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Breast Cancer Update 2006 (7)

DR VICTOR G VOGEL: Using archival tissue blocks from past trials, Genomic Health and Dr Soon Paik from the NSABP analyzed approximately 200 genes that were reported to possibly relate to outcome in breast cancer to develop the Oncotype DX assay. They narrowed that set down to just 16 genes that could be sorted into logical groups based on the estrogen receptor, the HER2 protein and proliferation and invasion characteristics of the cells.

That set of 16 genes plus five reference genes was used to see if breast cancer patients could be sorted into prognostic and predictive groups. When I say “prognostic” I mean to predict the likelihood of recurrence, and when I say “predictive” I mean to predict patients who would benefit from chemotherapy.

So the investigators examined the archival subsets and were able to determine that those 16 genes and five reference genes could be used to sort patients along a continuum they called the recurrence score, which varies from zero to 100. Using simple mathematic regression procedures, that recurrence score could then be translated into a probability of recurrence over 10 years.

The investigators were able to determine that patients who had low recurrence scores — that is, scores lower than 18 — benefited from hormonal therapy but derived no additional benefit from the addition of chemotherapy to their hormonal therapy regimens. Conversely, patients with high recurrence scores — scores of 31 or higher — showed a clear, statistically significant and large benefit when cytotoxic chemotherapy was added to hormonal therapy — that is, tamoxifen.

In the intermediate group, the group with scores between 18 and 30, no benefit was apparent from the addition of chemotherapy, but the confidence intervals — the statistical certainty of no benefit — were not established.

Oncotype DX Assay

DR HUDIS: I find it interesting that these data from Figure 21 demonstrate a more rapid utilization of the Oncotype DX assay by the clinical investigators. In that group, it’s virtually 100 percent, whereas of the practicing oncologists, only three quarters of them are using it in 2007. It surprises me that so many investigators use it because, in their world, there’s a pretty deep understanding of the limitations of the Oncotype data, how it was generated, what the data sets mean and what the limits are on interpreting it.

The TAILORx study is predicated on using Oncotype DX , and it’s accruing well in the community. That makes me wonder, if you ask this question in early 2008, whether it will be a wash between practitioners and clinicians.

Breast Cancer Update 2007 (3)

DR SOONMYUNG PAIK: Two interesting issues were raised by many people regarding the Oncotype DX assay. Our data showed that if patients had HER2 amplification, they were usually categorized as being at high or intermediate risk and none of them were at low risk.

Steve Shak has screened approximately 10,000 patients and has found that some patients have HER2 amplification but are still at low recurrence scores. So he believes they still must be tested, but my bias considering the NSABP-B-14 data is that they don’t need to be tested.

Because of those data, some people are arguing that if you take out the patients with HER2 amplification, then the Oncotype DX assay will not be as strong a prognosticator for patients with HER2-negative disease. We assessed the HER2-negative subset in B-14, and it worked exactly as it did for the overall cohort.

The other issue is that everyone wants to find out whether the Oncotype DX assay can be used for patients with node-positive disease. For that, we are eagerly waiting for Kathy Albain’s SWOG study (SWOG-S8814A-ICSC) to learn whether it is also predictive of benefits of chemotherapy for patients with node-positive disease.

Breast Cancer Update 2007 (4)

DR SANDRA M SWAIN: I now use Oncotype DX for all my patients who have ER-positive, HER2-negative, node-negative breast cancer, and I’ve found that it’s helpful. I also use Oncotype DX for patients with larger tumors. I believe it’s all about the biology and not about the size, particularly.

The other important benefit of Oncotype DX , which was presented at the San Antonio Breast Cancer Symposium, is its reliability in measuring the estrogen receptor. I believe RT-PCR may be the best way to measure the estrogen receptor. We know immunohistochemistry (IHC) is fraught with problems, and I’m uncomfortable when I receive an estrogen receptor assay result from a small laboratory.

Breast Cancer Update 2006 (8)

DR HAROLD J BURSTEIN: I use the Oncotype DX assay in my practice, and I find it is very helpful. Patients understand it, and it resonates with other measures in breast cancer pathology. It gives you a quantitative readout. Patients readily understand that this is an extra piece of information that can help us stratify risk and therefore allow them to make a better-informed choice about chemotherapy.

I believe this will remarkably change the playing field for ER-positive breast cancer. Many of these women will no longer be receiving chemotherapy. They simply won’t need it, based on their prognosis. However, we need to refine that.

The Oncotype DX test was developed with tamoxifen-treated patients who received what many would consider old-fashioned chemotherapy. I believe the principles will be the same, but we want to see studies in the adjuvant setting using aromatase inhibitors, and we want to see studies that use different chemotherapy programs and so on. This approach will also be extended to patients with node-positive disease.

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