With life span extending, breast cancer survivors may face the possibility of developing second primary cancers (SPCs). The objective of this research is to investigate the risk factors, risk attribute to radiotherapy and the survivalship for SPCs.A total of 445 523 breast cancer patients were enrolled from Surveillance, Epidemiology, and End Results database in 2000-2018. The risk factors for SPCs development were confirmed by competing risk model, and then were integrated to the nomogram establishment. The cumulative incidence of SPCs including SBC (second breast cancer), SGC (second gynecological cancer), and SLC (second lung cancer) were estimated. The radiotherapy-associated risk for SPCs were evaluated by Poisson regression in radiotherapy and no-radiotherapy. Propensity score matching was used to reduce possible bias for survival comparison.There were 57.63% patients in radiotherapy. The risk factors for developing SPCs were age, year, race, tumor size, stage, radiotherapy, grade, surgery, and histology. The cumulative incidence of SPCs was 7.75% in no-radiotherapy and 10.33% in radiotherapy. SLC, SBC, and SGC also appeared the similar results. The increased risk of developing SPCs were associated with radiotherapy in majority subgroups. The dynamic radiotherapy-associated risk for SPCs by age slightly increased risk was observed. Regardless radiotherapy or no-radiotherapy, the 10-year overall survival for SBC (radiotherapy: 59.41%; no-radiotherapy: 55.53%) and SGC (radiotherapy: 48.61%; no-radiotherapy: 35.53%) were worse than that among matched patients with only primary cancers.Breast cancer survivors remained a high radiotherapy-associated risk for developing SPCs. The prognosis in radiotherapy was better than in no-radiotherapy for some specific SPCs. Largely attention should be paid to these patients.Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.