A view on the landscape of breast cancer brain metastases.

Introduction to breast cancer & brain metastases & why subtypes matter Metastases to the central nervous system (CNS) are an unfortunate complication of breast cancer, second only to lung cancer [1–4]. The incidence of breast cancer brain metastases (BCBM) are approximated to be 5–16% in studies [1,5–7]; however, at autopsy the incidence is in fact much higher [1,6,8]. The development of BCBM can be associated with neurologic morbidity and augurs an inferior prognosis [9–11]. Moreover, BCBM are not limited to advanced stage disease, as the CNS is a site for relapse even in early stage breast cancer [5]. Presently, routine screening is not recommended, thus there is no precise understanding of CNS disease burden at diagnosis as typically BCBMs are captured due to symptoms and/or examination findings [6,8]. Steadily, this incidence has been increasing, in part due to advancements in systemic therapies which have improved survival; patients are living longer so as to develop BCBM as well as progress in radiographic techniques which have led to enhanced detection [1,2,5,7,9,12]. Certain patient and tumor characteristics have been shown to be associated with a higher risk of developing BCBM and these include younger age (<35 years), positive nodal status, ethnicity, presence of visceral metastases, estrogen receptor negative disease, HER2 disease, grade III tumors and tumor size [1,5,6]. In addition, the number of BCBM has prognostic relevance [6] as does the size of the BCBM and the patient’s performance status [4]. Ultimately, it is necessary to not view breast cancer as a single disease but as a group of diseases [2,12,13], as its subtypes are associated with varying patterns of metastatic spread and prognosis [8,14–16]. The different subtypes based on hormone receptor status and HER2 status are associated with a difference in incidence [11,17,18]. The time from diagnosis of the initial breast cancer to the development of BCBM is longer in patients with estrogen receptor positive (ER+) disease versus those with triple-negative breast cancer (TNBC) or HER2-positive cancer [11].