Monitoring response to neoadjuvant chemotherapy in triple negative breast cancer using circulating tumor DNA.

BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive subtype with poor prognosis. We aimed to determine whether circulating tumor DNA (ctDNA) and circulating tumor cell (CTC) could predict response and long-term outcomes to neoadjuvant chemotherapy (NAC). METHODS: Patients with TNBC were enrolled between 2017-2021 at The University of Texas MD Anderson Cancer Center (Houston, TX). Serial plasma samples were collected at four timepoints: pre-NAC (baseline), 12-weeks after NAC (mid-NAC), after NAC/prior to surgery (post-NAC), and one-year after surgery. ctDNA was quantified using a tumor-informed ctDNA assay (SignateraTM, Natera, Inc.) and CTC enumeration using CellSearch. Wilcoxon and Fisher's exact tests were used for comparisons between groups and Kaplan-Meier analysis used for survival outcomes. RESULTS: In total, 37 patients were enrolled. The mean age was 50 and majority of patients had invasive ductal carcinoma (34, 91.9%) with clinical T2, (25, 67.6%) node-negative disease (21, 56.8%). Baseline ctDNA was detected in 90% (27/30) of patients, of whom 70.4% (19/27) achieved ctDNA clearance by mid-NAC. ctDNA clearance at mid-NAC was significantly associated with pathologic complete response (p = 0.02), whereas CTC clearance was not (p = 0.52). There were no differences in overall survival (OS) and recurrence-free survival (RFS) with positive baseline ctDNA and CTC. However, positive ctDNA at mid-NAC was significantly associated with worse OS and RFS (p = 0.0002 and p = 0.0034, respectively). CONCLUSIONS: Early clearance of ctDNA served as a predictive and prognostic marker in TNBC. Personalized ctDNA monitoring during NAC may help predict response and guide treatment.

Diffusion Tensor Imaging for Characterizing Changes in Triple-Negative Breast Cancer During Neoadjuvant Systemic Therapy.

BACKGROUND: Assessment of treatment response in triple-negative breast cancer (TNBC) may guide individualized care for improved patient outcomes. Diffusion tensor imaging (DTI) measures tissue anisotropy and could be useful for characterizing changes in the tumors and adjacent fibroglandular tissue (FGT) of TNBC patients undergoing neoadjuvant systemic treatment (NAST). PURPOSE: To evaluate the potential of DTI parameters for prediction of treatment response in TNBC patients undergoing NAST. STUDY TYPE: Prospective. POPULATION: Eighty-six women (average age: 51 ± 11 years) with biopsy-proven clinical stage I-III TNBC who underwent NAST followed by definitive surgery. 47% of patients (40/86) had pathologic complete response (pCR). FIELD STRENGTH/SEQUENCE: 3.0 T/reduced field of view single-shot echo-planar DTI sequence. ASSESSMENT: Three MRI scans were acquired longitudinally (pre-treatment, after 2 cycles of NAST, and after 4 cycles of NAST). Eleven histogram features were extracted from DTI parameter maps of tumors, a peritumoral region (PTR), and FGT in the ipsilateral breast. DTI parameters included apparent diffusion coefficients and relative diffusion anisotropies. pCR status was determined at surgery. STATISTICAL TESTS: Longitudinal changes of DTI features were tested for discrimination of pCR using Mann-Whitney U test and area under the receiver operating characteristic curve (AUC). A P value <0.05 was considered statistically significant. RESULTS: 47% of patients (40/86) had pCR. DTI parameters assessed after 2 and 4 cycles of NAST were significantly different between pCR and non-pCR patients when compared between tumors, PTRs, and FGTs. The median surface/average anisotropy of the PTR, measured after 2 and 4 cycles of NAST, increased in pCR patients and decreased in non-pCR patients (AUC: 0.78; 0.027 ± 0.043 vs. -0.017 ± 0.042 mm2 /s). DATA CONCLUSION: Quantitative DTI features from breast tumors and the peritumoral tissue may be useful for predicting the response to NAST in TNBC. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 4.

A phase II study of neoadjuvant atezolizumab and nab-paclitaxel in patients with anthracycline-resistant early-stage triple-negative breast cancer.

