ESMO guideline update: Breast cancer

What’s new in metastatic breast cancer management?

The 2026 European Society for Medical Oncology (ESMO) Clinical Practice Guideline provides updated recommendations for the diagnosis, treatment, and follow-up of metastatic breast cancer (MBC).¹ The guideline includes new recommendations for biomarker testing, subtype-specific treatment selection, management of metastatic sites, and survivorship care.

Expanded biomarker testing supports treatment selection for metastatic breast cancer

The guideline recommends biopsy at first diagnosis of metastatic disease to confirm histology and reassess estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) status, where feasible. In patients with discordant receptor status between the primary tumor and recurrence, treatment decisions can generally be guided by the receptor status of the metastatic biopsy.

Updated recommendations also support evaluation of:

• Programmed death-ligand 1 (PD-L1) status in triple-negative breast cancer
• Germline and somatic BRCA1/2 mutations in HER2-negative MBC
• PALB2 mutations in HER2-negative MBC
• PIK3CA mutations and pathway alterations in ER-positive, HER2-negative MBC
• ESR1 mutations following aromatase inhibitor treatment in ER-positive, HER2-negative MBC
• HER2-low and HER2-ultralow expression, where relevant for treatment selection

Genomic profiling is recommended if the results could impact the treatment approach or when appropriate clinical trials are available.

Refining disease monitoring recommendations for metastatic breast cancer

The guideline recommends a CT scan of the chest and abdomen with bone scintigraphy as the minimum staging workup alongside blood tests, with a PET–CT scan as an additional option.

Response assessment is recommended every 2–4 months according to:

• Disease characteristics (dynamics, location, extent of metastasis)
• Symptoms
• Treatment type

The guideline does not recommend shortening monitoring intervals routinely because evidence does not demonstrate an overall survival benefit.

Brain imaging (MRI) is recommended for symptomatic patients. Subtype-oriented brain imaging may be considered for asymptomatic patients when identifying central nervous system metastases would change the choice of systemic therapy, particularly in HER2-positive disease and triple-negative breast cancer.

Treatment pathways for ER-positive, HER2-negative metastatic breast cancer

For patients with de novo ER-positive, HER2-negative MBC or recurrent disease occurring more than 12 months after the end of adjuvant endocrine therapy, an aromatase inhibitor (AI) plus a cyclin-dependent kinase (CDK)4/6 inhibitor is recommended.

The guideline also recommends considering multiple endocrine-based treatment lines before transitioning to non-endocrine therapies in endocrine-sensitive disease.

Updated recommendations for HER2-positive metastatic breast cancer

For HER2-positive MBC, the guideline continues to recommend dual HER2 blockade with chemotherapy (i.e., docetaxel–pertuzumab–trastuzumab) in the first-line setting, regardless of ER status.

Updated treatment pathways incorporate additional HER2-targeted therapies in later lines of treatment, including trastuzumab deruxtecan, which is the preferred option when available regardless of brain metastases. For patients with brain metastases, the HER2-targeted combination (tucatinib–trastuzumab–capecitabine) is recommended.

For patients who are not candidates for chemotherapy, the guideline recommends:

• HER2-targeted therapy, such as trastuzumab, with endocrine therapy for selected patients with HER2-positive, ER-positive MBC
• Single-agent endocrine therapy for patients with HER2-positive, ER-positive MBC when comorbidities preclude the safe use of HER2-directed therapies
• Consideration of capecitabine or vinorelbine when taxane-based chemotherapy is contraindicated

The guideline also provides recommendations for maintenance treatment following induction therapy, including:

• Pertuzumab, trastuzumab, endocrine therapy, and palbociclib for HER2-positive, ER-positive tumors
• Pertuzumab, trastuzumab, and endocrine therapy for HER2-positive, ER-positive tumors
• Pertuzumab, trastuzumab, and tucatinib regardless of ER status
• Pertuzumab and trastuzumab for HER2-positive, ER-negative tumors

Immunotherapy and antibody–drug conjugates incorporated into triple-negative breast cancer management

For metastatic triple-negative breast cancer, immune checkpoint inhibitor–based combinations are recommended for eligible patients with PD-L1–positive breast cancer.

The guideline also incorporates antibody–drug conjugates and PARP inhibitors into treatment pathways, with therapy selection guided by:

• PD-L1 status
• BRCA1/2 mutation status
• Prior treatments
• Disease characteristics (presentation, disease-free interval)
• Patient considerations

Multidisciplinary management emphasized for metastatic sites

The guideline includes updated recommendations for the management of:

• Oligometastatic disease
• Bone metastases
• Brain metastases
• Leptomeningeal disease

Multidisciplinary evaluation is recommended when considering local therapies, including surgery and radiotherapy, or systemic treatment strategies. Bone-modifying agents are recommended for patients with bone metastases regardless of symptoms.

Survivorship and quality of life integrated into metastatic breast cancer care

The guideline recommends a multidisciplinary approach throughout the disease course, including:

• Specialist nursing support
• Proactive toxicity management
• Patient education
• Assessment of quality of life

Routine management also includes counseling on:

• Fertility and fertility preservation
• Contraception
• Symptom management
• Sexual health
• Supportive care needs

Reference

1. ESMO Guideline Committee, 2026. Metastatic breast cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. https://www.doi.org/10.1016/j.annonc.2026.05.707

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