HER2DX Affected Approximately 50% of Treatment Decisions for HER2+ Breast Cancer

The genomic diagnostic test HER2DX supported treatment adjustments and improved physician confidence (P < .001) when using the assay in patients with stage I to III HER2-positive breast cancer, according to findings from a study conducted in Spain and published in ESMO Real World Data and Digital Oncology.1

Findings from the first prospective real-world investigation assessing the impact of HER2DX results on treatment decision-making in clinical practice revealed that 48.1% (95% CI, 42.5%-53.7%) of patients (n = 297) had treatment adjustments after the HER2DX assay was used by oncologists (n = 34).1,2 The changes included reduced treatment intensity (73.5%), increased treatment intensity (24.5%), and mixed adjustments (2.0%).1 Reductions in treatment intensity encompassed reductions with chemotherapy (56.2%), anti-HER2 therapy (26.7%), and both chemotherapy and anti-HER2 therapy (17.1%), which included avoiding anthracycline-based regimens (40.8%), removing 1 anti-HER2 agent (29.5%), and/or shortening the duration of trastuzumab (Herceptin) therapy (15.2%).

“Conversely, in 24.5% of cases with therapeutic modifications, HER2DX results prompted an increase in therapy intensity,” study authors wrote. “Within these cases, 57.1% involved the addition of another anti-HER2 agent, such as pertuzumab [Perjeta] and/or neratinib [Nerlynx], 20.0% involved more intensive chemotherapy, and 22.9% involved both.”

Further data revealed that the pathologic complete response (pCR) likelihood score was a significant predictor of pCR (P < .001) for patients where pathological data was available at surgery (n = 182).1 Patients with pCR-high disease (n = 69) experienced a pCR rate of 81.5% when given less intensive treatment vs 69.0% among those who received multi-agent chemotherapy (OR = 1.97; P = .256) in the study.

Additionally, the pCR rate was comparable between patients who did not have HER2DX-driven treatment changes (n = 89) and those who did have treatment changes (n = 93; OR, 1.03; 95% CI, 0.57-1.86, P = .912). Investigators also found that independent of hormone receptor status, type of systemic treatment, and clinical stage, the HER2DX pCR likelihood score was significantly associated with pCR (adjusted OR per 10-unit increase, 1.31; 95% CI, 1.12-1.53, P = .001).

Moreover, an estimated total cost savings of €98,031 also occurred as of the September 30, 2024, data cutoff. Cost savings included direct drug costs, vein access devices, and HER2DX costs (the retail price of the HER2DX assay is €2950 per test).

“This study represents a significant step forward in personalized oncology. HER2DX enables physicians to make precision-guided decisions with greater confidence, improving patient care,” Olga Martínez Sáez, MD, PhD, a breast medical oncologist at Clinic Barcelona Comprehensive Cancer Center in Spain and principal investigator of the study, said in a news release.2

Examining HER2DX and the Prospective Study

HER2DX is a laboratory-developed test that has been analytically and clinically validated and provides prognostic information, predictive information, and HER2 expression level data.1 The assay integrates clinical data including tumor stage and nodal status when evaluating 27 genes involved in immune infiltration, luminal differentiation, tumor cell proliferation, and HER2 amplicon expression.

The observational study was conducted between November 2021 and September 2024 across 12 hospitals in Spain. It included patients with newly diagnosed stage I to III HER2-positive breast cancer at the time of diagnosis or following primary surgery. The primary end point was the effect of the HER2DX assay on therapeutic decision-making. Secondary objectives included test turnaround time, association between pCR likelihood score and actual pCR rates, changes in physician confidence before and after receiving the assay report, and cost analysis.

Additionally, no physicians who used the test in the study had prior experience with it and before receiving the test’s results, they completed a questionnaire on their initial treatment plan and level of confidence on the proposed approach. Physicians then completed an identical follow-up questionnaire after HER2DX’s results became available.

The median turnaround time for the HER2DX test was 7 working days (range, 3-19) and this was defined as the time from sample receipt at the central laboratory to report release. According to the HER2DX assay relapse risk score, patients had low-risk (52.5%) and high-risk (47.5%) breast cancer. Additionally, per the pCR likelihood score, patients had pCR-low (36.7%), pCR-medium (28.6%), and pCR-high (34.7%) disease, and per the HER2 mRNA score, HER2 status was low (10.4%), medium (18.9%), and high (70.7%).

Patients included in the study were a median age of 54 years (range, 28-90) and most had ductal histology (91.2%), hormone receptor–positive disease (61.3%), and a HER2 immunohistochemistry score of 3+ (80.2%). Additionally, patients were postmenopausal (60.7%), had a median Ki67 score of 35 (range, 2-95), and had received adjuvant (22.2%) or neoadjuvant (77.8%) treatment. Disease stages included I (28.0%), II (56.2%), and III (15.8%) and grades of disease were 1 (7.8%), 2 (56.9%), and 3 (35.3%). Furthermore, patients had T1 (42.1%), T2 (43.1%), T3 (10.4%), and T4 (4.4%) and N0 (60.0%), N1 (32.3%), N2 (6.7%), and N3 (1.0%) breast cancer.

What’s Next With HER2DX?

Next steps with the assay include ongoing research with a cost-effectiveness analysis in the prospective DEFINITIVE trial (NCT06446882) and prospective validation of the test in the DEFINITIVE and CompassHER2 pCR (EA1181, NCT04266249) trials.

“The HER2DX genomic assay provides precise information to guide critical treatment decisions through 3 key scores offering a more comprehensive understanding of each patient’s prognosis and response potential, helping clinicians navigate the complexities of personalized treatment strategies,” the study authors wrote. “Overall, this dual capability to adjust treatment intensity highlights the value of HER2DX in providing an unbiased, evidence-based assessment of patient risk profiles. By tailoring treatment strategies to individual risk and across different settings, HER2DX supports more personalized and effective clinical decision-making, potentially improving long-term survival outcomes and reducing the overall burden of managing recurrent disease.”

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. Biospace. March 10, 2025. Accessed March 11, 2025. https://www.biospace.com/press-releases/groundbreaking-study-confirms-clinical-decision-impact-of-her2dx-genomic-assay-in-early-stage-her2-positive-breast-cancer