Systemic therapy following craniotomy in patients with a solitary breast cancer brain metastasis

Alexander F C Hulsbergen,Timothy R Smith,Nancy U Lin,Logan D Cho,Marike L D Broekman,Marco Mammi,Priscilla K Brastianos,Nayan Lamba

doi:10.1007/s10549-020-05531-7

Abstract

PurposeTo describe practice patterns and patient outcomes with respect to the use of postoperative systemic therapy (ST) after resection of a solitary breast cancer brain metastasis (BCBM).MethodsA multi-institutional retrospective review of consecutive patients undergoing resection of a single BCBM without extracranial metastases was performed to describe subtype-specific postoperative outcomes and assess the impact of types of ST on site of recurrence, progression-free survival (PFS), and overall survival (OS).ResultsForty-four patients were identified. Stratified estimated survival was 15, 24, and 23 months for patients with triple negative, estrogen receptor positive (ER+), and HER2+ BCBMs, respectively. Patients receiving postoperative ST had a longer median PFS (8 versus 4 months, adjusted p-value 0.01) and OS (32 versus 15 months, adjusted p-value 0.21). Nine patients (20%) had extracranial progression, 23 (52%) had intracranial progression, three (8%) had both, and nine (20%) did not experience progression at last follow-up. Multivariate analysis showed that postoperative hormonal therapy was associated with longer OS (HR 0.26; 95% CI 0.08–0.89; p = 0.03) but not PFS (HR 0.35, 95% CI 0.08–1.47, p = 0.15) in ER+ patients. Postoperative HER2-targeted therapy was not associated with longer OS or PFS in HER2+ patients.ConclusionsDisease progression occurred intracranially more often than extracranially following resection of a solitary BCBM. In ER+ patients, postoperative hormonal therapy was associated with longer OS. Postoperative HER2-targeted therapy did not show survival benefit in HER2+ patients. These results should be validated in larger cohorts.

Highlights

Brain metastases are the most common intracranial tumors and frequently originate from lung cancer, melanoma, or breast cancer [1, 2]
Since only four patients received postoperative chemotherapy, we were unable to meaningfully analyze the effects of this treatment on progression-free survival (PFS) and overall survival (OS). This retrospective, multi-institutional study analyzed the outcomes of breast cancer patients after resection of a solitary breast cancer brain metastases (BCBM) and explored the impact of postoperative systemic therapy (ST) strategies on PFS and OS
In approximately half of patients, the brain was the first site of subsequent progression, whereas extracranial progression was the first site of subsequent progression in only 20% of patients

Summary

Introduction

Brain metastases are the most common intracranial tumors and frequently originate from lung cancer, melanoma, or breast cancer [1, 2]. The prognosis of patients with breast cancer brain metastases (BCBM) has historically been poor, but advances in systemic therapy (ST) have prolonged survival primarily by providing better extracranial control [3, 4]. The blood–brain barrier (BBB) denies many systemic agents optimal access to the central nervous system (CNS), creating a sanctuary site for distant metastases [5]. This has led to an increase in the incidence of BMs, including those in the absence of extracranial disease [6, 7]. In the absence of extracranial metastases, there is considerable practice variation in the administration of postoperative ST for these patients, due to a lack of data demonstrating benefit [10]

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