Management of Advanced Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer and Brain Metastases

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 )

If a patient has a favorable prognosis^a 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 )

If a patient has a favorable prognosis^a 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 )

If a patient has a favorable prognosis^a 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 )

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 )

If a patient has a favorable prognosis^a 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 )

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 )

If a patient has a favorable prognosis^a 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. (, , )

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

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 )

For patients with limited metastases^b <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 )

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 )