The incidence of brain metastases among patients with metastatic breast cancer: a systematic review and meta-analysis

Abstract

Background Patients with metastatic breast cancer (MBC) are living longer, but development of brain metastases often limits their survival. We conducted a systematic review and meta-analysis to determine the incidence of brain metastases in this patient population. Methods Articles published from January 2000 to January 2020 were compiled from four databases using search terms related to: breast cancer, brain metastasis, and incidence. The overall and per patient-year incidence of brain metastases were extracted from studies including patients with HER2+, triple negative, and hormone receptor (HR)+/HER2- MBC; pooled overall estimates for incidence were calculated using random effects models. Results 937 articles were compiled, and 25 were included in the meta-analysis. Incidence of brain metastases in patients with HER2+ MBC, triple negative MBC, and HR+/HER2- MBC was reported in 17, 6, and 4 studies, respectively. The pooled cumulative incidence of brain metastases was 31% for the HER2+ subgroup (median follow-up: 30.7 months, IQR: 24.0 – 34.0), 32% for the triple negative subgroup (median follow-up: 32.8 months, IQR: 18.5 – 40.6), and 15% among patients with HR+/HER2- MBC (median follow-up: 33.0 months, IQR: 31.9 – 36.2). The corresponding incidences per patient-year were 0.13 (95% CI: 0.10 – 0.16) for the HER2+ subgroup, 0.13 (95%CI: 0.09 – 0.20) for the triple negative subgroup, and only 0.05 (95%CI: 0.03 – 0.08) for patients with HR+/HER2- MBC. Conclusion There is high incidence of brain metastases among patients with HER2+ and triple negative MBC. The utility of a brain metastases screening program warrants investigation in these populations.

Treatment Patterns and Outcomes of Women with Symptomatic and Asymptomatic Breast Cancer Brain Metastases: A Single-Center Retrospective Study

“…Although such data may suggest a benefit for earlier detection of breast cancer BrM, these findings are subject to lead-time-bias. Results of ongoing prospective randomized (NCT03881605, NCT04030507) and nonrandomized (NCT03617341) clinical trials are awaited to better understand the potential utility of a screening program for patients with breast cancer BrM, Previous studies have shown that patients with metastatic TNBC and HER2+ breast cancer, which represent approximately 15% and 15-20% of breast cancer cases respectively, have the highest risk of BrM [51,52]. In contrast, patients with HR+/HER2-disease represent approximately 65% of the MBC population [53,54] and have the lowest risk of BrM.…”

“…Previous studies have shown that patients with metastatic TNBC and HER2+ breast cancer, which represent approximately 15% and 15%–20% of breast cancer cases, respectively, have the highest risk of BrM [50, 51]. In contrast, patients with HR+/HER2− disease represent approximately 65% of the MBC population [52, 53] and have the lowest risk of BrM.…”

“…In the future, data regarding the intracranial efficacy of systemic therapies may be improved with enrollment of more patients with breast cancer BrM in clinical trials [61–63] and evaluation of CNS‐specific outcomes within those trials [60]. Given the very high risk of BrM among patients with HER2+ MBC [51], strategies for secondary prevention of BrM (e.g., using temozolomide [64]) are also being investigated.…”

Central Nervous System Metastases from Triple-Negative Breast Cancer: Current Treatments and Future Prospective

“…A recent meta-analysis showed that approximately one-third of those with TNBC will eventually develop brain metastasis. 19 A systematic review by Koniali et al identified younger age, hormonal and Her-2 receptor status, higher tumor stage and size, higher histological grade, high Ki67 labeling index as independent risk factors for Breast Cancer Brain Metastasis (BCBM). 20 Symptoms are variable and can be nausea, headaches, personality changes, seizures, paralysis, and cognitive impairment.…”

Atypical Presentation of Triple-Negative Breast Cancer

“…It's more probably that Metastatic TNBC affect to organs such as the brain by up to 32% compared to 15% of receptor-positive tumor [23]. They are less likely to affect bones (6.4%) in contrast to their luminal counterpart (9.4%), especially on patients under 40-years-old [24].…”