Leukemia Risk Higher Following Chemotherapy for Early-Stage Breast Cancer

Results of a large retrospective study of more than 20,000 women treated for early-stage breast cancer are shedding light on how much treatment may be too much for these early-stage cancers.

Antonio Wolff, MD

Results of a large retrospective study of more than 20,000 women treated for early-stage breast cancer are shedding light on how much treatment may be too much for these early-stage cancers. Although still very small, the risk to patients of developing leukemia after radiation and/or chemotherapy was found to be twice as high as previously reported, suggesting that practitioners carefully weigh the merits of providing chemotherapy “just in case” when the risk of recurrence is low.

“Our study provides useful information for physicians and patients to consider a potential downside of preventive or adjuvant chemotherapy in patients with very low risk of breast cancer recurrence,” Antonio Wolff, MD, lead author of the study, said in a statement. “It could be a false and dangerous security blanket to some patients by exposing them to a small risk of serious late effects with little or no real benefit from the treatment.”

For the study, researchers at the Johns Hopkins Kimmel Cancer Center examined data included in the NCCN database from 20,063 breast cancer patients with stage I-III disease treated between 1998 and 2007. They found that 50 of these patients developed some form of leukemia (myeloid, n = 42; lymphoid, n = 8) after a median follow-up of 5.1 years and that the risk of developing a marrow neoplasm was increased significantly after surgery with chemotherapy or after all treatment modes (surgery, chemotherapy, and radiation), versus no treatment with chemotherapy.

To calculate the cumulative risk of leukemia over 10 years, the team used each patient’s time path from breast cancer diagnosis to either: last known follow-up medical record, diagnosis of another cancer, death, or diagnosis of leukemia. Based on its analysis, the team estimated that the cumulative risk of developing leukemia by 10 years was 0.5%—a rate double what was reported in earlier randomized clinical trials which indicated that 0.25% of breast cancer patients developed leukemia as a late effect of chemotherapy.

“The frequency of bone marrow cancers such as leukemia is small; there’s no question about it,” Judith Karp, MD, professor emerita of oncology at the Johns Hopkins School of Medicine said in a statement. “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.”

“Most medical oncologists have come to think that the risk is early and short-lived,” said Karp. “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 team also included a hypothetical case to put the risks of early-stage breast cancer and chemotherapy treatment in perspective, based on a 60-year-old woman in average health, diagnosed with stage I breast cancer that was rapidly growing and ER-positive, and who is calculated to have a 12.3% risk of dying of breast cancer after 10 years. She could improve her 10-year survival rate by 1.8% with four cycles of chemotherapy, but she would also increase her risk of leukemia over that same time by 0.5%.

Wolff, a professor of oncology at the Johns Hopkins University School of Medicine, said that each patient’s treatment plan for early-stage cancer could differ depending on a variety of factors, including the size of the tumors; whether the cancer has spread to the lymph nodes; and whether the tumor tests positive for certain breast cancer-related hormone and growth receptors, such as estrogen receptors (ER) and human epidermal growth factor receptor 2 (HER2).

Wolff AC, Blackford AL, Visvanathan K, et al. Risk of marrow neoplasms after adjuvant breast cancer therapy: the National Comprehensive Cancer Network experience [published online ahead of print December 22, 2014]. J Clin Oncol.