Abstract 5327: Upregulation of miR-10b associated with breast cancer metastasis to brain .

Abstract Background: Breast cancer is the most common non-skin cancer amongst women in the US. Breast cancer-related mortality is primarily due to metastatic disease, especially brain metastasis which also impacts patient's quality of life. The molecular mechanism of brain metastasis of breast cancer is largely unknown; however, finding molecular signatures of the primary breast cancer that have the propensity for brain metastasis would be very important for designing optimal primary treatment of breast cancer to prevent and eliminate brain metastasis. To that end targeting MicroRNAs (miRNAs) could become a novel prognostic and therapeutic strategy to prevent the future development of brain metastasis. Design: Breast cancer cases with brain metastasis diagnosed from 1994-2011 were retrieved from the computerized hospital database. The study cohort comprised of breast cancer cases with brain metastasis (n=18) and age, stage and follow-up matched breast cancer cases without brain metastasis (n= 10). All cases were microscopically reviewed to select tumor blocks with >50% tumor cells. RNA was extracted from formalin fixed paraffin embedded tumor tissue blocks. The miRNA expression analysis was done using RT-PCR. Data was statistically analyzed to determine the clinical significance using the Wilcoxon signed rank test. Results: Among several miRNAs that were analyzed in this study, we found that miR-10b was highly expressed in the primary breast cancer specimens of patients who subsequently developed brain metastasis compared to those who did not develop brain metastasis. Interestingly, the expression of miR-10b was reduced in brain metastatic specimens compared to primary breast cancer specimens. Using Wilcoxon signed rank test, there was statistically significant difference between the paired tumors from breast cancers and brain metastasis (p value <0.001). Conclusions: Increased expression of miR-10b appears to be associated with metastatic potential of the primary breast cancer; however, once the cancer metastasized to the brain (homing), its level was reduced. This interesting finding requires further mechanistic studies. Clinical relevance: Our findings are clinically very relevant since miR-10b could serve as a potential target for anti-metastatic therapy. The expression of miR-10b could be silenced using miR-10b antagomirs (chemically modified anti-miRNA oligonucleotides) for the prevention of brain metastasis, whereas once brain metastasis develops then it could be treated with miR-10b mimics for inducing its expression for the treatment. Therefore, development of miRNA-based prophylactic therapies could serve as personalized medicine against future brain metastasis of breast cancer which will improve patients’ quality of life and improve overall survival. Citation Format: Seema Sethi, Aamir Ahmad, Sandeep Mittal, Rouba Ali, Wei Chen, Fazlul H. Sarkar. Upregulation of miR-10b associated with breast cancer metastasis to brain . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5327. doi:10.1158/1538-7445.AM2013-5327