A novel 7-gene biosignature, DCISionRT, has been shown to successfully identify a subset of patients with HER2(3+)-positive ductal carcinoma in situ (DCIS) who are at an elevated risk of residual disease following breast-conserving surgery and radiotherapy. The study, published in Clinical Breast Cancer, highlights the potential for tailored treatments in this patient population.
Identifying Residual Risk in HER2+ DCIS
Researchers analyzed data from 178 patients with HER2(3+) DCIS who underwent breast-conserving surgery with radiotherapy. The DCISionRT biosignature stratified patients into those with and without the Residual Risk subtype. Sixty-three percent of patients (n = 113) had the DCISionRT Residual Risk subtype, while the remaining 65 patients did not.
The primary objective of the trial was to determine if patients with the Residual Risk subtype had higher total in-breast recurrence (IBR) rates compared to those without the subtype.
Elevated Recurrence Rates
The study revealed that patients with the Residual Risk subtype had a significantly higher 10-year IBR rate of 16.2% (95% CI, 9.7%-26.5%) compared to those without the subtype, who had an IBR rate of only 1.6% (95% CI, 0.2%-10.9%; P = .012). The total IBR rate among patients with the Residual Risk subtype was significantly higher than all other HER2(3+) patients (HR, 8.3; 95% CI, 1.1-50).
Implications for Treatment
"The identification of this residual risk subtype opens new avenues for tailored treatments," said Frank Vicini, MD, of Michigan Healthcare Professionals. He further noted the potential benefit of trastuzumab in this subset of patients, as being investigated in the NSABP-B43 trial (NCT00769379). These results could significantly impact how clinicians approach treatment for patients with HER2-positive DCIS moving forward.
Biosignature and Clinicopathological Factors
Notably, the Residual Risk subtype cohort had a higher proportion of patients with nuclear grade 3 disease compared to the cohort without the Residual Risk subtype (87% vs 63%, P < .001). However, age (P = .09), lesion size (P = .16), and nuclear grade (P = .42) were not significantly associated with IBR rate per univariate analysis. Multivariate analysis showed that the Residual Risk subtype was uniquely associated with IBR rate (HR, 7.9; 95% CI, 1.0-63; P = .05) after accounting for age, size, and grade.
Composition of Recurrences
The total IBR rates included both DCIS and invasive breast cancer recurrences. Six of the 14 recurrences in the Residual Risk subtype were classified as invasive breast cancer recurrences, while no invasive breast cancer recurrences were observed among patients without the Residual Risk subtype.
PreludeDx's Perspective
"We’re very encouraged by the latest publication," said Dan Forche, president and chief executive officer of PreludeDx. "This study represents a significant opportunity to bring companion diagnostics and targeted treatment into the area of DCIS, marking a pivotal step in PreludeDx’s commitment to advancing personalized medicine in breast cancer treatment."
