Skip to main content
Top
Published in: Breast Cancer Research and Treatment 2/2017

01-01-2017 | Epidemiology

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)

Authors: Rachel A. Freedman, D. K. Seisler, J. C. Foster, J. 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, A. Jatoi, H. D. Klepin, M. Citron, D. A. Berry, L. N. Shulman, A. U. Buzdar, V. J. Suman, H. B. Muss

Published in: Breast Cancer Research and Treatment | Issue 2/2017

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z,Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds) (2015) SEER cancer statistics review, 1975–2012, National Cancer Institute. Bethesda. http://seer.cancer.gov/csr/1975_2012/, based on November 2014 SEER data submission, posted to the SEER web site Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z,Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds) (2015) SEER cancer statistics review, 1975–2012, National Cancer Institute. Bethesda. http://​seer.​cancer.​gov/​csr/​1975_​2012/​, based on November 2014 SEER data submission, posted to the SEER web site
6.
go back to reference Wolff AC, Blackford AL, Visvanathan K, Rugo HS, Moy B, Goldstein LJ, Stockerl-Goldstein K, Neumayer L, Langbaum TS, Theriault RL et al (2015) Risk of marrow neoplasms after adjuvant breast cancer therapy: the national comprehensive cancer network experience. J Clin Oncol 33(4):340–348CrossRefPubMed Wolff AC, Blackford AL, Visvanathan K, Rugo HS, Moy B, Goldstein LJ, Stockerl-Goldstein K, Neumayer L, Langbaum TS, Theriault RL et al (2015) Risk of marrow neoplasms after adjuvant breast cancer therapy: the national comprehensive cancer network experience. J Clin Oncol 33(4):340–348CrossRefPubMed
7.
go back to reference Smith RE, Bryant J, DeCillis A, Anderson S, National Surgical Adjuvant B, Bowel Project E (2003) Acute myeloid leukemia and myelodysplastic syndrome after doxorubicin-cyclophosphamide adjuvant therapy for operable breast cancer: the National Surgical Adjuvant Breast and Bowel Project Experience. J Clin Oncol 21(7):1195–1204CrossRefPubMed Smith RE, Bryant J, DeCillis A, Anderson S, National Surgical Adjuvant B, Bowel Project E (2003) Acute myeloid leukemia and myelodysplastic syndrome after doxorubicin-cyclophosphamide adjuvant therapy for operable breast cancer: the National Surgical Adjuvant Breast and Bowel Project Experience. J Clin Oncol 21(7):1195–1204CrossRefPubMed
8.
go back to reference Muss HB, Berry DA, Cirrincione C, Budman DR, Henderson IC, Citron ML, Norton L, Winer EP, Hudis CA (2007) Toxicity of older and younger patients treated with adjuvant chemotherapy for node-positive breast cancer: the Cancer and Leukemia Group B Experience. J Clin Oncol 25(24):3699–3704CrossRefPubMed Muss HB, Berry DA, Cirrincione C, Budman DR, Henderson IC, Citron ML, Norton L, Winer EP, Hudis CA (2007) Toxicity of older and younger patients treated with adjuvant chemotherapy for node-positive breast cancer: the Cancer and Leukemia Group B Experience. J Clin Oncol 25(24):3699–3704CrossRefPubMed
9.
go back to reference Le Deley MC, Suzan F, Cutuli B, Delaloge S, Shamsaldin A, Linassier C, Clisant S, de Vathaire F, Fenaux P, Hill C (2007) Anthracyclines, mitoxantrone, radiotherapy, and granulocyte colony-stimulating factor: risk factors for leukemia and myelodysplastic syndrome after breast cancer. J Clin Oncol 25(3):292–300CrossRefPubMed Le Deley MC, Suzan F, Cutuli B, Delaloge S, Shamsaldin A, Linassier C, Clisant S, de Vathaire F, Fenaux P, Hill C (2007) Anthracyclines, mitoxantrone, radiotherapy, and granulocyte colony-stimulating factor: risk factors for leukemia and myelodysplastic syndrome after breast cancer. J Clin Oncol 25(3):292–300CrossRefPubMed
