This podcast episode is made possible in part by a grant from Lilly.
Welcome to The Breastcancer.org Podcast, the podcast that brings you the latest information on breast cancer research, treatments, side effects, and survivorship issues through expert interviews, as well as personal stories from people affected by breast cancer. Here's your host, Breastcancer.org Senior Editor, Jamie DePolo.
Jamie DePolo: Hello, I’m Jamie DePolo, senior editor at Breastcancer.org. I’m podcasting live from the 2023 San Antonio Breast Cancer Symposium. My guest is Dr. Seema Khan, professor of surgery and the Bluhm Family Professor of Cancer Research at the Feinberg School of Medicine and Lurie Comprehensive Cancer Center at Northwestern University.
At this conference she presented results from E4122 study, which looked at whether skipping radiation after lumpectomy to remove low-risk DCIS affected outcomes. She’s going to discuss the findings with us.
Dr. Khan, welcome to the podcast.
Dr. Seema Khan: Thank you very much. I’m happy to be here.
Jamie DePolo: So, first, for this study how did you decide if the DCIS was low-risk or not?
Dr. Seema Khan: We used a molecular assay called DCIS Score. It’s based on the measurement of gene expression of 12 different genes, a score that was developed based on what, what your audience may know about, the Oncotype DX, which is used for women with invasive cancer to make decisions about chemotherapy use or not.
So, the DCIS Score is derived from the same group of genes, but this one has 12 genes rather than 21, and prior studies have shown that the DCIS Score is able to categorize women with DCIS at being low, at low, intermediate, or high-risk of recurrence within the breast. The prior studies have all been retrospective, but they have been pretty consistent in showing that the DCIS score does predict risk of recurrence.
So, we performed the first prospective study to use DCIS Score to advise women about whether or not radiation would be beneficial for them. And that assessment of benefit is, is basically… so it was a single-arm study, a study I think that’s important to note, and the assessment of risk was simply based on whether the recurrences that happened on the trial matched expectations based on the DCIS Score.
So, the expectations were that women with a low DCIS Score would have a low-risk of recurrence, for women with a high or intermediate DCIS Score, the expectation was that they would have a high-risk of recurrence and that is why they were advised to receive radiation.
By and large, most women followed the advice they were given and what we observed in the high DCIS Score group was that the use of, with the use of radiation, their risk was decreased by a lot.
It was decreased from the expected 10% or 12% at five years to 5% at five years. So, that group of women who had intermediate or high DCIS Scores, they experienced a risk that was far lower than predicted with the use of radiotherapy, and the group who had low DCIS Scores and were advised to avoid radiation, they had low rates of recurrence even without the use of radiation. So, the use of the Score allowed us to advise women about their treatment strategy and the advice seems to have worked out as expected.
Jamie DePolo: Great. I have a couple of questions about whether hormonal therapy, or anti-estrogen therapy, was used, because my understanding is that most DCIS is hormone receptor positive. So, did you look at that or did that play a role at all in this study?
Dr. Seema Khan: So, about 80% of the DCIS lesions were estrogen receptor-positive and those women were advised to use anti-estrogen treatment. In general, in pre-menopausal women, this is tamoxifen and in post-menopausal women it’s an aromatase inhibitor. And of the women in the trial about 60% used, about 67% actually across the whole trial, did use an anti-estrogen.
When we looked at the combined use of anti-estrogen with radiation we found that the women who avoided radiation, because they had a low DCIS Score in the DCIS lesion, they were more likely to accept the anti-estrogen use and so 80% of them used an anti-estrogen in the absence of radiotherapy. So, women who didn’t have radiotherapy were more likely to accept the anti-estrogen.
Women who did receive radiotherapy were less likely to accept the anti-estrogen, even if their DCIS was hormone receptor-positive, so their acceptance rate was about 60%. Twenty percent difference than in women who received radiation and accepted anti-estrogens and women, sorry, women who didn’t receive radiation and accepted anti-estrogens 80%, and women who received radiotherapy and didn’t use anti-estrogens that was 40%. So, there was a difference according to radiotherapy use.
Jamie DePolo: And did any of the women with a low-risk Score who didn’t receive radiation, had hormone receptor-positive disease, choose not to take anti-estrogen therapy? I just wondered if that figured into the results at all.
Dr. Seema Khan: No, we don’t have enough events in the study. So, the women, there were only eight women who received, who experienced a recurrence in the breast. It was a small study. It was a single-arm study. It was a small study, these are some of the limitations. And so, there were only eight women who experienced a recurrence and with that small number we can’t really look into how that, we can’t slice and dice that number any smaller in order to look for these sorts of effects.
Jamie DePolo: Okay. So, it sounds like the study offers promising evidence that the Oncotype DCIS Score can be used to help make radiation decisions. Am I interpreting that correctly? Like, could you put the results in context for us, please?
Dr. Seema Khan: Right. So, for women who have a low DCIS Score, particularly if they’re over 50, that’s the other limitation, because there were only 33 women in the study who were under 50 years of age. So, women who are over 50 and have a low DCIS Score can consider omission, avoidance, of radiation treatment and expect that they will have a low-risk of DCIS recurrence, at least at the five-year time point.
Now, the five-year time point is probably insufficient for a full evaluation of this strategy and we are planning 10-year results as well. At the moment, based on the five-year results, it seems like a reasonable thing to do and it is reassuring for women with low DCIS score to avoid radiation based on that score result.
Jamie DePolo: Dr. Khan, thank you so much.
Dr. Seema Khan: You are very welcome. Thank you.
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