Breast cancer metastasis: issues for the personalization of its prevention and treatment

Abstract

Despite important progress in adjuvant and neoadjuvant therapies, metastatic disease often develops in breast cancer patients and remains the leading cause of their deaths. For patients with established metastatic disease, therapy is palliative, with few breaks and with mounting adverse effects. Many have hypothesized that a personalized or precision approach (the terms are used interchangeably) to cancer therapy, in which treatment is based on the individual characteristics of each patient, will provide better outcomes. Here, we discuss the molecular basis of breast cancer metastasis and the challenges in personalization of treatment. The instability of metastatic tumors remains a leading obstacle to personalization, because information from a patient's primary tumor may not accurately reflect the metastasis, and one metastasis may vary from another. Furthermore, the variable presence of tumor subpopulations, such as stem cells and dormant cells, may increase the complexity of the targeted treatments needed. Although molecular signatures and circulating biomarkers have been identified in breast cancer, there is lack of validated predictive molecular markers to optimize treatment choices for either prevention or treatment of metastatic disease. Finally, to maximize the information that can be obtained, increased attention to clinical trial design in the metastasis preventive setting is needed.

Figure 1

The complex of challenges in personalizing therapy in breast cancer metastasis. Metastasis is an intricate disease state, and many aspects of its biology and origin remain poorly understood. Thus, the complexity of the disease (with its genetic instability, tumor heterogeneity, and dormancy phenotype) limits accurate diagnosis and tailoring of treatments for patients. The lack of validated predictive biomarkers able to determine treatment choice and scarcity of metastasis-specific clinical trials constitutes a further limitation for implementation of personalized medicine in breast cancer metastasis.