Abstract 31: Favorable impact of higher environmental temperature on clinical outcomes in breast cancer - Does residence matter? A NCDB and SEER population-based study
Authors: Gupta Ashish , Attwood Kristopher , Gupta Kush , Gandhi Asha , Edge Stephen , Takabe Kazuaki , Repasky Elizabeth , Gandhi Shipra 
Published: June 2022

Abstract
Background: Murine tumor models show that cold stress increases tumor growth rate by norepinephrine release, altering the tumor microenvironment (TME). Tumor-bearing mice when housed at standard temperature of 22°Celsius (°C) exhibited a pro-tumorigenic TME (with fewer CD8+ T Cells and an increase in immunosuppressive cells) than mice housed at 30°C. The incidence of cancer has been shown to be higher in colder climates. Achievement of pathologic complete response (pCR) following neoadjuvant chemotherapy (NAC) for early stage breast cancer (BC) is associated with improved overall survival (OS) and disease specific survival (DSS). Based on these findings, we hypothesized that pCR would be increased while mortality would be decreased in BC patients (pts) living in warmer climates.
Methods: A retrospective, population-based analysis was conducted utilizing the Surveillance, Epidemiology and End Results (SEER) from 1996-2017 and 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 and DSS) methods. Associations between AAT and both pCR and OS/DSS were evaluated using logistic and Cox regression models, respectively, adjusting for confounders (age, race, education, insurance, BC subtype, treatment).
Results: A total of 1,209,332 and 270,496 stage I-III BC pts in the US were analyzed using NCDB and SEER, respectively. In NCDB, 52.1% were hormone receptor (HR)+/HER2-, 8.6% triple negative (TNBC), 7.2% HR+/HER2+ and 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 ranged from 44.7°Fahrenheit (°F) to 62.3°F with median 50.9°F. When adjusting for covariates, pts in regions with AAT &gt; 60.9°F, had a greater chance of achieving pCR compared to AAT &lt; 60.9°F with odds ratio (OR) 1.12 (95% CI 1.07-1.18), p &lt;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. There was a 2% improvement in OS with every 5°F increment, HR 0.98 (95% CI 0.97-0.99), p &lt; 0.001. In SEER, 22.4% were HR+/HER2-, 4.4% TNBC, 4.0% HR+/HER2+, 1.8% HR-/HER2+ and 68.5% unknown. 43.4% received chemotherapy, 49.7% radiation and 94.2% surgery. The AAT ranged from 33.6°F to 67.3°F with median 57.4°F. There was a 3% improvement in OS [HR 0.97 (95% CI 0.968-0.977), p &lt; 0.001] and 2.5% improvement in DSS [HR 0.98 (95% CI 0.968-0.982), p&lt;0.001] with every 5°F increment.
Conclusions: Higher environmental temperatures are associated with significant improvements in rate of pCR, OS and DSS in Stage I-III BC pts. Research focusing on underlying mechanisms and therapeutic strategies to abrogate this disparity is warranted.
Citation Format: Ashish Gupta, Kristopher Attwood, Kush Gupta, Asha Gandhi, Stephen Edge, Kazuaki Takabe, Elizabeth Repasky, Shipra Gandhi. Favorable impact of higher environmental temperature on clinical outcomes in breast cancer - Does residence matter? A NCDB and SEER population-based study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 31.