10.
go back to reference Kaplan HG, Malmgren JA, Atwood MK (2011) Increased incidence of myelodysplastic syndrome and acute myeloid leukemia following breast cancer treatment with radiation alone or combined with chemotherapy: a registry cohort analysis 1990–2005. BMC Cancer 11:260CrossRefPubMedPubMedCentral Kaplan HG, Malmgren JA, Atwood MK (2011) Increased incidence of myelodysplastic syndrome and acute myeloid leukemia following breast cancer treatment with radiation alone or combined with chemotherapy: a registry cohort analysis 1990–2005. BMC Cancer 11:260CrossRefPubMedPubMedCentral
11.
go back to reference Kaplan HG, Malmgren JA, Li CI, Calip GS (2013) Age related risk of myelodysplastic syndrome and acute myeloid leukemia among breast cancer survivors. Breast Cancer Res Treat 142(3):629–636CrossRefPubMed Kaplan HG, Malmgren JA, Li CI, Calip GS (2013) Age related risk of myelodysplastic syndrome and acute myeloid leukemia among breast cancer survivors. Breast Cancer Res Treat 142(3):629–636CrossRefPubMed
12.
go back to reference Patt DA, Duan Z, Fang S, Hortobagyi GN, Giordano SH (2007) Acute myeloid leukemia after adjuvant breast cancer therapy in older women: understanding risk. J Clin Oncol 25(25):3871–3876CrossRefPubMed Patt DA, Duan Z, Fang S, Hortobagyi GN, Giordano SH (2007) Acute myeloid leukemia after adjuvant breast cancer therapy in older women: understanding risk. J Clin Oncol 25(25):3871–3876CrossRefPubMed
13.
go back to reference Azim HA Jr, de Azambuja E, Colozza M, Bines J, Piccart MJ (2011) Long-term toxic effects of adjuvant chemotherapy in breast cancer. Ann Oncol 22(9):1939–1947CrossRefPubMed Azim HA Jr, de Azambuja E, Colozza M, Bines J, Piccart MJ (2011) Long-term toxic effects of adjuvant chemotherapy in breast cancer. Ann Oncol 22(9):1939–1947CrossRefPubMed
14.
go back to reference Cox DR (1972) Regression models and life-tables. J R Stat Soc 34(2):187–220 Cox DR (1972) Regression models and life-tables. J R Stat Soc 34(2):187–220
15.
go back to reference Fine JP, Gray RJA (1999) Proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 94:496–509CrossRef Fine JP, Gray RJA (1999) Proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 94:496–509CrossRef
16.
go back to reference Early Breast Cancer Trialists’ Collaborative G, Peto R, Davies C, Godwin J, Gray R, Pan HC, Clarke M, Cutter D, Darby S, McGale P et al (2012) Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet 379(9814):432–444CrossRef Early Breast Cancer Trialists’ Collaborative G, Peto R, Davies C, Godwin J, Gray R, Pan HC, Clarke M, Cutter D, Darby S, McGale P et al (2012) Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet 379(9814):432–444CrossRef
17.
go back to reference Giordano SH, Duan Z, Kuo YF, Hortobagyi GN, Goodwin JS (2006) Use and outcomes of adjuvant chemotherapy in older women with breast cancer. J Clin Oncol 24(18):2750–2756CrossRefPubMed Giordano SH, Duan Z, Kuo YF, Hortobagyi GN, Goodwin JS (2006) Use and outcomes of adjuvant chemotherapy in older women with breast cancer. J Clin Oncol 24(18):2750–2756CrossRefPubMed
18.
go back to reference Elkin EB, Hurria A, Mitra N, Schrag D, Panageas KS (2006) Adjuvant chemotherapy and survival in older women with hormone receptor-negative breast cancer: assessing outcome in a population-based, observational cohort. J Clin Oncol 24(18):2757–2764CrossRefPubMed Elkin EB, Hurria A, Mitra N, Schrag D, Panageas KS (2006) Adjuvant chemotherapy and survival in older women with hormone receptor-negative breast cancer: assessing outcome in a population-based, observational cohort. J Clin Oncol 24(18):2757–2764CrossRefPubMed
