Brain Metastasis from Breast Cancer: Molecular Mechanisms

Introduction

Breast cancer is a frequent source of systemic metastatic disease. The spread of cancer cells, from a primary location to multiple sites in the body, was first labeled as “metastasis” (Greek: displacement, μɛτα′ = next + στα′σιζ = placement) by Jean Claude Recamier in 1829. The dissemination of breast cancer to the central nervous system has been reported by to occur in approximately 30% of patients with invasive breast cancer. Consequently, metastatic breast cancer afflicts a large number of patients and is a major challenge for routine oncology practice as reviewed by .

As reported by and , many clinical features have been depicted as being associated with a higher risk of developing brain metastasis (BM) from breast cancer; for example, patient age less than 50 years, or that four or more axillary lymph nodes are involved with metastatic disease and a high tumor grade. Existing therapeutic strategies for BM comprise whole-brain radiation therapy, stereotactic radiosurgery, or surgery combined with radiotherapy.

The “seed and soil” hypothesis

raised the question of whether the spread of metastases across different organs could be just a matter of chance. In his study, autopsy records of women with breast cancer revealed a nonrandom pattern of metastatic colonization. Therefore, the hypothesis that tumor cells (the “seed”) could have a specific affinity for the microenvironment of certain organs (the “soil”) was contemplated.

During the metastasis development, most neoplastic cells will be cleared from sites of trapping (lungs for instance) within a day or two. The fate of the survivors that succeed in extravasating is unclear. A few cells are believed to survive as indolent micrometastases and others would be capable of proliferating and give rise to a macroscopic and clinical significant metastasis. The latter event is the colonization process. The acquired ability to colonize is likely to involve significant changes in cell phenotype that depend in turn on multiple changes in the genetic and epigenetic regulators of cell proliferation, motility, and invasiveness. In keeping with Paget’s “soil and seed hypothesis,” it has been shown in animal models that specific sets of genes can increase the potential of breast cancer cell lines to colonize distant specific sites, for instance, brain ( ) and lung (reported by ).

You're Reading a Preview

Become a Clinical Tree membership for Full access and enjoy Unlimited articles

Become membership

If you are a member. Log in here