Decreased breast cancer-specific mortality risk in patients with a history of thyroid cancer

Previous studies have documented an intrinsic association between breast cancer (BC) and thyroid cancer (TC), but the clinical relevance of this relationship is not well defined. In the present study, we specifically investigated the impact of a history of TC on clinical outcomes of BC. We performed a population-based comparative analysis of tumor behaviors and BC-specific mortalities in 427,893 female patients with BC in the USA Surveillance, Epidemiology and End Results 9 database (1973-2013). In this cohort of subjects, 2,569 patients also had a history of differentiated TC (BC/TC), including BC diagnosed before TC (BC-1st) and BC diagnosed after TC (TC-1st), with the median follow-up time of 81 (IQR, 33-160) months. We found that, compared with matched BC-only patients, less aggressive BC tumor behaviors occurred in BC/TC patients, as exemplified by a distant metastasis rate of 7.0% in the former versus 3.3% in the latter (P<0.001). In BC/TC, BC-1st, and TC-1st patients versus their matched BC-only patients, BC-specific mortalities were 11.3% versus 21.0%, 9.9% versus 26.4%, and 12.4% versus 16.9%. These corresponded to hazard ratios (HR) (95% CI) of 0.47 (0.42-0.53), 0.31 (0.26-0.37), and 0.72 (0.61-0.84), respectively (all P<0.001), being lowest in BC-1st patients <50 years old [HR = 0.22 (0.16-0.31)], which remained significant after adjustment for clinicopathological and socioeconomic factors. Estrogen/progesterone receptor expression in BC tumors was significantly higher in patients with BC/TC than matched BC-only patients, providing evidence that BC in the former was biologically unique. Thus, a history of TC, particularly in younger BC-1st patients, may identify BC as a unique disease entity characterized by a decreased disease-specific mortality risk. The results have potentially important clinical and biological implications for BC in this special patient population and encourage further studies to confirm.