In a ground-breaking study published today in JAMA Oncology, researchers shed light on the complex landscape of ERBB2/HER2-positive breast cancer treatment, offering crucial insights into personalised therapy approaches.
ERBB2/HER2-positive breast cancer, which constitutes 20% of all breast tumours, has historically posed significant challenges in treatment. However, recent advancements in ERBB2/HER2-targeting drugs have dramatically improved patient outcomes. Notably, neoadjuvant treatment, which involves administering therapy before surgery, has emerged as the standard of care due to its benefits in downstaging tumours and tailoring subsequent treatment based on the response observed.
One of the key findings of the study is the significant association between pathologic complete response (pCR) and event-free survival (EFS) in ERBB2/HER2-positive breast cancer patients. Previous trials had shown higher pCR rates with dual ERBB2/HER2-targeting therapy compared to single-agent therapy. However, the magnitude of this effect varied across different trial populations and drugs, with inconsistent long-term outcome data.
To address this inconsistency, researchers conducted a comprehensive analysis of three phase 3 clinical trials – NeoALTTO, CALGB 40601, and NSABP B-41 – with similar designs. By performing individual patient-level biomarker analysis, they sought to understand the impact of intrinsic subtype, immune activation status, and other gene expression signatures on treatment response and survival outcomes.
The results revealed intriguing insights into the heterogeneous nature of ERBB2/HER2-positive breast cancer. The study found that the association between pCR and EFS differed significantly based on tumour intrinsic subtype, with the benefit of dual ERBB2/HER2-blockade observed primarily in ERBB2-enriched tumours.
Furthermore, immune activation signatures emerged as powerful predictors of treatment response and prognosis. Patients with higher levels of tumour-infiltrating lymphocytes (TILs) and T-cell expression signatures demonstrated higher pCR rates and better EFS, underscoring the prognostic significance of the immune microenvironment.
Importantly, the study highlights the potential for personalised treatment strategies guided by intrinsic subtype and immune gene expression biomarkers. By integrating these factors into treatment decision-making, clinicians may optimise therapeutic outcomes and improve survival rates for patients with ERBB2/HER2-positive breast cancer.
Despite the ground-breaking findings, the study has some limitations, including variations in trial designs and the use of lapatinib, which is currently not approved for neoadjuvant therapy in ERBB2/HER2-positive breast cancer.
Overall, the study represents a significant step forward in our understanding of ERBB2/HER2-positive breast cancer and lays the groundwork for future research aimed at refining personalised treatment approaches for this challenging disease.
