Genomic Assay Yields Strong Predictive Accuracy in HER2+ Breast Cancer

The test led to a modification in treatment plan for 48.1% of those with stage I to III HER2-positive breast cancer, 73.5% of which were reductions.

HER2DX®, a genomic diagnostic test, helped identify patients with early-stage HER2-positive breast cancer with a higher likelihood of achieving a pathological complete response (pCR), according to data from a prospective real-world study published in ESMO Real World Data and Digital Oncology.1

Findings showed that among 297 patients with HER2-positive breast cancer, 143 (48.1%; 95% CI, 42.5%-53.7%) experienced modifications in treatment based on HER2DX results. Furthermore, among the cases resulting in treatment modification, 73.5% involved reduced treatment intensity, including 56.2% with a reduction in chemotherapy intensity, 26.7% with a reduction in anti-HER2 therapy, and 17.1% experiencing reductions in both.

Additionally, the HER2DX pCR likelihood score was significantly associated with pCR, with an adjusted odds ratio (OR) per 10-unit increase of 1.31 (95% CI, 1.12-1.53; P = .001). The pCR rate between those with (n = 93) or without HER2DX-driven treatment changes (n = 89) were comparable: 57.0% (95% CI, 46.3%-67.2%) vs 56.2% (95% CI, 45.3%-66.7%), resulting in an OR of 1.03 (95% CI, 0.57-1.86; P = .912).

Furthermore, among 69 patients classified as HER2DX pCR-high, 39.1% received a 3-month regimen of paclitaxel, trastuzumab (Herceptin), and pertuzumab (Perjeta). This population achieved a comparable pCR rate to patients treated with multi-agent anthracycline- or carboplatin/taxane-based chemotherapy, trastuzumab, and pertuzumab: 81.5% (95% CI, 61.9%-93.7%) vs 69.0% (95% CI, 52.9%-82.4%), eliciting an OR of 1.97 (95% CI, 0.61-6.36; P = .256).

“[T]he HER2DX genomic assay has the potential to become an important tool in the personalized management of early-stage HER2–positive breast cancer guiding treatment intensity adjustments, enhancing physician confidence, and potentially reducing health care costs,” principal study investigator Olga Martinez Sáez, MD, breast medical oncologist at Clinic Barcelona Comprehensive Cancer Center, wrote in the publication with study coauthors.1 “Notably, this study is the first to prospectively demonstrate the feasibility of incorporating the HER2DX pCR likelihood score in selecting patients for a 3-month therapy regimen with single-agent taxane-based chemotherapy, showing that those identified for less intensive treatment achieve comparable pCR rates to patients receiving more intensive regimens.”

The observational, prospective real-world study was conducted from November 2021 to September 2024 and enrolled patients with early-stage HER2-positive breast cancer to evaluate the impact of HER2DX on clinical decision-making. Study responses were based on clinicians’ reported treatment intentions from questionnaires. Additionally, physician confidence in therapeutic decision-making was measured using a 5-point Likert scale, and questionnaire responses were analyzed to identify drug changes resulting from therapy modifications.

Patients enrolled on the study had a median age of 54 years (range, 28-90). Most patients had ductal histology (91.2%), were postmenopausal (60.7%), and had stage II disease (56.2%). Additionally, 40.0% of patients had nodal involvement, and 80.2% had IHC HER2 3+.

The primary end point of the study was the evaluation of HER2DX on clinical decision-making. Secondary end points included test turnaround time, association between pCR likelihood and actual pCR rates, changes in physician confidence, and a cost analysis.

Data from the cost-savings analysis revealed that despite the cost of the test (€2950), net savings for patients following HER2DX testing was €98,031.4 euros across 302 patients treated for HER2-positive breast cancer. Additionally, the median physician confidence score increased significantly, from 4 (IQR, 3-5) to 5 (IQR, 4-5) on a 5-point scale following use of HER2DX (P <.001).

“This study represents a significant step forward in personalized oncology. HER2DX enables physicians to make precision-guided decisions with greater confidence, improving patient care,” Sáez stated in a press release on these findings.2

References

1. Martínez-Sáez O, Tapia M, Marín-Aguilera M, et al. Clinical decision impact of HER2DX, an algorithm-powered genomic diagnostic in early-stage HER2-positive breast cancer: results from a prospective real-world study. ESMO Real World Data and Digital Oncology. 2025;8:100123. doi:10.1016/j.esmorw.2025.100123
2. Groundbreaking study confirms clinical decision impact of HER2DX® genomic assay in early-stage HER2-positive breast cancer. News release. Reveal Genomics. March 10, 2025. Accessed March 11, 2025. https://tinyurl.com/9zc6jzst