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

Abstract

Purpose 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. Methods We conducted a retrospective cohort study of women ages ≥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. Results 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). Conclusions 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.

Myelodysplastic syndrome and acute myeloid leukemia after receipt of granulocyte colony‐stimulating factors in older patients with non‐Hodgkin lymphoma

“…Few large epidemiological studies have investigated the association between receipt of G‐CSF and the risk of MDS/AML among elderly patients with NHL, although leukemogenesis associated with G‐CSF has been suggested in studies of other cancer sites, such as breast cancer . In a study using the SEER‐Medicare–linked database by Gruschkus et al, patients who had NHL diagnosed between 1992 and 2002 and received chemotherapy had a 5‐year cumulative risk of MDS/AML of approximately 7% if they received G‐CSF, compared with approximately 4% if they did not receive it.…”

“…Our analyses revealed neither an association between pegfilgrastim and MDS/AML risk nor a trend toward an increased risk with greater number of pegfilgrastim doses. Another study of older patients with breast cancer who were identified in the SEER‐Medicare–linked database between 2001 and 2009 reported an increased risk of MDS/AML that was exclusive to filgrastim and was not observed with pegfilgrastim . The risk associated with filgrastim was highest among women who received treatment with an anthracycline‐based chemotherapy regimen for breast cancer (HR, 2.11; 95% CI, 1.29‐3.30).…”

“…Granulocyte colony‐stimulating factors (G‐CSFs) are efficacious in reducing the severity and duration of neutropenia and the risks of febrile neutropenia and infection‐related mortality while enabling an increase in the dose intensity of multiple chemotherapy regimens, including those commonly used in the treatment of NHL . However, there is concern about leukemogenesis with the use of G‐CSFs, and there is a higher observed incidence of MDS/AML with its use in the treatment of many cancers, including NHL and breast cancer . It is suspected that G‐CSFs may help prevent apoptosis of the mutant, myeloid lineage‐specific stem cells that result from cytotoxic therapy, thus permitting the survival of subsets of myeloid cells with genomic alterations and ultimately leading to an increased risk of second primary myeloid malignancies …”

Maintenance treatment of recurrent ovarian cancer: Is it ready for prime time?

“…There are a number of factors that may contribute to the risk of developing MDS/AML concurrent with PARPi treatment, but it is important to keep in mind that the overall risk is quite low. Treatment with chemotherapy has also been shown to increase the risk of developing MDS/AML [78]. Most patients who participated in PARPi clinical studies were heavily pre-treated with chemotherapy, with some patients receiving three or more lines of chemotherapy prior to PARPi treatment [49,50,52,54].…”

A Value of Information Analysis of Research on the 21-Gene Assay for Breast Cancer Management

“…1,2 Chemotherapy reduces the risk of disease recurrence and improves survival. 3 Nevertheless, it is associated with risks of adverse events and toxicities, [4][5][6] particularly among low-risk patients, 7 leading to increased healthcare expenditures and reduced health-related quality of life 8 that may outweigh its benefits.…”