ADVANCES IN BREAST CANCER DIAGNOSIS AND TREATMENT: ESSENTIALS

Advances in breast cancer diagnosis and treatment Essentials_kapak

MANAGEMENT OF METASTATIC BREAST CANCER

Oğuzcan Kınıkoğlu

Kartal Dr. Lütfi Kırdar City Hospital, Department of Medical Oncology, İstanbul, Türkiye

Kınıkoğlu O. Management of Metastatic Breast Cancer. In: Citgez B editor. Advances in Breast Cancer Diagnosis and Treatment Essentials. 1st ed. Ankara: Türkiye Klinikleri; 2025. p.145-156.

ABSTRACT

Metastatic breast cancer (MBC) represents the most advanced stage of breast malignancy and, while currently incurable, it can be effectively managed through therapeutic strategies aimed at prolonging survival and preserving quality of life. The identification of molecular subtypes, the development of targeted therapies, and the implementation of biomarker-driven treatment approaches have significantly reshaped the landscape of MBC treatment. In cases of hormone receptor-positive/HER2-negative (HR+/HER2−) disease, the use of CDK4/6 inhibitors like palbociclib, ribociclib, and abemaciclib, when paired with endocrine therapy, has shown significant enhancements in both progression-free survival (PFS) and overall survival (OS). Nevertheless, the emergence of therapeutic resistance has necessitated the development of novel agents targeting the PI3K/AKT/mTOR pathway, ESR1 mutations, and epigenetic alterations. Agents like alpelisib, everolimus, elacestrant, and entinostat have provided promising options in this setting. HER2-positive MBC has undergone a paradigm shift with the advent of HER2-directed therapies. Beginning with trastuzumab and followed by pertuzumab, T-DM1, and more recently trastuzumab deruxtecan (T-DXd), these agents have significantly extended patient survival. The DESTINY-Breast03 trial, demonstrating the superiority of T-DXd over T-DM1, has redefined second-line treatment strategies. In addition, tucatinib, a next-generation tyrosine kinase inhibitor, has shown meaningful clinical benefit in patients with brain metastases, addressing an important unmet need. Triple-negative breast cancer (TNBC) is known for its aggressive nature and has traditionally had few treatment options. Nonetheless, significant progress has been achieved in recent years with the introduction of immunotherapy, antibody-drug conjugates (ADCs), and PARP inhibitors. Atezolizumab and pembrolizumab have demonstrated efficacy in PD-L1-positive TNBC, while PARP inhibitors such as olaparib and talazoparib have proven effective in BRCA-mutated cases. In conclusion, personalized treatment strategies based on molecular profiling, combined with an evolving understanding of resistance mechanisms, are essential to improving long-term survival outcomes in patients with MBC. Ongoing translational research and clinical trial efforts will continue to drive innovation and shape the future of metastatic breast cancer care.

Keywords: Metastatic breast cancer; Targeted therapy; Endocrine resistance; CDK4/6 inhibitors; HER2 positivity; Triple-negative breast cancer; Immunotherapy; Biomarkers

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