Do modern chemo drugs raise the risk of leukemia in some older patients?

Older patients with non-metastatic breast cancer who have been treated modern chemotherapy drugs have a greater risk of secondary acute myeloid leukemia (AML) and/or myelodysplastic syndrome (MDS), according to researchers at MD Anderson Cancer Center.

The study, published in Cancer, provides updated information about a small but significant increase in the risk of secondary AML/MDS in this patient population. The findings should be part of an informed discussion between patients and their physicians when considering adjuvant chemotherapy, or that given after surgery, explained Mariana Chavez Mac Gregor, M.D., assistant professor of Health Services Research and Breast Medical Oncology.

According to large retrospective analysis, the eight-year cumulative incidence of AML and MDS was 0.45% and 1.11%, respectively, among those who did not receive chemotherapy. For patients who received anthracycline (A) or anthracycline and taxane (A+T) regimens, the incidence was significantly higher for both AML (0.90 and 0.84%, respectively) and MDS (2.24 and 1.55%, respectively).

“Overall our data provide valid estimations of the risk of a devastating complication secondary to chemotherapy usage,” said Chavez Mac Gregor. “The greatest strength of our analysis is that it is the largest study to date evaluating incidence rates of AML and MDS among breast cancer patients who received no chemotherapy and those treated with contemporary adjuvant chemotherapy regimens.”

Multiple clinical trials previously have identified an increased risk of AML/MDS for breast cancer patients following chemotherapy, but those studies did not take into account modern chemotherapies routinely used in the adjuvant setting. These include A, A+T, and docetaxel and cyclophosphamide (TC) regimens, which have increased in frequency since 2005.

Chemotherapy treatments come with short- and long-term complications, and there may be concerns about adjuvant chemotherapy in older patients, which, Chavez Mac Gregor explained, is why it’s important to understand the risk of secondary malignancies following modern regimens in these patients.

For this study, the researchers performed a retrospective analysis of 92,110 patients included in the Surveillance, Epidemiology, and End Results (SEER) and Texas Cancer Registry (TCR)–Medicare linked databases. All patients were 65 or older, and diagnosed with Stage I-III advanced breast cancer between 2003 and 2009. Patients who received chemotherapy other than a taxane or cyclophosphamide, methotrexate and 5-fluorouracil (CMF) were excluded.

The authors report comprehensive data on cumulative incidence at three, five and eight years following chemotherapy treatments. That data is available in the full study. Patients treated with A-based and A+T therapies were more likely to have developed AML/MDS at all time points compared with those who did not have chemotherapy.

“The risk of AML/MDS, while small, should be discussed with patients and should be part of the decision-making process,” said Chavez Mac Gregor. “This is particularly relevant for patients that are being treated with adjuvant chemotherapy for a small benefit. It is important to carefully select patients who will truly benefit from chemotherapy and select the appropriate regimen according to each patient’s risk.”