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Purpose: Increasing tumor-infiltrating lymphocytes (TIL) is associated with higher rates of pathologic complete response (pCR) to neoadjuvant therapy (NAT) in patients with triple-negative breast cancer (TNBC). However, the presence of TILs does not consistently predict pCR, therefore, the current study was undertaken to more fully characterize the immune cell response and its association with pCR. Experimental Design: We obtained pretreatment core-needle biopsies from 105 patients with stage I–III TNBC enrolled in ARTEMIS (NCT02276443) who received NAT from Oct 22, 2015 through July 24, 2018. The tumor-immune microenvironment was comprehensively profiled by performing T-cell receptor (TCR) sequencing, programmed death-ligand 1 (PD-L1) IHC, multiplex immunofluorescence, and RNA sequencing on pretreatment tumor samples. The primary endpoint was pathologic response to NAT. Results: The pCR rate was 40% (42/105). Higher TCR clonality (median = 0.2 vs. 0.1, P = 0.03), PD-L1 positivity (OR: 2.91, P = 0.020), higher CD3+:CD68+ ratio (median = 14.70 vs. 8.20, P = 0.0128), and closer spatial proximity of T cells to tumor cells (median = 19.26 vs. 21.94 μm, P = 0.0169) were associated with pCR. In a multivariable model, closer spatial proximity of T cells to tumor cells and PD-L1 expression enhanced prediction of pCR when considered in conjunction with clinical stage. Conclusions: In patients receiving NAT for TNBC, deep immune profiling through detailed phenotypic characterization and spatial analysis can improve prediction of pCR in patients receiving NAT for TNBC when considered with traditional clinical parameters.

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.

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%; Vo2max: 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.

Background: Triple negative breast cancer (TNBC) disproportionally impacts Black and Hispanic women and is suggested to be partly responsible for disparities observed in breast cancer mortality. We sought to evaluate the impact of race/ethnicity on TNBC molecular subtype, immune profile, pathologic complete response (pCR) and recurrence free survival (RFS). Methods: The ARTEMIS trial (NCT02276443) uses imaging response and molecular profiling to personalize neoadjuvant chemotherapy in early stage TNBC. After 4 cycles of AC, patients with chemo-sensitive disease receive standard taxane-based therapy, while those with chemo-resistant disease are offered therapeutic trials based upon molecular profiling. Pathologic response was assessed at surgery. Patients self-reported race/ethnicity was categorized as Asian, Black/African-American, Hispanic/Latino and White (non-Hispanic). Patients were excluded if no race or ethnicity was reported. Clinical and pathologic factors were recorded and compared. Gene expression profiling was performed by RNAseq to determine Vanderbilt signature. PD-L1 and Androgen Receptor (AR) were determined by immunohistochemistry. Frequencies at which various factors were observed by race/ethnicity were calculated and Fisher’s exact test performed to determine statistical significance. Kaplan-Meier analysis was used to estimate survival stratified by pCR status and race/ethnicity. Results: Among 321 women enrolled in ARTEMIS, 26 (8.1%) were classified as Asian, 50 (15.6%) as Black, 59 (18.4%) as Hispanic and 186 (57.9%) as White. Demographic and clinical features were similar, except Black women were more likely to have BMI ≥30 (70.0%, p Conclusion: Among this population of patients with TNBC treated with neoadjuvant chemotherapy there was no statistically significant difference observed in TNBC Vanderbilt signature, PD-L1 staining, sTIL, pCR or RFS by race/ethnicity. Asian women were found to have a higher incidence of AR-positive subtype. Numerically higher rates of N3 stage in Black women and RCB-III classification in Black and Hispanic women were identified, however not statistically significant. Larger cohorts of patients are needed to further investigate these findings. Table 1. TNBC profiling compared by race/ethnicity.Total n (%)Asian n (%)Black n (%)Hispanic/Latino n (%)White n (%)p valueVanderbilt signature n (%) Basal like (BL1) Basal like 2 (BL2) Immunomodulatory (IM) Luminal androgen receptor (LAR) Mesenchymal (M) Mesenchymal stem-like (MSL) Unstable (UNS)231 50 (21.6) 25 (10.8) 42 (18.2) 22 (9.5) 48 (20.8) 14 (6.0) 30 (13.0)21 (9.1) 0 (0.0) 4 (19.0) 5 (23.8) 3 (14.3) 5 (23.8) 1 (4.8) 3 (14.3)35 (15.2) 9 (25.7) 5 (14.3) 6 (17.1) 2 (5.7) 7 (20.0) 1 (2.9) 5 (14.3)43 (18.6) 14 (32.5) 3 (7.0) 10 (23.2) 5 (11.6) 6 (14.0) 2 (4.7) 3 (7.0)132 (57.1) 27 (20.5) 13 (9.8) 21 (15.9) 12 (9.1) 30 (22.7) 10 (7.6) 19 (14.4)NSAndrogen Receptor n (%) Positive (>=10%) Negative (1298 212 (71.1) 86 (28.9)24 (8.1) 15 (62.5) 9 (37.5)47 (15.8) 33 (70.2) 14 (29.8)57 (19.1) 40 (70.2) 17 (29.8)170 (57.0) 124 (72.9) 46 (27.1)NSStromal tumor infiltrating lymphocytes (sTIL) n (%) High (>=20%) Low ( Citation Format: Mediget Teshome, Ryan Sun, Elizabeth E. Ravenberg, Abenaa Brewster, Mariana Chavez-MacGregor, Jason B. White, Stacy Moulder. Impact of race/ethnicity on triple negative breast cancer molecular features, treatment response and clinical outcomes in patients receiving neoadjuvant therapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-12.

