Risk, molecular subtype and prognosis of second primary breast cancer: an analysis based on first primary cancers.

Second primary breast cancer (SPBC) was potentially related to other cancers, which may impact its incidence, prognosis and therapeutic approaches. Nevertheless, few studies have characterized this relationship and analyzed the subtypes of SPBC. Our study intended to investigate the occurrence and prognosis of SPBC. We analyzed the patterns, clinical characteristics, standardized incidence ratio (SIR) and standardized mortality ratio (SMR) of patients with SPBC. The propensity score matching (PSM) approach was further used to balance the differences in clinical features between patients with primary breast cancer (PBC) and SPBC, then Kaplan-Meier (KM) survival analysis was used to compare their overall survival and breast cancer-specific survival. Finally, a predictive model was constructed to estimate the 3- and 5-year survival rates of SPBC patients. We found that the SIR of individuals with SPBC was significantly higher in cancer survivors than in the general population (SIR=1.16, 95% CI=1.15-1.17, P<0.05). SPBC patients with first primary lung/bronchus cancer had a much higher SMR (SMR=1.71, 95% CI=1.58-1.85, P<0.05) compared with survivors of other malignancies. Individuals with SPBC had a larger proportion of the HR-/HER2- subtype than those with PBC. Particularly among survivors of estrogen-dependent ovarian and breast cancer, the proportion of the HR-/HER2- subtype of SPBC considerably rose. After propensity score matching, we discovered that SPBC patients' overall survival remained poorer than that of PBC patients (HR=1.43, 95% CI=1.39-1.47, P<0.001). However, the prognosis of SPBC in first primary thyroid cancer survivors was better than PBC patients (HR=0.64, 95% CI=0.55-0.75, P<0.001). Also, an extreme gradient boosting (XGBoost) model was developed to evaluate the 3-year (AUC=0.817) and 5-year survival (AUC=0.825) of SPBC patients. Our data demonstrated the distinct biological performance of SPBC with various first primary cancers. Furthermore, our findings revealed an indispensable role of first primary cancer (FPC) in the development of SPBC and provided an additional theoretical basis for the clinical follow-up and identification of SPBC.