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)

Rachel A. Freedman, D. K. Seisler, J. C. Foster, Jeff A Sloan, J. M. Lafky, G. G. Kimmick, A. Hurria, H. J. Cohen, E. P. Winer, C. A. Hudis, A. H. Partridge, L. A. Carey, Aminah Jatoi, H. D. Klepin, M. Citron, D. A. Berry, L. N. Shulman, A. U. Buzdar, Vera Jean Suman, H. B. Muss

Research output: Contribution to journalArticle

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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 developing 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 developing 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.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalBreast Cancer Research and Treatment
DOIs
StateAccepted/In press - Nov 19 2016

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Anthracyclines
Myelodysplastic Syndromes
Adjuvant Chemotherapy
Acute Myeloid Leukemia
Breast Neoplasms
Confidence Intervals
Insurance Coverage
Cyclophosphamide
Leukemia
Clinical Trials

Keywords

  • Breast cancer
  • Chemotherapy
  • Leukemia
  • Myelodysplastic syndrome
  • Older patients

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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). / Freedman, Rachel A.; Seisler, D. K.; Foster, J. C.; Sloan, Jeff A; Lafky, J. M.; Kimmick, G. G.; Hurria, A.; Cohen, H. J.; Winer, E. P.; Hudis, C. A.; Partridge, A. H.; Carey, L. A.; Jatoi, Aminah; Klepin, H. D.; Citron, M.; Berry, D. A.; Shulman, L. N.; Buzdar, A. U.; Suman, Vera Jean; Muss, H. B.

In: Breast Cancer Research and Treatment, 19.11.2016, p. 1-11.

Research output: Contribution to journalArticle

Freedman, RA, Seisler, DK, Foster, JC, Sloan, JA, Lafky, JM, Kimmick, GG, Hurria, A, Cohen, HJ, Winer, EP, Hudis, CA, Partridge, AH, Carey, LA, Jatoi, A, Klepin, HD, Citron, M, Berry, DA, Shulman, LN, Buzdar, AU, Suman, VJ & Muss, HB 2016, '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 Research and Treatment, pp. 1-11. https://doi.org/10.1007/s10549-016-4051-1
Freedman, Rachel A. ; Seisler, D. K. ; Foster, J. C. ; Sloan, Jeff A ; Lafky, J. M. ; Kimmick, G. G. ; Hurria, A. ; Cohen, H. J. ; Winer, E. P. ; Hudis, C. A. ; Partridge, A. H. ; Carey, L. A. ; Jatoi, Aminah ; Klepin, H. D. ; Citron, M. ; Berry, D. A. ; Shulman, L. N. ; Buzdar, A. U. ; Suman, Vera Jean ; Muss, H. B. / 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). In: Breast Cancer Research and Treatment. 2016 ; pp. 1-11.
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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 developing 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 developing 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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author = "Freedman, {Rachel A.} and Seisler, {D. K.} and Foster, {J. C.} and Sloan, {Jeff A} and Lafky, {J. M.} and Kimmick, {G. G.} and A. Hurria and Cohen, {H. J.} and Winer, {E. P.} and Hudis, {C. A.} and Partridge, {A. H.} and Carey, {L. A.} and Aminah Jatoi and Klepin, {H. D.} and M. Citron and Berry, {D. A.} and Shulman, {L. N.} and Buzdar, {A. U.} and Suman, {Vera Jean} and Muss, {H. B.}",
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TY - JOUR

T1 - 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)

AU - Freedman, Rachel A.

AU - Seisler, D. K.

AU - Foster, J. C.

AU - Sloan, Jeff A

AU - Lafky, J. M.

AU - Kimmick, G. G.

AU - Hurria, A.

AU - Cohen, H. J.

AU - Winer, E. P.

AU - Hudis, C. A.

AU - Partridge, A. H.

AU - Carey, L. A.

AU - Jatoi, Aminah

AU - Klepin, H. D.

AU - Citron, M.

AU - Berry, D. A.

AU - Shulman, L. N.

AU - Buzdar, A. U.

AU - Suman, Vera Jean

AU - Muss, H. B.

PY - 2016/11/19

Y1 - 2016/11/19

N2 - 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 developing 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 developing 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.

AB - 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 developing 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 developing 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.

KW - Breast cancer

KW - Chemotherapy

KW - Leukemia

KW - Myelodysplastic syndrome

KW - Older patients

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