Advanced Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer – Brain Metastases

Last updated June 9, 2022

Key Points

Key Points

Human epidermal growth factor receptor 2 (HER2)-targeted therapy is recommended for patients with HER2-positive advanced breast cancer, except for those with clinical congestive heart failure or significantly compromised left ventricular ejection fraction, who should be evaluated on a case-by-case basis.

Local Therapy

Local Therapy

Brain Metastases

Recommendation 1.0

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. ( EB , B , I , S )
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Recommendation 2.1. (single brain metastasis, favorable prognosisa)

If a patient has a favorable prognosisa 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 to 4 cm and/or if there is evidence of symptomatic mass effect. (Recommendation Type: FC/IC) ( IC , , I , S )
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Recommendation 2.2

If a patient has a favorable prognosisa and a single brain metastasis <3 to 4 cm without symptomatic mass effect, clinicians may offer either stereotactic radiosurgery (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. (Recommendation Type: FC) (, , I , W )
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Recommendation 2.3

If a patient has a favorable prognosisa and a single brain metastasis <2 cm without symptomatic mass effect and who has an option to proceed with HER2-directed therapy with known central nervous system (CNS) activity, then clinicians and patients may discuss options including SRS or deferring local therapy with a multidisciplinary team (MDT). ( IC , , L , M )
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Recommendation 2.4

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 whole-brain radiation therapy-memantine plus hippocampal avoidance [WB-M + HA]) to the resection bed to reduce the risk of local recurrence. (Recommendation Type: FC/IC) ( IC , , I , W )
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Recommendation 2.5

If a patient has a favorable prognosisa and a single brain metastasis >3 to 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. (Recommendation Type: FC/IC) ( IC , , L , W )
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Recommendation 2.6

After treatment, serial imaging every 2 to 4 months may be used to monitor for local and distant brain failure (also known as local recurrence or new brain disease). (Recommendation Type: FC) (, , L , W )
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Recommendation 3.0

If a patient has a favorable prognosisa and presents with multiple, but limited, metastases (defined as two to four lesions) treatment options depend on the size, resectability, and mass effect of the lesions. (, , )
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Recommendation 3.1

In a patient who presents with limited metastasesb (defined as two to four lesions) suitable for SRS, clinicians may discuss SRS without WB-M + HA. (Recommendation Type: FC) (, , I , W )
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Recommendation 3.2

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. (Recommendation Type: FC/IC) ( IC , , L , W )
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Recommendation 3.3

For patients with limited metastasesb <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. ( IC , , L , M )
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Recommendation 3.4

In a patient who has a large (>3 to 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, HSRT with or without WB-M + HA. Clinicians should also provide symptom management. (Recommendation Type: FC) (, , I , W )
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Diffuse Disease or Extensive Metastasesc

Recommendation 4.1

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. (Recommendation Type: FC) (, , L , M )
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Recommendation 4.2.1

If a patient has a more favorable prognosisa and presents with many diffuse and/or extensive brain metastasesc (≥ 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. (Recommendation Type: FC/IC) ( IC , , L , M )
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Recommendation 4.2.2

Patients with favorable prognosesa are those with good performance status and effective systemic therapy options. The criteria may include Karnofsky performance status (KPS) >70, controlled extracranial disease, and/or whether good additional systemic therapy options for extracranial disease are available. (Recommendation Type: FC) (, , L , W )
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Recommendation 5.0 (patients with poor prognosis)

If a patient has brain metastases and a poor prognosis, clinicians should discuss the options of best supportive care (BSC) and/or palliative care, which may or may not include radiation therapy, on a case-by-case basis. (Recommendation Type: FC) (, , L , W )
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Recommendation 5.1

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 neuro-cognitive function. (Recommendation Type: FC) (, , L , W )
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Recommendation 6.0 (patients with intracranial metastases which progress despite initial therapy)

If a patient has intracranial metastases, which progress despite initial therapy, treatment options will depend on the patient’s prior therapies, burden of disease, performance status, and overall prognosis. (, , )
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Recommendation 6.1 (brain recurrence and prior WBRT; limited recurrenceb)

