Risk factors and prediction of second primary cancer in primary female non-metastatic breast cancer survivors

This study aimed to investigate the risk factors of second primary cancer among female breast cancer (BC) survivors, with emphasis on the prediction of the individual risk conditioned on the patient’s characteristics. We identified 208,474 BC patients diagnosed between 2004 and 2010 from the Surveillance, Epidemiology and End Results (SEER) database. Subdistribution proportional hazard model and competing-risk nomogram were used to explore the risk factors of second primary BC and non-BC, and to predict the 5- and 10-year probabilities of second primary BC. Model performance was evaluated via calibration curves and decision curve analysis. The overall 3-, 5-, and 10-year cumulative incidences for second primary BC were 0.9%, 1.6% and 4.4%, and for second primary non-BC were 2.3%, 3.9%, and 7.8%, respectively. Age over 70 years at diagnosis, black race, tumor size over 2 cm, negative hormone receptor, mixed histology, localized tumor, lumpectomy alone, and surgeries plus radiotherapy were significantly associated with increased risk of second BC. The risk of second non-BC was only related to age, race and tumor size. The proposed risk model as well as its nomogram was clinically beneficial to identify patients at high risk of developing second primary breast cancer.

Keywords: breast cancer; competing risk; nomogram; second primary cancer.