PURPOSE: Neoadjuvant anti-PD-(L)1 therapy improves the pathological complete response (pCR) rate in unselected triple-negative breast cancer (TNBC). Given the potential for long-term morbidity from immune-related adverse events (irAEs), optimizing the risk-benefit ratio for these agents in the curative neoadjuvant setting is important. Suboptimal clinical response to initial neoadjuvant therapy (NAT) is associated with low rates of pCR (2-5%) and may define a patient selection strategy for neoadjuvant immune checkpoint blockade. We conducted a single-arm phase II study of atezolizumab and nab-paclitaxel as the second phase of NAT in patients with doxorubicin and cyclophosphamide (AC)-resistant TNBC (NCT02530489). METHODS: Patients with stage I-III, AC-resistant TNBC, defined as disease progression or a < 80% reduction in tumor volume after 4 cycles of AC, were eligible. Patients received atezolizumab (1200 mg IV, Q3weeks × 4) and nab-paclitaxel (100 mg/m2 IV,Q1 week × 12) as the second phase of NAT before undergoing surgery followed by adjuvant atezolizumab (1200 mg IV, Q3 weeks, × 4). A two-stage Gehan-type design was employed to detect an improvement in pCR/residual cancer burden class I (RCB-I) rate from 5 to 20%. RESULTS: From 2/15/2016 through 1/29/2021, 37 patients with AC-resistant TNBC were enrolled. The pCR/RCB-I rate was 46%. No new safety signals were observed. Seven patients (19%) discontinued atezolizumab due to irAEs. CONCLUSION: This study met its primary endpoint, demonstrating a promising signal of activity in this high-risk population (pCR/RCB-I = 46% vs 5% in historical controls), suggesting that a response-adapted approach to the utilization of neoadjuvant immunotherapy should be considered for further evaluation in a randomized clinical trial.

Physiological and biomechanical responses to exercise on two different types of rowing ergometers in NCAA Division I oarswomen.

BACKGROUND: Stationary (SE) and dynamic (DE) rowing ergometers, that are utilized for indoor training and physical assessment of competitive rowers, may elicit different physiological and biomechanical responses. The present study used SE and DE ergometers to examine submaximal and peak physiological and biomechanical responses during an incremental rowing test. METHODS: Twelve National Collegiate Athletic Association (NCAA) Division I oarswomen performed seven-stage rowing tests with the last stage performed with maximal effort. Heart rate (HR), lactate (LA), oxygen uptake (VO2), ventilation (VE), stroke rate (SR), gross efficiency (GE), and rating of perceived exertion (RPE) were obtained; while trunk, hip, knee, shoulder, and elbow ranges of motion (ROM) were measured. RESULTS: SR was higher at maximal stage DE (29.3 vs. 34.8 strokes/min, p = 0.018, d = 1.213). No difference occurred in responses of maximal stage HR, RPE, VO2, VE, LA, or GE between the two ergometers. Submaximal LA and SR were greater on the DE for all submaximal stages. Submaximal VE was greater on the DE for all submaximal stages except Stage 3 (p = 0.160, d = 0.655). VO2 was higher on the DE Stages 2-5. GE was higher on the SE for Stages 2-5. Athletes showed increased trunk (p = 0.025, [Formula: see text] = 0.488) and knee (p = 0.004, [Formula: see text] = 0.668) ROM on SE. CONCLUSION: Rowing on the DE appears to elicit a greater stroke rate and more optimal joint angles especially at high intensities. Hence, the DE is worthy of consideration as a preferred ergometer for women rowers.

The difference between several neuromuscular tests for monitoring resistance-training induced fatigue.

The purposes of this study were to investigate the acute effects of resistance training protocol on kinetic changes in squat jump (SJ), shortened isometric mid-thigh pull (IMTP), and isometric squat (ISQ) and to examine the relationship of dynamic maximum strength with performance changes over 48 hours in resistance-trained individuals. Participants completed performance tests at pre-, post-24 hours, and post-48 hours resistance training protocol (Baseline, Post24, and Post48). The training protocol consisted of 5 sets of 10 repetitions of back squat (BSQ) at 60% of 1 repetition maximum (1RM). SJ variables included jump height (JH), peak power (PP), and relative PP. For the IMTP and ISQ, isometric peak force (IPF), relative IPF, rate of force development at 250 milliseconds (RFD250), and impulse at 250 milliseconds (IMP250) were calculated. Significant decreases were observed from Baseline to Post24 (p = 0.023, Cohen's dz effect size [dz] = 1.00) and Post48 (p = 0.032, dz = 0.94) in SJ JH. IMTP IMP250 significantly decreased from Baseline to Post48 (p = 0.046, dz = 0.88). Significant negative correlation was found between relative 1RM BSQ and the changes from Baseline to Post48 in ISQ RFD250 (p = 0.046,r = -0.61). Acute performance decreases might remain until 48 hours after resistance training in explosive strength and impulse regardless of isometric testing type.

