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Association of microRNAs and pathologic response to preoperative chemotherapy in triple negative breast cancer: preliminary report
Authors:Agnieszka Kolacinska  Jan Morawiec  Wojciech Fendler  Beata Malachowska  Zbigniew Morawiec  Janusz Szemraj  Zofia Pawlowska  Dipanjan Chowdhury  Young Eun Choi  Robert Kubiak  Lukasz Pakula  Izabela Zawlik
Institution:1. Department of Surgical Oncology, Copernicus Memorial Hospital, Cancer Center, Paderewskiego 4, 93-509, Lodz, Poland
2. Department of General and Colorectal Surgery, Medical University of Lodz, Hallera Sq. 1, 90-647, Lodz, Poland
3. Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, Sporna 36/50, 91-738, Lodz, Poland
4. Department of Medical Biochemistry, Medical University of Lodz, Mazowiecka 6/8, 92-215, Lodz, Poland
5. Central Laboratory Corelab, Medical University of Lodz, Mazowiecka 6/8, 92-215, Lodz, Poland
6. Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Av, Boston, MA, 02215, USA
7. Department of Pathology, Medical University of Lodz, Pabianicka 62, 93-513, Lodz, Poland
8. Department of Anesthesiology, Copernicus Memorial Hospital, Pabianicka 62, 93-513, Lodz, Poland
9. Department of Medical Genetics, Institute of Nursing and Health Sciences, Medical Department, University of Rzeszow, Rejtana 16c, 35-959, Rzeszow, Poland
Abstract:Triple negative breast cancer (TNBC) has caught the attention of oncologists worldwide because of poor prognosis and paucity of targeted therapies. Gene pathways have been widely studied, but less is known about epigenetic factors such as microRNAs (miRNAs) and their role in tailoring an individual systemic and surgical approach for breast cancer patients. The aim of the study was to examine selected miRNAs in TNBC core biopsies sampled before preoperative chemotherapy and the subsequent pathologic response in mastectomy or breast conservation specimens. Prior to treatment, core needle biopsies were collected from 11 female patients with inoperable locally advanced TNBC or large resectable tumors suitable for down-staging. In all 11 TNBC core biopsies we analyzed 19 miRNAs per sample: 512, 190, 200, 346, 148, 449, 203, 577, 93, 126, 423, 129, 193, 182, 136, 135, 191, 122 and 222 (miRCURY LNA? Universal RT microRNA polymerase chain reaction Custom Pick & Mixpanels). The Wilcoxon signed-rank test was used to compare related samples. Ingenuity pathway analysis was used to evaluate potential functional significance of differentially expressed miRNAs. Statistical analysis showed that 3 of 19 miRNAs differed in relation to pathologic response i.e. good versus poor. These differences failed to reach statistical significance, although a trend was observed (p = 0.06). Among these miRNAs, we identified—miR-200b-3p, miR-190a and miR-512-5p. In summary, our results indicate that higher miR-200b-3p, higher miR-190a and lower miR-512-5p expression levels in core biopsies sampled from TNBC patients may be associated with better pathologic response to chemotherapy and the increased feasibility of breast conserving surgery in these patients. Although these results were from a small cohort, they provide an important basis for larger, prospective, multicenter studies to investigate the potential role of miRNAs in neoadjuvant setting.
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