Breast Cancer Update for Surgeons, Issue 1, 2017 (Video Program)Use of the DCIS Score as a tool for identifying risk of BC recurrence and to facilitate decision-making regarding radiation therapy
7:05 minutes.
TRANSCRIPTION:
DR SPARANO: The DCIS Score is a 7-gene signature. It’s driven by 5 proliferation genes, PR and another gene that was developed and then prospectively validated for the first time in the E-5194 cohort. This was women with largely mammographically detected DCIS who had a tumor less than 1 centimeter that was high grade or less than 2.5 centimeters that was intermediate or low grade. They underwent wide excision, and they were followed for recurrence. They did not have radiation. In the midst of the trial, the results of the B-24 trial became available showing a potential benefit from the use of adjuvant tamoxifen in that setting. And the trial was modified, the 5194 trial was modified to allow adjuvant tamoxifen at the discretion of the treating physician. So there were about 650 or so patients enrolled in the trial. The primary results were reported. It was shown that the risk of recurrence of DCIS at 5 and 7 years was in the range of 10% to 15%, so it was higher than what we had hoped it would be. About 30% of the women in the trial received adjuvant tamoxifen. A subset of those women where we had the tissues available, 327, who had clinical characteristics similar to the overall cohort, were evaluated in a prospective retrospective way by applying this 7-gene signature of the DCIS Score. It was found that about 70% of the patients had a low-risk tumor — as prespecified by the DCIS Score. So 70% were low risk, 30% were intermediate or high risk. It turns out that the 10-year risk of an ipsilateral breast event, which was defined as either DCIS or invasive cancer, was about 10% in the 70% of patients who had a low DCIS score and about 25% in the patients who had an intermediate or high DCIS score. So what this tells us is that for patients who have low-risk clinical features, as was in this trial, who are treated with wide excision without radiation who may or may not receive tamoxifen, overall you’ll have somewhere in the range of a 15% to 20% risk of having a breast event at about 10 years. And what the score does is that it allows you to more accurately classify or predict who is going to have an event. If you fall into the 70% of patients who have a low score, you have about a 10% risk of having an event. If you’re in the 30% who have an intermediate or high score, your event rate’s more like 25%. And so that’s a group of patients for whom radiation may — is probably wise. And this is probably not a group of patients who should be spared radiation. Now, for the low-risk group, we know from other studies that no matter what the underlying risk of recurrence is in DCIS, that radiation is going to reduce that risk of recurrence. So this cohort in this trial — and the assay was not designed to identify a group of patients who don’t benefit from radiation. But it does provide prognostic information to select who would be a candidate who would most likely benefit from radiation. And I should say also that the score was validated in a second cohort, a population-based cohort. DR LOVE: And do you utilize this assay in your practice? DR SPARANO: I do utilize the assay in my practice. It’s mainly ordered and used by radiation oncologists to make their decision about the use of radiation. DR LOVE: I’m curious. You get up to 25%, do you think it’s also something that maybe could be considered in a patient who might be thinking about mastectomy? DR SPARANO: The factors that drive a decision that relate to mastectomy, I think, are more driven by the extent of the disease and the surgical considerations and the patient’s fear. Now, having said that, if you have a patient who is a candidate for wide excision, who’s had a wide excision, and they have a DCIS score that’s high and, therefore, is someone who would more likely benefit from radiation, then that patient, if they really don’t want radiation, if they really want to avoid radiation, that patient could use that decision to have a mastectomy. DR LOVE: I was thinking about the fact — I mean, what would your best estimate be if you gave radiation therapy to a patient with a high-risk score, how that would reduce it? How low do you think it would reduce it to? DR SPARANO: On average, if you look at the meta-analysis and all of the studies in their totality, radiation reduces the risk of having an event by about one half. DR LOVE: So that’s what I was thinking. And so you’re saying to this woman, “Okay. We’re going to give you radiation therapy, but you’re still going to have a residual risk on top of that of more than 10%.” It seems like if I were a woman in that situation, it might make me think more about mastectomy for that reason, just not to have to go through that experience. DR SPARANO: I think one of the issues is that the outcomes are really good for patients with DCIS. So obviously we want to be able to adequately treat the patient with as little therapy as possible and to minimize overtreatment and that was really what drove the 5194 trial design, right? We were trying to avoid the use of radiation based on the clinical features, the best available clinical features that we had at the time and that we still have. And what we found was that the event rates were still high, if we spared radiation based on clinical features alone. So I think for those clinicians and for those patients who wished to spare radiation, this can be a useful test that can help them make a more informed decision about what’s the most appropriate choice for that particular situation. |