Introduction CEST MRI permits quantitation of macromolecules such as amide proteins that are of interest in cancer metabolism. However, optimal CEST acquisition and analysis methods remain undetermined. In this study, we investigated CEST MRI as an imaging biomarker for early treatment response in 51 TNBC patients receiving NAST and compared the performance with two different CEST saturation power levels and two analysis methods. Methods A total of 51 stage I-III TNBC patients enrolled in the prospective ARTEMIS trial (NCT02276443) had CEST imaging performed on a 3T MRI scanner at baseline before NAST (BL, N = 51), after 2 cycles (C2, N = 37), and 4 cycles (C4, N = 44) of NAST. 33 of the 51 patients had imaging at all 3 time points. 29 of the 33 patients had pathological findings, with N = 16 with pathological complete response (pCR) and N = 13 with non-pCR. Two sets of CEST images using 0.9 and 2.0 µT saturation power levels were acquired and analyzed using the magnetization transfer ratio asymmetry (MTRasym) and the Lorentzian line fitting (Mag3.5) methods, for a total of 4 acquisition/analysis combinations. The group averaged CEST signals, MTRasym at 0.9 and 2.0 µT and Mag3.5 at 0.9 and 2.0 µT, at BL, C2 and C4 were determined and evaluated using unpaired (51 patients) and paired (33 patients) Kruskal-Wallis tests. The Mag3.5 at 0.9 µT and the MTRasym at 2.0 µT were further compared between pCR and non-pCR. The group averaged CEST signals at BL, C2, and C4 were evaluated using the Friedman test for the pCR and the non-PCR groups. Separately, the change in the CEST signal from BL to C2 and C4 was determined for each patient and evaluated using the Mann-Whitney test for both groups. P < 0.05 was considered statistically significant. Results The MTRasym at BL was higher at 2.0 µT than at 0.9 µT. In contrast, the Mag3.5 at BL was higher at 0.9 µT than at 2.0 µT. The MTRasym at 2.0 µT and the Mag3.5 at 0.9 µT decreased during treatment while the MTRasym at 0.9 µT and the Mag3.5 at 2.0 µT were similar. Both the unpaired and the paired Mag3.5 at 0.9 µT showed a significant decrease at C2 and C4 vs. BL (p < 0.01). The unpaired and paired MTRasym at 2.0 µT showed a decrease, although the change was not significant except for the unpaired data at C4. The decrease in the group averaged Mag3.5 at 0.9 µT was significant at C2 vs. BL for the pCR group (p = 0.04), while it was not significant for the pCR group at C4 vs. BL and for the non-pCR group at either C2 or C4 vs. BL. The group averaged MTRasym at 2.0 µT changes were not significant for either the pCR or the non-pCR groups. None of the CEST signal changes on a per patient basis at C2-BL, C4-BL and C4-C2 were significantly different between the pCR and the non-pCR groups. Further, none of the group averaged CEST signals at BL, C2 and C4 were significantly different between the pCR and the non-pCR groups. Conclusion Our study demonstrates that the CEST quantitation in TNBC patients undergoing NAST depends on acquisition and analysis. For a maximum change in the CEST effect, Lorentzian line fitting is better paired with acquisition at a low saturation power (0.9 µT) and MTRasym is better paired with acquisition at a high saturation power (2.0 µT). Further, a significant CEST signal decrease was observed in TNBC patients with pCR after NAST when a 0.9 µT saturation power and the Lorentzian line fitting were used. In comparison, the decrease was not significant in non-pCR patients using the same saturation power and analysis method. The results suggest that the CEST signal acquired at 0.9 µT saturation power and analyzed using Lorentzian line fitting may be able to differentiate between pCR and non-pCR among TNBC patients undergoing NAST. Additional studies with a larger patient population are ongoing to further validate our findings and their potential for determining pCR. Citation Format: Shu Zhang, Gaiane M Rauch, Beatriz E Adrada, Medine Boge, Rania MM Mohamed, Abeer H Abdelhafez, Jong Bum Son, Jia Sun, Nabil A Elshafeey, Jason B White, Deanna L Lane, Jessica WT Leung, Marion E Scoggins, David A Spak, Elsa Arribas, Elizabeth Ravenberg, Lumarie Santiago, Tanya W Moseley, Gary J Whitman, Huong Le-Petross, Benjamin C Musall, Mitsuharu Miyoshi, Xinzeng Wang, Brandy Willis, Stacy Hash, Aikaterini Kotrotsou, Peng Wei, Ken-Pin Hwang, Alastair Thompson, Stacy L Moulder, Rosalind P Candelaria, Wei Yang, Jingfei Ma, Mark D Pagel. Assessment of early response to neoadjuvant systemic therapy (NAST) of triple-negative breast cancer (TNBC) using chemical exchange saturation transfer (CEST) MRI: A pilot study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS3-08.

