Abstract A82: Identifying differentially expressed microRNAs as investigational tools in postpartum breast cancer in Hispanic women Free

The risk of breast cancer transiently increases immediately following pregnancy; peaking between 3-7 years. The biology that underlies this risk window and the effect on the natural history of the disease is unknown. MicroRNAs (miRNAs) are small, non-coding RNAs that have been shown to be dysregulated in breast cancer. Utilizing a quantitative RT-PCR approach, we profiled the expression pattern of 355 miRNAs across 56 formalin-fixed, paraffin embedded breast tumor tissue samples from multiparous Hispanic women. Based on a data-driven splitting of the expression pattern of the 355 miRNAs, the case series was separated into two groups based on time since last full-term pregnancy (TSLFTP): a) an early group representing women diagnosed with breast cancer ≤ 5.2 years postpartum (n=12); and b) a late group representing women diagnosed with breast cancer ≥ 5.3 years postpartum (n=44). We identified 15 miRNAs with significant differential expression between the early and late postpartum groups. Ten miRNAs had a two-fold or higher difference in expression, with miR-138, miR-660, miR-31, miR-135b, miR-17, miR-454, and miR-934 overexpressed in the early versus the late group; while miR-892a, miR-199a-5p, and miR-542-5p were overexpressed in the late versus the early postpartum group. Further analysis of the miRNA expression data demonstrated that 60% of the identified differentially expressed miRNAs are encoded on the X chromosome, with several miRNAs found together in miRNA gene clusters. Additionally, DNA methylation, measured using a Sequenom MassARRAY, demonstrated that three out of five tested miRNA genes (mir-31, mir-135b, and mir-138-2) had a lower mean methylation in the early versus late postpartum group, and negatively correlated with miRNA expression. In summary, we have identified miRNAs that are differentially expressed and differentially methylated between tumors of the early versus late postpartum, suggesting that potential differences in epigenetic regulation may exist in the postpartum breast cancers.

Citation Format: José L. Muñoz-Rodríguez, Lukas Vrba, Chengcheng Hu, Patricia A. Thompson, Maria Elena Martinez, Bernard W. Futscher. Identifying differentially expressed microRNAs as investigational tools in postpartum breast cancer in Hispanic women. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr A82.