Advances in the management of breast cancer brain metastases

Abstract

The development of breast cancer (BC) brain metastases (BrM) is a common complication of advanced disease, occurring in up to half of the patients with advanced disease depending on the subtype. The management of BCBrM requires complex multidisciplinary care including local therapy, surgical resection and/or radiotherapy, palliative care, and carefully selected systemic therapies. Significant progress has been made in the human epidermal growth factor receptor 2-positive (HER2+) BCBrM population due to novel brain penetrable systemic therapies. Increased inclusion of patients with BCBrM in clinical trials using brain-penetrant systemic therapies recently led to the first FDA approval of a HER2-directed therapy specifically in the BCBrM population in the last year. Advances for the treatment of HR+/HER2− and TNBC BCBrM subgroups continue to evolve. In this review, we will discuss the diagnosis and multidisciplinary care of BCBrM. We focus on recent advances in neurosurgery, radiation therapy, and systemic treatment therapies with intracranial activity. We also provide an overview of the current clinical trial landscape for patients with BCBrM.

Heterogeneity of HER2 Expression in Circulating Tumor Cells of Patients with Breast Cancer Brain Metastases and Impact on Brain Disease Control

“…The significantly longer DBFFS in patients with HER2-positive CTC at any moment suggests that a focal approach with SRT for BCBM should be prioritized over WBRT to avoid the potential cognitive and quality of life impairments. In fact, there is a trend to consider SRT for patients with a better prognosis, or when active systemic therapy to the central nervous system is available [27][28][29]. The prospective observational study JLGK0901, involving 1194 patients with 1 to 10 newly diagnosed brain metastases treated exclusively with SRS, revealed that the median OS did not differ between the patients with 2 to 4 tumors and those with 5 to 19 (10.8 months in both groups), suggesting that SRT might be a suitable alternative for patients with up to 10 brain metastases [30].…”

“…Between November 2016 and February 2018, 39 women were accrued. Patients underwent SRT with radiosurgery (SRS) or stereotactic fractionated radiotherapy (SFRT) in 68% (27) and 31% (12) of cases, respectively, with a median prescribed dose of 20 Gy (15)(16)(17)(18)(19)(20)(21)(22) with SRS and 27.5 Gy (25-30) in five fractions with SFRT.…”

Systemic Therapy for HER2-Positive Metastatic Breast Cancer: Moving Into a New Era

“…In the curative intent setting, risk factors for developing brain metastases include HER2-positive or triple-negative subtype, young age, high grade, node positivity, and a diagnosis of inflammatory breast cancer. [26][27][28][29][30] Populationbased studies within the Surveillance, Epidemiology, and End Results database have reported that 11.5% of patients with de novo HER2-positive MBC 31 have brain metastases on initial presentation. Once a patient develops metastatic disease, the risk of brain metastases accumulates over time, reaching up to 50% cumulative incidence in patients with HER2-positive breast cancer.…”

Systemic Therapy Type and Timing Effects on Radiation Necrosis Risk in HER2+ Breast Cancer Brain Metastases Patients Treated With Stereotactic Radiosurgery

“…As many as 30% of patients with advanced, metastatic HER2+ breast cancer will develop BrM ( 6 ). Current standard of care options for HER2+ BCBrM include radiation therapy (stereotactic radiosurgery [SRS] or whole brain radiation therapy [WBRT]), brain permeable systemic therapies, and/or neurosurgical resection when appropriate ( 7 ). A multimodal approach combining these different treatment modalities has improved the overall survival and functional outcomes of patients with BCBrM.…”