Folate receptor alpha (FRα) has been reported to be expressed in up to 80% of triple-negative breast cancers (TNBC) with limited expression in normal tissues, making it a promising therapeutic target. Mirvetuximab soravtansine (mirvetuximab-s) is an antibody drug conjugate which has shown promise in the treatment of FRα-positive solid tumors in early phase clinical trials. Herein, are the results of the first prospective phase II trial evaluating mirvetuximab-s in metastatic TNBC. Patients with advanced, FRα-positive TNBC were enrolled on this study. Mirvetuximab-s was administered at a dose of 6.0 mg/kg every 3 weeks. 96 patients with advanced TNBC consented for screening. FRα staining was performed on tumor tissue obtained from 80 patients. The rate of FRα positivity by immunohistochemistry was 10.0% (8/80). Two patients were treated on study, with best overall responses of stable disease in one and progressive disease in the other. Adverse events were consistent with earlier studies. The study was terminated early due to the low rate of FRα positivity in the screened patient population and lack of disease response in the two patients treated. The observed rate of FRα positivity was considerably lower than previously reported and none of the patients had a partial or complete response. Treatment with mirvetuximab-s should only be further explored in TNBC if an alternate biomarker strategy is developed for patient selection on the basis of additional preclinical data.

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.

Background:While TNBC patients with pathologic complete response (pCR) or residual cancer burden (RCB-I) have good survival rates, those with extensive residual disease (RCB-II or RCB-III) after neoadjuvant chemotherapy (NACT) have poor prognosis. Patients without response to their first chemotherapeutic regimen have very low chance (5%) of achieving pCR. We have created a biomarker-driven drug development strategy, ARTEMIS (A Randomized, TNBC Enrolling trial to confirm Molecular profiling Improves Survival) to identify novel targeted therapies focusing on chemo-insensitive disease. The PI3K/Akt/mTOR pathway is a critical regulator of cell growth, apoptosis, metabolism in cancer cells and its activation is known to play an important role in resistance to chemotherapy. Clinical studies have shown that the combination of PI3K pathway inhibitors with taxanes are associated with improvement in response rates and survival. Alpelisib is approved for hormone receptor positive, HER2 negative, metastatic breast cancer patients with activating PIK3CA mutations. This study hypothesizes combination of alpelisib with nab-paclitaxel will improve PCR/RCB-1 in treatment-resistant early stage TNBC patients with activating PIK3CA or PTEN loss of function alterations. Trial Design: This will be a non-randomized, two- arm, open label, phase II study to evaluate the clinical activity of alpelisib and nab-paclitaxel in high-risk TNBC patients with PIK3CA or PTEN alterations with refractory or suboptimal response to anthracycline-based NACT. Eligibility criteria Stage 1-3 TNBC defined as ER Specific aims To determine if alpelisib in combination with nab-paclitaxel will improve rates of pathologic response (pCR/RCB-0 or RCB-I) from 5% to 20% in patients with chemotherapy insensitive TNBC with activating PIK3CA alterations (Arm-1) or PTEN loss of function alterations (Arm-2)To determine the radiographic response rate for alpelisib in combination with nab-paclitaxel in chemotherapy insensitive TNBC with PIK3CA (Arm-1) or PTEN (Arm-2) alterationsDetermine toxicity of alpelisib in combination with nab-paclitaxel given in the neoadjuvant settingDetermine progression free survival (PFS) at 3 years for patients treated with alpelisib in combination with nab-paclitaxel given in the neoadjuvant setting Statistical methods Primary objective is to determine if alpelisib in combination with nab-paclitaxel in the neoadjuvant setting will improve rates of pathologic response (counting pCR/RCB-0 or RCB-I as response) from 5% (control) to 20% (experimental arms). A Simon two-stage design will be employed with 12 patients in the first stage. If at least one patient has pCR/RCB-1, 25 more patients will be added for a total of 37 patients (alpha = beta = 10%). This design has a 54% probability of early termination after the first stage if the true pCR or RCB-I probability is 5%. Contact information for people with a specific interest in the trial sdamodaran@mdanderson.org Citation Format: Senthil Damodaran, Jennifer K Litton, Kenneth R. Hess, Colleen T. Eppig, Krzysztof J. Grzegorzewski, Funda Meric-Bernstam, Ignacio I. Wistuba, Jason B White, Gaiane M. Rauch, Rosalind P. Candelaria, Beatriz E. Adrada, Bora Lim, Stacy L. Moulder, Debu Tripathy. A phase-2 trial of neoadjuvant alpelisib and nab-paclitaxel in anthracycline refractory triple negative breast cancers with PIK3CA or PTEN alterations [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT2-06-01.

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.

