Introduction: Breast cancer related mortality is primarily due to metastatic disease. Brain metastases from primary breast cancer are difficult to treat and associated with poor prognosis. Our understanding of the molecular basis for the development of such cancers is sparse. We hypothesized that the pro-metastatic microRNA-10b (miR-10b) plays a role in breast cancer brain metastasis.
Methods: The study cohort comprised of twenty patients with breast cancer and brain metastasis as well as ten control patients (age, stage, and follow-up matched) with breast cancer without brain metastasis. All cases were microscopically reviewed to select tumor blocks with >50% tumor cells. RNA was extracted from formalin fixed paraffin embedded (FFPE) tumor tissue blocks. Expression of miR-10b was analyzed using qRT-PCR. The relevance of miR-10b expression was also tested using human breast cancer cell lines.
Results: An increased expression of miR-10b was noted in the primary breast cancer specimens of patients who subsequently developed brain metastasis, compared to those who did not. miR-10b also increased the invasive potential of breast cancer cells in vitro. Wilcoxon signed rank test revealed a statistically significant difference between the paired tumors from breast cancers and brain metastasis (p<0.001).
Conclusions: Increased expression of miR-10b appears to be associated with breast cancer brain metastasis. These findings are clinically very relevant since miR-10b could serve as a prognostic and/or therapeutic target for anti-metastatic therapy. Identifying molecular signatures of primary breast cancer which have a propensity for brain metastasis is critical for designing novel therapies to prevent and eliminate or delay the development of brain metastasis in patients diagnosed with breast cancer.
Patient Care: Development of microRNA-based therapies could serve as personalized medicine that might ultimately improve patients’ quality of life, reduce healthcare costs, and improve overall survival.
Learning Objectives: By the conclusion of this session, participants should be able to:
1) Describe the importance of the small non-coding microRNAs in development of brain metastases.
2) Discuss the role of microRNA-10b in breast cancer brain metastasis.
3) Discuss the potential of microRNAs a prognostic and therapeutic targets.