Short-term effects of cyclopentolate and tropicamide eye drops on macular choroidal thickness in myopic children.

BACKGROUND: To investigate the short-term effects of cyclopentolate and tropicamide eyedrops on choroidal thickness (ChT) in myopic children using placebo or low-dose atropine eyedrops. METHODS: The analysis included 242 myopic individuals (7-19 years) enrolled in two randomised placebo-controlled clinical trials of low-dose atropine eyedrops. Cycloplegia was induced using either one drop of 1% cyclopentolate (n = 161), two drops of 1% cyclopentolate (n = 32) or two drops of 1% tropicamide (n = 49). ChT measurements were taken using swept-source optical coherence tomography before and 30 min after administering the cycloplegic eye drops. A subset of 51 participants underwent test-retest measurements prior to cycloplegia. RESULTS: Mean changes in subfoveal ChT after two drops of tropicamide and one and two drops of cyclopentolate were -2.5 µm (p = 0.10), -4.3 µm (p < 0.001) and -9.6 µm (p < 0.001), respectively. Subfoveal ChT changes after one and two drops of cyclopentolate were significantly greater than the test-retest changes (test-retest mean change: -3.1 µm; p < 0.05), while the tropicamide group was not significantly different (p = 0.64). Choroidal thinning post-cyclopentolate was not significantly different between atropine and placebo treatment groups (p > 0.05 for all macular locations). The coefficient of repeatability (CoR) in the tropicamide group (range: 8.2-14.4 µm) was similar to test-retest (range: 7.5-12.2 µm), whereas greater CoR values were observed in the cyclopentolate groups (one drop: range: 10.8-15.3 µm; two drops: range: 12.2-24.6 µm). CONCLUSIONS: Cyclopentolate eye drops caused dose-dependent choroidal thinning and increased variation in pre- to post-cycloplegia measurements compared with test-retest variability, whereas tropicamide did not. These findings have practical implications for ChT measurements when cyclopentolate is used, particularly for successive measurements.

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.

Relevance of the 21-gene expression assay in male breast cancer: A systematic review and meta-analysis.

INTRODUCTION: The 21-gene assay provides prognostication for estrogen receptor positive, human epidermal growth factor receptor-2 negative (ER+/HER2-) early female breast cancer patients. This signature has not been validated in male breast cancer (MBC). METHODS: A systematic review and meta-analysis was performed in accordance to the PRISMA guidelines. Retrospective cohort studies comparing 21-gene assay scores in female and MBC were included. Dichotomous variables were pooled as odds ratios (OR) and associated 95% confidence intervals (CI) using the Mantel-Haenszel method. RESULTS: Six studies including 176,338 patients were included (mean age of 63.4 years, range: 33-88). Of these, 1.0% had MBC (1826/176,338) and 99.0% were female patients (174,512/176,338). MBC patients were more likely to have increased tumour stage, nodal involvement, and grade 3 disease (all P < 0.001) In MBC patients, the mean score was 18.8 (range: 11-26) vs. 13.4 (range 0-33) in female patients (P < 0.001). In MBC patients, 22.4% had scores >30 (408/1822) versus 18.3% in female patients (31,852/174,500). In female patients, 52.0% had scores <18 (90,787/174,500) versus 47.8% in MBC (471/1822). Overall, patients with female patients were as likely to have scores <18 (OR: 1.04, 95% CI: 0.94-1.16), scores 18-30 (OR: 1.12, 95% CI: 1.00-1.26) and scores >30 (OR: 0.69, 95% CI: 0.45-1.07) as MBC patients. CONCLUSION: There are similar anticipated scores for female and MBC undergoing 21-gene expression assay testing for early stage, ER+/HER2-breast cancer. In the absence of stage matching, cautious interpretation of these results is required. Validation of the 21-gene assay in MBC is still required.

Clinicopathological response to neoadjuvant therapies and pathological complete response as a biomarker of survival in human epidermal growth factor receptor-2 enriched breast cancer - A retrospective cohort study.

BACKGROUND: Human epidermal growth factor receptor-2 (HER2) is overexpressed in 20-25% of breast cancers. Complete eradication of disease following neoadjuvant therapies and chemotherapy has been referred to as pathological complete response (pCR). AIMS: To determine clinicopathological predictors of pCR to neoadjuvant therapies and to evaluate pCR as a surrogate to enhanced survival. METHODS: Consecutive female patients with HER2 positive (HER+) breast cancer managed surgically in a single institution between 2005 and 2015 were included. Descriptive statistics and binary logistic regression were used to determine predictors of pCR. Appraisal of pCR as a predictor of survival was performed using Kaplan-Meier curves and Cox regression analysis. RESULTS: 451 patients were included with a mean age of 56.6 ± 13.4 years (range 23-95). Disease-free (DFS) and overall survival (OS) was 82.3% (371/451) and 82.6% (376/451) respectively with a median follow-up of 108.0 months (range 3-184.0). 118 were treated in the neoadjuvant setting (26.2%): tumour size <50 mm (Odds Ratio (OR): 12.156, P = 0.023) and progesterone receptor negativity (OR: 2.762, P = 0.008) independently predicted breast pCR, while ductal carcinoma (OR: 3.203, P = 0.030) and grade 3 disease (OR: 2.788, P = 0.018) predicted axillary pCR. Both breast and axillary pCR predicted enhanced DFS (Hazard Ratio (HR): 0.470 & HR: 0.449) and OS (HR: 0.383 & HR: 0.307). Axillary pCR independently predicted improved OS (HR: 0.326). CONCLUSION: pCR is sensitive biomarker and surrogate to survival outcomes in HER2+ breast cancer. Patients likely to achieve pCR may be predicted from traditional clinicopathological characteristics and molecular parameters.