The purpose of the study was to investigate the effects of using compound sets during a 12-week lower body resistance training program on muscle strength, endurance, hypertrophy, architecture, and soreness. Thirty-one recreationally active females were randomly assigned to one of three groups: traditional sets, compound sets, or control. The training groups performed Smith Machine squat and leg press at matched intensities, volumes, and cumulative rest per session. During compound sets, the squat was performed immediately prior to the leg press, while 1 min rest separated the exercises during traditional sets. A non-exercise control group did not perform resistance training. One-repetition maximum strength, muscle endurance, muscle thickness, cross-sectional area, pennation angle, training session time, and soreness were compared from pre- to post-training (α level 0.80), 24 (P > 0.50), or 48 (P > 0.30) h post-workout. In conclusion, compound set training, with equated rest, is a method of resistance training that elicits gains similar to traditional sets in young females.

PURPOSE: To investigate the value of performing mid-treatment axillary ultrasound (AUS) in triple-negative breast cancer (TNBC) patients who are undergoing neoadjuvant systemic therapy (NAST) by determining the optimal cutoff number of abnormal nodes associated with residual nodal disease on surgical pathology. MATERIALS AND METHODS: This sub-study, an interim analysis of an ongoing single-institution clinical trial enrolling patients with stage I-III TNBC, included 106 patients. Number of abnormal nodes at mid-treatment was assessed and recorded by experienced breast radiologists, who empirically categorized lymph nodes using a binary approach of sonographically-normal versus abnormal. Pathologic lymph node positivity was defined as presence of macrometastasis or micrometastasis in ≥1 axillary node from sentinel lymph node biopsy and/or axillary lymph node dissection. RESULTS: Of 106 patients, 26 (25 %) had residual nodal disease and 80 (75 %) had no nodal disease at surgery. Median number of abnormal nodes at mid-treatment was 5 (standard deviation [SD], 5) for patients with residual nodal disease and 0 (SD, 2) for patients with no nodal disease at surgery (p < 0.0001). TNBC patients with > 4 abnormal nodes at mid-treatment had a significantly higher chance of being node-positive at surgery (AUC = 0.908, p < 0.0001; PPV = 90 %). CONCLUSION: Our data suggest that a cutoff of > 4 abnormal nodes on mid-treatment AUS is associated with residual disease post-NAST. If our findings are substantiated by subsequent analyses, then mid-treatment AUS could be used to identify patients unlikely to achieve nodal pathologic complete response and who should be offered alternative therapy.

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. 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. Sex differences existed in all muscle characteristics (p

Background and Purpose:There is currently a lack of recognized imaging criteria for prediction of treatment response to NAST in breast cancer patients with recent reports showing that breast MRI is the most accurate modality for evaluation of NAST response. DCE-MRI evaluates tumor perfusion that influences tumor enhancement at the post-contrast subtraction images and allows for more accurate measurement of changes in tumor volume during NAST. In this study, we evaluated the ability of tumor volumetric changes after 2 and 4 cycles of NAST by longitudinal ultrafast DCE-MRI to predict pathologic complete response (pCR) in TNBC undergoing NAST. Materials and Methods: Stage I-III TNBC patients enrolled in an IRB approved prospective clinical trial (ARTEMIS, NCT02276433) who had ultrafast DCE-MRI at baseline (BL, N=103), post 2 cycles (C2, N=59), and post 4 cycles (C4, N=103) of anthracycline-based NAST,and had surgery, were included in this analysis. Tumor volume was calculated using 3D measurements of the index lesion at BL, C2, and C4. Percent change of tumor volume (%TV) between BL, C2, and C4 was calculated at early (9-12 sec) and delayed (360-480 sec) phases of DCE-MRI. The largest lesion was used for analysis in patients with multicentric or multifocal disease. Demographic, clinical, and pathologic data and treatment response at surgery (pCR versus non-pCR) were documented. Receiver operating characteristics curve (ROC) analysis was performed for prediction of pCR status. Positive predictive value (PPV), negative predictive value (NPV) and Youden Index were used to select %TV cut-off thresholds for pCR prediction.Results: 103 patients (median age, 53 years; range, 24-79 years) were included, 48 (47%) had pCR, and 55 (53%) had non-pCR at surgical pathology. The %TV reduction at C2 DCE-MRI was predictive of pCR on both early phase DCE MRI (AUC, 0.873; CI:0.779-0.968, p < .0001) and delayed phase DCE MRI (AUC, 0.844; CI:0.742-0.947, p < .0001). Optimal thresholds were as follows: 70% TV reduction on early phase DCE MRI with Youden’s index of 1.58 was able to predict pCR correctly for 79% of patients with PPV of 81%; 75% TV reduction on delayed phase with Youden’s Index of 1.44 was able to predict pCR correctly for 71% of patients with PPV of 85%.%TV reduction was also predictive of pCR at the C4 time point on both early phase DCE MRI (AUC, 0.761; CI:0.665-0.856, p < .0001) and delayed phase DCE MRI (AUC, 0.737; CI:0.641-0.833, p < .0001). Optimal thresholds were as follows: 90% TV reduction on early phase DCE MRI with Youden’s index of 1.43 was able to correctly predict pCR in 72% of patients with PPV of 70%; and 90% TV reduction on delayed phase with Youden’s Index of 1.34 was able to predict pCR correctly in 68% of patients with PPV of 71%.Conclusion: Our data shows that percent tumor volume reduction by DCE-MRI after 2 and 4 cycles of NAST was able to predict pCR in TNBC with high accuracy and can be used as an early imaging biomarker of NAST response prediction. Volumetric changes by longitudinal DCE-MRI can be used to differentiate chemoresistant and chemosensitive TNBC patients as early as after 2 cycles of NAST, and can help to triage patients for treatment de-escalation or targeted therapy. Citation Format: Gaiane Margishvili Rauch, Adrada E Beatriz, Rosalind P Candelaria, Nabil Elshafeey, Abeer H Abdelhafez, Benjamin C Musall, Jia Sun, Medina Boge, Rania M.M Mohamed, Jong Bum Son, Shu Zhang, Jessica Leung, Deanna Lane, Marion Scoggins, David Spak, Elsa Arribas, Lumarie Santiago, Gary J Whitman, Huong T. Le-Petross, Tanya W Moseley, Jason B. White, Elizabeth Ravenberg, Ken-Pin Hwang, Peng Wei, Lei Huo, Jennifer K Litton, Vicente Valero, Debu Tripathy, Alastair M Thompson, Mark D Pagel, Jingfei Ma, Wei T Yang, Stacy Moulder. Volumetric changes on longitudinal dynamic contrast enhanced MR imaging (DCE-MRI) as an early treatment response predictor to neoadjuvant systemic therapy (NAST) in triple negative breast cancer (TNBC) patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD6-07.

