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Multigene test predicted DCIS recurrence risk after breast-conserving surgery
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SAN ANTONIO — A 12-gene test accurately predicted the risk for recurrence of ductal carcinoma in situ among women who had undergone breast-conserving surgery, according to study results presented at the San Antonio Breast Cancer Symposium.
“Guidelines recommend that breast-conserving surgery alone may be an option for individuals at low risk for recurrence,” Eileen Rakovitch, MD, radiation oncologist at Sunnybrook Health Sciences Centre and adjunct scientist at the Institute for Clinical Evaluative Sciences of the University of Toronto, said during a press conference. “The challenge is that currently clinical factors and the pathologic features of [ductal carcinoma in situ (DCIS)] do not help clinicians reliably identify individuals at low risk for recurrence. So some women who are at low risk are over-treated, while those at higher risk may not be receiving helpful treatment. Biomarkers are needed to improve risk assessment and management of DCIS.”
The test (Oncotype DX DCIS Score, Genomic Health Inc.) calculates risk on the presence of 12 genes, which included proliferation genes such as
Rakovitch and colleagues previously demonstrated the utility of the DCIS score in a cohort of women who were selected for a nuclear grade 1 or 2 with tumors ˂2.5 cm or a nuclear grade 3 with tumors ˂1 cm with clear margins of at least 3 mm.
Those defined as having a low risk for recurrence demonstrated a 10-year risk for recurrence of 10.6% (95% CI, 6.9-16.2), whereas those classified as high risk demonstrated a risk of 25.9% (95% CI, 14.8-43.1).
In the current analysis, researchers sought to confirm the accuracy of the assay in a cohort of diverse and unselected women with DCIS.
Researchers calculated the DCIS score of 517 patients who underwent breast-conserving surgery alone and who had negative resection margins. Overall, 355 were classified as low risk, 95 were classified as intermediate risk and 121 were classified as high risk.
Median follow-up was 9.4 years.
One hundred patients developed disease recurrence in the same breast; of these cases, 44 were DCIS and 56 were invasive.
Overall, researchers found a 50-point increase in the test score was associated with a two-fold increase in risk for recurrence.
Results showed 10-year recurrence risks were 12.7% (95% CI, 9.5-16.9) among women classified as low risk; 33% (95% CI, 23.6-44.8) for those classified as intermediate risk; and 27.8% (95% CI, 20-37.8) for those classified as high risk.
The test also accurately established risks for invasive local recurrence and DCIS local recurrence. Patients with a low DCIS score had an 8% (95% CI, 5.5-11.5) 10-year risk for invasive local recurrence and a 5.4% (95% CI, 3.4-8.6) 10-year risk for DCIS local recurrence. Patients with a high DCIS score had a 15.5% (95% CI, 9.3-25.1) 10-year risk for invasive local recurrence and a 13.7% (95% CI, 8.5-21.8) 10-year risk for DCIS local recurrence.
“This is the first multigene biomarker assay in DCIS that can provide individualized estimates of the risk of recurrence in women who are treated by breast-conserving surgery alone,” Rakovitch said. “This can help clinicians and patients make more informed decisions about their own risks of local recurrence, and better understand the potential benefits of treatment. Hopefully this can lead to improvements of management of DCIS by reducing over-treatment for those at low risk and reducing under-treatment for those at higher risk of recurrence.”
Researchers are currently conducting analyses on the accuracy of the test in the cohort of patients who underwent surgery and irradiation, Rakovitch said.
For more information:
Rakovitch E. Abstract #S5-04. Presented at: San Antonio Breast Cancer Symposium; Dec. 9-13, 2014; San Antonio.
Disclosure: The study was funded in part by Genomic Health Inc. Researchers report research funding from, employment with and stock ownership in Genomic Health Inc.
Perspective
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Leif W. Ellisen, MD, PhD
The assay reported in the Rakovitch study is a test of the ductal carcinoma in situ (DCIS) tumor itself to ask the question: Is this an aggressive tumor or is it not? There are two issues about the results that need further analysis. Number one, do the findings of this test tell us something beyond what we would have learned from the clinical factors alone? We have been treating this disease for many years, and we know many different risk factors for high or low recurrence. How much does this molecular test add to all of the factors we already know are important for understanding recurrence risk?The other point — a note of caution — is that even in the low-risk group, they reported a 12.7% risk for recurrence of either DCIS and/or invasive cancer. Some women as well as physicians would consider that an unacceptably high risk. I’m sure there would be some people who would say this test isn’t that useful, because we would still treat even the lowest-risk group identified in this study with radiotherapy. I’m guessing that they had hoped that they would find a lower low-risk group.
This study was done only in women who didn’t receive radiotherapy after excision, and the majority of women in the United States treated for DCIS do receive radiotherapy. Data like these explain why they do. Even if you identify a “low-risk” population, the recurrence risk is still relatively high — especially because many of these recurrences are invasive cancers and not preinvasive.
Perspective
Back to TopC. Kent Osborne, MD
Patients and physicians are often confused about DCIS because it has the word “cancer” in it. However, many people don’t consider it a cancer; it is a pre-cancerous lesion. There have been several discussions over the past decade about renaming it. Because it has the word cancer in it, we tend to treat it more aggressively when many of these patients probably don’t need any treatment at all. The problem is that we can’t identify those patients. This is one of the first steps to show that we can start backing off on treatment in some of those patients.
Reimbursement agencies will probably [cover this test] because it saves them money. Radiation therapy is expensive, and if you can save patients from having an expensive therapy, and it’s just as good in terms of an ultimate outcome, it’s likely to be reimbursed.
Perspective
Back to TopJohn Robertson, MD
This gives the patient and the doctor more information, but it doesn’t say that you can withdraw treatment. That still has to be proven. It identifies patients who would be at low risk, and then if you are to withdraw radiation therapy, it has to be proven that that actually works. It is helpful for the patient, but the value of the test still has to be proven in clinical practice.Click Here to Manage Email Alerts