Does Prematch Neuromuscular Performance Affect Running Performance in Collegiate Elite Female Soccer?

ABSTRACT: Ishida, A, Draper, G, White, JB, and Travis, SK. Does prematch neuromuscular performance affect running performance in collegiate elite female soccer? J Strength Cond Res 37(4): 854-858, 2023-The purpose of this study was to investigate whether prematch neuromuscular performance affected match physical performance by player position in Division I collegiate female soccer. Fourteen players participated (20.7 ± 1.3 years; 165.1 ± 6.0 cm; 63.3 ± 7.0 kg) in this study. Players were selected based on being free from injuries, playing for a duration of ≥72 minutes, and match intervals were ≥2 days. Data included 73 observations ( n = 5 defenders, n = 7 midfielders, and n = 2 forward) from 14 official matches. Prematch neuromuscular performance was assessed using countermovement jump (CMJ) with polyvinyl chloride pipe on dual force plates. Countermovement jump variables included jump height (JH) and relative peak power (RPP). Match physical performance included average speed, high-speed running (HSR), and number of high accelerations and decelerations. Linear mixed model was compiled with fixed effects of loaded with fixed effect of JH, RPP, and position and random effects per individual player. In CMJ and player position model, RPP was a significant predictor for average HSR ( p = 0.003) while fixed effects of JH and position were not significant ( p = 0.15-0.86). The fixed and random effects explained 34.8 and 42.1% of variances in average HSR. In CMJ-only model, RPP significantly predicted the variances in average HSR ( p = 0.001). The fixed effects and random effects of the model explained 22.7 and 51.8% of the variance in average HSR. However, position-only was not a significant predictor for average HSR in the position-only model ( p = 0.26 and 0.33). Prematch CMJ RPP may be the greatest predictor of average HSR in collegiate female soccer.

Intrasession and Intersession Reliability of Isometric Squat, Midthigh Pull, and Squat Jump in Resistance-Trained Individuals.

ABSTRACT: Ishida, A, Suarez, DG, Travis, SK, Slaton, JA, White, JB, Bazyler, CD, and Stone, MH. Intrasession and intersession reliability of isometric squat, midthigh pull, and squat jump in resistance-trained individuals. J Strength Cond Res 37(1): 18-26, 2023-The purposes of this study were to investigate intrasession and intersession reliability of variables obtained from squat jump (SJ), shortened isometric midthigh pull (IMTP), and isometric squat (ISQ) protocols and to evaluate relationships between isometric and dynamic performance and 1 repetition maximum (1RM) back squat (BSQ). Eleven moderately resistance-trained men participated (27.8 ± 3.9 years; 175.0 ± 7.2 cm; 87.2 ± 11.4 kg). Subjects completed familiarization in the IMTP and ISQ, followed by 1RM BSQ at least 48 hours before the first performance test. Two performance tests occurred at 7-day intervals including SJ, IMTP, and ISQ. SJ variables included jump height (SJH), body mass (BM), peak force (PF), and peak power (PP). Isometric midthigh pull and ISQ variables included isometric peak force (IPF); relative IPF; rate of force development at 90, 200, and 250 milliseconds; and impulse at 90, 200, and 250 milliseconds. SJ, IMTP, and ISQ kinetic variables were considered reliable if intraclass correlations (ICCs) and coefficients of variations (CVs) were >0.80 and <10%. Intrasession and intersession reliability criteria were met for SJH, BM, PF, and PP (ICC = 0.91-1.00, CV = 0.5-9.1%). Isometric peak force and impulse at 200 and 250 milliseconds met intrasession and intersession reliability criteria for IMTP and ISQ (ICC = 0.90-0.99, CV = 2.1-8.1%). Significant large correlation was observed between 1RM BSQ and ISQ peak force (p = 0.038, r = 0.63), but not between 1RM BSQ and shortened IMTP peak force (p = 0.11, r = 0.50). Shortened IMTP and ISQ peak force and impulse are reliable kinetic variables, and ISQ peak force is indicative of 1RM BSQ in moderately resistance-trained men.

Quantitative Apparent Diffusion Coefficients From Peritumoral Regions as Early Predictors of Response to Neoadjuvant Systemic Therapy in Triple-Negative Breast Cancer.

