The prospective pilot study is small, and the researchers didn’t report on how the patients fared, according to a poster presented at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress. Plus, the test itself hasn’t been analyzed prospectively. But the study’s lead author, Olga Martínez-Sáez, MD, PhD, said in an interview that the 56% number is significant.
“We consider this percentage to be clinically very relevant,” said Dr. Martínez-Sáez, an oncologist at Hospital Clinic of Barcelona and the University of Barcelona. “HER2DX can change practice.”
Also in an interview, Kent Hoskins, MD, associate chief of hematology/oncology at University of Illinois at Chicago, described HER2DX as a next-generation genomic test that builds on assays developed 2 decades ago to help identify patients who would benefit – or not – from adjuvant chemotherapy.
Dr. Hoskins, who isn’t connected to the new study but has studied genomic tests for breast cancer, said the HER2DX test seeks to provide guidance to oncologists about which of several treatments are most effective in treating patients with HER2+ breast cancer.
“The overall trend in the HER2+ space is escalating therapy, and the cure rates have improved quite substantially,” he said. “But do they all need that much therapy? That’s the clinical question that this assay is addressing.”
The assay examines clinical features and the expression of 4 gene signatures, Dr. Martínez-Sáez said. It provides a risk score estimating the likelihood of recurrence plus a score that estimates the likelihood of achieving pathological complete response (pCR) with trastuzumab-based neoadjuvant therapy and an ERBB2 mRNA score.
Inin eBioMedicine, researchers reported that the assay “predicts response following neoadjuvant letrozole in combination with dual HER2 blockade with trastuzumab and pertuzumab in early-stage HER2-positive/hormone receptor–positive breast cancer.”
In the 2022 study, researchers wrote that assay results and other scores “might help better tailor systemic therapy in this context and identify candidates for avoiding chemotherapy, a therapy associated with short- and long-term toxicities and impact in quality of life.”
For the new study, a decision-impact analysis, researchers tracked 89 patients with HER2+ breast cancer (median age = 53 years, range 30-79, and 52% postmenopausal), the poster says. Most had T1-2 tumors (87%), negative nodes (64%), grade 2 (56%) or 3 (41%) tumors, and ductal histology (87%). And most were hormone receptor positive (65%). Seventy-eight percent of patients received neoadjuvant therapy (NAT), and 22% underwent upfront surgery.
In 56% of cases, oncologists changed their treatment decisions after getting the results of the HER2DX assays. In 59% of these cases, oncologists de-escalated therapy; in 41%, they escalated therapy, opting for more intense chemotherapy 65% of the time, according to the poster.
Clinician confidence in their decisions improved in 67% of cases, the researchers reported in their poster. Among 56 patients treated with neoadjuvant therapy who could be evaluated, “HER2DX pCR score was significantly associated with pCR (81% in pCR-medium/high and 32% in pCR-low; odds ratio=9.3, P = 0.001) independently of the rest of variables.”
Dr. Hoskins said the new report suggests that the assay can change treatment decisions, although he cautioned that “this study does not in itself establish its place in standard of care.” Large, prospective, randomized research is still needed, he said.
Dr. Martínez-Sáez said, in an interview, that the HER2DX assay should cost about as much as genomic assays for other breast cancer subtypes. These kinds of tests have cost several thousand dollars each in recent years.
What’s next? The decision impact study is ongoing. As for research into the assay itself, “prospective clinical trials are planned to demonstrate its clinical utility to de-escalate and guide therapy,” Dr. Martínez-Sáez said.
No funding is reported. Reveal Genomics is the developer of the HER2DX assay. Dr. Martinez- Saez reports financial relationships with Novartis, Eisai, Roche, and Reveal Genomics. Other study authors report multiple disclosures. Dr. Hoskins discloses non-financial research support from Agendia, which makes the MammaPrint early-breast-cancer assay.