Background: Locally advanced triple negative breast cancer (laTNBC) patient's exhibits resistance to neoadjuvant chemotherapy (NC) and poor survival. Distinct therapeutic combinations have been used to reduce high mortality. Recently, novel regimens of NC for laTNBC have achieved pathological complete response (pCR) rates of 10-50%. Evaluation of pCR during oncologic treatment is decisive to identify those patients that response or not response to NC. MicroRNAs (miRNAs) are small non-coding RNAs that represent novel and potential predictive biomarkers useful to identify the patients who will get pCR in cancer.
Methods: Thirty-five patients diagnosed with laTNBC, were invited to participate in this study and enrolled after they signed an informed consent. The 22 patients with pCR and 13 patients without pCR received the experimental NC fluorouracil, adriamycin, cyclophosphamide, cisplatin, paclitaxel (FAC--CDDP/paclitaxel). MiRNA expression profiling was evaluated for 754 miRNAs. A discovery cohort (n=10 pCR and n=8 no-pCR) and a validation cohort (n=12 pCR and n=5 no-pCR). Bioinformatics analysis revealed the affected cellular pathways in pCR group. After a median clinical follow-up of 60 months, statistical analysis was performed to identify miRNAs that could discriminate pCR from no-pCR by using FAC--CDDP/paclitaxel.
Results: MiRNAs expression profiling identified 11 miRNAs that showed significant differences between pCR and no-pCR (p<0.05 and fold change >1.5) groups. Eight miRNAs (miR-9-3p, -30a-3p, -135b, -135b*, -380-5p, -941, -652 and miR-181c*) were upregulated and three miRNAs (miR-770-5p, -584 and miR-143) were downregulated in pCR patients. The altered cellular pathways for the set of miRNAs were PI3K/AKT, FoxO, Ras and ERBB (p<0.05). Four differentially expressed miRNAs (miR-770-5p, miR-143-5p, miR-30a-3p, miR-9-3p) were confirmed in the validation phase. Expression of these miRNAs above the median level was a significant predictor of pCR to experimental NC in laTNBC patients (p<0.001).
Conclusions: These four validated miRNAs could be used as predictors of pCR in response to FAC---CDDP/Paclitaxel treatment in laTNBC patients.
Citation Format: Vázquez RG, Camarillo CL, Marchau LM, García ER, Miranda AA, Martínez HM, Parra AC, De la Vega HA, Barrios AG, Cuevas SR. A microRNA signature associated with pathological complete response to a novel neoadjuvant therapy regimen in triple negative breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-10-11.