BACKGROUND: Pathologic complete response (pCR) to neoadjuvant systemic therapy (NAST) in triple-negative breast cancer (TNBC) is a strong predictor of patient survival. Edema in the peritumoral region (PTR) has been reported to be a negative prognostic factor in TNBC. PURPOSE: To determine whether quantitative apparent diffusion coefficient (ADC) features from PTRs on reduced field-of-view (rFOV) diffusion-weighted imaging (DWI) predict the response to NAST in TNBC. STUDY TYPE: Prospective. POPULATION/SUBJECTS: A total of 108 patients with biopsy-proven TNBC who underwent NAST and definitive surgery during 2015-2020. FIELD STRENGTH/SEQUENCE: A 3.0 T/rFOV single-shot diffusion-weighted echo-planar imaging sequence (DWI). ASSESSMENT: Three scans were acquired longitudinally (pretreatment, after two cycles of NAST, and after four cycles of NAST). For each scan, 11 ADC histogram features (minimum, maximum, mean, median, standard deviation, kurtosis, skewness and 10th, 25th, 75th, and 90th percentiles) were extracted from tumors and from PTRs of 5 mm, 10 mm, 15 mm, and 20 mm in thickness with inclusion and exclusion of fat-dominant pixels. STATISTICAL TESTS: ADC features were tested for prediction of pCR, both individually using Mann-Whitney U test and area under the receiver operating characteristic curve (AUC), and in combination in multivariable models with k-fold cross-validation. A P value < 0.05 was considered statistically significant. RESULTS: Fifty-one patients (47%) had pCR. Maximum ADC from PTR, measured after two and four cycles of NAST, was significantly higher in pCR patients (2.8 ± 0.69 vs 3.5 ± 0.94 mm2 /sec). The top-performing feature for prediction of pCR was the maximum ADC from the 5-mm fat-inclusive PTR after cycle 4 of NAST (AUC: 0.74; 95% confidence interval: 0.64, 0.84). Multivariable models of ADC features performed similarly for fat-inclusive and fat-exclusive PTRs, with AUCs ranging from 0.68 to 0.72 for the cycle 2 and cycle 4 scans. DATA CONCLUSION: Quantitative ADC features from PTRs may serve as early predictors of the response to NAST in TNBC. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 4.

Player Position Affects Relationship Between Internal and External Training Loads During Division I Collegiate Female Soccer Season.

ABSTRACT: Ishida, A, Travis, SK, Draper, G, White, JB, and Stone, MH. Player position affects relationship between internal and external training loads during Division I collegiate female soccer season. J Strength Cond Res 36(2): 513-517, 2022-The purpose of this study was to investigate how competition phase and player position affect the relationship between internal and external training loads (ITL and ETL, respectively) in collegiate female soccer. Seventeen players participated (21.8 ± 1.7 years; 165.1 ± 6.2 cm; and 63.7 ± 7.9 kg). Nineteen match-plays (10 nonconference and 9 conference) were completed during the 2019 competitive season, including 270 observations of 17 players (defenders = 5, midfielders = 9, and forwards = 3). Internal training load was assessed using session rating of perceived exertion (sRPE). External training load included total distance and high-speed running (HSR) distance. A linear mixed model was compiled with fixed effects of total distance, HSR, competition phase, and player position (defenders, midfielders, and forwards) and random effects of player. There were statistically significant main effects for total distance (p < 0.001), HSR (p = 0.047) and player position (p = 0.045) on the prediction model of sRPE. However, the main effect of competition phase did not statistically contribute to the prediction model of sRPE (p = 0.38). In the final model, total distance (p < 0.001) and player position for forwards (p = 0.008) were significant predictors of sRPE. However, there was no statistically significant fixed effect of HSR on sRPE (p = 0.15). The final model explained 60.6% of the variance in sRPE (R2 = 0.60), whereas the random effect also explained 6.1% of the variance (R2 = 0.06). Our findings indicated that total distance and player position were strong predictors of sRPE. The relationship between ITL and ETL should be monitored by player position in female soccer players.

Early ultrasound evaluation identifies excellent responders to neoadjuvant systemic therapy among patients with triple-negative breast cancer.

