Chemotherapy Raises Leukemia Risk in Early Breast Cancer
Patients with early-stage breast cancer treated with preventive or adjuvant chemotherapy face an increased risk for leukemia that does not justify the modest survival benefit of additional treatment, say US researchers.
They found that early-stage breast cancer patients treated with adjuvant or preventive chemotherapy have a cumulative risk of developing leukemia at 10 years of 0.5%, almost twice the rate reported in previous studies.
In a release, study author Judith Karp, MD, professor emerita of oncology at the Johns Hopkins University School of Medicine in Baltimore, Maryland, commented: “The frequency of bone marrow cancers such as leukemia is small, there’s no question about it.”
“However, the cumulative risk over a decade is now shown to be twice as high as we thought it was, and that risk doesn’t seem to slow down 5 years after treatment,” Dr Karp said.
She added, “Most medical oncologists have come to think that the risk is early and short-lived. So this was a little bit of a wake-up call that we are not seeing any plateau of that risk, and it is higher.”
The study was published online December 22 in the Journal of Clinical Oncology.
In this study, Dr Karp and colleagues examined data from the National Comprehensive Cancer Network Breast Cancer Outcomes Database on 20,063 patients with stage I–III breast cancer treated at eight centers between 1998 and 2007. The patients were assessed at baseline and at 4, 9, and 18 months, and then annually.
The team identified those who developed lymphoid and myeloid neoplasms (MNs). Time-to-event analyses were performed for the first data of a new cancer event, the last contact date, or death and were stratified by surgery alone, surgery with radiation, surgery with chemotherapy, and by all three modalities.
The observed incidence rates per 1000 person-years were calculated and compared with the number of expected MNs from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program database.
Higher Risk for Myeloid Neoplasms
After a median follow-up of 5.1 years, 50 patients developed MN. Compared with patients who did not develop MN, these patients were significantly older, at 59.1 years vs 53.9 years (P = .03); distributions with regard to breast cancer stage, race, and chemotherapy exposure were similar.
As compared with no chemotherapy, the risk of developing MN was significantly increased after surgery plus chemotherapy and after exposure to all modalities, at hazard ratios of 6.8 and 7.6, respectively.
The incidence rates of MN per 1000 person-years were 0.16 after surgery, 0.43 after surgery plus radiotherapy, 0.46 after surgery plus chemotherapy, and 0.54 for all three modalities. The cumulative risk doubled between 5 and 10 years of follow-up, from 0.24% to 0.48%; 9% of patients were alive at 10 years.
This compares with data from previous randomized clinical trials suggesting that around 0.25% of breast cancer patients develop leukemia as a late effect of chemotherapy. However, the researchers point out that those studies typically included only a few hundred patients.
Coauthor Kala Visvanathan, MD, of Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, toldMedscape Medical News that this finding “highlights the importance…of following patients over time to capture this sort of data.”