Risk of Secondary Breast Cancer in Female Non-Hodgkin Lymphoma Survivors: 40 Years of Follow-Up Assessed by Treatment Modality

Abstract

Survivors of non-Hodgkin lymphoma (NHL) are at increased risk of treatment associated secondary malignancies. We quantified the risk of developing a secondary breast cancer (SBC) in female NHL survivors with over 40 years of follow-up, and evaluated differences in risk by treatment modality.Standardized incidence ratios (SIR, observed-to-expected [O/E] ratio), which accounts for patient years at risk, and absolute excess risk of SBC were assessed in 65,123 female patients diagnosed with NHL as a first malignancy between 1975 and 2016 in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Only invasive disease was considered SBC, ductal carcinoma in situ was excluded. Follow up was available through 2016. SIRs were also evaluated for patients stratified by age at and latency from diagnosis.In all, 7,010 (10.8%) patients received radiotherapy alone (RT), 30,393 (46.7%) received chemotherapy alone (CT), and 7,845 (12.0%) received chemotherapy and radiation (CRT). In total, there were 1,480 female SBCs with NHL survivors having a lower incidence of SBC than the endemic rate (O/E 0.91, 95 % CI 0.87-0.96, P < 0.05. Patients treated with RT were at a higher risk of SBC than those who did not receive RT (O/E 1.02, 95% CI 0.93-1.12 vs O/E 0.87, 95% CI 0.82-0.93 respectively; P < 0.05). When stratified by treatment groups (No therapy, RT alone, CT alone, and CRT) there was a significantly higher risk of SBC in the CRT group than any other treatment group (O/E 1.18, 95% CI 1.03-1.34, P < 0.05). When patients were stratified by age at diagnosis, there was a significantly increased risk of SBC in patients who were diagnosed at age < 25 years irrespective of RT status with O/E ratios of 3.07 and 3.97 in the RT and no RT groups, respectively. However, there was no significant difference between these two treatment groups. This effect decreased with increasing age at diagnosis of NHL. The risk of developing SBC was significantly higher at > 10 years from NHL diagnosis (O/E 1.12) compared to < 10 years (O/E 0.82).This is the largest study to examine SBC risk in patients with NHL. These results demonstrate that survivors of NHL have a lower incidence of invasive breast cancer compared to the general population. Patients treated with RT did have an increased risk over those with no RT; however, this did not exceed endemic breast cancer rate. The use of CRT and time > 10 years from NHL diagnosis were associated with higher risk of developing an SBC. Importantly, women diagnosed with NHL < 25 yrs of age had a higher rate of SBCs regardless of RT use. These results may help inform breast cancer screening protocols for women with a history of NHL.