BACKGROUND: Heterogeneity exists in the response of triple-negative breast cancer (TNBC) to standard anthracycline (AC)/taxane-based neoadjuvant systemic therapy (NAST), with 40% to 50% of patients having a pathologic complete response (pCR) to therapy. Early assessment of the imaging response during NAST may identify a subset of TNBCs that are likely to have a pCR upon completion of treatment. The authors aimed to evaluate the performance of early ultrasound (US) after 2 cycles of neoadjuvant NAST in identifying excellent responders to NAST among patients with TNBC. METHODS: Two hundred fifteen patients with TNBC were enrolled in the ongoing ARTEMIS (A Robust TNBC Evaluation Framework to Improve Survival) clinical trial. The patients were divided into a discovery cohort (n = 107) and a validation cohort (n = 108). A receiver operating characteristic analysis with 95% confidence intervals (CIs) and a multivariate logistic regression analysis were performed to model the probability of a pCR on the basis of the tumor volume reduction (TVR) percentage by US from the baseline to after 2 cycles of AC. RESULTS: Overall, 39.3% of the patients (42 of 107) achieved a pCR. A positive predictive value (PPV) analysis identified a cutoff point of 80% TVR after 2 cycles; the pCR rate was 77% (17 of 22) in patients with a TVR ≥ 80%, and the area under the curve (AUC) was 0.84 (95% CI, 0.77-0.92; P < .0001). In the validation cohort, the pCR rate was 44%. The PPV for pCR with a TVR ≥ 80% after 2 cycles was 76% (95% CI, 55%-91%), and the AUC was 0.79 (95% CI, 0.70-0.87; P < .0001). CONCLUSIONS: The TVR percentage by US evaluation after 2 cycles of NAST may be a cost-effective early imaging biomarker for a pCR to AC/taxane-based NAST.

Tumor necrosis by pretreatment breast MRI: association with neoadjuvant systemic therapy (NAST) response in triple-negative breast cancer (TNBC).

PURPOSE: To determine if tumor necrosis by pretreatment breast MRI and its quantitative imaging characteristics are associated with response to NAST in TNBC. METHODS: This retrospective study included 85 TNBC patients (mean age 51.8 ± 13 years) with MRI before NAST and definitive surgery during 2010-2018. Each MRI included T2-weighted, diffusion-weighted (DWI), and dynamic contrast-enhanced (DCE) imaging. For each index carcinoma, total tumor volume including necrosis (TTV), excluding necrosis (TV), and the necrosis-only volume (NV) were segmented on early-phase DCE subtractions and DWI images. NV and %NV were calculated. Percent enhancement on early and late phases of DCE and apparent diffusion coefficient were extracted from TTV, TV, and NV. Association between necrosis with pathological complete response (pCR) was assessed using odds ratio (OR). Multivariable analysis was used to evaluate the prognostic value of necrosis with T stage and nodal status at staging. Mann-Whitney U tests and area under the curve (AUC) were used to assess performance of imaging metrics for discriminating pCR vs non-pCR. RESULTS: Of 39 patients (46%) with necrosis, 17 had pCR and 22 did not. Necrosis was not associated with pCR (OR, 0.995; 95% confidence interval [CI] 0.4-2.3) and was not an independent prognostic factor when combined with T stage and nodal status at staging (P = 0.46). None of the imaging metrics differed significantly between pCR and non-pCR in patients with necrosis (AUC < 0.6 and P > 0.40). CONCLUSION: No significant association was found between necrosis by pretreatment MRI or the quantitative imaging characteristics of tumor necrosis and response to NAST in TNBC.

Functional Tumor Volume by Fast Dynamic Contrast-Enhanced MRI for Predicting Neoadjuvant Systemic Therapy Response in Triple-Negative Breast Cancer.

BACKGROUND: Dynamic contrast-enhanced (DCE) MRI is useful for diagnosis and assessment of treatment response in breast cancer. Fast DCE MRI offers a higher sampling rate of contrast enhancement curves in comparison to conventional DCE MRI, potentially characterizing tumor perfusion kinetics more accurately for measurement of functional tumor volume (FTV) as a predictor of treatment response. PURPOSE: To investigate FTV by fast DCE MRI as a predictor of neoadjuvant systemic therapy (NAST) response in triple-negative breast cancer (TNBC). STUDY TYPE: Prospective. POPULATION/SUBJECTS: Sixty patients with biopsy-confirmed TNBC between December 2016 and September 2020. FIELD STRENGTH/SEQUENCE: A 3.0 T/3D fast spoiled gradient echo-based DCE MRI ASSESSMENT: Patients underwent MRI at baseline and after four cycles (C4) of NAST, followed by definitive surgery. DCE subtraction images were analyzed in consensus by two breast radiologists with 5 (A.H.A.) and 2 (H.S.M.) years of experience. Tumor volumes (TV) were measured on early and late subtractions. Tumors were segmented on 1 and 2.5-minute early phases subtractions and FTV was determined using optimized signal enhancement thresholds. Interpolated enhancement curves from segmented voxels were used to determine optimal early phase timing. STATISTICAL TESTS: Tumor volumes were compared between patients who had a pathologic complete response (pCR) and those who did not using the area under the receiver operating curve (AUC) and Mann-Whitney U test. RESULTS: About 26 of 60 patients (43%) had pCR. FTV at 1 minute after injection at C4 provided the best discrimination between pCR and non-pCR, with AUC (95% confidence interval [CI]) = 0.85 (0.74,0.95) (P < 0.05). The 1-minute timing was optimal for FTV measurements at C4 and for the change between C4 and baseline. TV from the early phase at C4 also yielded a good AUC (95%CI) of 0.82 (0.71,0.93) (P < 0.05). DATA CONCLUSION: FTV and TV measured at 1 minute after injection can predict response to NAST in TNBC. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: 4.

