Kevin Kalinsky, MD, MS, on the Importance of Gene-Profiling for Early-Stage Breast Cancer

In an interview with Oncology Learning Network, Kevin Kalinsky, MD, MS, Herbert Irving Associate Professor of Medicine, NewYork-Presbyterian Hospital/Columbia University Medical Center, discussed why gene profiling plays such an important role in the management of patients with early-stage breast cancer.



I'm Kevin Kalinsky. I'm a Herbert Irving Associate Professor of Medicine, at Columbia University, Irving Medical Center, NewYork-Presbyterian Hospital.

Gene profiling has become increasingly important in patients with early‑stage breast cancer, in particular, patients with hormone receptor (HR)‑positive and HER2‑negative disease who do not have nodes involved. In particular, this has significant implications in terms of whether or not we would utilize chemotherapy in patients who would be getting anti‑estrogen therapy.

One of the questions that has remained is whether or not this could be extended to patients who have node‑positive breast cancer. There are a number of gene assays that are commercially available, and I'm going to talk about a few of them.

There was enthusiasm of utilizing the 21-gene recurrence score, which is something that we utilize in patients with early‑stage node‑negative breast cancer.

There was a prospective/retrospective study in a SWOG trial—it's SWOG‑8814which demonstrated that in patients who had node‑positive disease the recurrence score may identify who's most likely to benefit from chemotherapy.

As a result, there have been prospective studies that have been performed. One has been reported called the PlanB Study. In this study, part of the design was looking at patients with HR‑positive disease.

If the recurrence score was low, meaning 11 or less, patients who had no nodes, or if they had 1 to 3 lymph nodes involved, would get endocrine therapy alone. These data had been reported, and the 5‑year disease‑free survival was reported in which we saw that, for that small population who had N1 disease, that they seemed to do just as well as those patients who had node‑negative disease.

There have been a number of observational studies which have also looked at the potential role for the 21‑gene assay in those patients who have N1 disease. And, you know, there has been some demonstration that maybe we could identify and utilize this assay based upon those observational studies, as well. I think we're really waiting for the results of RxPONDER, which is large, randomized study of >4000 patients in which, if patients have a recurrence score that's ≤25, they’re randomized to hormone therapy, versus hormone plus chemotherapy. Ultimately, we'll see, I think, this will help define the role of the Oncotype recurrence score in those patients and exactly what the best cutoff will be.

So I mentioned that I talk about other gene assays as well. There is a 70‑gene assay known as MammaPrint. This was studied in a randomized trial called the MINDACT trial.

One of the notable findings in this study is that for those patients who had node‑positive disease that if patients were at high clinical risk and low genomic risk that there didn't seem to be a benefit in terms of the addition of chemotherapy in terms of prevention of distant metastasis‑free survival for those patients who are node‑positive in that scenario. Versus those that were node‑negative, specifically in those patients who had HR‑positive and HER2‑negative disease.

Based upon these data, the American Society of Clinical Oncology guidelines do include this particular platform for those patients who have N1 disease.

There are other platforms that are being utilized right now, and we'll ultimately see which has the best indicator for how patients do in terms of distant recurrence.

Then the last thing that I would mention is that there are other assays that are also looking at “What is the role for extending anti‑estrogen therapy for patients with HR‑positive and HER2‑negative disease?”

So, you know, our standard of care is to give at least 5 years of hormonal therapy to patients with this positive type of breast cancer. And there have been some large studies that have demonstrated that there may be some patients who really benefit from giving extended hormonal therapy, say, up to 10 years.

We use standard pathologic features, like node‑positivity, to help define who that population is, but there are some biologic platforms that are also evaluating this question, as well.

There have been some data utilizing the breast cancer index, which looks at a score of H/I. And this particular assay has been performed in various prospective/retrospective studies. One of the most recent ones was looking at patients in the TransATAC study, which were patients with node‑positive disease.

In this, they could see and help demonstrate that those patients who had a high H/I score seemed to have a higher absolute benefit of extending tamoxifen compared to those who had a low H/I score.

Then I think the other question that's remaining in the field is whether there will be a benefit for CDK4/6 inhibitors. There are a number of studies that are looking at giving this in combination with hormonal therapy and we're awaiting those trials. Of course, it would be extremely helpful to have a biologic predictor for who would benefit from those particular class of drugs.

To summarize, we have data with various genomic platforms about the potential role of the de-escalation of chemotherapy for those with N1 disease, and we're awaiting further important studies, like the RxPONDER trial. There are also platforms that are looking at the role of extending anti‑estrogen therapy, such as the breast cancer index, that one could consider for utilization in patients with N1 disease.

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