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Risk of acute myeloid leukemia and myelodysplastic syndrome among older women receiving anthracycline-based adjuvant chemotherapy for breast cancer on Modern Cooperative Group Trials (Alliance A151511)

  • Epidemiology
  • Published:
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Abstract

Purpose

We examined acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) events among 9679 women treated for breast cancer on four adjuvant Alliance for Clinical Trials in Oncology trials with >90 months of follow-up in order to better characterize the risk for AML/MDS in older patients receiving anthracyclines.

Methods

We used multivariable Cox regression to examine factors associated with AML/MDS, adjusting for age (≥65 vs. <65 years; separately for ≥70 vs. <70 years), race/ethnicity, insurance, performance status, and anthracycline receipt. We also examined the effect of cyclophosphamide, the interaction of anthracycline and age, and outcomes for those develo** AML/MDS.

Results

On Cancer and Leukemia Group B (CALGB) 40101, 49907, 9344, and 9741, 7290 received anthracyclines; 15% were in the age ≥65 and 7% were ≥70. Overall, 47 patients developed AML/MDS (30 AML [0.3%], 17 MDS [0.2%]); 83% of events occurred within 5 years of study registration. Among those age ≥65 and ≥70, 0.8 and 1.0% developed AML/MDS (vs. 0.4% for age <65), respectively. In adjusted analyses, older age and anthracycline receipt were significantly associated with AML/MDS (adjusted hazard ratio [HR] for age ≥65 [vs. <65] = 3.13, 95% confidence interval [CI] 1.18–8.33; HR for anthracycline receipt [vs. no anthracycline] = 5.16, 95% CI 1.47–18.19). There was no interaction between age and anthracycline use. Deaths occurred in 70% of those develo** AML/MDS.

Conclusions

We observed an increased risk for AML/MDS for older patients and those receiving anthracyclines, though these events were rare. Our results help inform discussions surrounding anticipated toxicities of adjuvant chemotherapy in older patients.

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Acknowledgements

We thank all patients enrolled to Alliance trials over time as well as the study teams who previously collected and shared the data for analysis. We also thank Kaitlyn Bifolck for her administrative support with manuscript submission.

Funding

This study was supported by the National Cancer Institute of the National Institutes of Health under the Award Number UG1CA189823 (Alliance for Clinical Trials in Oncology NCORP Grant), U10CA032291, U10CA047559, U10CA047577, U10CA077597, U10CA077651, U10CA180790, U10CA180791, U10CA180838, U10CA180857, U10CA180867. RAF also receives funding Susan G. Komen (Grant No. CCR14298143) and American Cancer Society (Grant No. 125912-MRSG-14-240-01-CPPB). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA

    Rachel A. Freedman, E. P. Winer & A. H. Partridge

  2. Alliance Statistics and Data Center, Mayo Clinic and Mayo Cancer Center, Rochester, MN, USA

    D. K. Seisler, J. C. Foster, J. A. Sloan & V. J. Suman

  3. Mayo Clinic College of Medicine, Rochester, MN, USA

    J. M. Lafky & A. Jatoi

  4. Duke University School of Medicine, Durham, NC, USA

    G. G. Kimmick & H. J. Cohen

  5. Department of Medical Oncology and Therapeutics Research and Department of Population Sciences, City of Hope, Duarte, CA, USA

    A. Hurria

  6. Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    C. A. Hudis

  7. Division of Hematology/Oncology, University of North Carolina, Chapel Hill, NC, USA

    L. A. Carey & H. B. Muss

  8. Department of Hematology and Oncology, Wake Forest University, Winston-Salem, NC, USA

    H. D. Klepin

  9. ProHEALTH Care Associates, Lake Success, NY, USA

    M. Citron

  10. Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    D. A. Berry & A. U. Buzdar

  11. Division of Hematology and Oncology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA

    L. N. Shulman

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  1. Rachel A. Freedman
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  19. V. J. Suman
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Corresponding author

Correspondence to Rachel A. Freedman.

Ethics declarations

Conflict of interest

Rachel Freeman has received institutional funding from Genentech, Puma, and Eisai. Drew Seisler reports renumeration from Mayo Clinic. Jared Foster declares that he has no conflict of interest. Jeff Sloan declares that he has no conflict of interest. Jacqueline Lafky declares that she has no conflict of interest. Gretchen Kimmick has served on speakers bureaus and has consultant/advisory roles for Pfizer, Astra Zeneca, Novartis, Genomic Health, and Genentech, and has received funding from Wyeth, Astra Zeneca, Glaxo Smith Kline, Novartis, PUMA, Bristol Meyers Squibb, and Bionovo. Arti Hurria has consultant/advisory roles for Boehringer Ingelheim Pharmaceuticals, Carevive, Sanofi, and GTx, Inc, and has received funding from Celegene, Novartis, and GSK. Harvey Cohen declares that he has no conflict of interest. Eric Winer declares that he has no conflict of interest. Clifford Hudis declares that he has no conflict of interest. Ann Partridge declares that she has no conflict of interest. Lisa Carey declares that she has no conflict of interest. Aminah Jatoi declares that he has no conflict of interest. Heidi Klepin declares that she has no conflict of interest. Marc Citron reports speakers bureau roles for Genentech and Pfizer, consultant/advisory roles for Genentech and Pfizer, and funding from Genentech, Pfizer, Celldex, Merck, Puma, and Macrogenics. Donald Berry reports renumeration from Berry Consultants, LLC, a consultant/advisory role for Berry Consultants, LLC, and stock ownership in Berry Consultants, LLC (co-owner). Lawrence Shulman declares that he has no conflict of interest. Aman Buzdar declares that he has no conflict of interest. Vera Suman declares that she has no conflict of interest. Hyman Muss declares that he has no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors. The manuscript only includes secondary analysis of pre-existing data that were collected as part of the included clinical trials.

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Freedman, R.A., Seisler, D.K., Foster, J.C. et al. Risk of acute myeloid leukemia and myelodysplastic syndrome among older women receiving anthracycline-based adjuvant chemotherapy for breast cancer on Modern Cooperative Group Trials (Alliance A151511). Breast Cancer Res Treat 161, 363–373 (2017). https://doi.org/10.1007/s10549-016-4051-1

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