Posted on Mar 29, 2024
One of our four key goals for clinical validation in 2024 is to demonstrate that progesterone receptor (PR) testing with MammaTyper® could be used for predicting risk of recurrence. In this article, we assess the current role of PR, where IHC testing falls short, and how MammaTyper® could provide a reliable, more accessible option for risk scoring.
PR – the forgotten marker?
In breast cancer testing, progesterone receptor (PR) is sometimes considered the ‘forgotten marker’. Unlike ER or HER2, there are no treatments in current clinical practice linked to the presence or absence of PR. As a result, testing for PR is not routinely carried out in some countries, most notably the UK.
However, even if it’s not currently a treatment biomarker, PR expression has long been linked to better outcomes for patients. According to ASCO-CAP guidelines: “Overall survival, time to treatment failure/progression, response to endocrine therapy, and time to recurrence [are] positively related to PgR levels”.
PR as a marker of recurrence risk
Recent evidence of this link was presented at San Antonio Breast Cancer Symposium (SABCS) in 2023. Analysis of samples from the OPTIMA trial and a German study demonstrated there was excellent negative correlation between PR expression levels, measured by MammaTyper®, and OncotypeDX Recurrence Score (RS).
High levels of PGR expression could predict low RS scores in up to 70% of patients, so identifying those who are unlikely to gain benefit from chemotherapy.
The results of this study confirm what we already suspected: that the Oncotype DX recurrence score is heavily influenced by PGR expression in the tumour. The results also show that MammaTyper® – a cheap, accurate RT-qPCR test, performed locally – could prevent the need to send samples away for expensive Oncotype DX testing, for many patients.
Crucially, this link between PR and recurrence risk is not apparent with immunohistochemistry (IHC) testing. PR expression by IHC was only weakly predictive of RS, yet again highlighting the shortfalls of IHC in the genomic era.
What does the future hold for PR?
Speaking to Dr Ralph Wirtz, one of the authors of the SABCS study above and co-developer of MammaTyper®, he thinks there’s great potential in confirming the utility of PGR expression as a marker of survival.
“We are now in the position to look at whether the MammaTyper® progesterone assessment is highly prognostic, whether you can safely say [to a patient] ‘you don't need chemotherapy, you have a very, very good chance of survival’,” Dr Wirtz says. “I’m quite optimistic that we can realise a good prediction of good outcome.”
There is also growing interest in revisiting treatment with PR agonists. The results of the SABCS study reaffirm that MammaTyper® is well placed to provide simple and accurate PGR expression testing in the future.
Cerca Biotech is looking for study collaborators
Following extensive technical validation, we have already shown that MammaTyper® is a linear, quantitative, reproducible, and standardised test for PR and other key breast cancer markers: ER, HER2, and Ki67. Our mission for 2024 is to further demonstrate the clinical utility of the assay.
We are looking for collaborators to participate in our next multi-centre retrospective comparison using MammaTyper® PGR results to correlate with the Oncotype DX Recurrence Score.
We are also interested in collaborating on studies monitoring response to neoadjuvant therapy using serial testing of biopsies. If you are interested in discussing a potential collaboration, please contact us at: info@cercabiotech.com