Abstract
Patients with HER2-positive metastatic breast cancer (MBC) with central nervous system (CNS) metastasis have a poor prognosis. We report treatments and outcomes in patients with HER2-positive MBC and CNS metastasis from the Systemic Therapies for HER2-positive Metastatic Breast Cancer Study (SystHERs). SystHERs (NCT01615068) was a prospective, U.S.-based, observational registry of patients with newly diagnosed HER2-positive MBC. Study endpoints included treatment patterns, clinical outcomes, and patient-reported outcomes (PRO). Among 977 eligible patients enrolled (2012-2016), CNS metastasis was observed in 87 (8.9%) at initial MBC diagnosis and 212 (21.7%) after diagnosis, and was not observed in 678 (69.4%) patients. White and younger patients, and those with recurrent MBC and hormone receptor-negative disease, had higher risk of CNS metastasis. Patients with CNS metastasis at diagnosis received first-line lapatinib more commonly (23.0% vs. 2.5%), and trastuzumab less commonly (70.1% vs. 92.8%), than patients without CNS metastasis at diagnosis. Risk of death was higher with CNS metastasis observed at or after diagnosis [median overall survival (OS) 30.2 and 38.3 months from MBC diagnosis, respectively] versus no CNS metastasis [median OS not estimable: HR 2.86; 95% confidence interval (CI), 2.05-4.00 and HR 1.94; 95% CI, 1.52-2.49]. Patients with versus without CNS metastasis at diagnosis had lower quality of life at enrollment. Despite advances in HER2-targeted treatments, patients with CNS metastasis continue to have a poor prognosis and impaired quality of life. Observation of CNS metastasis appears to influence HER2-targeted treatment choice.
Highlights
HER2-positive metastatic breast cancer (MBC) is associated with a high incidence of central nervous system (CNS) metastasis [1,2,3,4,5,6], a development typically associated with poor survival and a negative impact on quality of life [7]
Risk of death was higher with CNS metastasis observed at or after diagnosis [median overall survival (OS) 30.2 and 38.3 months from MBC diagnosis, respectively] versus no CNS metastasis [median OS not estimable: HR 2.86; 95% confidence interval (CI), 2.05–4.00 and HR 1.94; 95% CI, 1.52–2.49]
Eighty-seven patients (8.9%) had CNS metastasis reported at initial MBC diagnosis, 212 (21.7%) had CNS metastasis detected after MBC diagnosis, and 678 (69.4%) had no observed CNS metastasis as of the October 3, 2017, data cutoff date
Summary
HER2-positive metastatic breast cancer (MBC) is associated with a high incidence of central nervous system (CNS) metastasis [1,2,3,4,5,6], a development typically associated with poor survival and a negative impact on quality of life [7]. Diagnoses of CNS metastasis have increased over time in patients with HER2-positive MBC, likely due to improved detection and longer survival associated with the advent of HER2-targeted therapies over the past two decades [8]. The first HER2-targeted treatment, trastuzumab, was approved in the United States in 1998. An analysis of data from registHER, a prospective, observational study that enrolled patients with HER2-positive MBC, found that trastuzumab-based regimens were significantly associated with increased overall survival (OS) in patients with CNS metastasis [3]. In the time since registHER completed enrollment, several additional HER2-targeted therapies have been approved for HER2-positive MBC in the United States, including lapatinib, a small-molecule tyrosine kinase inhibitor, in 2007; pertuzumab, a HER2-targeted antibody, in 2012; and trastuzumab emtansine (T-DM1), an antibody–drug conjugate, in 2013. On the basis of results from the pivotal phase III CLEOPATRA trial [9,10,11], the www.aacrjournals.org
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