Leptomeningeal Metastasis in ER + HER2- Advanced Breast Cancer Patients: A Review of the Cases in a Single Institute Over a 15-year Period.

Junichiro Watanabe,Hideyuki Harada,Nakamasa Hayashi,Shoichi Deguchi,Koichi Mitsuya,Yoko Nakasu,Shogo Nakamoto

doi:10.1007/s10549-021-06246-z

Abstract

While leptomeningeal metastasis (LM) from estrogen receptor-positive, HER2-negative advanced breast cancer (ER + HER2-ABC) has a poor prognosis, the details of ER + HER2-LM are unclear. We therefore retrospectively investigated patients with LM from ER + HER2-ABC. ER + HER2-ABC patients who received any therapy at Shizuoka Cancer Center between October 2002 and December 2017 were retrospectively analyzed. Patients with central nervous system (CNS) metastases were divided into three groups: brain metastasis (BM) only (B group); BM with LM (BL group); and LM only (L group). Among 369 patients, 102 developed CNS metastases: 70 (68.6%), 13 (12.8%), and 19 (18.6%) in the B, BL, and L groups, respectively. The L group showed a later onset, poorer performance status, more symptoms, and more skull metastasis than the other groups. Radiotherapy as the initial treatment was introduced to 13/13 (100%) and 15/19 (78.9%) in the BL and L groups, respectively. Subsequent systemic therapy excluding best supportive care was introduced to 5/13 (38.5%) and 5/19 (26.3%) in the BL and L groups, respectively. The median overall survival from the diagnosis of CNS lesions was 295.0, 146.0, and 99.0 days in the B, BL, and L groups, respectively, and worsening of CNS lesions was the major cause of death in the BL and L groups. Multivariate analyses showed that concurrent soft tissue metastasis (hazard ratio, 4.620) and subsequent systemic therapy (hazard ratio, 0.063) were prognostic for the L group. Management of LM from ER + HER2-ABC remains challenging, so a multimodal approach with novel systemic therapy is warranted.

Highlights

Metastases to the central nervous system (CNS) is commonly seen in up to 25% of advanced breast cancer (ABC) patients [1]; the pattern of development of CNS metastases and the prognosis after the diagnosis of CNS metastases differ among ABC subtypes [2]
HER2 + subtypes; the epidemiology and outcome of patients with leptomeningeal metastasis (LM) from ER + HER2-ABC remain unclear because of the notably poor outcome compared with brain metastasis (BM) [6,7,8,9].in the present study, we retrospectively investigated the actual situation of ER + HER2-ABC patients with LM in a single institute
The majority of patients with CNS lesions were classified into the B group (n = 70, 68.6%), followed by the L group (n = 19, 18.6%) and BL group (n = 13, 12.8%)

Summary

Introduction

Metastases to the central nervous system (CNS) is commonly seen in up to 25% of advanced breast cancer (ABC) patients [1]; the pattern of development of CNS metastases and the prognosis after the diagnosis of CNS metastases differ among ABC subtypes [2]. In patients with human epidermal growth factor receptor-2-positive (HER2+) ABC, CNS metastases develop in the late phase of the disease and in its early phase. HER2-negative (HER2-) ABC patients develop CNS metastases mostly in the late phase of the illness (i.e. when patients become refractory to systemic therapies) [2, 3]. In HER2 + ABC, novel systemic therapies (e.g. tyrosine kinase inhibitor [TKI] [4] and antibody drug conjugate [ADC] [5]) are expected to improve the patient survival, regardless of concomitant CNS metastases. The outcomes of patients with CNS metastases may differ by the primary disease subtype and by the metastasis pattern.

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Discussion

Conclusion