KEY TAKEAWAYS
- The phase II study explored the utility of the HER2DX risk-score in contexts beyond pCR in HER2+ BC.
- The HER2DX risk-score, assessed from initial pre-treatment biopsies, offered additional prognostic insights beyond pCR for early-stage HER2+ breast cancer patients undergoing anti-HER2 therapies.
The validity of the HER2DX genomic test’s risk-score was initially confirmed in a separate dataset of 268 individuals diagnosed with early-stage HER2+ breast cancer who underwent treatment involving both neoadjuvant and adjuvant anti-HER2 therapies (published in EBioMedicine 2022). This updated survival analysis extended the follow-up period and specifically explored the utility of the HER2DX risk-score in contexts beyond pathological complete response (pCR).
To independently validate the standardized HER2DX risk-score, researchers used a dataset of 268 patients (pts) with early-stage HER2+ breast cancer, gathered from three different neoadjuvant studies. This dataset included 147 pts from Hospital Clinic, 84 from the PAMELA trial, and 37 from Padova University’s cohort.
All pts underwent chemotherapy and one year of trastuzumab treatment; 56% received dual HER2 blockade; and 9% with remaining disease were treated with adjuvant T-DM1. Hazard ratios (HRs) estimating the relationship between HER2DX and disease-free survival (DFS) were calculated using the Kaplan-Meier method and stratified Cox models.
With a median follow-up time of 73.2 months (compared to 52.7 months in the previous report), researchers found a significant correlation between the continuous HER2DX score and both DFS (HR=1.97, p=0.003) and overall survival (HR=2.23, p=0.009). Based on a predetermined cut-off, the low-risk HER2DX group demonstrated longer DFS than the high-risk group (7-year DFS was 94.6% vs. 77.5%; HR=0.4, p=0.002). The HER2DX risk-score remained a significant predictor of DFS, irrespective of pCR and hormone receptor status.
Among pts who achieved a pCR (n=118), low-risk HER2DX individuals had longer DFS than high-risk ones (5-year DFS was 96.5% vs. 88.4%; HR=0.33, p=0.178). For pts without a pCR (n=148), the low-risk group also showed longer DFS (5-year DFS was 95.6% vs. 85.3%; HR=0.20, p=0.004), and the risk-score was significantly linked with DFS, regardless of hormone receptor and adjuvant T-DM1 status.
The HER2DX risk-score, assessed in pre-treatment core biopsies, offered valuable prognostic insights beyond just pCR status for those with early-stage HER2+ breast cancer undergoing both neoadjuvant and adjuvant anti-HER2 therapies.
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT02411344
Saez, O.M., Brasó-Maristany, F., Griguolo, G., Pare Brunet, L., Dieci, M.V., Cortes, J., Cussac, A.L., Villacampa, G., Marín-Aguilera, M., Rey, M., Goberna, G., Munoz, M., Vivancos, A., Gonzalez, P.V., Parker, J., Conte, P.F., Prat, A., Pascual, T., Guarneri, V. 5P – HER2DX risk-score in HER2-positive (HER2+) breast cancer following neoadjuvant and adjuvant anti-HER2-based treatment: an updated survival analysis. Annals of Oncology (2023) 8 (1suppl_4): 101218-101218. 10.1016/esmoop/esmoop101218.
