Abstract
COVID-19 severity is uneven between genders. A role for sex hormones is possible and has been postulated. Considering this idea, we hypothesized hormonal therapies might influence the severity of COVID-19 in breast cancer (BC) patients. We mined the Emilia-Romagna region (Italy) registries to compare the rates of hospitalization and mortality by COVID-19 in 2020 amongst 22,987 BC patients treated with tamoxifen, aromatase inhibitors (AIs), fulvestrant, and anti-HER2 therapies (trastuzumab and pertuzumab) in 2020, the latter used as reference group. The hospitalization rate observed in 4719 tamoxifen-treated BC patients was the lowest (0.61%, OR, 0.38; 90% CI, 0.20-0.76; p = 0.03) among hormonal therapies. Importantly, only one COVID-19 fatality was observed in tamoxifen-treated BC patients, who showed a striking 0.02% COVID-19 death frequency as compared to 0.24% observed for the whole BC patients population. In addition, tamoxifen emerged in the sex and age adjusted analysis as the only agent significantly decreasing the standard mortality rate (SMR) by COVID-19 as compared to the regional population consisting of 2,296,559 female residents from the Emilia Romagna region in 2020. Our results show that BC patients are at increased risk of COVID-19 hospitalization and that COVID-19 mortality is hindered by SERM-based therapies like tamoxifen. These findings are relevant to choose adequate treatments in order to protect cancer patients from concomitant SARS-CoV-2 contagion and related symptoms and contribute to the idea that SERMs could be used as prophylactic agents and therapeutics to prevent the progression of severity of COVID-19.