Evaluating the Role of Circulating MicroRNAs to Aid Therapeutic Decision Making for Neoadjuvant Chemotherapy in Breast Cancer

Abstract

Objective: To evaluate whether circulating micro ribonucleic acids (miRNAs) predict response to neoadjuvant chemotherapy (NAC) and inform decision-making in breast cancer patients. Introduction: Deciphering response to NAC remains a challenge. Those unlikely to respond may benefit from NAC de-escalation before completion, while “responders” should complete treatment. Establishing biomarkers which identify response to NAC is imperative to personalize treatment strategies. miRNAs are small noncoding RNA molecules which modulate genetic expression. miRNAs are believed to inform response to NAC. Methods: This prospective, multicenter trial (NCT01722851) recruited 120 patients treated with NAC across 8 Irish treatment sites. Predetermined miRNAs were quantified from patient whole bloods using relative quantification polymerase chain reactiond. Venous sampling was performed at diagnosis and midway during NAC. Trends in miRNA expression between timepoints were correlated with treatment response. Data analysis was performed using R 3.2.3. Results: A total of 120 patients were included (median age: 55 years). Overall, 49.2% had luminal breast cancers (59/120), 17.5% luminal B (L/HER2) (21/120), 12.5% human epidermal growth factor receptor-2 positive (HER2+) (15/120), and 20.8% triple negative disease (25/120). In total, 46.7% of patients responded to NAC (56/125) and 26.7% achieved a pathological complete response (pCR) (32/120). For patients with L/HER2, increased Let-7a predicted response to NAC (P=0.049), while decreased miR-145 predicted response to NAC in HER2+ (P=0.033). For patients with luminal breast cancers, reduced Let-7a predicted achieving a pCR (P=0.037) and reduced miR-145 predicted achieving a pCR to NAC in HER2+ (P=0.027). Conclusions: This study illustrates the potential value of circulatory miRNA measurement in predicting response to NAC. Further interrogation of these findings may see miRNAs personalize therapeutic decision-making for patients undergoing NAC for early breast cancer.

Evaluating the Fragility of Long-Term Outcomes for Neoadjuvant versus Adjuvant Chemotherapy Prescription in Early Breast Cancer: Pooled Data from 10 Randomised Clinical Trials

“…Furthermore, these data demonstrated little “fragility” with respect to the use of NAC to increase patient eligibility for BCS, therefore fortifying the increase in NAC prescription which has come into vogue in recent times, due to the advantages of this strategy in substraifiying cancer subtypes. 4 , 26 Notwithstanding, judicious application of FI is warranted, as “fragility” analyses alone are not robust enough to revoke multidisciplinary decisions regarding systemic therapies when treating patients with early breast cancer.…”

Assessing the Role of MicroRNAs in Predicting Breast Cancer Recurrence—A Systematic Review

“…MicroRNAs (miRNAs) are small non-coding RNAs which are approximately 19 to 25 nucleotides in length [ 5 ] which are now recognised as key modulators of genetic expression [ 6 ]. MicroRNAs act at a post-transcriptional level by binding to messenger RNA (mRNA) and influencing protein synthesis at a cellular level [ 7 ]. Recent data has illustrated the relevance of miRNA measurement to predict response to therapeutic strategies [ 7 , 8 , 9 , 10 ], enhancing cancer diagnostics [ 11 , 12 ], and predicting long-term outcomes for those diagnosed with malignancy [ 13 , 14 ].…”

“…MicroRNAs act at a post-transcriptional level by binding to messenger RNA (mRNA) and influencing protein synthesis at a cellular level [ 7 ]. Recent data has illustrated the relevance of miRNA measurement to predict response to therapeutic strategies [ 7 , 8 , 9 , 10 ], enhancing cancer diagnostics [ 11 , 12 ], and predicting long-term outcomes for those diagnosed with malignancy [ 13 , 14 ]. In combination, these favourable characteristics illustrate the candidacy of miRNAs as biomarkers in the context of breast cancer research [ 15 , 16 , 17 , 18 ].…”

The Potential of MicroRNAs as Clinical Biomarkers to Aid Ovarian Cancer Diagnosis and Treatment

“…The molecules are approximately 19 to 25 nucleotides in length and have been illustrated to play an integral role in regulating gene expression [ 23 , 24 ]. MiRNAs were first described by Lee et al in 1993 when studying developmental timing of Caenorhabditis elegans [ 25 ], and the scientific understanding of the role of miRNA has exponentially grown in recent years, with aberrant miRNA expression profiles now understood to correlate with several diverse pathological processes, including oncogenesis [ 26 , 27 , 28 , 29 ]. MiRNAs regulate gene expression at a post-transcriptional level by binding to the 3′ or 5′ untranslated regions of target messenger RNA (mRNA), hindering mRNA expression through degradation or translation inhibition.…”