Improved survival outcomes in cancer patients with hereditary hemorrhagic telangiectasia.

BACKGROUND Hereditary hemorrhagic telangiectasia (HHT) is a genetic disorder characterized by deficiency in endoglin, an angiogenic protein. The net effect of endoglin expression on cancer outcomes from animal studies has proven controversial. We evaluated whether reduced systemic endoglin levels, expected in patients diagnosed with HHT, impacted clinical outcomes for cancer. METHODS A retrospective cohort analysis using Surveillance, Epidemiology, and End Results-Medicare was conducted to evaluate the effect of HHT on survival among patients diagnosed with breast, colorectal, lung, or prostate cancer between 2000 and 2007 (n = 540,520). We generated Kaplan-Meier survival curves and Cox models to compare the effect of HHT on all-cause survival for a composite of the four cancers, and separate models by cancer, adjusting for demographic variables, cancer type, cancer stage, and comorbidities. RESULTS All-cause survival analysis for a composite of the four cancers showed an adjusted HR of 0.69 [95% confidence interval (CI) of 0.51-0.91; P = 0.009] for HHT, indicating significantly improved survival outcome. When stratified by cancer type, HHT diagnosis showed a significant protective effect among breast cancer patients with an adjusted HR of 0.31 (95% CI, 0.13-0.75; P = 0.009). CONCLUSIONS There was a significant association between HHT and improved survival outcome for a composite of patients with breast, prostate, colorectal, and lung cancer, and in analysis stratified by cancer, the association was significant for HHT patients with breast cancer. IMPACT This study supports the hypothesis that systemically educed endoglin expression is associated with improved survival outcome in multiple cancers, and suggests that anti-endoglin antibody therapy may have broad-based application.