New progress and challenges of targeted therapies for breast cancer

Abstract

Breast cancer, a heterogeneous malignancy with a significant global burden, necessitates evolving therapeutic strategies. With nearly two million new cases diagnosed annually, metastatic dissemination remains a critical clinical challenge despite advancements in surgery, radiotherapy, and cytotoxic chemotherapy. The emergence of targeted therapies, including monoclonal antibodies, small-molecule inhibitors, and antibody-drug conjugates (ADCs), has revolutionized breast cancer management by selectively modulating oncogenic signaling pathways to inhibit tumor proliferation and spread. This approach offers a more focused treatment strategy with the potential for reduced systemic toxicities. Targeted therapies have demonstrated significant clinical efficacy across breast cancer subtypes. For instance, agents such as trastuzumab, pertuzumab, and trastuzumab emtansine (T-DM1) improved survival in human epidermal growth factor receptor 2 (HER2)-positive disease. Similarly, cyclin dependent kinase 4/6 (CDK4/6) and poly (ADP-ribose) polymerase (PARP) inhibitors have yielded substantial benefits in hormone receptor-positive and breast cancer gene (BRCA)-mutated breast cancers, respectively, by modulating endocrine resistance and DNA repair pathways. Furthermore, phosphoinositide 3-kinase (PI3K) inhibitors for PIK3CA-mutant tumors and immune checkpoint inhibitors for triple-negative breast cancer (TNBC) have expanded the available therapeutic measures. However, despite these advancements, challenges such as acquired resistance, often driven by pathway reactivation or gene mutations, continue to limit optimal patient outcomes. Additionally, treatment-related toxicities demand rigorous management, therefore ongoing identification of robust predictive biomarkers to refine patient selection and treatment strategies remains a critical focus of research. This mini-review provides a comprehensive overview of current targeted therapies in breast cancer, detailing their mechanisms of action, clinical efficacy, and associated toxicities. It addresses relevant challenges such as resistance pathways, financial toxicity, and gaps in biomarker research, while emphasizing the importance of patient-centered decision-making and multidisciplinary care. Future directions include the development of next-generation sequencing, refined drug designs, and the integration of immunotherapies to further improve patient outcomes and quality of life, ultimately striving towards personalized cancer care.

Keywords: Breast cancer; drug resistance; immunotherapy; palliative care; targeted therapy.