Myelodysplastic Syndrome and Acute Myeloid Leukemia Incidence Following Primary Breast Cancer Treatment.

Purpose We reviewed follow-up of patients treated in 19 randomized trials of adjuvant epirubicin in early breast cancer to determine incidence, risk, and risk factors for subsequent acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Patients and Methods The patients (N = 9,796) were observed from the start of adjuvant treatment (53,080 patient-years). Cases of AML or MDS (AML/MDS) were reported, with disease characteristics. Incidence and cumulative risk were compared for possible risk factors, for assigned regimens, and for administered cumulative doses of epirubicin and cyclophosphamide. Results In 7,110 patients treated with epirubicin-containing regimens (92% of whom also received cyclophosphamide), 8-year cumulative probability of AML/MDS was 0.55% (95% CI, 0.33% to 0.78%). The risk of developing AML/MDS increased in relation to planned epirubicin dose per cycle, planned epirubicin dose-intensity, and administered cumulative doses of epirubicin and cyclophosphamide. Patients with administered cumulative doses of both epirubicin and cyclophosphamide not exceeding those used in standard regimens (≤ 720 mg/m2 and ≤ 6,300 mg/m2, respectively) had an 8-year cumulative probability of developing AML/MDS of 0.37% (95% CI, 0.13% to 0.61%) compared with 4.97% (95% CI, 2.06% to 7.87%) for patients administered higher cumulative doses of both epirubicin and cyclophosphamide. Conclusion Patients treated with standard cumulative doses of adjuvant epirubicin (≤ 720 mg/m2) and cyclophosphamide (≤ 6,300 mg/m2) for early breast cancer have a lower probability of secondary leukemia than patients treated with higher cumulative doses. Increased risk of secondary leukemia must be considered when assessing the potential benefit to risk ratio of higher than standard doses.

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Acute myeloid leukemia and myelodysplastic syndrome after adjuvant chemotherapy: A population-based study among older breast cancer patients

Cancer ◽

10.1002/cncr.31144 ◽

2017 ◽

Vol 124 (5) ◽

pp. 899-906 ◽

Cited By ~ 9

Author(s):

Aron S. Rosenstock ◽

Jiangong Niu ◽

Sharon H. Giordano ◽

Hui Zhao ◽

Antonio C. Wolff ◽

...

Keyword(s):

Breast Cancer ◽

Acute Myeloid Leukemia ◽

Adjuvant Chemotherapy ◽

Myelodysplastic Syndrome ◽

Cancer Patients ◽

Myeloid Leukemia ◽

Population Based ◽

Breast Cancer Patients ◽

Population Based Study ◽

Acute Myeloid

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P4-12-11: Myelodysplastic Syndrome Post Primary Breast Cancer Treatment: Cases from a Community Cancer Center: 1990–2010.

10.1158/0008-5472.sabcs11-p4-12-11 ◽

2011 ◽

Author(s):

HG Kaplan ◽

JA Malmgren ◽

MK Atwood

Keyword(s):

Breast Cancer ◽

Myelodysplastic Syndrome ◽

Cancer Treatment ◽

Primary Breast Cancer ◽

Breast Cancer Treatment ◽

Cancer Center

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Acute Myeloid Leukemia and Myelodysplastic Syndrome After Doxorubicin-Cyclophosphamide Adjuvant Therapy for Operable Breast Cancer: The National Surgical Adjuvant Breast and Bowel Project Experience

Journal of Clinical Oncology ◽

10.1200/jco.2003.03.114 ◽

2003 ◽

Vol 21 (7) ◽

pp. 1195-1204 ◽

Cited By ~ 232

Author(s):

Roy E. Smith ◽

John Bryant ◽

Arthur DeCillis ◽

Stewart Anderson

Keyword(s):

Breast Cancer ◽

Acute Myeloid Leukemia ◽

Myelodysplastic Syndrome ◽

Cumulative Incidence ◽

Myeloid Leukemia ◽

Incidence Rates ◽

Breast Radiotherapy ◽

Increased Risk ◽

Breast Cancer Relapse ◽

Acute Myeloid

Purpose: We reviewed data from all adjuvant NSABP breast cancer trials that tested regimens containing both doxorubicin (A) and cyclophosphamide (C) to characterize the incidence of subsequent acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Materials and Methods: Six complete NSABP trials have investigated AC regimens (B-15, B-16, B-18, B-22, B-23, and B-25). Six distinct AC regimens have been tested and are distinguished by differences in cyclophosphamide intensity and cumulative dose and by the presence or absence of mandated prophylactic support with growth factor and ciprofloxacin. In all regimens, A was given at 60 mg/m2 q 21 days × 4. C was given as follows: 600 mg/m2 q 21 days × 4 (“standard AC”); 1,200 mg2 q 21 days × 2; 1,200 mg/m2 q 21 days × 4; 2,400 mg/m2 q 21 days × 2; and 2,400 mg/m2 q 21 days × 4. Occurrence of AML/MDS was summarized by incidence per 1,000 patient-years at risk and by cumulative incidence. Rates were compared across regimens, by age, and by treatment with or without breast radiotherapy. Results: The incidence of AML/MDS was sharply elevated in the more intense regimens. In patients receiving two or four cycles of C at 2,400 mg/m2 with granulocyte colony-stimulating factor (G-CSF) support, cumulative incidence of AML/MDS at 5 years was 1.01% (95% confidence interval [CI], 0.63% to 1.62%), compared with 0.21% (95% CI, 0.11% to 0.41%) for patients treated with standard AC. Patients who received breast radiotherapy experienced more secondary AML/MDS than those who did not (RR = 2.38, P= .006), and the data indicated that G-CSF does may possibly also be independently correlated with increased risk. Conclusion: AC regimens employing intensified doses of cyclophosphamide requiring G-CSF support were characterized by increased rates of subsequent AML/MDS, although the incidence of AML/MDS was small relative to that of breast cancer relapse. Breast radiotherapy appeared to be associated with an increased risk of AML/MDS.

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