ABSTRACT
Background: Studies evaluating COVID-19 in cancer patients beyond the effects of the infection itself are generally from single institutions, voluntary surveillance registries, or surveys. To extend the limited evidence available, we analyzed both the incidence and one-year mortality of breast cancer (BC) female patients at a population level in Lombardy, the first Italian region affected by the pandemic and the most populous one. Method(s): The regional COVID-19 database, including all SARS-CoV2 cases based on a positive swab result, was integrated with the Regional Health Information System, collecting data from 10 million habitants on primary medical care;hospitalization;pharmaceuticals;and survival status. From the database, we extracted data of newly-diagnosed not previously treated BC patients, including patient characteristics and comorbidities (respiratory insufficiency, diabetes, chronic kidney disease, cerebral vasculopathy, hypertension and cardiovascular disease), BC stage, and treatment. Result(s): The study population consisted of 12912 newlydiagnosed/ not previously treated BC patients, 7349 in 2019 and 5563 in 2020. There were two drops of newly diagnosed cases, one in the first wave (March-May 2020;-37.2%), the other in the second wave (October-December 2020;-15.8%). No major differences were found between characteristics of cases occurring in 2019 and 2020;with the exception of a reduced use of both chemotherapy (86.2% vs 53.4%) and radiotherapy (65.7% vs 42.1%) in 2020. One-year overall survival was 97.6% in 2020 vs 98.3% in 2019, Hazard Ratio [HR] (95% Confidence Interval [95%CI]): 1.51 (1.18-1.93);p=0.0010 at univariate analysis;HR 0.91 (0.71-1.17), p= 0.47, after adjusting for age, stage, BC treatment and comorbidities at multivariable analysis. COVID-19 occurred in 250 of 5563 (4.5%) newly-diagnosed BC cases in 2020. Notably, the time-dependent COVID-19 effect was significantly associated with mortality (multivariable Cox analysis HR 2.25 (1.35-3.74);p=0.0018) even after adjusting for age, stage, treatment and comorbidities. Conclusion(s): Breast cancer incidence and survival were both reduced in 2020, and COVID-19 was an independent predictor of death in BC patients. While follow-up is ongoing to assess long sequelae of COVID-19, these results encourage prevention of infection regardless of BC stage;and at the same time warn against suboptimal treatment and overlooking new diagnoses to ensure a favourable prognostic outcome.
ABSTRACT
Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters into target cells by exploiting the cellular transmembrane protease serine 2 (TMPRSS2) for spike protein cleavage. Male gender, age, obesity, diabetes, hypertension are some of the factors related to coronavirus disease 2019 (COVID-19) severity and mortality. Prostate cancer (PCa) patients (pts) are expected to be at higher risk for COVID-19 due to age and disease related comorbidities. TMPRSS2 transcription depends on androgens and androgen receptor and it is significantly downregulated by hormone therapies commonly used to treat PCa in different settings. Supposing that in PCa pts androgen deprivation therapy (ADT) could hamper SARS-CoV-2 cell entry, we aim to evaluate if the presence of single nucleotide polymorphisms (SNPs) in the androgen responsive elements (AREs) in the TMPRSS2 promoter is associated to COVID-19 outcomes. Trial design: The present exploratory biological study is part of an ongoing retrospective-prospective multicenter cohort trial designed to verify whether PCa pts on ADT develop milder clinical presentation of COVID-19 than the general male population. The cohort trial collects real world data since February 2020 through regional databases that identified 200,000 potential pts to be enrolled to compare the clinical outcome of COVID-19 between PCa pts on active therapy (Study Group) and non-PCa pts (Control Group). Within the Study Group, we will compare the COVID-19 outcome between treatment subgroups: ADT alone, ADT plus antiandrogens, CYP17 inhibitors or chemotherapy. To identify SNPs in AREs of the TMPRSS2 gene and to describe possible associations with COVID-19 outcome, blood samples will be collected from 50 PCa pts treated at selected centers. Pts will participate voluntarily and sign an informed consent approved by local ethical committees. We will centrally perform PBMCs isolation and DNA extraction by using quiagen QIAamp DNA Mini Kit. SNPs will be evaluated with the Axiom™ Human Genotyping SARS-CoV-2 array. The effect of ADT will be corrected depending on identified SNPs and associated to COVID-19 outcome. The study is ongoing: we processed blood samples from 21 pts. Final results are awaited by the end of 2021. Legal entity responsible for the study: The authors. Funding: Fondazione IRCCS Istituto Nazionale Tumori di Milano. Disclosure: All authors have declared no conflicts of interest.