1044 Background: Tucatinib is a potent and highly selective HER2-targeted tyrosine kinase inhibitor approved for use in combination with trastuzumab and capecitabine for patients with metastatic HER2+ breast cancer (MBC) who have received ≥1 prior HER2-based regimen in the metastatic setting, including patients with brain metastases (BM). TBCRC049 (NCT03501979) is an investigator-initiated phase 2 single-arm study currently enrolling to evaluate the safety and efficacy of tucatinib, trastuzumab and capecitabine in HER2+ BC with newly diagnosed LM. Here, we report the pre-specified pharmacokinetic (PK) analysis for the first 15 patients to determine bioavailability of tucatinib and its predominant metabolite, ONT-993, in the CSF. Methods: Eligible patients included adults with HER2+ MBC, KPS > 50, and newly diagnosed, untreated LM (defined as positive CSF cytology and/or radiographic evidence of LM, plus clinical signs/symptoms). Patients with treated or concurrent/new BM were allowed. The primary endpoint is overall survival with an accrual goal of 30 pts. Parallel PK samples were collected in plasma and CSF via Ommaya reservoir on day 1 of cycles 1 and 2 at 0h (baseline), 2-3h, 5-7h and 24h (optional) following initiation of tucatinib 300 mg BID. Tucatinib and ONT-993 were quantified in plasma (n=15) and CSF (n=13) using validated liquid chromatography-mass spectrometry methods. Results: Tucatinib and ONT-993 plasma concentrations were consistent with previous studies and exhibited high interindividual variability. Tucatinib and ONT-993 were detectable in the CSF within 2 hours post tucatinib administration; concentrations ranged from 0.57 to 25 ng/mL for tucatinib (IC50 for tucatinib against HER2 is 3.3 ng/mL) and 0.28 to 4.7 ng/mL for ONT-993. Tucatinib concentrations in the CSF per timepoint were in a similar range to unbound plasma (plasmaub) tucatinib. CSF to plasmaub ratios were generally consistent over time; the steady-state (cycle 2) median tucatinib CSF to plasmaub ratio was 0.83 (0.19 to 2.1). ONT-993 CSF to plasmaub ratios were similar to tucatinib CSF to plasmaub ratios. Conclusions: In patients with LM from HER2+MBC who were treated with tucatinib, trastuzumab, and capecitabine, tucatinib and ONT-993 were detectable in the CSF of all patients at median levels similar to plasmaub tucatinib. This is the first documented evidence of tucatinib distributing into the CSF in patients with HER2+MBC. Efficacy and safety of tucatinib, trastuzumab, and capecitabine in patients with HER2+ LM will be reported upon completion of TBCRC 049 accrual. Clinical trial information: NCT03501979 .

590 Background: The impact of gut microbiome on tumor biology, progression and response to immunotherapy has been shown across cancer types. However, there is little known about the impact of gut microbial composition on response to chemotherapy. We have previously shown that the gut microbiome remains unaltered during NACT in a cohort of 32 patients. Here we investigate the association between gut microbiome and response to NACT in a larger cohort of early-stage TNBC. Methods: Longitudinal fecal samples were collected from 85 patients with newly-diagnosed, early-stage TNBC patients enrolled in the ARTEMIS trial (NCT02276443). Patients all received standard NACT with adriamycin/cyclophosphamide (AC); volumetric change was assessed using ultrasound and patients with < 70% volumetric reduction (VR) after 4 cycles of AC were recommended to receive targeted therapy in addition to standard NACT to improve response rates. We performed 16S sequencing on bacterial genomic DNA extracted from 85 pre-AC fecal samples using the 2x250 bp paired-end read protocol. Quality-filtered sequences were clustered into Operational Taxonomic Units and classified using Mothur method with the Silva database version 138. For differential taxa-based univariate analysis, abundant microbiome taxa at species, genus, family, class, and order levels were analyzed using DESeq2 after logit transformation. Alpha-diversity indices within group categories were calculated using phyloseq. Microbial alpha diversity (within-sample diversity) was measured by Simpson's reciprocal index. β-diversity was measured using weighted UniFrac distances between the groups. The association between microbiota abundance and pathologic complete response (pCR) or residual disease (RD) was assessed using DESeq2 analysis. Results: Pre-AC fecal samples from 85 patients were available for analysis. Amongst them, there were 46 patients with pCR and 39 patients with RD. There was no significant difference in alpha diversity (p = 0.8) or beta-diversity (p = 0.7) between the pCR and RD groups. However, relative to patients with RD, the gut microbiome in patients with pCR was enriched for the Bifidobacterium longum species (p = 0.03). The gut microbiome in patients with RD was enriched for Lachnospiraceae (p = 0.03) at the genus level and the Bacteroides thetaiotaomicron species (p = 0.02). Conclusions: We have demonstrated significant differences in the gut microbial composition in patients with pCR as compared to patients with RD. Further investigation in larger studies is needed to support therapeutic exploration of gut microbiome modulation in TNBC patients receiving chemotherapy such as probiotic supplementation or fecal microbiota transplant.

