Oncotype DX: changing breast cancer treatment

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Published: 19 Dec 2013
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Dr Norman Wolmark - National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, USA

Dr Norman Wolmark speaks to ecancer from the San Antonio Breast Cancer Conference (SABCS) about the Oncotype DX assay. Describing it as an important advance in the armamentarium to treat breast cancer, he notes the 10th anniversary of the initial data that led to the process for recognising the value of Oncotype DX, and outlines the history of the test

Dr Wolmark reviews how Oncotype DX has changed the standard of care. He also outlines how genomic therapy benefits patients, and how it should be used; this includes outlining the drop in chemotherapy as a test of Oncotype DX assay use.

Dr Wolmark talks about the various on-going studies with Oncotype DX that are looking to review its potential use in a wider cohort of patients.

Finally, he summarises the dramatic impact that the Oncotype DX assay has had on breast cancer management, and notes research into the next generation of assays to continue to make progress in the understanding of breast cancer treatment.


This programme has been supported by sponsorship from Genomic Health.

The Oncotype DX is an important advance in the armamentarium to treat breast cancer, specifically node negative, ER positive breast cancer. During this meeting we’ve celebrated the tenth anniversary of the presentation of the definitive data from NSABP protocol B14 which really started the process to recognise the value of the Oncotype DX.

In your own experience, how has the treatment landscape in breast cancer changed over the past ten years?

Over those ten years we’ve seen some dramatic changes in the way breast cancer is treated and we have also seen that over 400,000 women have utilised the assay to determine whether they ought or ought not receive chemotherapy for their node negative, ER positive breast cancer. It might be worthwhile to put the story into perspective to review what the standard of care was ten years ago, at the time that we first presented the data from NSABP protocol B14. That was documented very clearly in the consensus statement that was published by the National Institutes of Health in the year 2001 but the meeting took place in the year 2000. They stated unequivocally that the standard of care for node negative women with tumours greater than 1cm should consist of adjuvant chemotherapy. They also went on to state that for women with tumours smaller than 1cm the treatment should be individualised, but based on what? Based on physician bias? On patient bias? We felt particularly guilty about this because the consensus statement was driven predominantly by data that was generated by the NSABP, namely protocol B13 and B20 where we saw an overall advantage for a CMF based chemotherapy, a 5% reduction in distant recurrence. So for that 5% reduction the recommendation was that everybody be treated and we knew very well that everyone didn’t benefit, the majority of women didn’t benefit from adjuvant chemotherapy; we simply couldn’t determine who they were.

What is your own experience of using genomic testing and how does genomic testing benefit patients?

There was clear necessity to develop a robust molecular algorithm that could identify those women who would benefit and those women who would not benefit. That’s when the NSABP developed a relationship with Genomic Health of Redwood City, California to evolve and to validate the Oncotype DX. The first part of that was the presentation of the data from B14 and that consisted of women who were node negative whose tumours were ER positive. Dr Soon Paik presented the data here at this meeting in San Antonio ten years ago, almost to the day. The next year we presented the data from NSABP protocol B20 with adjuvant chemotherapy. Then we made some statements that weren’t particularly reticent or diffident; Steve Shak and I spent the next day after the data were presented fielding questions and reviewing various press releases. We made statements that weren’t reticent or recalcitrant or diffident, nor did they have any hint of humility but I think they’ve stood the test of time; the fact that we’ve had a tenth anniversary speaks more eloquently to the value of the assay than anything else. We stated that the Oncotype DX was highly significantly associated with a likelihood of distant recurrence, that it was superior to standard measures such as tumour size, such as tumour grade which was a commonly used determinant, patient age, algorithms that were available on the web and in particular adjuvant online, for example. We also, based on the B20 data, noted that the Oncotype DX was highly predictive of chemotherapy benefit. So, whereas before we saw an overall effect of 5%, that the high risk group based on the Oncotype DX which consisted of 20% of the population showed a 28% absolute benefit from CMF based chemotherapy. Just as important, we saw that 50% of women did not benefit, not one iota, from the use of chemotherapy. So, for the first time we saw an overall drop in the use of chemotherapy as a result of the use of this assay to the extent that when Francis Collins was interviewed in 2010 by Newsweek he estimated that the use of this assay would reduce the overall cost of chemotherapy to this country about a $100 million per year. So the assay, of course, has been endorsed by various august agencies such as ASCO, NCCN, ESMO, St Gallen’s, it’s even been recommended by NICE but what’s far more important is that it has been embraced by the medical oncologists of this country who have used the assay in over 60% of eligible women to the extent that 400,000 assays have been performed to date.

So it doesn’t stop there, of course. There are two large trials that are determining whether those patients who fall into the intermediate group would benefit from the use of adjuvant chemotherapy and we expect that the results of the TAILORx trial, which randomised 7,000 women in the intermediate group to chemotherapy or no chemotherapy to be reported in 2015, is a very interesting and courageous trial; the ReSPONDER trial that’s on-going for patients who are node positive, one to three positive nodes, with a recurrent score of 25 or less who are also being randomised to chemotherapy or no chemotherapy to determine if this assay applies to node positive women with the criteria that were just reviewed. So the assay has made a significant impact on the way that the disease is treated. I think it has changed the standard of care and how many of us can really say that we left the field in better shape than we found the field? The Oncotype DX has done that and it’s to the credit of Genomic Health for supporting these ongoing clinical trials providing the assays for this trial. It’s equally important to state that this assay is not the be all and the end all; we’re aware of that, Genomic Health is aware of it. They’re evolving a robust platform for next gen sequencing in order to embrace the next generation of assays that will continue to make significant progress in our understanding and treatment of breast cancer.

What does the future look like for genomic testing per se – and hold for breast cancer patients in particular?

Right now the standard is for node negative, ER positive breast cancer. The other trials, the ReSPONDER trial in particular, is going to determine whether it can be used in women with one to three positive nodes with a recurrent score equal to or less than 25. Certainly you can apply it to node positive patients who’ve received chemotherapy, for example, as we did retrospectively in B28 and it’s certainly highly prognostic but not predictive of the addition of taxane, for example.