What is very important for the future is to identify patients with breast cancer that are more likely responsive to immune checkpoint inhibitors. The activity in clinical practice is very limited, 18% response rate is not a breakthrough for patients with a triple negative breast cancer. That’s why what we did in this study is to identify genetic determinants that may predict response to immune checkpoint inhibitors. We identified some metagenes that are upregulated in patients without immune disease and we checked whether these metagenes are overexpressed in breast cancer patients. What we found is that there is a sub-population of breast cancer patients in which there is an upregulation of genes involved in the activation of the immune response. We called this metagene immunological constant of rejection and we identified patients according to the immunological constant of rejection four to one, according to the overexpression of these genes. The final message is that if you have an ICR4, I mean overexpression of these genes, your prognosis will be better and maybe you will respond better to immune checkpoint inhibitors.

What are the primary subtypes you are focusing on?

We explored all the subtypes. This is a very interesting question because what we observed is that the ICR4 is overexpressed just in triple negative disease and HER2 positive disease. We don’t have upregulation of immunological constant of rejection metagenes in the luminal cancers. So this matches with the observation that triple negative and HER2 positive disease are the most frequently involved in tumour infiltrating lymphocyte predominance and this is also related to many other observations of other gene signatures of immune activation that are most prevalent in triple negative and HER2 positive disease.

What is the potential clinical benefit?

I believe we need, for future trials, to stratify patients with breast cancer according to immune markers. It’s very important to select the patients in order to achieve much more results in terms of clinical benefit. So up to now we have tumour infiltrating lymphocytes, this will be an important stratification factor in future trials, PD-L1 expression and finally the immunological constant of rejection. I believe we need a multidimensional evaluation of factors related to the patient, factors related to the tumours and to the microenvironment.

Any take home messages for clinicians or researchers watching this video?

If you will design future trials in the breast cancer field first concentrate in triple negative and HER2 positive because these are the patients more likely responsive to immune checkpoint inhibitors. Secondly, if you design a type of trial like this do a lot of translational research and include assessment of tumour infiltrating lymphocytes, genetic determinants and microbiome assessment.