Posted on Jul 23, 2024
Ki67 testing could play a vital role in helping tailor treatments for people with ER-positive breast cancers. However, long-standing problems with immunohistochemistry (IHC) are preventing patients from benefitting from this biomarker. In this blog post, we outline the potential of Ki67 in the neoadjuvant setting, and why we need to look at alternatives to IHC.
Ki67 testing was included for the first time in 2024 in the ESMO guidelines for early breast cancer. One of the emerging applications for Ki67 is in assessing response to neoadjuvant endocrine therapy (NET), a useful tool for downstaging ER-positive tumours.
When measured by immunohistochemistry (IHC), a reduction in the percentage of Ki67-positive cells indicates a strong effect of NET. And this can also be used to predict the outlook for patients. For example, results from the POETIC trial showed that patients whose tumours had lower levels of Ki67-positivity after two weeks of NET had a lower risk of recurrence in the long-term, compared to those with tumours with higher Ki67-positivity.
However, despite the utility of Ki67 testing, it is not widely adopted in clinical practice. Why?
IHC is not suitable for Ki67 testing
We believe IHC is not a suitable test for Ki67, for two main reasons. Firstly, there is a lack of consensus on a suitable threshold for deciding whether a cell is positive or not, which could lead to significant disagreements between laboratories.
The other major challenge is that there are many pre-analytical variables that affect the measurement of Ki67 using IHC – something acknowledged even by the authors the POETIC study.
Despite the best efforts of endeavours like the International Ki67 in Breast Cancer Working Group, problems with the reproducibility of IHC testing remain.
In their international reproducibility study, Polley and colleagues concluded that “substantial variability in Ki67 scoring was observed among some of the world’s most experienced laboratories,” and that the analytical validity of Ki67 testing with IHC is limited.
Meanwhile, people with breast cancer are not benefitting from the accurate Ki67 testing they deserve. The result is they might not receive the treatment they need to give them the best chance of survival in the future.
Could MammaTyper® be a better option for Ki67 testing?
We believe that, as far as Ki67 testing is concerned, we need to move away from IHC and look towards other options.
An alternative approach may finally allow Ki67 to achieve its promise of tailoring breast cancer treatment. MammaTyper®, a RT-qPCR based tool, has already shown excellent analytical validity and inter-laboratory reproducibility for Ki67.
Following extensive technical validation, we have already shown that MammaTyper® is a linear, quantitative, reproducible, and standardised test for Ki67 and other key breast cancer markers. Our mission for 2024 is to further demonstrate the clinical utility of the assay – for predicting response to neoadjuvant endocrine therapy, and other applications.
If you would like to try MammaTyper® testing of Ki67 for yourself, or you would like to help collaborate on studies that prove its clinical utility, we’d love to hear from you – please contact us at info@cercabiotech.com.