Genetic and clinical factors best for predicting late recurrence in oestrogen receptor positive breast cancer

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Published: 15 May 2013
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Dr Ivana Sestak - Queen Mary University of London, UK

ecancer reporter Peter Goodwin talks to Dr Sestak at the 2013 IMPAKT conference in Brussels about a new analysis which has provided a comprehensive comparison of scores designed to predict which women with oestrogen-receptor positive breast cancer are at high risk of recurrence beyond five years after diagnosis, and may benefit from prolonged endocrine treatment.

The ATAC trial included nearly 10,000 women who were treated with surgery followed by five years of treatment with the drugs anastrozole, tamoxifen or a combination of both. Of these 1,125 from the monotherapy arms (tamoxifen, anastrozole) were included in the transATAC study.

The five scores being compared were:

  • Clinical Treatment Score, which includes information on the patient’s disease and treatments so far;
  • IHC4 score, which characterises the presence of cell surface markers on cancer cells;
  • The Oncotype Dx Recurrence Score;
  • The PAM50 Risk of Recurrence Score;
  • The Breast Cancer Index score.

The results showed that the clinical treatment score alone was the best for predicting late recurrence, the researchers report. The components of this score include some that are already widely used by doctors, such as whether the cancer has spread to sentinel lymph nodes, the tumour size and grade.
Among the other tests, the PAM50 risk of recurrence score and the Breast Cancer Index score added the most significant prognostic value between years 5 and 10 after diagnosis.


ecancer's filming at IMPAKT has been kindly supported by Amgen through the ECMS Foundation. ecancer is editorially independent and there is no influence over content.

IMPAKT Breast Cancer Conference 2013

Genetic and clinical factors best for predicting late recurrence in oestrogen receptor positive breast cancer

Dr Ivana Sestak - Queen Mary University of London, UK


One of the amazing bits of progress in recent decades has been the treatment of hormone responsive breast cancer. Huge progress and yet there are recurrences. You’ve been looking specifically at recurrence in hormone treated breast cancer, what have you come up with? First of all, what have you been doing?

Well we were specifically interested in late recurrence because we know that hormone receptor positive breast cancer patients will recur, will have a great risk of late recurrence. So we were interested to see if five different scores can predict late recurrence in hormone receptor positive breast cancer patients.

So this is recurrence beyond five years?

That’s recurrence beyond five years; after the initial five years of treatment basically.

And tell me about these scores because one of them is clinical.

One is clinical, called the Clinical Treatment Score, includes information on nodal status, tumour size, tumour grade, age and treatment. Then we have the so-called IHC4 score that contains information on oestrogen and progesterone receptor.

That’s cell surface markers?

That’s cell surface markers, yes, and HER2 status and Ki67. And then we have the genetically based score, the Oncotype Dx Recurrence score. Then we have the PAM50 Risk of Recurrence score which includes fifty genes and tumour size. Then finally the Breast Cancer Index.

Right, so you’ve got gene tests, a number of different gene tests, which are sort of competing for the business at the moment. Now how did all these do and, indeed, did the gene ones do any better than the others?

Yes, we’ve seen that actually the ROR and the PCI did best.

That’s the PAM50?

That’s the PAM50, yes, PAM50 ROR. That they predict best who is going to have a late recurrence after five years. And actually the IHC4 and the Recurrence Score, that these two scores didn’t give us any additional prognostic information.

Oncotype Dx Recurrence didn’t add?

It didn’t, only the ROR; from the genetically based scores, only the ROR and the PCI gave us any valuable information after five years.

Right, now that’s important knowledge. How do you think doctors will be able to apply this?

Well at the moment obviously these are not definite results. This has been the first time we compared these five scores in the transATAC cohort and these results certainly need to be validated in other cohorts. But potentially we can say that hopefully taking these scores and the results of these scores and saying these women, or this group of women, is at a high increased risk that she needs either additional adjuvant hormonal therapy or maybe she will need extended chemotherapy.

And looking at the PAM50 ROR and the BCI Index, the BCI score, how much extra information or refined knowledge did that give you over and above the cell surface markers and the Clinical Treatment Score?

It’s difficult to put, obviously at the presentation I reported the values, the chi-squared values, but it’s difficult to put that in percentage. But they were significantly adding more information than the Oncotype Recurrence score.

And clinically, of course, if the patients can actually benefit from more treatment then that’s a good thing. Is there an indication that they will benefit?

Well, we don’t know yet if additional hormonal therapy, apart from Tamoxifen, we know that longer Tamoxifen up to 10-15 years is beneficial. For aromatase inhibitors, like anastrozole in this case, we don’t have this knowledge yet. But we would assume that extended therapy would benefit the patient.

And can you see this being applied to withhold therapy that isn’t going to be needed?

Certainly. I think these scores, specifically now the ROR and the PCI again, can divide patients into low risk and high risk groups and so therefore the women who are in the low risk group will actually probably not need any additional or further treatment and maybe they will just be fine after 2-3 years of hormonal treatment. And it’s as important to identify the high risk women as the low risk women because we don’t want to over-treat women who don’t need actual treatment.

Right. So you’ve made important distinctions between the different methods of scoring recurrence. What should cancer professionals be making of this, finally? What’s the clarity for them?

Well, as I said before, this needs to be validated in other studies but I think from these results we can take that we are able to categorise women into high risk, as well intermediate and low risk. I think this is an important first step to take further before we can put it into clinical implications.

And you’re endorsing two, at least, of the genetic tests.

Well, I’m not endorsing anything. We did a head to head comparison of these five scores and they both showed that they are…

Moderate approval of two of them.

And both showed that they can predict late recurrence very well.

Yes, more work needs to be done, of course.

And yet again more work needs to be done, yes.

Well we’d like to do some more work with you in the future to find out more of this but thanks for coming in today.

Thank you.