CLO22-051: Influence of Environmental Temperature on Pathological Complete Response and Overall Survival in Breast Cancer: A National Cancer Database Population-Based Study

Background: Animal models show that cold stress increases tumor growth by norepinephrine release which alters the tumor microenvironment (TME). Tumor-bearing mice at standard temperature of 22°Celsius (°C) exhibited a pro-tumorigenic TME [lower CD8 + T Cells and higher immunosuppressive cells] than mice housed at 30°C. The incidence of cancer has been shown to be higher in colder climates. A pathologic complete response (pCR) following neoadjuvant chemotherapy (NAC) for early-stage breast cancer (BC) is associated with improved overall survival (OS). Based on these findings, we hypothesized that pCR increases and BC mortality decreases in patients (pts) living in warmer climates. Methods: A retrospective, population-based analysis was conducted utilizing the National Cancer Database (NCDB) from 2004-2018 and average annual temperature (AAT) data from the National Centers for Environmental Information. Cut-offs for AAT were obtained using the Youden’s index (for pCR) and maximum log-rank (for OS) methods. Associations between AAT and both pCR and OS were evaluated using logistic and Cox regression models, respectively, adjusting for relevant confounders (age, race, education, insurance, BC subtype, treatment). Results: A total of 1,209,332 stage I-III BC pts in the United States were analyzed using the NCDB. 83.9% were White and 68.1% were > 55 years old. 52.1% were hormone receptor (HR)+/HER2-, 8.6% triple negative (TNBC), 7.2% HR+/HER2+, 3.1% HR-/HER2+ and 29% unknown. 37.7% received chemotherapy, 62.6% radiation and 94.3% surgery. 10.2% pts received NAC and 19.5% (19,021/97,669) achieved pCR. The AAT for all the regions ranged from 44.7°Fahrenheit (°F)/7.1°C to 62.3°F/16.8°C with median 50.9°F/10.5°C. When adjusting for covariates for pts in regions with AAT > 60.9°F, there was a higher incidence of pCR compared to AAT < 60.9°F with odds ratio (OR) 1.12 (95% CI 1.07-1.18), p <0.001. This was consistent in the TNBC and HR-/HER2+ subgroups with OR 1.14 (95% CI 1.07-1.23) and 1.15 (95% CI 1.04-1.27), respectively. Temperature was analyzed in 5°F increments. With every 5°F increase, there was a 2% improvement in OS with HR 0.98 (95% CI 0.97-0.99), p < 0.001. Conclusions: Higher environmental temperatures are associated with significant improvements in rate of pCR as well as OS in Stage I-III BC pts. Further research focusing on therapeutic strategies to abrogate this outcome disparity is warranted.