Comparison of Targeted Therapy Efficacy in HER2-Positive Versus HER2-Negative Breast Cancer Patients

HER2 status is an important therapeutic and prognostic biomarker in the molecularly heterogeneous disease of breast cancer. HER2-targeted therapies such as trastuzumab, pertuzumab and trastuzumab deruxtecan have transformed survival outcomes for HER2-positive breast cancers, which account for 15–20% of cases. Similarly, HER2-negative breast cancers do not have HER2 as a potential therapeutic target and generally rely on other approaches (e.g. hormone receptor modulation, CDK4/6 inhibitors, PARP inhibitors) to exert control over tumor growth. Methods: A systematic review of the literature and meta-analysis for randomized controlled trials comparing HER2-positive versus HER2-negative breast cancer in patients receiving targeted therapy, assessing key endpoints such as PFS, OS and quality of life. A systematic review of clinical trials between 2013 and 2023 was performed that included studies assessing targeted therapy effects in either subgroup. Results of these studies showed that HER2-positive patients should benefit more in terms of survival and response from specific HER2-targeted therapies, compared to less specific agents used in the HER2-negative patient population. Still, challenges remain with resistance mechanisms and therapy availability. HER2-negative cancers, particularly triple-negative breast cancer (TNBC), represent indications of high unmet therapeutic need. The comparison illustrates the importance of HER2 as a predictive biomarker, as well as the necessity for further advancement in precision medicine. As these drugs continue into clinical practice, future investigations aiming to overcome HER2-positive disease resistance to these agents, as well as trying to identify viable targets for HER2-negative cancer, will be critical to achieving similar therapeutic outcomes across these two cancer subtypes.