov, Katrina A.B. Goddard, Robert Davis, Laurel A. Habel, Marianne Ulcickas Yood, Catherine McCarty, David J. Magid, Edward H. Wagner

Research output: Contribution to journalArticle

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Abstract

Background Clinical trials demonstrated that women treated for breast cancer with anthracycline or trastuzumab are at increased risk for heart failure and/or cardiomyopathy (HF/CM), but the generalizability of these findings is unknown. We estimated real-world adjuvant anthracycline and trastuzumab use and their associations with incident HF/CM.Methods We conducted a population-based, retrospective cohort study of 12 500 women diagnosed with incident, invasive breast cancer from January 1, 1999 through December 31, 2007, at eight integrated Cancer Research Network health systems. Using administrative procedure and pharmacy codes, we identified anthracycline, trastuzumab, and other chemotherapy use. We identified incident HF/CM following chemotherapy initiation and assessed risk of HF/CM with time-varying chemotherapy exposures vs no chemotherapy. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for age at diagnosis, stage, Cancer Research Network site, year of diagnosis, radiation therapy, and comorbidities. Results Among 12 500 women (mean age = 60 years, range = 2299 years), 29.6% received anthracycline alone, 0.9% received trastuzumab alone, 3.5% received anthracycline plus trastuzumab, 19.5% received other chemotherapy, and 46.5% received no chemotherapy. Anthracycline and trastuzumab recipients were younger, with fewer comorbidities than recipients of other chemotherapy or none. Compared with no chemotherapy, the risk of HF/CM was higher in patients treated with anthracycline alone (adjusted HR = 1.40, 95% CI = 1.11 to 1.76), although the increased risk was similar to other chemotherapy (adjusted HR = 1.49, 95% CI = 1.25 to 1.77); the risk was highly increased in patients treated with trastuzumab alone (adjusted HR = 4.12, 95% CI = 2.30 to 7.42) or anthracycline plus trastuzumab (adjusted HR = 7.19, 95% CI = 5.00 to 10.35). Conclusions Anthracycline and trastuzumab were primarily used in younger, healthier women and associated with increased HF/CM risk compared with no chemotherapy. This population-based observational study complements findings from clinical trials on cancer treatment safety.

Original languageEnglish (US)
Pages (from-to)1293-1305
Number of pages13
JournalJournal of the National Cancer Institute
Volume104
Issue number17
DOIs
StatePublished - Sep 5 2012

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Anthracyclines
Cohort Studies
Heart Failure
Retrospective Studies
Breast Neoplasms
Drug Therapy
Cardiomyopathies
Confidence Intervals
Therapeutics
Comorbidity
Trastuzumab
Clinical Trials
Neoplasms
Proportional Hazards Models
Research
Population
Observational Studies
Radiotherapy
Safety

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Bowles, E. J. A., Wellman, R., Feigelson, H. S., Onitilo, A. A., Freedman, A. N., Delate, T., ... Wagner, E. H. (2012). Risk of heart failure in breast cancer patients after anthracycline and trastuzumab treatment: A retrospective cohort study. Journal of the National Cancer Institute, 104(17), 1293-1305. https://doi.org/10.1093/jnci/djs317

Risk of heart failure in breast cancer patients after anthracycline and trastuzumab treatment : A retrospective cohort study. / Bowles, Erin J.Aiello; Wellman, Robert; Feigelson, Heather Spencer; Onitilo, Adedayo A.; Freedman, Andrew N.; Delate, Thomas; Allen, Larry A.; Nekhlyudov, Larissa; Goddard, Katrina A.B.; Davis, Robert; Habel, Laurel A.; Yood, Marianne Ulcickas; McCarty, Catherine; Magid, David J.; Wagner, Edward H.

In: Journal of the National Cancer Institute, Vol. 104, No. 17, 05.09.2012, p. 1293-1305.

