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Published by American Society of Clinical Oncology (ASCO) · Cochrane Risk of Bias tool, GRADE, and ASCO method
Brain metastases are common in patients with advanced HER2-positive breast cancer, with up to half of patients experiencing brain relapse over time. Improved systemic therapies for extracranial disease have extended survival, creating a need to optimize initial brain metastasis treatments and strategies for subsequent intracranial progression.
Key Takeaways
Updates include a new option to defer local therapy for a subset of the target population with asymptomatic brain metastases (utilizing the HER2CLIMB regimen) and changing the recommendation on screening to note insufficient data to recommend for or against routine surveillance with brain MRI.
Multidisciplinary collaboration to formulate treatment and care plans and disease management for patients with HER2-positive metastatic breast cancer should be the standard of care.
If a patient has a favorable prognosis for survival and a single brain metastasis, the patient should be evaluated by an experienced neurosurgeon for discussion of the option of surgical resection, particularly if the metastasis is > 3-4 cm and/or if there is evidence of symptomatic mass effect.
If a patient has a favorable prognosis and a single brain metastasis < 3-4 cm without symptomatic mass effect, clinicians may offer either SRS or surgical resection, depending on the location and surgical accessibility of the tumor, need for tissue diagnosis, and other considerations, such as medical risk factors for surgery and patient preference.
If a patient has a favorable prognosis and a single brain metastasis < 2 cm without symptomatic mass effect and who has an option to proceed with HER2-directed therapy with known CNS activity, then clinicians and patients may discuss options including SRS or deferring local therapy with a MDT.
For most patients with brain metastases who undergo surgical resection, clinicians should recommend postoperative radiotherapy (includes SRS, hypofractionated stereotactic radiotherapy [HSRT], and for large or multiple resection beds possibility of WB-M + HA) to the resection bed to reduce the risk of local recurrence.
If a patient has a favorable prognosis and a single brain metastasis > 3-4 cm, which clinicians and a MDT deem unresectable and unsuitable for SRS, clinicians may discuss the options of HSRT or WB-M+HA. MDTs should consult with patients in this situation.
After treatment, serial imaging every 2-4 months may be used to monitor for local and distant brain failure (also known as local recurrence or new brain disease).
If a patient has a favorable prognosis and presents with multiple, but limited, metastases (defined as two-four lesions), treatment options depend on the size, resectability, and mass effect of the lesions.
In a patient who presents with limited metastases (defined as two-four lesions) suitable for SRS, clinicians may discuss SRS without WB-M + HA.
In a patient with symptomatic lesions that are unresectable and unsuitable for SRS HSRT, clinicians may recommend WBRT plus memantine and, if feasible, hippocampal avoidance and may discuss SRS after WB-M + HA.
For patients with limited metastases < 2 cm and not associated with symptomatic mass effect, and who have an option to proceed with HER2-directed therapy with known CNS activity, then clinicians and patients may discuss deferring local therapy with a MDT.
In a patient who has a large (> 3-4 cm) lesion associated with symptomatic mass effect, clinicians may discuss surgical resection of the larger lesion, if the lesion is deemed resectable. The remaining lesions and resection bed may be treated with SRS, or HSRT with or without WB-M + HA. Clinicians should also provide symptom management.
If a patient has brain metastases and a poor prognosis, clinicians should discuss the options of best supportive care and/or palliative care, which may or may not include radiation therapy, on a case-by-case basis.
For a patient with symptomatic brain metastases and poor prognosis, WB-M+HA may be offered if there is a reasonable expectation of symptomatic improvement that outweighs the acute and subacute treatment-related toxicities, including fatigue and decline in neurocognitive function.
If a patient has intracranial metastases that progressed despite initial therapy, treatment options will depend on the patient’s prior therapies, burden of disease, performance status, and overall prognosis.
For a patient with a favorable prognosis and limited recurrence after treatment with WBRT, clinicians may discuss SRS, surgery, systemic therapy, and/or additional palliative options. For a patient with a favorable prognosis and limited recurrence after treatment with SRS, clinicians may discuss repeat SRS, surgery, WB-M+HA, systemic therapy, and/or additional palliative options.
If a patient has diffuse recurrence after treatment with WBRT, clinicians may discuss palliative options such as systemic therapy (preferred) or repeat reduced-dose WBRT plus memantine and/or other palliative care options.
If a patient has diffuse recurrence after treatment with SRS, clinicians may discuss palliative options such as WB-M + HA or systemic therapy, and/or other palliative care options.
If a patient has symptomatic brain leptomeningeal metastases, clinicians may recommend WBRT plus memantine. The management of leptomeningeal metastases is complex, and recommendations regarding intrathecal therapy and/or systemic therapy for leptomeningeal metastases are outside the scope of this practice guideline.
If a patient has a more favorable prognosis and presents with many diffuse and/or extensive brain metastases (≥ five metastases) without leptomeningeal disease, clinicians may recommend SRS or WB-M + HA. For patients with metastases < 2 cm and not associated with symptomatic mass effect, and who have an option to proceed with HER2-directed therapy with known CNS activity, then clinicians and patients may discuss deferring local therapy with a MDT.
Patients with favorable prognoses are those with good performance status and effective systemic therapy options. The criteria may include KPS > 70, controlled extracranial disease, and/or whether good additional systemic therapy options for extracranial disease are available.
The combination of tucatinib, and capecitabine and trastuzumab may be offered to patients with HER2-positive metastatic breast cancer who have brain metastases without symptomatic mass effect and whose disease has progressed on at least one previous HER2-directed therapy for metastatic disease. If these agents are used, local therapy may be delayed until there is evidence of intracranial progression.
For a patient who receives a standard surgical or radiotherapy-based approach to treat brain metastases and is receiving anti-HER2–based therapy and whose systemic disease is not progressive at the time of brain metastasis diagnosis, clinicians should not switch systemic therapy.
For a patient who receives a standard surgical and/or radiotherapy-based approach to treatment of brain metastases and whose systemic disease is progressive at the time of brain metastasis diagnosis, clinicians should offer HER2-targeted therapy according to the algorithms for treatment of HER2-positive metastatic breast cancer.
If a patient develops intracranial disease progression after WBRT or SRS (including when a patient is not a candidate for reirradiation), clinicians may discuss offering systemic therapy using a regimen with some evidence of activity in the setting of CNS disease.
If a patient does not have a known history or symptoms of brain metastases, there are insufficient data to recommend for or against performing routine surveillance with brain magnetic resonance imaging (MRI). Clinicians and patients may discuss options using shared decision-making processes.
Clinicians should have a low threshold for performing diagnostic brain MRI testing in the setting of any neurologic symptoms suggestive of brain involvement, such as new-onset headaches, unexplained nausea or vomiting, or change in motor or sensory function.
Clinical Topic
Breast Cancer and Brain Metastases
Objectives
To provide updated evidence- and consensus-based guideline recommendations to practicing oncologists and others on the management of brain metastases for patients with human epidermal growth factor receptor 2 (HER2)–positive advanced breast cancer up to 2021.
Target Patient Population
Individuals with advanced human epidermal growth factor receptor (HER2)–positive breast cancer and brain metastases.
Target Providers
Therapeutic Area
OncologyGuideline Scope
Inclusion Criteria
Exclusion Criteria
System: Cochrane Risk of Bias tool, GRADE, and ASCO method
Evidence Levels
Recommendation Strength
Monitoring Guidance
After treatment, serial imaging every 2-4 months may be used to monitor for local recurrence or new brain disease.
Difficulty
advanced
Learning Paths