Biosignature Test May Predict Residual Risk Post-BCS/RT in HER2+ DCIS

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Use of DCISionRT may open new options for tailored treatments among patients with HER2-positive ductal carcinoma in situ.

Use of DCISionRT may open new options for tailored treatments among patients with HER2-positive ductal carcinoma in situ.

Use of DCISionRT may open new options for tailored treatments among patients with HER2-positive ductal carcinoma in situ.

The 7-gene biosignature test DCISionRT may help identify a subset of patients with an increased risk of in-breast recurrence (IBR) following breast-conserving surgery (BCS) and radiotherapy for HER2-positive ductal carcinoma in situ (DCIS), according to findings from a study published in Clinical Breast Cancer.1

Of 178 patients who underwent treatment with BCS plus radiotherapy, the test identified 113 (63%) as having residual risk subtype (RRt) disease, 28 as having low-risk disease, and 37 as having elevated-risk disease. Overall, the total IBR risk was significantly higher for patients with RRt disease compared with all other subtypes (HR, 8.3; 95% CI, 1.1-50.0; P = .01). At 10 years, the IBR rates were 16.2% (95% CI, 9.7%-26.5%) in the RRt subgroup compared with 1.6% (95% CI, 0.2%-10.9%) for all other patients with HER2-positive disease.

Based on univariate analysis, factors such as tumor size (P = .16), grade (P = .42), or age (P = .09) did not significantly correlate with IBR. Per multivariate analysis, however, the RRt subtype uniquely correlated with IBR rate (HR, 7.9; 95% CI, 1.0-63.0; P = .05) when adjusting for size (P = .17), grade (P = .98), and age (P = .07), which did not have a significant association with IBR.

“The identification of this residual risk subtype opens new avenues for tailored treatments. It particularly highlights the possible benefit of trastuzumab [Herceptin] in this subset of patients, as we've been investigating in the NSABP-B43 trial [NCT00769379],” lead study author Frank Vicini, MD, a radiation oncologist of Michigan Healthcare Professionals, stated in a press release on these data.2 “These results could significantly impact how we approach treatment for [patients with] HER2-positive DCIS moving forward.”

Developers designed DCISionRT to provide a personalized recurrence risk and elucidate pathologic risk factors in patients with DCIS by combining molecular biology with risk-based assessment scores. The assay generates a Decision Score that may help identify low or elevated risks among patients. Compared with other tests, DCISionRT employs protein expression from 7 biomarkers and 4 clinicopathologic factors with a non-linear algorithm that adjusts for interactions across several individual factors to more accurately interpret complex biological information.

The study included patients with HER2-positive DCIS who received BCS plus radiotherapy and were selected from a combined international cohort. The primary end point was testing the hypothesis that patients identified as having the RRt subtype would experience a higher likelihood of IBR compared with those who do not have the RRt subtype. Investigators calculated IBR curves by using Kaplan-Meier analysis.

Regarding clinicopathologic factors in the RRt subtype group and non-RRt subtype group, investigators reported no significant differences in age or size. There was a comparable proportion of patients who were younger than 50 years and those who were 50 years or younger who were classified as having the RRt subtype (P = .15).

Data also showed similar rates of patients who had lesions of 1 cm or smaller or larger than 1 cm among those classified as having the RRt subtype (P = .44). Investigators reported that a higher proportion of those in the RRt subtype group had high nuclear grade compared with low or intermediate nuclear grade (P <.001).

“We're very encouraged by the latest publication. 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,” Dan Forche, president and chief executive officer at PreludeDx, the developer of DCISionRT, concluded.2

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. Clinical Breast Cancer. Published September 4, 2024. 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://tinyurl.com/43m545uw
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