For a patient with a favorable prognosisa and limited recurrenceb after treatment with WBRT, clinicians may discuss SRS, surgery, systemic therapy, and/or additional palliative options. (Recommendation Type: FC/IC) ( IC , , L , M )
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For a patient with a favorable prognosisa and limited recurrenceb after treatment with SRS, clinicians may discuss repeat SRS, surgery, WB-M + HA, systemic therapy, and/or additional palliative options. (Recommendation Type: FC/IC) ( IC , , L , M )
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Recommendation 6.2 (diffuse recurrencec)

If a patient has diffuse recurrencec after consensus 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. (Recommendation Type: FC/IC) ( IC , , L , W )
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Recommendation 6.3 (diffuse recurrencec)

If a patient has diffuse recurrencec after treatment with SRS, clinicians may discuss palliative options such as WB-M + HA or systemic therapy, and/or other palliative care options. (Recommendation Type: FC) (, , L , M )
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a Favorable prognosis: Those with good performance status and eligible for and access to effective systemic therapy options. The criteria may include Karnofsky performance status (KPS) >70, controlled extracranial disease, and/or whether good salvage systemic therapy options for extracranial disease are available.
b Limited metastases: Two to four metastases.
c Diffuse/extensive brain metastases: ≥ five metastases.

Systemic Therapy

Systemic Therapy

Recommendation 7.1

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. ( EB , , L , W )
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Recommendation 8.1 (brain recurrence and systemic therapy)

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. (Recommendation Type: FC) (, , L , M )
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Recommendation 8.2

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. (Recommendation Type: FC) (, , I , M )
Qualifying Statement: Recommendation 8.2 applies with one exception. In addition to trastuzumab deruxtecan in the second-line setting, the HER2CLIMB regimen of tucatinib and capecitabine and trastuzumab may be offered to patients with stable brain metastases after local therapy.
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Recommendation 9.1

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. (Recommendation Type: FC) (, , I , M )
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a Favorable prognosis: Those with good performance status and eligible for and access to effective systemic therapy options. The criteria may include Karnofsky performance status (KPS) >70, controlled extracranial disease, and/or whether good salvage systemic therapy options for extracranial disease are available.
b Limited metastases: Two to four metastases.
c Diffuse/extensive brain metastases: ≥ five metastases.

Screening

Screening

Recommendation 10.1 (screening)

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. Clinicians and patients may discuss options using shared decision-making processes. (Recommendation Type: FC/IC) ( IC , , L , W )
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Recommendation 10.2

Clinicians should have a low threshold for performing diagnostic brain magnetic resonance imaging (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. (Recommendation Type: FC) (, , L , S )
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Figure 1. Algorithm for Patients with HER2+ Metastatic Breast Cancer with CNS Metastasis

a After consultation with a MDT.
b Upfront systemic therapy can be discussed for select cases.


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Recommendation Grading

Abbreviations

  • ASCO: American Society Of Clinical Oncology
  • BSC: Best Supportive Care
  • CNS: Central Nervous System
  • HA: Hippocampal Avoidance
  • HER2: Human Epidermal Growth Factor Receptor 2
  • HSRT: Hypofractionated Stereotactic Radiotherapy
  • KPS: Karnofsky Performance Status
  • M: Memantine
  • MDT: Multidisciplinary Team
  • MRI: Magnetic Resonance Imaging
  • RT: Radiation Therapy
  • SRS: Stereotactic Radiosurgery
  • WB: Whole-brain Radiation Therapy
  • WBRT: Whole-brain Radiotherapy
  • cm: Centimeters

Source Citation

Ramakrishna N, Anders CK, Lin NU, et al. Management of Advanced Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer and Brain Metastases: ASCO Guideline Update. J Clin Oncol. 2022 May 31. doi: 10.1200/JCO.22.00520.

Disclaimer

This pocket guide is derived from recommendations in the American Society of Clinical Oncology Guideline. This resource is a practice tool based on ASCO® practice guidelines and is not intended to substitute for the independent professional judgment of the treating physician. Practice guidelines do not account for individual variation among patients. This pocket guide does not purport to suggest any particular course of medical treatment. Use of the practice guidelines and this resource are voluntary. The practice guidelines and additional information are available at www.asco.org/supportive-care-guidelines. Copyright © 2021 by American Society of Clinical Oncology. All rights reserved.