Central nervous system miliary metastasis in breast cancer: a case series analysis and proposed identification criteria of a rare metastasis subtype

Abstract

Background: CNS miliary metastasis (MiM) is poorly recognised in breast and other malignancies. Given its rarity, little epidemiologic, radiographic and clinical data are known. Although usually identified on neuroimaging, criteria for radiographic diagnosis do not exist. In this analysis, we establish its presence in breast cancer and identify factors contributing to outcome.

Methods: We identified 546 female patients with brain metastasis from breast cancer between 2000 and 2015. Radiographic criteria were established through review of neuroimages by a senior Neuroradiologist, and defined as: (1) ≥20 lesions per image on ≥2 non-contiguous MRI images or ≥10 lesions per image on ≥2 non-contiguous CT images, and (2) bilateral lesions located in both the supratentorial and infratentorial compartments.

Results: Twenty-one MiM cases were identified (3.8%). Number and anatomical distribution of metastases best identified MiM, while lesion size did not. Ten patients were diagnosed with MiM as initial CNS metastasis; 11 developed MiM following known CNS metastasis. Breast cancer subtype did not influence MiM development before or after other CNS metastasis.

Conclusions: This is the first study to propose radiographic criteria for MiM diagnosis. Additional analysis is needed to verify data, but our results may enable a standardised approach for future MiM research.

Fig. 1. Flow chart of patients assessed for eligibility, those excluded, and final study cohort according to type of brain metastasis identified.

IP intraparenchymal; CNS MiM central nervous system miliary metastasis; LMD leptomeningeal disease.

Fig. 2. Kaplan–Meier curve representing survival after miliary metastasis diagnosis according to breast cancer subtype.

HR+/HER2+ hormone receptor positive and human epithelial growth factor 2 positive; HR+/HER2− HR positive but HER2 negative; HR−/HER2+ HR negative but HER2 positive; TNBC triple-negative breast cancer (HR−/HER2−).

Fig. 3. Patients with typical miliary metastatic lesions seen on neuroimaging.

a Example of miliary metastasis with concomitant imaging diagnosis of leptomeningeal disease (LMD denoted by arrow). b Example of miliary metastasis with lesions of various sizes, reinforcing our decision to include lesion number and anatomical distribution in our radiographic definition but not rely on lesion size.