HER2DX Test Transforms Treatment Decisions in HER2+ Breast Cancer
A real-world study showed HER2DX guided treatment changes in approximately 48% of HER2-positive breast cancer cases.
Breast cancer cells: © LASZLO- stock.adobe.com
The significant clinical utility of the HER2DX genomic assay in guiding treatment decisions for patients with stage I-III HER2-positive breast cancer has been shown in a prospective real-world study published in ESMO Real World Data and Digital Oncology.1
The study, led by Olga Martínez-Sáez, MD, PhD, Juan Miguel Cejalvo, MD, and Antonio Llombart-Cussac, MD, PhD, evaluated 297 patients across 12 hospitals in Spain from November 2021 to September 2024, and found that HER2DX led to treatment modifications in 48.1% of cases, with 75.5% of these changes involving a reduction in treatment intensity—such as less chemotherapy or anti-HER2 therapy—without compromising outcomes.
HER2DX influenced treatment decisions in nearly half of the cases, with most adjustments reducing treatment intensity. For the primary end point of assessing changes in therapeutic modifications following HER2DX testing, data showed that 56.2% of these adjustments involved reducing chemotherapy, 26.7% involved reducing anti-HER2 therapy, and 17.1% involved reductions in both.
The genomic assay also accurately predicted the likelihood of achieving a pathologic complete response (pCR), with the pCR likelihood score significantly associated with pCR rates (P <.001). Notably, patients with pCR-high disease achieved similar pCR rates with less intensive treatment compared with multi-agent chemotherapy (81.5% vs 69.0%; P =.256).
“This study represents a significant step forward in personalized oncology. HER2DX enables physicians to make precision-guided decisions with greater confidence, improving patient care,” said Martínez-Sáez, breast medical oncologist at Clinic Barcelona Comprehensive Cancer Center and principal investigator of the study, in a press release.1
“These results confirm that HER2DX provides valuable information that can refine treatment strategies, allowing for more personalized care while maintaining excellent outcomes,” Cejalvo, breast medical oncologist at Hospital Clínico Universitario de Valencia/INCLIVA, and co-principal investigator of the study, added in the press release.
Looking at the assay's economic and clinical benefits, the test improved physician confidence in treatment decisions (P <.001) and resulted in an estimated total cost savings of €98,031, factoring in drug costs, vein access devices, and HER2DX testing expenses. Overall, this study highlights potential cost savings with the use of the HER2DX test.
Notably, this is the first study to prospectively show the feasibility of including the HER2DX pCR likelihood score when selecting patients for a 3-month therapy regimen with single-agent taxane-based chemotherapy. The results demonstrate that those identified for less intensive treatment have pCR rates that are comparable to patients being treated with more intensive regimens.2
“The capacity to forecast a patient's therapeutic response prior to treatment initiation allows oncologists to adjust treatment intensity appropriately, effectively reducing unnecessary toxicity and healthcare costs,” said Llombart-Cussac, head of the medical oncology department at Hospital Arnau de Vilanova in Valencia, and investigator of the study, in the press release.1
HER2DX Study Background
The observational, prospective, multicenter study sought to assess the impact of HER2DX on clinical decision making for patients with early-stage HER2-positive breast cancer. Patients with newly diagnosed stage I-III HER2-positive breast cancer, either at the time of diagnosis or after primary surgery, were eligible for enrollment.2
The primary end point was to evaluate the impact of the HER2DX genomic assay on therapeutic decision-making, and secondary end points were to examine the turnaround time of the test, the association between the pCR likelihood score and actual pCR rates, and changes in physician confidence both before and after receiving the HER2DX report. Additionally, investigators carried out a cost analysis that included the cost of the test, direct drug expenses, and vein access devices.
As of the data cutoff date of September 30, 2024, 304 patients with stage I-III HER2-positive breast cancer were recruited for the study. In 7 cases (2.3%), an HER2DX ERBB2-low score classification led to tumor reclassification as HER2-negative by immunohistochemistry. Those patients were excluded from the analysis.
For the remaining 297 patients with early-stage HER2-positive breast cancer, the median age was 54 years (range, 28-90 years). Most patients had stage II disease (54.2%), 40% had nodal involvement, and 61.3% of tumors were hormone receptor–positive.
About the HER2DX Test
HER2DX, developed by REVEAL GENOMICS, is the first diagnostic test specifically designed for patients with HER2-positive breast cancer. The test integrates clinical data, like tumor size and nodal status, with genomic information, like immune response, luminal differentiation, tumor cell proliferation, and ERBB2 gene expression.
The genomic assay predicts 3 key scores, including the risk of relapse score, which predicts recurrence risk in patients with early-stage HER2-positive breast cancer, the pCR likelihood score, which estimates the likelihood of achieving pCR with anti-HER2-based treatment, and the ERBB2 score, which quantifies ERBB2 mRNA expression across HER2-negative, HER2-low, and HER2-positive breast cancer.
To fully establish HER2DX's role in the evolving treatment landscape for HER2-positive breast cancer, additional research, including long-term follow-up studies and detailed cost-effectiveness analyses, will be critical.
REFERENCES:
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 10, 2025. https://tinyurl.com/rfkzhzfy
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 Open. 2025;8(Suppl):100123. doi:10.1016/j.esmorw.2025.100123
