DCISionRT Biosignature Identifies Residual Recurrence Risk in HER2(3+) Breast Cancer

Frank Vicini, MD

The 7-gene biosignature DCISionRT successfully identified a subset of patients with HER2(3+)-positive breast cancer who could not be identified via traditional clinicopathologic factors and were at elevated risk of having residual disease following treatment with breast-conserving surgery plus radiotherapy, according to study findings that were published in Clinical Breast Cancer.¹

Sixty-three percent of patients with HER2(3+)-positive DCIS (n = 178) had the DCISionRT Residual Risk subtype (n = 113) and had a significantly higher 10-year in-breast recurrence (IBR) rate than those without the Residual Risk subtype (n = 65), at 16.2% (95% CI, 9.7%-26.5%) vs 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).

“The identification of this residual risk subtype opens new avenues for tailored treatments,” Frank Vicini, MD, of Michigan Healthcare Professionals in Farmington Hills, stated in a news release.² “It particularly highlights the possible benefit of trastuzumab [Herceptin] in this subset of patients, as we’ve been investigating in the [phase 3] NSABP-B43 trial [NCT00769379]. These results could significantly impact how we approach treatment for [patients with] HER2-positive ductal carcinoma in situ [DCIS] moving forward.”

Investigators selected 178 patients with HER2(3+) DCIS who received breast-conserving surgery with radiotherapy from a combined multinational patient cohort (n = 926) treated with breast-conserving surgery with or without radiotherapy and with or without endocrine therapy.¹ Treatment decisions were not randomized or rules based. Patients were excluded if they had a history of breast cancer or a simultaneous invasive breast cancer. Patients were deemed evaluable if they had undergone breast-conserving surgery with negative margins and had complete biomarker data. HER2(3+) disease was defined as those with HER2(3+) expression by immunohistochemistry per CAP/ASCO guidelines adapted to DCIS.

The trial’s primary objective was to test the hypothesis that among the patients with HER2(3+) DCIS who received breast-conserving surgery plus radiotherapy, those with the Residual Risk subtype would have higher total IBR rates vs those who did not have the Residual Risk subtype.

All patients underwent biosignature testing and were stratified into 2 previously defined groups. Group 1 combined the Low Risk group (n = 28), which consisted of patients with a DS of 2.8 or lower, and the Elevated Risk group (n = 37), which consisted of patients with a DS higher than 2.8. All patients in group 1 did not have the Residual Risk subtype; group 2 consisted of patients with the Residual Risk subtype.

Regarding baseline characteristics, the Residual Risk subtype cohort had a higher proportion of patients with nuclear grade 3 disease than the cohort without Residual Risk subtype, at 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. The Residual Risk subtype was uniquely associated with IBR rate on multivariate analysis (HR, 7.9; 95% CI, 1.0-63; P = .05) after accounting for age (P = .07), size (P = .17), and grade (P = .98), which were not significantly associated with IBR.

The total IBR rates were composed of DCIS and invasive breast cancer recurrences. However, 6 of the 14 recurrences in the Residual Risk subtype were classified as invasive breast cancer recurrences, whereas no invasive breast cancer recurrences were observed among patients without the Residual Risk subtype.

“We’re very encouraged by the latest publication,” Dan Forche, president and chief executive officer of PreludeDx, added in the news release.² “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.”

References

1. Vicini F, Shah C, Mittal K, et al. A 7-gene biosignature for ductal carcinoma in situ of the breast identifies subpopulations of HER2-positive patients with distinct recurrence rates after breast-conserving surgery and radiation therapy. Clin Breast Cancer. 2024:S1526-8209(24)00227-1. doi:10.1016/j.clbc.2024.08.016
2. PreludeDX announces groundbreaking study results on HER2-positive DCIS patients. News release. PreludeDx. October 2, 2024. Accessed October 2, 2024. https://preludedx.com/wp-content/uploads/2024/10/PreludeDx-Announces-Groundbreaking-Study-Results-on-HER2.pdf