Differential Second Primary Malignancy Occurrence After Breast Cancer According to HER2 Status: A Population-Based Study

PURPOSE: Our study aims to analyze the association between HER2 status of breast cancer (BC) and second primary malignancy (SPM) occurrence. MATERIALS AND METHODS: Based on BC patients registered between 2010 and 2018 in the NCI SEER database, we utilized standardized incidence ratio (SIR) and Poisson regression to quantify SPM occurrence compared with the general population. Then, adjusted for competing death risk, cumulative incidence function and Gray’s test were adopted to estimate the probability of SPM. Subsequent proportional subdistribution hazards regression was executed to identify the HER2 status impact on SPM risk. Finally, survival analysis was performed. RESULTS: A total of 409,796 first BC patients were included and 18,283 were identified with at least one SPM. The SIR of SPM after HER2+ BC was significantly lower than HER2- BC (1.03 vs 1.13; RR, 0.92; 95% CI, 0.88–0.96; p<0.001). The predominantly declining SPM risk was only observed for second BC (RR, 0.89; 95% CI, 0.82–0.96; p=0.003) and lung cancer (RR, 0.84; 95% CI, 0.74–0.95; p=0.007). Furthermore, competing risk analysis verified the protective effect of HER2 positivity status on SPM occurrence. The 5-year cumulative incidence of SPM following HER2+ and HER2- BC were 4.09% and 5.16%, respectively (p<0.001). In addition, among patients suffering from SPM, HER2 positivity status contributed to better overall survival. CONCLUSION: It is demonstrated that HER2+ BC patients had lower SPM incidence, which was remarkable for second BC and lung cancer.