Circulating microRNAs can predict chemotherapy-induced toxicities in patients being treated for primary breast cancer.

PURPOSE: Prescribing NAC for breast cancer is a pragmatic treatment strategy for several reasons; however, certain patients suffer chemotherapy-induced toxicities. Unfortunately, identifying patients at risk of toxicity often proves challenging. MiRNAs are small non-coding RNA molecules which modulate genetic expression. The aim of this study was to determine whether circulating miRNAs are sensitive biomarkers that can identify the patients likely to suffer treatment-related toxicities to neoadjuvant chemotherapy (NAC) for primary breast cancer. METHODS: This secondary exploratory from the prospective, multicentre translational research trial (CTRIAL ICORG10/11-NCT01722851) recruited 101 patients treated with NAC for breast cancer, from eight treatment sites across Ireland. A predetermined five miRNAs panel was quantified using RQ-PCR from patient bloods at diagnosis. MiRNA expression was correlated with chemotherapy-induced toxicities. Regression analyses was performed using SPSS v26.0. RESULTS: One hundred and one patients with median age of 55 years were recruited (range: 25-76). The mean tumour size was 36 mm and 60.4% had nodal involvement (n = 61) Overall, 33.7% of patients developed peripheral neuropathies (n = 34), 28.7% developed neutropenia (n = 29), and 5.9% developed anaemia (n = 6). Reduced miR-195 predicted patients likely to develop neutropenia (P = 0.048), while increased miR-10b predicted those likely to develop anaemia (P = 0.049). Increased miR-145 predicted those experiencing nausea and vomiting (P = 0.019), while decreased miR-21 predicted the development of mucositis (P = 0.008). CONCLUSION: This is the first study which illustrates the value of measuring circulatory miRNA to predict patient-specific toxicities to NAC. These results support the ideology that circulatory miRNAs are biomarkers with utility in predicting chemotherapy toxicity as well as treatment response.

Evaluating the Necessity for Routine Sentinel Lymph Node Biopsy in Postmenopausal Patients Being Treated for Clinically Node Negative Breast Cancer the Era of RxPONDER.

INTRODUCTION: Traditionally, sentinel lymph node biopsy (SLNB) was performed to inform adjuvant chemotherapy prescription and prognosis in breast cancer. Following RxPONDER, the OncotypeDX Recurrence Score (RS) guides adjuvant chemotherapy prescription for all postmenopausal patients with estrogen receptor positive, human epidermal growth factor receptor-2 negative (ER+/HER2-) breast cancer with 0 to 3 positive lymph nodes (0-3 + LN). AIMS: To establish the oncological safety of omitting SLNB in postmenopausal patients with ER+/HER2- breast cancer indicated to undergo SLNB and to evaluate the primary determinants of chemotherapy prescription for these patients. PATIENTS AND METHODS: A retrospective cohort study was undertaken. Cox regression and Kaplan-Meier analyses were performed. Data analytics was performed using SPSS v26.0. RESULTS: Five hundred and seventy five consecutive patients were included (mean age: 66.5 years, range: 45-96). The median follow-up was 97.2 months (range: 3.0-181.6). Of the 575 patients, just 12 patients had positive SLNB (SLNB+) (2.1%). Using Kaplan-Meier analyses, SLNB+ failed to impact recurrence (P = .766) or mortality (P = .310). However, using Cox regression analyses, SLNB+ independently predicted poorer disease-free survival (hazard ratio: 1.001, 95% confidence interval (95% CI): 1.000-1.001, P = .029). Logistic regression analysis identified RS as the sole predictor of chemotherapy prescription (odds ratio: 1.171, 95% CI: 1.097-1.250, P < .001). CONCLUSION: Omitting SLNB may be safe and justifiable in postmenopausal patients with ER+/HER2- breast cancer with clinically negative axillae. Following RxPONDER, RS is the most important guide of chemotherapy use in these patients and SLNB may be less important than previously perceived. Prospective, randomized clinical trials are required to fully establish the oncological safety of omitting SLNB in this setting.

Comparison of the Nottingham Prognostic Index and OncotypeDX© recurrence score in predicting outcome in estrogen receptor positive breast cancer.

INTRODUCTION: Traditionally, Nottingham prognostic index (NPI) informed prognosis in patients with estrogen receptor positive, human epidermal growth factor receptor-2 negative, node negative (ER+/HER2-/LN-) breast cancer. At present, OncotypeDX© Recurrence Score (RS) predicts prognosis and response to adjuvant chemotherapy (AC). AIMS: To compare NPI and RS for estimating prognosis in ER + breast cancer. METHODS: Consecutive patients with ER+/HER2-/LN- disease were included. Disease-free (DFS) and overall survival (OS) were determined using Kaplan-Meier and Cox regression analyses. RESULTS: 1471 patients met inclusion criteria. The mean follow-up was 110.7months. NPI was calculable for 1382 patients: 19.8% had NPI≤2.4 (291/1471), 33.0% had NPI 2.41-3.4 (486/1471), 30.0% had NPI 3.41-4.4 (441/1471), 10.9% had NPI 4.41-5.4 (160/1471), and 0.3% had NPI>5.4 (4/1471). In total, 329 patients underwent RS (mean RS: 18.7) and 82.1% had RS < 25 (270/329) and 17.9% had RS ≥ 25 (59/329). Using multivariable Cox regression analyses (n = 1382), NPI independently predicted DFS (Hazard ratio (HR): 1.357, 95% confidence interval (CI): 1.140-1.616, P < 0.001) and OS (HR: 1.003, 95% CI: 1.001-1.006, P = 0.024). When performing a focused analysis of those who underwent both NPI and RS (n = 329), neither biomarker predicted DFS or OS. Using Kaplan Meier analyses, NPI category predicted DFS (P = 0.008) and (P = 0.026) OS. Conversely, 21-gene RS group failed to predict DFS (P = 0.187) and OS (P = 0.296). CONCLUSION: In our focused analysis, neither NPI nor RS predicted survival outcomes. However, in the entire series, NPI independently predicted both DFS and OS. On the 40th anniversary since its derivation, NPI continues to provide accurate prognostication in breast cancer, outperforming RS in the current study.