The STO-3 trial was run from 1976 until 1990 and all patients were postmenopausal breast cancer patients and they had a tumour size of less than 30mm. They were randomised to either receive tamoxifen or no tamoxifen but all patients underwent surgery.
What did you aim to find out in your retrospective analysis?
We have previously done a study where we saw that the oestrogen receptor changes between the primary tumour and relapse. From that study we were interested to understand whether intra-tumour heterogeneity might also impact patient survival because what we saw was that patients that lost their ER expression at relapse actually had worse survival. So therefore we wanted to evaluate intra-tumour heterogeneity in a new trial. So that was the background.
What were the findings?
We found that intra-tumour heterogeneity impacts survival and we see that patients with high intra-tumour heterogeneity have a more than twofold increased risk to die from breast cancer at a very long-term follow-up. So we followed patients up to 25 years and we have complete follow-up for the patients through national registers in Sweden such as the Cause of Death Registry. We also saw, interestingly, that this is also true for luminal A patients. We see that in luminal A patients we have a similar risk increase in patients with high intra-tumour heterogeneity and this is interesting because generally the luminal A subtype is a very low risk or a low risk phenotype or characteristic. Therefore it was quite interesting to see that patients with high intra-tumour heterogeneity with luminal A subtype also have a twofold increased risk to die at 25 years. But this needs to be validated in other trials so this is the first trial where we looked at it.
What is the next step for your research?
We are currently collecting the high risk part of this trial and that trial is called the STO-2 trial. We are collecting the blocks to do an also retrospective analysis of long-term follow-up for that trial. So that would be the next step for us.
What are the potential clinical implications?
If validated it could be another way of understanding risk in patients that generally have low risk. You could have another characteristic to look at to understand whether the patient has true low risk at long-term follow-up because in the end we’re interested in long-term survival for breast cancer patients. So that could be important but it needs to be validated of course.
What would be your take home message?
Intra-tumour heterogeneity is important. We looked at intra-tumour heterogeneity of the oestrogen receptor at whole tumour slides, just stained as is done routinely in the clinic. Already looking at an IHC marker, the oestrogen receptor, such intra-tumour heterogeneity impacts patient survival. So it might be a proxy course of other intra-tumour heterogeneity that a patient has in her tumour. So it’s a simple way of assessing intra-tumour heterogeneity of the oestrogen receptor. There will, of course, be other ways of doing it in the future as well.
