Reacción a "Respiratory viral infections activate metastatic breast cancer cells"

The findings presented are innovative and potentially of great clinical relevance. The study provides mechanistic evidence for how respiratory viral infections reactivate dormant disseminated cancer cells (DCCs) and promote metastasis. Although this possibility has been discussed before, the authors of the current study demonstrate a causal link using several approaches. In animal models in which the inflammatory hormone interleukin 6 (IL-6) was genetically removed, no activation of dormant cancer cells occurred after infection with influenza or SARS-CoV-2. The temporal course of this activation could also be described in the animal model, which appears to be initially IL-6-mediated and subsequently dependent on CD4+ T cells (T helper cells; editor's note). 

HER2-positive breast cancer is found in 15 to 20 per cent of cases and is an aggressive but treatable form of breast cancer. The study used two well-established transgenic MMTV-HER2+ mouse models (mouse model with susceptibility to HER2+ breast cancer and up to one year of dormant tumour cells in other organs; editor's note) and an orthotopic mouse model in which breast cancer cells are transplanted. The transgenic models in particular seem well suited to the questions being investigated, as they have a long dormancy phase (phase of inactive tumour cells; editor's note) of up to one year, which closely mimics the human situation. The use of multiple models in the present study strengthens the generalisability. 

I would like to note at this point that my expertise in the field of tumour animal models is limited. Mouse-adapted strains of influenza virus and SARS-CoV-2 are used as infection models, both of which are well established and widely used. ‘
’There are some indications that the present results could be relevant for humans. These include, for example, the fact that the IL-6 signalling pathways described are highly conserved between mice and humans (largely unchanged over the course of evolution; editor's note). 

At the same time, it's important to note that there are species differences and that results from animal models often can't be directly transferred to humans. The authors therefore also conducted an epidemiological analysis of human data from two large databases (the UK Biobank and the US Flatiron Health database). They concluded that COVID-19 triggers an increased risk of lung metastases in breast cancer patients. When reviewing this human data, it was not clear to me how valid and robust these data actually are in terms of the selected time periods, different potentially influencing factors, effect size and other factors. This may also be due to the fact that I do not have any specialised epidemiological expertise. 

The study provides an important explanation for the increased COVID-19 mortality in cancer patients: it describes a direct mechanism by which respiratory viral infections can influence the reactivation of the DCC via inflammatory mediators such as IL-6 and immune cells and ultimately promote metastasis. The combination of experimental data and large epidemiological cohorts provides an important contribution to understanding the consequences of the COVID-19 pandemic in cancer patients. However, I assume that other factors also influence the observed increased mortality of cancer patients after SARS-CoV-2 infection.