Abstract

Breast cancer survivors are at an increased risk of developing certain types of hematologic malignant neoplasm after diagnosis. To estimate the incidence of various types of hematologic malignant neoplasm in breast cancer survivors, both in absolute terms and in association with the general population. This nationwide cohort study conducted in France used data from the French National Health Data System, a database that contains all of French residents' health-related expenses. All French women aged 20 to 85 years with an incident breast cancer diagnosis between July 1, 2006, and December 31, 2015, were included (n = 439 704) and followed up until hematologic malignant neoplasm occurrence, death, loss of follow-up, or December 31, 2016, whichever came first. Comparisons were made with all French women in the general population who were registered in the French general health insurance program each year from January 1, 2007, and December 31, 2016. Data analysis was performed from January 23, 2018, to May 25, 2018. Main outcomes were incident hematologic malignant neoplasm cases occurring at least 6 months after breast cancer diagnosis. The various types of hematologic malignant neoplasm considered were acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPNs), multiple myeloma (MM), Hodgkin lymphoma or non-Hodgkin lymphoma (HL/NHL), and acute lymphoblastic leukemia or lymphocytic lymphoma (ALL/LL). Incidence of these various types was estimated among breast cancer survivors and compared with the incidence in women in the general population. The 439 704 women in the study had a median (interquartile range [IQR]) age of 59 (50-69) years and were followed up for a median (IQR) duration of 5 (2.8-7.5) years. Overall, 3046 cases of hematologic malignant neoplasm occurred: 509 cases (16.7%) of AML (crude incidence rate [CIR] per 100 000 person-years, 24.5; 95% CI, 22.4-26.8), 832 cases (27.3%) of MDS (CIR, 40.1; 95% CI, 37.4-42.9), and 267 cases (8.8%) of MPN (CIR, 12.8; 95% CI, 11.4-14.5). Lymphoid neoplasm cases included 420 cases (13.8%) of MM (CIR, 20.3; 95% CI, 18.4-22.3), 912 cases (29.9%) of HL/NHL (CIR, 44.4; 95% CI, 41.1-50.0), and 106 cases (3.5%) of ALL/LL (CIR, 5.1; 95% CI, 4.2-6.2). Compared with the general population, breast cancer survivors had statistically significantly higher incidence of AML (standardized incidence rate ratio [SIRR], 2.8; 95% CI, 2.5-3.2) and MDS (SIRR, 5.0; 95% CI, 4.4-5.7) and, to a lesser extent, MM (SIRR, 1.5; 95% CI, 1.3-1.7]) and ALL/LL (SIRR, 2.0; 95% CI, 1.3-3.0). The finding that AML and MDS still occur among breast cancer survivors today, and that ALL/LL and MM may also be of concern, merits the continuous monitoring of hematologic malignant neoplasms and the thorough investigations into their underlying mechanisms.

Highlights

  • Secondary malignant neoplasms, including hematologic malignant neoplasms, that develop for months or years after the diagnosis of a primary tumor, are increasingly becoming a concern given that the population of breast cancer survivors is growing substantially

  • 3046 cases of hematologic malignant neoplasm occurred: 509 cases (16.7%) of acute myeloid leukemia (AML), 832 cases (27.3%) of myelodysplastic syndrome (MDS) (CIR, 40.1; 95% CI, 37.4-42.9), and 267 cases (8.8%) of myeloproliferative neoplasms (MPNs) (CIR, 12.8; 95% CI, 11.4-14.5)

  • Compared with the general population, breast cancer survivors had statistically significantly higher incidence of AML and MDS (SIRR, 5.0; 95% CI, 4.4-5.7) and, to a lesser extent, MM (SIRR, 1.5; 95% CI, 1.3-1.7]) and acute lymphoblastic leukemia or lymphocytic lymphoma (ALL/LL) (SIRR, 2.0; 95% CI, 1.3-3.0)

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Summary

Introduction

Secondary malignant neoplasms, including hematologic malignant neoplasms, that develop for months or years after the diagnosis of a primary tumor, are increasingly becoming a concern given that the population of breast cancer survivors is growing substantially. Such secondary cancers, reported since the early 1980s,1-4 may be a consequence of genetic predisposition, environmental factors, previous malignant neoplasm treatments, or an interaction among all those factors.[5,6] Breast cancer is classified as the most prevailing malignant solid tumor associated with the risk of myeloid neoplasm development.[3,7,8]. Real-life data on secondary hematologic malignant neoplasm incidence are scarce, especially in the recent period marked by major advances in breast cancer treatments

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