A biosignature tool helps women avoid unnecessary radiotherapy after undergoing lumpectomy for ductal carcinoma in situ (DCIS) – and also identifies women who need more intense treatment.
The DCISionRT test (PreludeDx) and its response subtype (Rst) biosignature provide personalized risk assessment, explains Frank Vicini, MD, a radiation oncologist at GenesisCare and a member of NRG Oncology, Pontiac, Mich.
He presented data on the test at a poster at the recent American Society of Clinical Oncology Annual Meeting.
They can also identify patients who would likely benefit from radiotherapy, Dr. Vicini reported.
The tool shows promise for identifying those whose cancer is likely to recur despite undergoing postlumpectomy radiotherapy – women who might benefit from intensified or alternate treatment approaches, he added.
The latter finding is particularly provocative because it suggests that the biosignatures “may appropriately identify patients with very radioresistant ductal carcinoma in situ,” Benjamin D. Smith, MD, commented during a poster discussion session at the meeting.
“I think these findings merit validation in translational research models,” said Dr. Smith, a radiation oncologist and professor of radiation oncology and health services research at the University of Texas MD Anderson Cancer Center, Houston.
DCISionRT, Rst, and risk
DCISionRT combines molecular biology innovations with risk-based scores to assess risk for recurrence, which is classified as either low or elevated, according to the test developer, PreludeDx.
Dr. Vicini and colleagues used the test to classify tissue samples from 485 women who were part of previous DCISionRT validation cohorts in Sweden, Australia, and the United States. The patients underwent breast cancer surgery (BCS) with or without radiotherapy between 1996 and 2011.
The Rst biosignature was used to further categorize those in the elevated-risk group as having a good response subtype (good Rst) or a poor response subtype (poor Rst) after BCS plus radiotherapy.
Radiotherapy was associated with significantly reduced recurrence rates among women with elevated risk and a good Rst (the hazard ratios for ipsilateral breast tumor recurrence [IBTR] and invasive breast cancer [IBC] were 0.18 and 0.15, respectively).
No radiotherapy benefit was seen among those with elevated risk and poor Rst.
The investigators also reported that, among patients with a poor Rst, 10-year IBTR and IBC rates were 25% and 16%, respectively, regardless of whether they received radiotherapy. These rates were much higher than the rates among women with good Rst (6.6% and 4.5%; hazard ratio, 3.6 and 4.4, respectively).
No significant difference was seen in 10-year IBTR and IBC rates among patients in the low-risk group, with or without radiotherapy.
Traditional clinicopathologic risk factors, including age younger than 50 years, grade 3 disease, and tumor size greater than 2.5 cm, did not identify poor versus good response subtypes in this cohort, and on multivariable analysis, neither of these factors nor endocrine therapy was significantly associated with IBTR or IBC.
Prospective validation needed
In his discussion, Dr. Smith said that the study provides “important data” that further validate the DCISionRT platform alone for assessing risk among women with DCIS who undergo BCS. But it is the Rst biosignature, which allows clinicians to “predict radioresistance of residual malignant chromogens following lumpectomy plus radiation therapy,” that really stands out, he added.
From the data presented, “it is reasonable to conclude that patients with a poor Rst score treated with lumpectomy and radiation had a much higher risk of in-breast tumor recurrence than one might predict or anticipate based on existing published randomized clinical trial data,” he said.
“In my opinion, it is very important to prospectively validate this finding with other cohorts,” he said. “Moving forward, I think there may come a time where there may be interest in studying radiosensitizing agents for poor-Rst ductal carcinoma in situ that are resistant to standard doses of radiation, and it may be that we consider the Rst as a factor moving forward in selecting patients for BCT versus mastectomy.”
However, because 75% of patients at elevated risk with poor Rst who undergo lumpectomy and radiotherapy do not experience recurrence in the decade following their treatment, it would be “inappropriate and misguided” to start recommending mastectomy for patients at DCISionRT elevated risk who have poor Rst, he said.
The study was funded by PreludeDx. Dr. Vicini reported employment with 21st Century Oncology and financial relationships with ImpediMed, Prelude Therapeutics, and Concure Oncology. Dr. Smith, through his employer, has an equity interest in Oncora Medical through a partnership agreement. He also has an uncompensated relationship with the American Society for Radiation Oncology.
A version of this article first appeared on Medscape.com.