External and Internal Load Measures During Preseason Training in Men Collegiate Soccer Athletes.

ABSTRACT: Fields, JB, Merigan, JM, Gallo, S, White, JB, and Jones, MT. External and internal load measures during preseason training in men collegiate soccer athletes. J Strength Cond Res 35(9): 2572-2578, 2021-Collegiate athletes are exposed to high volume loads during preseason training. Monitoring training load can inform training and recovery periods. Therefore, the purpose was to examine changes in and bidirectional relationship between external and internal load metrics in men collegiate soccer athletes (n = 20; age, 20 ± 1 year). Internal load measures of heart rate variability (HRV), salivary testosterone (T) and cortisol (C), and self-assessment wellness and ratings of perceived exertion scales were collected daily. External load measures of total distance, player load, high-speed distance, high inertial movement analysis, and repeated high-intensity efforts were collected in each training session using global positioning system/global navigation satellite system technology. A 1-way analysis of variance determined weekly changes in external load, physiological, hormonal, and subjective self-assessment measures of internal load. Bidirectional prediction of external load markers and self-assessment measures on physiological and hormonal markers of internal load were assessed by hierarchical linear regression models (p < 0.05). External load measures, C, energy, sleep, and rate of perceived exertion (RPE) decreased (p < 0.01), whereas T, T:C ratio, anger, depression, and vigor increased (p < 0.01) from week 1 to week 2. Morning C positively predicted afternoon external load and post-training RPE (p < 0.05); T:C ratio negatively predicted afternoon external load and post-training RPE (p < 0.05); and morning HRV negatively predicted post-training RPE (p = 0.031). Despite reduced hormonal stress and external load across weeks, negative perceptions of fatigue increased, suggesting fatigue patterns may have a delayed response. Load may have a more belated, chronic effect on perceptions of fatigue, whereas hormonal changes may be more immediate and sensitive to change. Practitioners may wish to use a variety of external and internal load measures to understand athletes' stress responses to training.

Relationship Between External Load and Self-Reported Wellness Measures Across a Men's Collegiate Soccer Preseason.

ABSTRACT: Fields, JB, Lameira, DM, Short, JL, Merrigan, JM, Gallo, S, White, JB, and Jones, MT. Relationship between external load and self-reported wellness measures across a collegiate men's soccer preseason. J Strength Cond Res 35(5): 1182-1186, 2021-Monitoring athlete training load is important to training programming and can help balance training and recovery periods. Furthermore, psychological factors can affect athlete's performance. Therefore, the purpose was to examine the relationship between external load and self-reported wellness measures during soccer preseason. Collegiate men soccer athletes (n = 20; mean ± SD age: 20.3 ± 0.9 years; body mass: 77.9 ± 6.8 kg; body height: 178.87 ± 7.18cm; body fat: 10.0 ± 5.0%; V̇o2max: 65.39 ± 7.61ml·kg-1·min-1) participated. Likert scale self-assessments of fatigue, soreness, sleep, stress, and energy were collected daily in conjunction with the Brief Assessment of Mood (vigor, depression, anger, fatigue, and confusion). Total distance (TD), player load (PL), high-speed distance (HSD, >13 mph [5.8 m·s-1]), high inertial movement analysis (IMA, >3.5 m·s-2), and repeated high-intensity efforts (RHIEs) were collected in each training session using positional monitoring (global positioning system/global navigation satellite system [GPS/GNSS]) technology. Session rate of perceived exertion (sRPE) was determined from athlete's post-training rating (Borg CR-10 Scale) and time of training session. Multilevel models revealed the bidirectional prediction of load markers on fatigue, soreness, sleep, energy, and sRPE (p < 0.05). Morning ratings of soreness and fatigue were predicted by previous afternoon's practice measures of TD, PL, HSD, IMA, RHIE, and sRPE. Morning soreness and fatigue negatively predicted that day's afternoon practice TD, PL, HSD, IMA, RHIE, and sRPE. Morning ratings of negative mood were positively predicted by previous day's afternoon practice HSD. In addition, negative morning mood states inversely predicted HSD (p = 0.011), TD (p = 0.002), and PL (p < 0.001) for that day's afternoon practice. Using self-reported wellness measures with GPS/GNSS technology may enhance the understanding of training responses and inform program development.