592 Background: Neoadjuvant anti-PD-(L)1 therapy confers an improvement in pathological complete response (pCR) rate in unselected TNBC. However, given the potential for long-term morbidity from immune related adverse events (irAE), it is important to optimize the risk-benefit ratio for the use of these novel agents in the curative neoadjuvant setting. Suboptimal clinical response to neoadjuvant therapy (NAT) by sonography is associated with low rates of pCR rate (2-5%, GeparTrio and Aberdeen trials). Here, we report the results of a single arm phase II study of atezo and nab-p as the second phase of NAT in pts with TNBC with suboptimal clinical response to AC (NCT02530489). Methods: Pts with stage I-III TNBC showing suboptimal response to 4 cycles of doxorubicin and cyclophosphamide (AC), defined as disease progression or a

Background and Purpose:Early and accurate assessment ofbreast cancer response to NAST is important for patient management. In this study, we investigated the value of radiomic phenotypes derived from semi-quantitative and quantitative DCE-MRI parametric maps for early prediction of NASTresponse in TNBC patients. MATERIALS AND METHODS:This IRB approved study included 74 patients with stage I-III TNBC who were enrolled in the prospective ARTEMIS trial (NCT02276443). Pathologic complete response (pCR) and non-pCR were assessed by surgical histopathology after NAST (pCR=34; non-pCR=40).MRI scans were obtained at 3 time points during the NAST treatment with every 2-week anthracycline-based chemotherapy (AC): at baseline (BSL=74), post-2 cycles of AC (C2= 27) and post-4 cycles of AC (C4= 27). Patients went on to receive taxane-based chemotherapy prior to surgery. Tumor regions of interest (ROIs) were segmented by a breast radiologist at the early-phase subtractions of DCE-MRI scans using in-house developed software, followed by co-registration of the ROIs with quantitative (Ktrans, Veand Kep), and semi-quantitative DCE parametric maps (Maximum Slope Increase (MSI), Positive Enhancement Integral (PEI) and Peak Signal Enhancement Ratio (SER)).A total of 93 first order radiomic features were extracted from the tumor ROIs of each time point semi-quantitative DCE parametric map, while a total of 390 extracted radiomic features (first order-histogram features and second order grey-level-co-occurrence matrix) were extracted from each quantitative DCE parametric map using an in-house developed Matlab software.Radiomic features at each time point and changes between the 3 time points were compared between pCR and non-pCR using Wilcoxon Rank Sum test and Fisher’s exact test. Area under the receiver operating characteristics curve (AUC) was used to determine which features predicted pCR.Logistic regression was performed for feature selection, and used to build the radiomic phenotype model. The model performance was assessed by leave-one-out cross validation and 3-fold cross validation. RESULTS:Thirty-three radiomic features from PEI map were significantly different between pCR and non-pCR. The PEI most significant features were changesbetween BSL and C4 in skewness, mean and median (AUC=0.87, 0.85 and 0.87, p= Citation Format: Nabil Elshafeey, Beatriz E Adrada, Rosalind P Candelaria, Abeer H Abdelhafez, Benjamin C Musall, Jia Sun, Medine Boge, Rania M.M Mohamed, Hagar S Mahmoud, Jong Bum Son, Aikaterini Kotrosou, Shu Zhang, Jessica Leung, Deanna Lane, Marion Scoggins, David Spak, Elsa Arribas, Lumarie Santiago, Gary J. Whitman, Huong T Le-Petross, Tanya W Moseley, Jason B White, Elizabeth Ravenberg, Ken-Pin Hwang, Peng Wei, Jennifer K Litton, Lei Huo, Debu Tripathy, Vicente Valero, Alastair M Thompson, Stacy Moulder, Wei T Yang, Mark D Pagel, Jingfei Ma, Gaiane M Rauch. Radiomic phenotypes from dynamic contrast-enhanced MRI (DCE-MRI) parametric maps for early prediction of response to neoadjuvant systemic therapy (NAST) in triple negative breast cancer (TNBC) patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD6-06.

