KEY TAKEAWAYS
- The study evaluated the ability of HER2DX to predict the efficacy of a de-escalated, chemotherapy-free neoadjuvant regimen in HER2-positive/hormone receptor-positive breast cancer.
- The primary aim was to test the ability of HER2DX risk-score, HER2DX pCR score, and HER2DX ERBB2 mRNA score to predict pathological complete response (pCR) in patients with endocrine therapy sensitive disease (ESD).
- HER2DX pCR score and HER2DX ERBB2 mRNA score were significantly associated with pCR in patients with ESD.
- The pCR rate in low, medium, and high HER2DX pCR score groups was 7.7%, 46.2%, and 100.0%, respectively.
- HER2DX 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.
Based on clinical characteristics and the expression of 4 gene signatures (immune, proliferation, luminal differentiation, and HER2 amplicon), including ERBB2 mRNA levels, HER2DX is a prognostic and predictive assay in early-stage HER2-positive breast cancer. To this end, we analyzed how well HER2DX predicted response to a reduced, chemotherapy-free neoadjuvant regimen in HER2-positive, hormone receptor-positive breast cancer.
Tumour samples were taken from postmenopausal individuals enrolled in the PerELISA phase II research who were found to have operable HER2-positive/hormone receptor-positive breast cancer were used to test the performance of HER2DX prior to therapy. After a 2-week course of letrozole, patients had another biopsy performed to assess Ki67 expression. Letrozole and 5 cycles of trastuzumab and pertuzumab were maintained for patients with endocrine treatment sensitive disease (ESD; defined as >20.0% Ki67 relative decrease at week 2). Pathological complete response (pCR) was the primary endpoint, and the effectiveness of the HER2DX risk-score, HER2DX pCR score, and HER2DX ERBB2 mRNA score (as continuous variables and group categories) to predict pCR was investigated.
The correlations between HER2DX scores and pCR and ESD were analyzed using logistic regression and receiver…operator curve (ROC) analysis. Around 45 of 55 patients (86.0%) participating in PerELISA tested for HER2DX were found to have ESD. Patients with ESD had a pCR rate of 22.5% (9/40). In this cohort, the HER2DX pCR score and the HER2DX ERBB2 mRNA score were substantially linked with pCR
(p=0.008 and p=0.003, univariate logistic regression model; area under ROC [AUC].ß=.ß0.803 and 0.896, respectively). Seven percent (2/26) of patients with a low HER2DX pCR score achieved remission, while 46.2% (6/13) of patients with a medium score achieved remission, and 100% (1/1) of patients with a high score achieved remission.
Rates of pathologic complete response (pCR) were from 0% in the low HER2DX ERBB2 score group to 7.7% in the middle score group to 53.3% in the high score group. Furthermore, the Ki-67 response after 2 weeks of letrozole was substantially correlated with the HER2DX pCR score (p=0.0002, univariate logistic regression model; AUC=.0775). In the low HER2DX pCR score group (26/29), the rate of ESD was 89.7%; in the medium HER2DX pCR score group (13/20); and in the high HER2DX pCR score group (16.7%) (1/6). In HER2+/HR+ early-stage breast cancer, HER2DX predicts response to neoadjuvant letrozole in conjunction with dual HER2 blockade with trastuzumab and pertuzumab.
Source: https://pubmed.ncbi.nlm.nih.gov/36374768/
Clinical trial: https://clinicaltrials.gov/ct2/show/NCT02411344
Guarneri, V., Brasó-Maristany, F., Dieci, M.V., Griguolo, G., Paré, L., Marín-Aguilera, M., Miglietta, F., Bottosso, M., Giorgi, C.A., Blasco, P., Castillo, O., Galván, P., Vivancos, A., Villagrasa, P., Parker, J.S., Perou, C.M., Conte, P. and Prat, A. (2022). HER2DX genomic test in HER2-positive/hormone receptor-positive breast cancer treated with neoadjuvant trastuzumab and pertuzumab: A correlative analysis from the PerELISA trial. eBioMedicine, 85, p.104320. doi:https://doi.org/10.1016/j.ebiom.2022.104320.