Differences in elbow extensor muscle characteristics between resistance-trained men and women.

PURPOSE: Muscular strength is suggested to be dependent upon muscle characteristics. Yet, sex-specific relationships of muscle characteristics to strength in the resistance-trained require investigation. Therefore, the purpose was to evaluate sex differences in muscle characteristics and isometric strength in the elbow extensors, as well as their respective associations. METHODS: Resistance-trained men (n = 15, mean ± SD 22 ± 4 years, 87.5 ± 12.8 kg, 16.9 ± 2.9% body fat) and women (n = 15, mean ± SD 25 ± 5 years, 59.3 ± 7.3 kg, 22.4 ± 4.2% body fat) were tested. B-mode ultrasound images assessed muscle thickness, pennation angle, and echo intensity. Muscle volume and fascicle length were estimated from previously validated equations. Maximal voluntary isometric contraction measured elbow extensors isometric strength. Independent samples t-tests and Fisher's r-to-z test examined differences between sexes. RESULTS: Sex differences existed in all muscle characteristics (p < 0.05). Men's absolute strength (27.86 ± 3.55 kg) was significantly greater than women (16.15 ± 3.15 kg), but no differences were noted when controlling for muscle volume (men 0.069 ± 0.017, women 0.077 ± 0.022 kg/cm3). Sex differences did not exist in the relationships of muscle characteristics to strength with muscle size having the largest correlations. However, the relationship between echo intensity and body fat was different in men (r = - 0.311) and women (r = 0.541, p = 0.0143). CONCLUSIONS: Sex differences in isometric elbow extensor strength are eliminated when expressed relative to muscle volume. Relationships of echo intensity and body fat were different between men and women and may be indicative of greater adipose infiltration in women.

Body Composition Variables by Sport and Sport-Position in Elite Collegiate Athletes.

Fields, JB, Merrigan, JJ, White, JB, and Jones, MT. Body composition variables by sport and sport-position in elite collegiate athletes. J Strength Cond Res 32(11): 3153-3159, 2018-To assess body composition measures by sport and sport-position. Elite collegiate athletes participated (n = 475): men's and women's soccer (MSOC, n = 67; WSOC, n = 110); men's and women's swimming (MSWIM, n = 26; WSWIM, n = 22); men's and women's track and field (MTF, n = 29; WTF, n = 24); women's lacrosse and volleyball (WLAX, n = 84; WVB, n = 73); and baseball (BASE, n = 40). One-way analysis of variances assessed differences across sport and sport-position. Post hoc analysis was Tukey honestly significant difference (p ≤ 0.05). For men, BASE and MSWIM had the highest body fat percentage (BF%) (BASE: 16.3 ± 5.2%; MSWIM: 14.2 ± 3.5%). MSOC (11.5 ± 5.3%, 0.13 ± 0.72 kg) and MTF (9.8 ± 5.1%, 0.11 ± 0.08 kg) had the lowest BF% and fat mass (FM)-to-fat-free mass (FFM) ratio (FM:FFM). Fat mass did not differ between MSOC (9.1 ± 4.9 kg), MTF (7.7 ± 5.9 kg), and MSWIM (11.1 ± 3.1 kg). Fat mass for MSOC and MTF was lower than BASE (14.1 ± 5.2). For women, WVB displayed the highest BF% (25.4 ± 5.1%), FM (18.5 ± 5.2 kg), FFM (53.3 ± 5.1 kg), and body mass (BM) (71.8 ± 8.4 kg), but did not differ from WSWIM in BF%, FM, FFM, and BM. WTF had the lowest BF% (12.9 ± 4.0%), FM (7.5 ± 2.5 kg), BM (58.2 ± 4.4 kg), and FM:FFM (0.15 ± 0.05 kg). VB had the highest FFM (53.3 ± 5.1 kg). Body composition differences were observed between sport-positions (p < 0.01). Body composition differed across sport and sport-position, which may be attributed to sport-specific physiological demands.

Comparison of Physiological Variables Between the Elliptical Bicycle and Run Training in Experienced Runners.

