Breast Cancer Metastasis

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.

Mechanisms of disseminated cancer cell dormancy: an awakening field

“…Finally, proper clinical trials to test dormancy therapies are essential. As recently explained 135,136 , clinical trials that use the time to first metastasis and the time to next metastasis as clinical parameters may help to determine whether new drugs are affecting dormant DTCs or whether they are inducing dormancy of proliferative DTCs. Importantly, not all cancers may be clinically dormant after diagnosis and treatment as some, like triple-negative breast cancer or pancreatic cancer, can recur as early as 3 years after ending treatment.…”

Medicine in the early twenty-first century: paradigm and anticipation - EPMA position paper 2016

“…However, in order to make anticipation by personalised medicine as realistic as possible, this term should be pragmatically sub-divided into its clear subcategories, namely “semi-personalised” versus “true personalised” as it has been discussed and published elsewhere in scientific literature [10]. …”

Breast Cancer Recurrence Risk Assessment: Is Non-Invasive Monitoring an Option?

“…While the median survival was 53 months if only one focus was found, it dropped to a median survival of 22 months when > 3 osseous sites were involved. In contrast, follow-up studies of patients diagnosed early on with solitary MBC to the bone showed that disease remission – or complete cure in cases of oligometastatic BC – could be achieved by early therapeutic interventions such as radiotherapy, vertebroplasty and ky phoplasty, bisphosphonates, denosumab, and endocrine- and/or HER2-directed therapies [39, 40]. …”