Systemic Therapies for HER2-Positive Advanced Breast Cancer.
Vasileios AngelisAlicia F C OkinesPublished in: Cancers (2023)
Despite recent advances, HER2-positive advanced breast cancer (ABC) remains a largely incurable disease, with resistance to conventional anti-HER2 drugs ultimately unavoidable for all but a small minority of patients who achieve an enduring remission and possibly cure. Over the past two decades, significant advances in our understanding of the underlying molecular mechanisms of HER2-driven oncogenesis have translated into pharmaceutical advances, with the developing of increasingly sophisticated therapies directed against HER2. These include novel, more potent selective HER2 tyrosine kinase inhibitors (TKIs); new anti-HER2 antibody-drug conjugates; and dual epitope targeting antibodies, with more advanced pharmacological properties and higher affinity. With the introduction of adjuvant T-DM1 for incomplete responders to neoadjuvant therapy, fewer patients are relapsing, but for those who do relapse, disease that may be resistant to standard first- and second-line therapies requires new approaches. Furthermore, the risk of CNS relapse has not been abrogated by current (neo)adjuvant strategies; therefore, current research efforts are being directed towards this challenging site of metastatic disease. In this article, we review the currently available clinical data informing the effective management of HER2-positive breast cancer beyond standard first-line therapy with pertuzumab, trastuzumab, and taxanes, and the management of relapse in patients who have already been exposed to both these agents and T-DM1 for early breast cancer (EBC). We additionally discuss novel anti-HER2 targeted agents and combinations in clinical trials, which may be integrated into standard treatment paradigms in the future.
Keyphrases
- end stage renal disease
- clinical trial
- newly diagnosed
- ejection fraction
- chronic kidney disease
- cancer therapy
- small cell lung cancer
- squamous cell carcinoma
- multiple sclerosis
- prognostic factors
- positive breast cancer
- early stage
- peritoneal dialysis
- randomized controlled trial
- metabolic syndrome
- epidermal growth factor receptor
- stem cells
- patient reported outcomes
- bone marrow
- locally advanced
- machine learning
- study protocol
- mesenchymal stem cells
- quality improvement