Myelodysplastic syndrome and acute myeloid leukemia following adjuvant chemotherapy with and without granulocyte colony-stimulating factors for breast cancer

Abstract

Risk of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) post-breast cancer treatment with adjuvant chemotherapy and granulocyte colony-stimulating factors (G-CSF) is not fully characterized. Our objective was to estimate MDS/AML risk associated with specific breast cancer treatments. We conducted a retrospective cohort study of women aged ≥66 years with stage I-III breast cancer between 2001 and 2009 using the Surveillance, Epidemiology, and End Results-Medicare database. Women were classified as receiving treatment with radiation, chemotherapy, and/or G-CSF. We used multivariable Cox proportional hazards models to estimate adjusted hazard ratios (HR) and 95 % confidence intervals (CI) for MDS/AML risk. Among 56,251 breast cancer cases, 1.2 % developed MDS/AML during median follow-up of 3.2 years. 47.1 % of women received radiation and 14.3 % received chemotherapy. Compared to breast cancer cases treated with surgery alone, those treated with chemotherapy (HR = 1.38, 95 %-CI 0.98-1.93) and chemotherapy/radiation (HR = 1.77, 95 %-CI 1.25-2.51) had increased risk of MDS/AML, but not radiation alone (HR = 1.08, 95 % CI 0.86-1.36). Among chemotherapy regimens and G-CSF, MDS/AML risk was differentially associated with anthracycline/cyclophosphamide-containing regimens (HR = 1.86, 95 %-CI 1.33-2.61) and filgrastim (HR = 1.47, 95 %-CI 1.05-2.06), but not pegfilgrastim (HR = 1.10, 95 %-CI 0.73-1.66). We observed increased MDS/AML risk among older breast cancer survivors treated with anthracycline/cyclophosphamide chemotherapy that was enhanced by G-CSF. Although small, this risk warrants consideration when determining adjuvant chemotherapy and neutropenia prophylaxis for breast cancer patients.

Keywords: Acute myeloid leukemia; Adjuvant chemotherapy; Breast cancer; Granulocyte colony-stimulating factors; Myelodysplastic syndrome.

Figure 1

Cumulative hazard of MDS/AML among female Medicare beneficiaries diagnosed with incident stage I–III breast cancer between 2001 and 2009 by initial breast cancer treatment

Figure 2

Risk of MDS/AML among female Medicare beneficiaries diagnosed with incident stage I–III breast cancer between 2001 and 2009 in relation to primary breast cancer initial treatment and to chemotherapy regimen Abbreviations: MDS=myelodysplastic syndrome; AML=acute myeloid leukaemia; HR=hazard ratio; CI=confidence interval Chemotherapy agents: A=anthracyclines (doxorubicin or epirubicin); C=cyclophosphamide; T=taxanes (docetaxel or paclitaxel); F=fluorouracil; M=methotrexate Note: all hazard ratios are adjusted for age at diagnosis (66–70, 71–75, 76–80, 81–85, 86–95 years); diagnosis year; race (White, Black, other, unknown); Hispanic ethnicity (yes, no, unknown); AJCC stage (I, II, III); hormone receptor status (ER-positive or PR-positive, ER-negative/PR-negative, unknown); surgical procedure (mastectomy, breast-conserving surgery, surgery NOS); Charlson comorbidity index score (0, 1, 2+); any granulocyte colony-stimulating factors received (yes/no) * Hazard ratios for chemotherapy regimens (AC, ACT, FAC, TC, CF or CMF) are from a separate model adjusted for radiation therapy (yes/no) ** AC-containing regimens = AC, ACT, FAC

Figure 3

Risk of MDS/AML among female Medicare beneficiaries diagnosed with incident stage I–III breast cancer between 2001 and 2009 that received chemotherapy in relation to G-CSF treatment Abbreviations: MDS=myelodysplastic syndrome; AML=acute myeloid leukaemia; HR=hazard ratio; CI=confidence interval; G-CSF=granulocyte colony-stimulating factors Note: all hazard ratios are adjusted for age at diagnosis (66–70, 71–75, 76–80, 81–85, 86–95 years); diagnosis year; race (White, Black, other, unknown); Hispanic ethnicity (yes, no, unknown); AJCC stage (I, II, III); hormone receptor status (ER-positive or PR-positive, ER-negative/PR-negative, unknown); surgical procedure (mastectomy, breast-conserving surgery, unknown); radiation (yes/no); Charlson comorbidity index score (0, 1, 2+); chemotherapy regimen received (AC, ACT, FAC, TC, CF or CMF, other)