Klein, IE, White, JB, and Rana, SR. Comparison of physiological variables between the elliptical bicycle and run training in experienced runners. J Strength Cond Res 30(11): 2998-3006, 2016-A novel outdoor elliptical bicycle (EBIKE) has been designed to elicit running-similar physiological adaptations while reducing the impact forces that commonly lead to injury. Various cross-training methods have been used to reduce injury risk, restore or maintain fitness, and prevent detraining. The purpose of this study was to compare 4 weeks of EBIKE-only training to run-only training on maximal oxygen consumption, ventilatory threshold, respiratory compensation point, running economy, and 5,000 m time trial times. Twelve experienced runners (age, 22.33 ± 3.33 years; running experience, 9.25 ± 4.53 years) completed 4 weeks of randomly assigned EBIKE or run training. Physiological and performance testing procedures were repeated, and subjects then performed a second matched 4-week training period in a crossover design. Ventilatory threshold was significantly greater after EBIKE (p ≤ 0.05; 41.60 ± 6.15 ml·kg·min) and run training (p ≤ 0.05; 42.33 ± 6.96 ml·kg·min) compared with the initial time point (40.17 ± 6.47 ml·kg·min). There were no significant group differences (p > 0.05) for these variables at any time point. In conclusion, EBIKE-only training yielded similar physiological and performance maintenance or improvements compared with run-only training. These results suggest that EBIKE training can be an effective cross-training method to maintain and improve certain physiological and performance variables in experienced runners over a 4-week period.

Targeting neddylation and sumoylation in chemoresistant triple negative breast cancer.

Triple negative breast cancer (TNBC) accounts for 15-20% of breast cancer cases in the United States. Systemic neoadjuvant chemotherapy (NACT), with or without immunotherapy, is the current standard of care for patients with early-stage TNBC. However, up to 70% of TNBC patients have significant residual disease once NACT is completed, which is associated with a high risk of developing recurrence within two to three years of surgical resection. To identify targetable vulnerabilities in chemoresistant TNBC, we generated longitudinal patient-derived xenograft (PDX) models from TNBC tumors before and after patients received NACT. We then compiled transcriptomes and drug response profiles for all models. Transcriptomic analysis identified the enrichment of aberrant protein homeostasis pathways in models from post-NACT tumors relative to pre-NACT tumors. This observation correlated with increased sensitivity in vitro to inhibitors targeting the proteasome, heat shock proteins, and neddylation pathways. Pevonedistat, a drug annotated as a NEDD8-activating enzyme (NAE) inhibitor, was prioritized for validation in vivo and demonstrated efficacy as a single agent in multiple PDX models of TNBC. Pharmacotranscriptomic analysis identified a pathway-level correlation between pevonedistat activity and post-translational modification (PTM) machinery, particularly involving neddylation and sumoylation targets. Elevated levels of both NEDD8 and SUMO1 were observed in models exhibiting a favorable response to pevonedistat compared to those with a less favorable response in vivo. Moreover, a correlation emerged between the expression of neddylation-regulated pathways and tumor response to pevonedistat, indicating that targeting these PTM pathways may prove effective in combating chemoresistant TNBC.

Comprehensive Analysis Identifies Variability in PI3K Pathway Alterations in Triple-Negative Breast Cancer Subtypes.

PURPOSE: The PI3K pathway is frequently altered in triple-negative breast cancer (TNBC). Limited cell line and human data suggest that TNBC tumors characterized as mesenchymal (M) and luminal androgen receptor (LAR) subtypes have increased incidence of alterations in the PI3K pathway. The impact of PI3K pathway alterations across TNBC subtypes is poorly understood. METHODS: Pretreatment tumor was evaluated from operable TNBC patients enrolled on a clinical trial of neoadjuvant therapy (NAT; A Robust TNBC Evaluation fraMework to Improve Survival [ClinicalTrials.gov identifier: NCT02276443]). Tumors were characterized into seven TNBC subtypes per Pietenpol criteria (basal-like 1, basal-like 2, immunomodulatory, M, mesenchymal stem-like, LAR, and unstable). Using whole-exome sequencing, RNA sequencing, and immunohistochemistry for PTEN, alterations were identified in 32 genes known to activate the PI3K pathway. Alterations in each subtype were associated with pathologic response to NAT. RESULTS: In evaluated patients (N = 177), there was a significant difference in the incidence of PI3K pathway alterations across TNBC subtypes (P < .01). The highest incidence of alterations was seen in LAR (81%), BL2 (79%), and M (62%) subtypes. The odds ratio for pathologic complete response (pCR) in the presence of PIK3CA mutation, PTEN mutation, and/or PTEN loss was highest in the LAR subtype and lowest in the M subtype, but these findings did not reach statistical significance. Presence of PIK3CA mutation was associated with pCR in the LAR subtype (P = .02). CONCLUSION: PI3K pathway alteration can affect response to NAT in TNBC, and targeted agents may improve outcomes, particularly in patients with M and LAR TNBC.