Molecule subtypes play important roles for second primary malignancies development based on 324,661 breast cancer survivors.

The incidence trend of breast molecule subtypes was unclear. There was not quantified risk by subtype with the second primary malignancies (SPMs) and limited evidence about the risk factors for developing SPMs in first primary breast cancer(FPBC). Data from 18 SEER registries were used to identify FPBC, which were randomly selected for training and validation sets. The SPMs information of breast cancer survivors in Hebei were also collected to compare the distribution with SEER. Univariate and multivariate analysis were performed to explore the risk factors and integrated to the establishment of nomogram and risk stratification model. There was a decreased trend for TNBC, but an increased trend for Luminal A. The median survival months were 46, 46, 46 and 44 for Luminal A, Luminal B, HER2 enriched and TNBC, with the median latency time were 39, 39, 40 and 41.0 months, respecitvely, The cumulative incidence rates(CIR) of SPMs were 2.61%, 2.30%, 2.21% and 2.84%. Age at diagnosis, clinical lymph node status, radiotherapy and subtypes were independent risk factors for SPMs. A predict nomogram was established with the AUC of 0.682 and 0.679 for three- and five- year incidence risk in training set. Patients were divided into the low-risk (31.94%), intermediate-risk (51.83%) and high-risk (16.23%) groups by risk stratification model. The first common SPMs was second breast cancer in both SEER and Hebei cohort, the second and third rank SPMs were lung and gynecological cancer in SEER, but presented the opposite result in Hebei. The incidence rates and SPMs of subtypes were difference. The high risk individuals could be identified by risk stratification model, who need more closely followed up by Clinicians.