Background: MpBC is a rare breast cancer subtype that is commonly triple-negative and associated with a diminished response to NAT in published retrospective data sets, prompting some clinicians to recommend surgical resection followed by adjuvant therapy. Methods: The ARTEMIS trial (NCT02276443) uses imaging response and molecular profiling to personalize NAT in early stage TNBC. Patients with sensitive disease after 4 cycles of AC receive standard taxane-based NAT as the second phase of NAT, while those with resistant disease are offered biomarker-guided therapeutic trials. Pathologic response is assessed at surgical resection. Prospective data from 195 patients with early-stage TNBC (MpTNBC: N=37; Non-MpTNBC: N=158) enrolled on the ARTEMIS trial were evaluated. Due to short duration of follow-up, restricted mean survival time up to four years of follow-up was used to evaluate event-free survival (RM-EFS), metastasis-free survival (RM-MFS) and overall survival (RM-OS). RNAseq and whole exome sequencing (WES) were performed on pre-NAT core biopsies (155 and 158 non-MpTNBC respectively; 20 MpTNBC). Stromal tumor infiltrating lymphocytes (sTIL) and PD-L1 staining were also compared. Results: Pathologic complete response (pCR) rates were significantly lower in MpTNBC vs non-MpTNBC (18.9% vs. 41.4%, p=0.013). Among MpTNBC without pCR (n=30, 81%), 21 were detected early to have progression (PD) or suboptimal response to standard therapy with ultrasound and clinical exam and were offered the opportunity to participate in clinical trial. Notably, 6 patients (16.2%) had PD after 2 cycles of AC. There was a non-statistically significant trend of lower RM-EFS, RM-MFS, and RM-OS in MpTNBC; however, MpTNBCs with pCR had similar RM-OS compared to non-MpTNBCs with pCR. MpTNBCs had lower rates of high TIL (>20%) compared to non-MpTNBCs (16% vs. 36%, p=0.02) but similar rates of PD-L1+ disease. Compared to non-MpTNBCs, using Vanderbilt classification methods, MpTNBCs were more frequently M/MSL subtype (50% vs 22%, p=0.011) and less frequently BL-1 subtype (p=0.028). By RNAseq, MpTNBC tumors had significantly lower gene expression of epithelial markers CDH1, EPCAM, ESRP1, and increased expression of EMT inducer TWIST1. WES identified PIK3CA missense mutations in 15% of MpTNBCs. Unsupervised clustering based on expression profiles revealed that 85% of MpTNBCs had a Mp-like expression signature. Interestingly, the Mp-like expression signature was identified in 12% of histologically defined non-MpTNBC. The pCR rate was lowest in the MpTNBC (18.9%) but similar between Mp-like TNBC (36.8%) and non-MpTNBC (42.2%). Conclusion: Early-stage MpTNBC has lower rates of pCR with NAT however those with pCR appear to have similar survival rates to non-MpTNBC with pCR. Notably, 16.2% of MpTNBC had PD after 2 cycles of AC NAT suggesting that a neoadjuvant approach with frequent imaging would reduce unnecessary exposure to inactive chemotherapy. 81% of MpTNBCs had either PD or suboptimal response to AC chemotherapy, thus novel treatment strategies need to be developed for this chemorefractory subtype of TNBC. PAM (PI3K/mTOR/AKT) pathway alterations were frequently detected in MpTNBCs and novel inhibitors should be further tested. Citation Format: Nour Abuhadra, Clinton Yam, Ryan Sun, Lei Huo, Jason White, Elizabeth Ravenberg, Beatriz Adrada, Aysegul Sahin, Jennifer Litton, Bora Lim, Naoto T Ueno, Banu Arun, Debu Tripathy, Senthil Damodaran, Rashmi Murthy, Vicente Valero, Gabriel Hortobagyi, Nuhad Ibrahim, Alastair Thompson, Anthony Lucci, Elizabeth Mittendorf, Stacy Moulder, Jeffrey Chang. Prospective evaluation of patients with metaplastic (Mp) triple negative breast cancer (TNBC): Molecular characteristics and outcomes with neoadjuvant therapy (NAT) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS18-04.

595 Background: 40-50% of pts with TNBC develop pathologic complete response (pCR) with adriamycin/cyclophosphamide (AC)àtaxane (T) NAT; thus, most pts treated in randomized trials (RCTs) adding experimental drugs (ED) to standard NAT do not benefit from trial participation. A personalized trial design that enriches for non-pCR to standard NAT would diminish toxicity from ED in pts who do not need them and enrich ED in high-risk pts that are most likely to benefit. Methods: ARTEMIS (NCT02276443) is a non-randomized trial to study personalization of NAT in TNBC. Tumor biopsies were performed pre-NAT and volumetric change by ultrasound (VCU) after 4 cycles of AC (or upon clinical progression) assessed response. Pts with sensitive TNBC (VCU >=70% after AC) had T as the second phase of NAT. Pts with

