Transcript:Adam M. Brufsky, MD, PhD: The MINDACT study is an extraordinarily important study for a variety of reasons. We’re doing an incredible job now with the bread and butter breast cancer that we treat. I think that 67% of all breast cancer is ER positive, 0 to 3 nodes positive; usually T2 and below that is 5 cm and below. And, I think MINDACT really has looked at this disease entity and has tried to really, in a prospective manner, figure out how to optimize the therapy.

The idea behind MINDACT is they took probably, I think it’s about 6800 women, mostly in Europe, who had this early-stage breast cancer. It could be ER-positive, HER2-positive, any grade, 0 to 3 nodes positive. And, what they did is that they did a clinical score on them. They did Adjuvant! Online, and if the Adjuvant! Online predicted a 5-year distant metastasis-free survival was less than 92% when you put all the clinical parameters in, you were considered clinically high risk. If, however, the predicted disease-free survival was greater than 92%, you were considered low risk with endocrine therapy.

So, they did a genomic risk test, as well. And for their genomic risk test, they used the test by Agendia, MammaPrint. It’s a 70-gene assay that can differentiate low-risk versus high-risk after 5 years of therapy of distant metastasis. What they did is that if you were low-risk clinically and low-risk genomically, you just got hormone therapy. If you were high-risk clinically and high-risk genomically, you got chemotherapy. And in both of those arms—again, if you had about 6700 patients—both of those arms were about one-third each. One-third of the women, actually maybe 40% of the women, were clinical low/genomic low, they just got hormone therapy. The women who were clinical high/genomic high, were probably about 25% of the patients, and they got chemotherapy.

In the middle, I think, 1700 or 1800 women were randomized to two basic options—they were discordant. That means they were either clinically genomically low risk and clinically high risk, or clinically high risk and genomically low risk. Of the 1700 women, I believe about probably 300 or 400, 500 were clinically low/genomically high and they were separated. But the important ones were the 1500 women, 1400 women, who were clinically high/genomically low—that is, women, clinically, who you would give chemotherapy to in the adjuvant setting. Their risk was high enough to give them chemotherapy. But the test said they didn’t need it.

So, they randomized those women into two groups. Either they got chemotherapy based on the clinical high or hormone therapy alone based on the genomic low. And the idea behind the trial is that if you had a clinically high-risk disease that was genomically low by the genomic assay, your 5-year distant metastasis-free survival should be at least 92% or higher. And, in fact, what they found in that trial, in that group of patients, is that their 5-year distant metastasis-free survival was 95%.

What that suggests is that there is a group of patients, a substantial number of women, who basically have a clinical risk of greater than 8% recurrence at 5 years. Again, their distant metastasis-free survival with endocrine therapy alone in theory, based on clinical risk, was less than 92%. And you could select those women out and not give them chemotherapy based initially on the test in a prospective clinical trial. This is not retrospective. Most of the studies that have all been done have all been retrospective; this is prospective.

And, so, what that means, there’s a couple of things that come out of this. First of all, about 30% to 40% of these women who were clinical low and genomic low don’t even need a test. Because if you’re clinically low, you don’t even need a test. And the women who were clinically low and genomically high, they’re distant metastasis-free survival with endocrine therapy alone was still in the mid-90’s. So, you can take those out.

Now, you take that group of patients that are clinically high and genomically low—another 25%—you take them out. Suddenly, you’ve gone from a time where almost two-thirds of the women would be on chemotherapy to now only maybe one-third. You’ve taken chemotherapy away from probably 30% to 50% of women now. You ordinarily would have given it to them before with a substantially spectacular outcome. We’re talking distant metastasis-free survivals at 5 years, about 93%, 94%, 95%. Clearly, this is, I believe, once this is percolated through the community and through the oncology community, in general, really a practice-changing result.

I think that the real issue is what genomic test to use. In this case, they did use a 70-gene assay; it’s prospectively what’s been confirmed. There are other assays out there. I think that my own bias would be to use an assay that is based on intrinsic subtype, not necessarily ones that have ER (estrogen receptor)/PR (progesterone receptor) and HER2 in them like the 21-gene assay—Genomic Health basically is RT-PCR (reverse transcription polymerase chain reaction) for ER+ (estrogen receptor positive), or HER2 and Ki-67 among a few other things. I think I would look at assays that use the downstream genes going forward, and there are a few of them out there. The other thing is that there clearly now are a group of patients who probably—called low-risk luminal A—really do not derive any benefit from chemotherapy and don’t need the toxicity. I think that is a really big deal, from a prospective trial. The other thing that’s a big deal in this trial is that—for all-comers, all patients, even the ones getting chemotherapy that are high risk—again, with 3 ER nodes or less, even in those women, their 5-year metastasis-free survival’s like 91%, 92%.

So, we’re now in breast cancer, in the most common forms we treat, in the 90s in terms of, not to necessarily being cured of their disease, but basically being free of metastasis at 5 years and hopefully a little bit longer. I think this really is something that is a big deal.

Transcript Edited for Clarity