19.
go back to reference Praga C, Bergh J, Bliss J, Bonneterre J, Cesana B, Coombes RC, Fargeot P, Folin A, Fumoleau P, Giuliani R et al (2005) Risk of acute myeloid leukemia and myelodysplastic syndrome in trials of adjuvant epirubicin for early breast cancer: correlation with doses of epirubicin and cyclophosphamide. J Clin Oncol 23(18):4179–4191CrossRefPubMed Praga C, Bergh J, Bliss J, Bonneterre J, Cesana B, Coombes RC, Fargeot P, Folin A, Fumoleau P, Giuliani R et al (2005) Risk of acute myeloid leukemia and myelodysplastic syndrome in trials of adjuvant epirubicin for early breast cancer: correlation with doses of epirubicin and cyclophosphamide. J Clin Oncol 23(18):4179–4191CrossRefPubMed
20.
go back to reference Tallman MS, Gray R, Bennett JM, Variakojis D, Robert N, Wood WC, Rowe JM, Wiernik PH (1995) Leukemogenic potential of adjuvant chemotherapy for early-stage breast cancer: the Eastern Cooperative Oncology Group experience. J Clin Oncol 13(7):1557–1563CrossRefPubMed Tallman MS, Gray R, Bennett JM, Variakojis D, Robert N, Wood WC, Rowe JM, Wiernik PH (1995) Leukemogenic potential of adjuvant chemotherapy for early-stage breast cancer: the Eastern Cooperative Oncology Group experience. J Clin Oncol 13(7):1557–1563CrossRefPubMed
21.
go back to reference Muss HB, Woolf S, Berry D, Cirrincione C, Weiss RB, Budman D, Wood WC, Henderson IC, Hudis C, Winer E et al (2005) Adjuvant chemotherapy in older and younger women with lymph node-positive breast cancer. JAMA 293(9):1073–1081CrossRefPubMed Muss HB, Woolf S, Berry D, Cirrincione C, Weiss RB, Budman D, Wood WC, Henderson IC, Hudis C, Winer E et al (2005) Adjuvant chemotherapy in older and younger women with lymph node-positive breast cancer. JAMA 293(9):1073–1081CrossRefPubMed
22.
go back to reference Hurria A, Togawa K, Mohile SG, Owusu C, Klepin HD, Gross CP, Lichtman SM, Gajra A, Bhatia S, Katheria V et al (2011) Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol 29(25):3457–3465CrossRefPubMedPubMedCentral Hurria A, Togawa K, Mohile SG, Owusu C, Klepin HD, Gross CP, Lichtman SM, Gajra A, Bhatia S, Katheria V et al (2011) Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol 29(25):3457–3465CrossRefPubMedPubMedCentral
23.
go back to reference Extermann M, Boler I, Reich RR, Lyman GH, Brown RH, DeFelice J, Levine RM, Lubiner ET, Reyes P, Schreiber FJ 3rd et al (2012) Predicting the risk of chemotherapy toxicity in older patients: the Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score. Cancer 118(13):3377–3386CrossRefPubMed Extermann M, Boler I, Reich RR, Lyman GH, Brown RH, DeFelice J, Levine RM, Lubiner ET, Reyes P, Schreiber FJ 3rd et al (2012) Predicting the risk of chemotherapy toxicity in older patients: the Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score. Cancer 118(13):3377–3386CrossRefPubMed
Metadata
Title
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)
Authors
Rachel A. Freedman
D. K. Seisler
J. C. Foster
J. 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
A. Jatoi
H. D. Klepin
M. Citron
D. A. Berry
L. N. Shulman
A. U. Buzdar
V. J. Suman
H. B. Muss
Publication date
01-01-2017
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 2/2017
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-016-4051-1

Other articles of this Issue 2/2017

Breast Cancer Research and Treatment 2/2017 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine