Abstract
registHER is a prospective, observational study of 1,023 newly diagnosed HER2-positive metastatic breast cancer (MBC) patients. Baseline characteristics of patients with and without central nervous system (CNS) metastases were compared; incidence, time to development, treatment, and survival after CNS metastases were assessed. Associations between treatment after CNS metastases and survival were evaluated. Of the 1,012 patients who had confirmed HER2-positive tumors, 377 (37.3%) had CNS metastases. Compared with patients with no CNS metastases, those with CNS metastases were younger and more likely to have hormone receptor-negative disease and higher disease burden. Median time to CNS progression among patients without CNS disease at initial MBC diagnosis (n = 302) was 13.3 months. Treatment with trastuzumab, chemotherapy, or surgery after CNS diagnosis was each associated with a statistically significant improvement in median overall survival (OS) following diagnosis of CNS disease (unadjusted analysis: trastuzumab vs. no trastuzumab, 17.5 vs. 3.8 months; chemotherapy vs. no chemotherapy, 16.4 vs. 3.7 months; and surgery vs. no surgery, 20.3 vs. 11.3 months). Although treatment with radiotherapy seemed to prolong median OS (13.9 vs. 8.4 months), the difference was not significant (P = 0.134). Results of multivariable proportional hazards analyses confirmed the independent significant effects of trastuzumab and chemotherapy (HR = 0.33, P < 0.001; HR = 0.64, P = 0.002, respectively). The effects of surgery and radiotherapy did not reach statistical significance (P = 0.062 and P = 0.898, respectively). For patients with HER2-positive MBC evaluated in registHER, the use of trastuzumab, chemotherapy, and surgery following CNS metastases were each associated with longer survival.
Highlights
For women with advanced breast cancer, 10% to 16% develop central nervous system (CNS) metastases [1, 2]
For patients with HER2-positive metastatic breast cancer (MBC) evaluated in registHER, the use of trastuzumab, chemotherapy, and surgery following CNS metastases were each associated with longer survival
Thirty-seven percent (377 of 1,012) of patients with MBC had a diagnosis of CNS metastases, 7% (75 of 1,012) at the time of their initial MBC diagnosis and 30% (302 of 1,012) as a subsequent site of disease progression (Fig. 1A)
Summary
For women with advanced breast cancer, 10% to 16% develop central nervous system (CNS) metastases [1, 2]. In a study that required prescreening for CNS lesions, 14.8% of patients had occult lesions [3] and autopsy data have revealed that up to 30% of patients with advanced metastatic breast cancer (MBC) have CNS metastases [4]. Several risk factors have been associated with the development of CNS lesions in patients with MBC, including younger age (
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