What are the treatment options for metastatic breast cancer?

2026-09-15

The treatment strategy for metastatic breast cancer fundamentally depends on the molecular subtype of the tumour (hormone receptor status, HER2 status, and specific genetic mutations), as systemic therapy is the cornerstone of managing the disease.

In hormone receptor-positive (HR+), HER2-negative breast cancer, the first-line standard of care is endocrine therapy (such as an aromatase inhibitor or fulvestrant) combined with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors (e.g. ribociclib, palbociclib, abemaciclib), which significantly improves progression-free and overall survival. When resistance develops, targeted agents can be administered based on molecular testing (tissue or liquid biopsy ctDNA): in the presence of an ESR1 mutation, next-generation oral selective estrogen receptor degraders (SERDs, e.g. elacestrant), whereas when the PI3K/AKT/PTEN pathway is altered, combinations involving PI3K or AKT inhibitors (e.g. alpelisib, capivasertib, inavolisib) are recommended.

In HER2-positive metastatic breast cancer, dual HER2 blockade (trastuzumab and pertuzumab) combined with chemotherapy was the standard for decades; however, antibody-drug conjugates (ADCs), particularly trastuzumab deruxtecan (T-DXd) or trastuzumab emtansine (T-DM1), as well as newer tyrosine kinase inhibitors (e.g. tucatinib), have revolutionised treatment both in the first-line setting and following progression. Furthermore, T-DXd has also proven effective in HER2-low (showing low HER2 expression) tumours.

In triple-negative breast cancer (TNBC) and in later treatment lines, alongside conventional cytotoxic chemotherapy, immunotherapy (immune checkpoint inhibitors, e.g. pembrolizumab in the case of PD-L1 positivity), PARP inhibitors in the presence of a germline BRCA mutation, and antibody-drug conjugates targeting TROP-2 (e.g. sacituzumab govitecan, datopotamab deruxtecan) offer targeted treatment alternatives.

The role of local therapies (such as breast surgery or radiotherapy) in metastatic breast cancer is primarily limited to symptom relief and palliative purposes; routine resection of the primary tumour has not been proven to improve overall survival compared with comprehensive systemic therapy, but in oligometastatic or oligoprogressive cases, local ablative treatments may be considered to maintain systemic control.

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