Research output: Contribution to journalArticle

Bowles, EJA, Wellman, R, Feigelson, HS, Onitilo, AA, Freedman, AN, Delate, T, Allen, LA, Nekhlyudov, L, Goddard, KAB, Davis, R, Habel, LA, Yood, MU, McCarty, C, Magid, DJ & Wagner, EH 2012, 'Risk of heart failure in breast cancer patients after anthracycline and trastuzumab treatment: A retrospective cohort study', Journal of the National Cancer Institute, vol. 104, no. 17, pp. 1293-1305. https://doi.org/10.1093/jnci/djs317
Bowles, Erin J.Aiello ; Wellman, Robert ; Feigelson, Heather Spencer ; Onitilo, Adedayo A. ; Freedman, Andrew N. ; Delate, Thomas ; Allen, Larry A. ; Nekhlyudov, Larissa ; Goddard, Katrina A.B. ; Davis, Robert ; Habel, Laurel A. ; Yood, Marianne Ulcickas ; McCarty, Catherine ; Magid, David J. ; Wagner, Edward H. / Risk of heart failure in breast cancer patients after anthracycline and trastuzumab treatment : A retrospective cohort study. In: Journal of the National Cancer Institute. 2012 ; Vol. 104, No. 17. pp. 1293-1305.
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abstract = "Background Clinical trials demonstrated that women treated for breast cancer with anthracycline or trastuzumab are at increased risk for heart failure and/or cardiomyopathy (HF/CM), but the generalizability of these findings is unknown. We estimated real-world adjuvant anthracycline and trastuzumab use and their associations with incident HF/CM.Methods We conducted a population-based, retrospective cohort study of 12 500 women diagnosed with incident, invasive breast cancer from January 1, 1999 through December 31, 2007, at eight integrated Cancer Research Network health systems. Using administrative procedure and pharmacy codes, we identified anthracycline, trastuzumab, and other chemotherapy use. We identified incident HF/CM following chemotherapy initiation and assessed risk of HF/CM with time-varying chemotherapy exposures vs no chemotherapy. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95{\%} confidence intervals (CIs) with adjustment for age at diagnosis, stage, Cancer Research Network site, year of diagnosis, radiation therapy, and comorbidities. Results Among 12 500 women (mean age = 60 years, range = 2299 years), 29.6{\%} received anthracycline alone, 0.9{\%} received trastuzumab alone, 3.5{\%} received anthracycline plus trastuzumab, 19.5{\%} received other chemotherapy, and 46.5{\%} received no chemotherapy. Anthracycline and trastuzumab recipients were younger, with fewer comorbidities than recipients of other chemotherapy or none. Compared with no chemotherapy, the risk of HF/CM was higher in patients treated with anthracycline alone (adjusted HR = 1.40, 95{\%} CI = 1.11 to 1.76), although the increased risk was similar to other chemotherapy (adjusted HR = 1.49, 95{\%} CI = 1.25 to 1.77); the risk was highly increased in patients treated with trastuzumab alone (adjusted HR = 4.12, 95{\%} CI = 2.30 to 7.42) or anthracycline plus trastuzumab (adjusted HR = 7.19, 95{\%} CI = 5.00 to 10.35). Conclusions Anthracycline and trastuzumab were primarily used in younger, healthier women and associated with increased HF/CM risk compared with no chemotherapy. This population-based observational study complements findings from clinical trials on cancer treatment safety.",
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T1 - Risk of heart failure in breast cancer patients after anthracycline and trastuzumab treatment

T2 - A retrospective cohort study

AU - Bowles, Erin J.Aiello

AU - Wellman, Robert

AU - Feigelson, Heather Spencer

AU - Onitilo, Adedayo A.

AU - Freedman, Andrew N.

AU - Delate, Thomas

AU - Allen, Larry A.

AU - Nekhlyudov, Larissa

AU - Goddard, Katrina A.B.

AU - Davis, Robert

AU - Habel, Laurel A.

AU - Yood, Marianne Ulcickas

AU - McCarty, Catherine

AU - Magid, David J.

AU - Wagner, Edward H.

