Radiotherapy and increased risk of second primary cancers in breast cancer survivors: An epidemiological and large cohort study
Niuniu Hou,
Zhe Wang,
Yuwei Ling,
Guangdong Hou,
Bo Zhang,
Xue Zhang,
Mei Shi,
Zhuling Chu,
Yaoling Wang,
Jun Hu,
Chong Chen,
Rui Ling
Affiliations
Niuniu Hou
Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China; Department of General Surgery, Xijing 986 Hospital, Fourth Military Medical University, Xi'an, China
Zhe Wang
Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China
Yuwei Ling
Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China
Guangdong Hou
Department of Urology, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, China
Bo Zhang
Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China
Xue Zhang
Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China
Mei Shi
Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University, Xi an, 710032, China
Zhuling Chu
Department of General Surgery, Eastern Theater Air Force Hospital of PLA, Nanjing, China
Yaoling Wang
Center of Gerontology and Geriatrics, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, China
Jun Hu
Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University, Xi an, 710032, China; Corresponding author. Department of General Surgery, Eastern Theater Air Force Hospital of PLA, Nanjing, China.
Chong Chen
Department of General Surgery, Xijing 986 Hospital, Fourth Military Medical University, Xi'an, China; Corresponding author. Department of General Surgery, Xijing 986 Hospital, Fourth Military Medical University, Xi'an, China.
Rui Ling
Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China; Corresponding author. Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
Background: Radiotherapy (RT) for breast cancer (BC) may raise the risk of second primary cancers (SPCs), a relationship inadequately studied. Methods: We analyzed 248268 female BC patients from 9 SEER registries, 1988–2018, identifying SPCs >5 years after initial treatment, comparing SPC risks between RT and non-RT cohorts using Fine-Gray and Poisson regressions. Results: Of all participants, 55.4 % received surgery and RT. The RT group had a higher SPC incidence, with excess incidence significantly dropped from 6.9 % in 1990 to 0.2 % in 2012. The 30-year SPC incidence was 24.69 % in the RT cohort and 18.11 % in the NRT cohort. RT increased the risk of SPCs(HR, 1.29 [95%CI,1.26–1.33]; P < 0.001), BC(HR, 1.58[1.52–1.64]; P < 0.001), cancer of respiratory system(HR, 1.21[1.13–1.30]; P = 0.013), skin cancer(HR, 1.26[1.10–1.44]; P < 0.001), leukemia(HR, 1.30[1.11–1.54]; P = 0.001), soft tissue cancer(HR, 1.78[1.34–2.37]; P < 0.001), and eye & orbit cancer(HR, 2.21[1.02–4.80]; P = 0.044), except for reducing the risk of multiple myeloma (HR 0.76). Notably, RT-related risks(RR) for BC declined with increasing age and the year of BC diagnosed, increased with longer latency, but the dynamic RR for cancer of respiratory system presented the almost opposite trends. The RT cohort had higher standardized incidence ratios for SPCs compared to both the NRT cohort and the general population overall. Although 15-year overall survival for SPCs was similar between RT and NRT cohorts, SPC presence significantly lowered 30-year survival from 35.64 % to 23.90 %. Conclusions: RT might increase susceptibility to SPC in breast, respiratory system, skin, soft tissue, eye and orbit, and leukemia in BC survivors. Efforts should be made to timely diagnose SPCs based on their specific patterns to improve patient's quality of life.
