Abstract P3-12-05: Influence of environmental temperature on breast cancer outcomes: A SEER population-based study
Authors: Gupta Ashish , Attwood Kristopher , Gupta Kush , Catalfamo Kayla , Takabe Kazuaki , Gandhi Shipra 
Published: March 2022

Abstract
Background: Emerging data from basic research using animal models shows that cold stress increases tumor growth rate by altering the tumor microenvironment (TME). 4T1 tumor-bearing mice (murine breast cancer model) when housed at standard housing temperature of 22oCelsius (°C) exhibited a pro-tumor immune microenvironment with lower CD8+ T-cells and higher immunosuppressive myeloid derived suppressor cells and regulatory T-cells than mice that were kept at thermoneutral temperature of 30oC. Analysis of large genomic databases where cold stress was quantified by a thermogenesis score showed that triple negative breast cancer with high thermogenesis score was associated with worse disease specific survival (DSS) and a pro-tumor immune microenvironment. Additionally, it was observed that females in the United States (US) are susceptible to developing cancers if they live in regions with colder climates versus warmer climates. Based on these findings, we hypothesized that breast cancer mortality increases in patients living in colder versus warmer climates in the US and utilized Surveillance, Epidemiology, and End Results (SEER) database to investigate this hypothesis. Methods: We conducted a retrospective, population-based analysis utilizing the SEER database and analyzed DSS and overall survival (OS) with respect to the average annual temperature (AAT) of the county in which a patient with breast cancer was diagnosed in, from years 1996-2017. Data on AAT was obtained from the National Centers for Environmental Information https://www.ncdc.noaa.gov/cag/county/mapping/110/tavg/202005/1/value. Multivariate (MV) models were conducted to compare the associations between AJCC stages and demographic/tumor characteristics: age, race, marital status, insurance, rural or urban area, receptor status, and type of treatment received. All associations were compared using Fisher’s Exact and Kruskal-Wallis Tests respectively. All analysis was conducted in RStudio v4.02 at a significance level of 0.05. Results: A total of 284,100 (270,496 stage I-III and 13,604 stage IV) breast cancer patients residing in 3,136 counties in the US were analyzed using the SEER database. Of all patients, 77.9% were White, 62.6% were &gt; 55 years old, 54.9% were married, 54.2% were insured and 87.9% patients resided in urban area. Biomarker data was available for 32.5% patients with 22.4% hormone receptor (HR)-positive/HER2-negative, 4.4% triple negative, 4.0% HR-positive/HER2-positive and 1.8% HR-negative/HER2-positive. 43.4% received chemotherapy, 49.7% radiation and 94.2% had surgery. The AAT for all the counties ranged from 33.6° Fahrenheit (F)/0.89°C to 67.3°F/19.6°C with median temperature 57.4°F/14.11°C. 10-year OS rate for stage I-III patients was 71.1% versus 8.8% for stage IV patients (p &lt; 0.001). Similarly, 10-year DSS rate for stage I-III patients was 85.6% versus 12.1% for stage IV patients (p &lt; 0.001). Temperature was analyzed in 5° F increments. When adjusting for the covariates in a MV model, there was a 3% improvement in OS and 2.5% improvement in DSS for every 5°F increment in AAT for stage I-III breast cancer patients in a time dependent model with HR 0.973 (95% CI 0.968-0.977), p &lt; 0.001 and HR 0.975 (95% CI 0.968-0.982), p&lt;0.001, respectively. A similar trend of improvement in OS and DSS was noted for stage IV breast cancer patients with HR 0.982 (95%CI 0.971-0.994), p = 0.003 for OS and HR 0.976 (95% CI 0.964 - 0.988), p &lt; 0.001 for DSS with every 5°F increment in AAT. Conclusions: Higher environmental temperatures are associated with improved clinical outcomes both among stage I-III and stage IV breast cancer patients. These interesting findings should be validated using other databases and further research focusing on therapeutic strategies to abrogate this outcome disparity is warranted.
Citation Format: Ashish Gupta, Kristopher Attwood, Kush Gupta, Kayla Catalfamo, Kazuaki Takabe, Shipra Gandhi. Influence of environmental temperature on breast cancer outcomes: A SEER population-based study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-12-05.