PY - 2012/9/5

Y1 - 2012/9/5

N2 - Background Clinical trials demonstrated that women treated for breast cancer with anthracycline or trastuzumab are at increased risk for heart failure and/or cardiomyopathy (HF/CM), but the generalizability of these findings is unknown. We estimated real-world adjuvant anthracycline and trastuzumab use and their associations with incident HF/CM.Methods We conducted a population-based, retrospective cohort study of 12 500 women diagnosed with incident, invasive breast cancer from January 1, 1999 through December 31, 2007, at eight integrated Cancer Research Network health systems. Using administrative procedure and pharmacy codes, we identified anthracycline, trastuzumab, and other chemotherapy use. We identified incident HF/CM following chemotherapy initiation and assessed risk of HF/CM with time-varying chemotherapy exposures vs no chemotherapy. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for age at diagnosis, stage, Cancer Research Network site, year of diagnosis, radiation therapy, and comorbidities. Results Among 12 500 women (mean age = 60 years, range = 2299 years), 29.6% received anthracycline alone, 0.9% received trastuzumab alone, 3.5% received anthracycline plus trastuzumab, 19.5% received other chemotherapy, and 46.5% received no chemotherapy. Anthracycline and trastuzumab recipients were younger, with fewer comorbidities than recipients of other chemotherapy or none. Compared with no chemotherapy, the risk of HF/CM was higher in patients treated with anthracycline alone (adjusted HR = 1.40, 95% CI = 1.11 to 1.76), although the increased risk was similar to other chemotherapy (adjusted HR = 1.49, 95% CI = 1.25 to 1.77); the risk was highly increased in patients treated with trastuzumab alone (adjusted HR = 4.12, 95% CI = 2.30 to 7.42) or anthracycline plus trastuzumab (adjusted HR = 7.19, 95% CI = 5.00 to 10.35). Conclusions Anthracycline and trastuzumab were primarily used in younger, healthier women and associated with increased HF/CM risk compared with no chemotherapy. This population-based observational study complements findings from clinical trials on cancer treatment safety.

AB - Background Clinical trials demonstrated that women treated for breast cancer with anthracycline or trastuzumab are at increased risk for heart failure and/or cardiomyopathy (HF/CM), but the generalizability of these findings is unknown. We estimated real-world adjuvant anthracycline and trastuzumab use and their associations with incident HF/CM.Methods We conducted a population-based, retrospective cohort study of 12 500 women diagnosed with incident, invasive breast cancer from January 1, 1999 through December 31, 2007, at eight integrated Cancer Research Network health systems. Using administrative procedure and pharmacy codes, we identified anthracycline, trastuzumab, and other chemotherapy use. We identified incident HF/CM following chemotherapy initiation and assessed risk of HF/CM with time-varying chemotherapy exposures vs no chemotherapy. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for age at diagnosis, stage, Cancer Research Network site, year of diagnosis, radiation therapy, and comorbidities. Results Among 12 500 women (mean age = 60 years, range = 2299 years), 29.6% received anthracycline alone, 0.9% received trastuzumab alone, 3.5% received anthracycline plus trastuzumab, 19.5% received other chemotherapy, and 46.5% received no chemotherapy. Anthracycline and trastuzumab recipients were younger, with fewer comorbidities than recipients of other chemotherapy or none. Compared with no chemotherapy, the risk of HF/CM was higher in patients treated with anthracycline alone (adjusted HR = 1.40, 95% CI = 1.11 to 1.76), although the increased risk was similar to other chemotherapy (adjusted HR = 1.49, 95% CI = 1.25 to 1.77); the risk was highly increased in patients treated with trastuzumab alone (adjusted HR = 4.12, 95% CI = 2.30 to 7.42) or anthracycline plus trastuzumab (adjusted HR = 7.19, 95% CI = 5.00 to 10.35). Conclusions Anthracycline and trastuzumab were primarily used in younger, healthier women and associated with increased HF/CM risk compared with no chemotherapy. This population-based observational study complements findings from clinical trials on cancer treatment safety.

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