Breast cancer survivors should continue to be monitored for hematologic malignancies, especially acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), results of a population-based study from France suggest.
Among nearly 440,000 women with an incident breast cancer diagnosis, the incidence of AML was nearly three times higher and the incidence of MDS was five times higher than that of women in the general population. Women with breast cancer also were at higher risk for multiple myeloma (MM) and acute lymphoblastic leukemia/lymphocytic lymphoma (ALL/LL) compared with the background population, reported Marie Joelle Jabagi, PharmD, MPH, of the University of Paris Sud, France, and her colleagues.
“These findings serve to better inform practicing oncologists, and breast cancer survivors should be advised of the increased risk of developing certain hematologic malignant neoplasms after their first cancer diagnosis,” they wrote in JAMA Network Open.
Breast cancers are the malignant solid tumors most frequently associated with risk for myeloid neoplasms, but there is little information on the risk for secondary lymphoid malignancies among breast cancer patients, the investigators stated.
“In addition, real-life data on secondary hematologic malignant neoplasm incidence are scarce, especially in the recent period marked by major advances in breast cancer treatments,” they wrote.
To get better estimates of the incidence of myeloid and lymphoid neoplasms in this population, they conducted a retrospective review of information from the French National Health Data System on all French women from the ages of 20 to 85 years who had an incident breast cancer diagnosis from July 1, 2006, through Dec. 31, 2015.
In all, 439,704 women with a median age of 59 years were identified. They were followed until a diagnosis of a hematologic malignancy, death, or loss to follow-up, or until Dec. 31, 2016.
Data on the breast cancer patients were compared with those for all French women in the general population who were registered in the general national health insurance program from January 2007 through the end of 2016.
During a median follow-up of 5 years, there were 3,046 cases of hematologic neoplasms among the breast cancer patients, including 509 cases of AML, for a crude incidence rate (CIR) of 24.5 per 100,000 person-years (py); 832 cases of MDS for a CIR of 40.1/100,000 py; and 267 cases of myeloproliferative neoplasms (MPN), for a CIR of 12.8/100,000 py.
In addition, there were 420 cases of MM for a CIR of 20.3/100,000 py; 912 cases of Hodgkin or non-Hodgkin lymphoma (HL/NHL) for a CIR of 44.4/100,000 py, and 106 cases of ALL/LL for a CIR of 5.1/100,000 py.
Breast cancer survivors had significantly higher incidences, compared with the general population, of AML (standardized incidence ratio [SIR] 2.8, 95% confidence interval [CI], 2.5-3.2), MDS (SIR 5.0, CI, 4.4-5.7), MM (SIR 1.5, CI, 1.3-17), and ALL/LL (SIR 2.0, CI, 1.3-3.0). There was a trend toward significance for both MPN and HL/NHL, but the lower limit of the confidence intervals for these conditions either crossed or touched 1.
In a review of the literature, the authors found that “[s]everal studies linked AML and MDS to chemotherapeutic agents, radiation treatment, and supportive treatment with granulocyte colony-stimulating factor. These results are consistent with other available data showing a 2½-fold to 3½-fold increased risk of AML.”
They noted that their estimate of a five-fold increase in risk for MDS was higher than the 3.7-fold risk reported in a previous registry cohort analysis, suggesting that risk for MDS among breast cancer patients may be underestimated.
“The recent discovery of the gene signatures that guide treatment decisions in early-stage breast cancer might reduce the number of patients exposed to cytotoxic chemotherapy and its complications, including hematologic malignant neoplasm. Therefore, continuing to monitor hematologic malignant neoplasm trends is necessary, especially given that approaches to cancer treatment are rapidly evolving. Further research is also required to assess the modality of treatment for and the genetic predisposition to these secondary malignant neoplasms,” the authors concluded.
SOURCE: Jabagi MJ et al. JAMA Network Open. 2019 Jan 18. doi: 10.1001/jamanetworkopen.2018.7147.