Differential Second Primary Malignancy Occurrence After Breast Cancer According to HER2 Status: a SEER Population-Based Analysis

Abstract

Background: The survival improvement in breast cancer (BC) renders the long-termsurvivorsan increasedprobability of second primary malignancy (SPM), and thus excess mortality. Although previous evidence has indicated various predictorsofSPM, little is known whether SPM incidencevaries by HER2 status of first BC. Methods: Based on BC patients registered between 2010-2018 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 executedto identify the HER2 status impact on SPM risk. Finally, survival analysiswas performed.Results: A total of 409,796 first BC patients were includedand 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). But 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 and bronchus cancer (RR, 0.84; 95% CI, 0.74-0.95; p=0.007). Further 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 5.16% and 4.09%, respectively (p<0.001). In addition, among patients suffering from SPM,HER2 positivity status contributed tobetter overall survival. Conclusion: After considering intrinsic incremental risk with age and adjusting for competing risk of death, our study demonstrated that HER2+ BC patients had lower SPM occurrence, remarkable for second BC and lung and bronchus cancer. The disparity implies the relation between SPM occurrence and therapeutic along with genetic factors underlying BC HER2 status.