Association between Chemotherapy for Nonmetastatic Breast Cancer and Risk of Secondary Hematologic Malignancies

Hematologic malignancies, such as leukemia, were serious side-effects of chemotherapy to treat breast cancer. We sought to quantify the risks of developing secondary hematologic malignancies (SHMs) associated with chemotherapy and radiotherapy, respectively, among nonmetastatic breast cancer (BC) survivors. Using the Surveillance, Epidemiology, and End Results (SEER) 12 database, we estimated the adjusted relative risks (RRs) for developing SHMs associated with chemotherapy and radiotherapy (yes vs no/unknown), respectively, among 2-year survivors of nonmetastatic BC diagnosed at age 20-84 years who diagnosed during 1992-2017. Risks were assessed using multivariable Poisson regression models and adjusted for age, latency, and the log of expected number of SHMs as an offset. Among 432,073 nonmetastatic breast cancer (BC) survivors diagnosed between 1992-2017, 169,050 (39.1%) and 231,148 (53.5%) received chemotherapy and radiotherapy, respectively. Chemotherapy was significantly associated with an increased risk of SHMs (RR, 1.19 [95% CI, 1.11 to 1.27]), the elevated risk primarily driven by acute lymphocytic leukemia (ALL) and acute non-lymphocytic leukemia (ANLL) (RR, 1.72 95% [95% CI, 1.09 to 2.77] and 2.31 [95% CI, 1.77 to 3.01], respectively). Younger survivors and triple negative BC were at higher SHM risk post-chemotherapy (both P for interaction < 0.05). Similarly, radiotherapy was significantly associated with heightened risks of SHMs (RR, 1.11 [95% CI, 1.04 to 1.08]), which largely related subsequent ALL and chronic myeloid leukemia (RR, 1.76 [95% CI, 1.09 to 2.86] and 1.49 [95% CI, 1.09 to 2.02], respectively). Racial and ethnic disparities were observed for different SHM risk post-radiotherapy, with Non-Hispanic Whites had increased ALL risk (RR 1.97 [95% CI, 1.08 to 3.57]), while Hispanics showed elevated ANLL risk (RR 1.97 [95% CI, 1.25 to 3.10]). In conclusion, non-metastatic BC survivors exhibited an elevated SHM risk post-chemotherapy and radiotherapy. This finding necessitates rigorous post-treatment monitoring and prompts further exploration of treatment specifics to optimize survivor care.

No relevant conflicts of interest to declare.