583 Background: Pathologic complete response is an excellent surrogate for disease-free survival (DFS) and overall survival (OS) in TNBC. High sTIL is associated with improved pCR rates in TNBC. Recent data suggest that high sTIL is also associated with improved outcomes in patients who received no chemotherapy for early stage TNBC (Park, Annals of Oncology, 2019). Thus, we hypothesized that high sTIL may have prognostic impact in patients who do not achieve pCR to NAT. Methods: Pretreatment core biopsies from 182 patients with early-stage TNBC enrolled on the ARTEMIS trial (NCT02276443) were evaluated for sTIL by H&E. Patients were stratified according to sTIL (low < 30%, and high > 30%) and pCR (patients with pCR vs. no pCR). The primary outcome measure was DFS, defined from the date of diagnosis to the first local recurrence, distant metastases or death. Cox proportional hazards regression model was used. During follow-up 33 events for DFS were observed. Results: Among subjects who achieve pCR, DFS was excellent regardless of sTIL status and significantly better than those without pCR (p < 0.05). However, patients with high sTIL and no pCR demonstrated significantly worse DFS compared to all subjects having pCR (HR 0.18, 95% CI 0.04-0.76, p = 0.02). Additionally, we did not find a significant difference between high and low sTIL patients who did not achieve pCR. Conclusions: In early TNBC receiving NAT, for patients failing to achieve pCR, high sTIL was not associated with improved DFS; outcomes were comparable to those with low sTIL without pCR. Thus, high sTIL at baseline does not appear to confer an intrinsic prognostic benefit in the absence of pCR.

1546 Background: Previous studies have related germline BRCA mutations to pathologic complete response (pCR) in TNBC cohorts. However, prospective data is lacking on the frequency of non- BRCA germline mutations and pCR in TNBC patients who received neoadjuvant therapy (NAT). The aim of this study was to describe germline alterations in comparison with pCR in a prospective cohort of TNBC receiving NAT. Methods: Pre-NAT blood was drawn from patients enrolled in a clinical trial of genomically tailored NAT (ARTEMIS: NCT: 02276443, per eligibility patients had to have negative clinical BRCA tetsing). Germline DNA was extracted and sequenced on a HiSeq4000 sequencer (Illumina, coverage 60X). Reads were aligned to human reference hg19. Variants were filtered against public databases of normal cohorts: esp6500, 1000 genome, ExAC with a frequency cutoff at 1% in any ethnicity. Two integrative scores were used to evaluate the deleteriousness of the missense variants and the variants predicted to be damaging by both scores were included in the analyses. A 105 pan-cancer susceptibility gene panel was selected based on literature data and commercially available gene panels. NAT included anthracycline and taxane based chemotherapy +/- targeted therapy based on tumor genomic expression. Univariate logistic regression models were used to fit pCR for individual mutations, excluding genes mutated in fewer than three patients. All statistical analyses were performed using R version 3.6.1. with a significance of p=0.05. Results: Germline results and pCR were available for 152 patients. Median age was 55 yrs (range: 24-77). 7.9% were stage (st) I, 65.8% st II, 26.3% st III. 55 pts (36%) had pan-cancer associated germline mutations, whereas 33 (21%) had a breast-cancer associated mutation. Greater than 1% mutations were seen in seventeen genes (Table). There was no significant difference in pCR rate after NAT among pts with different germline mutations versus without mutation. Conclusions: Breast cancer related germline mutations other than BRCA in TNBC are relatively common supporting at least a breast panel (not only BRCA1/2) testing. Treatment implications of different germline mutations and their impact on pCR is ongoing on an extended series. [Table: see text]

Background and Purpose: TNBC is comprised of biologically aggressive tumors with diverse clinical behavior and response to chemotherapy. Prediction of disease response to NACT is critical to the development of personalized medicine in TNBC. We evaluated first-order radiomic features from quantitative ADC maps of the tumor and peritumoral region as discriminators of response to NACT in TNBC patients. Materials and Methods: This IRB-approved prospective study (ARTEMIS trial, NCT02276443) included 34 patients with biopsy proven stage I-III TNBC who underwent evaluation of treatment response by multi-parametric MRI. Patients had a baseline MRI (BL) and a second MRI after 4 cycles (C4) of their treatment. After completion of NACT, all patients underwent surgery and were classified as pathologic complete response (pCR) or non-pCR. Both MRI exams included T2W series, a dynamic contrast enhanced series (DCE), a conventional diffusion weighted imaging (DWI) series, and a reduced field of view (rFOV) DWI series. Tumor volumes were contoured by an experienced breast radiologist on ADC maps with reference to b1000 DWI images. Regions with necrosis or clip artifacts were excluded from the contour. Peritumoral regions were defined as a 5 mm rim of tissue surrounding the tumor based on DCE series, T2-weighted images with fat suppression and ADC maps. Thirteen first-order radiomic features, including mean, minimum, maximum, percentiles, kurtosis and skewness at a single measurement and the difference between BL and C4 were compared between pCR and non-pCR using Receiver Operating Characteristic (ROC) curve and Wilcoxon rank sum test. Results: The kurtosis of tumor at C4 by conventional DWI was significantly higher in non-pCR than in pCR patients (AUC=0.785, p=0.0097). The change in kurtosis from BL to C4 by conventional DWI was also significantly higher in non-pCR than in pCR patients (AUC=0.73, p=0.043). The skewness of tumor at C4 by rFOV DWI scan was significantly lower in pCR than non-pCR patients (AUC=0.73, p=0.023). The 10th percentile of the peritumoral region’s ADC was significantly different between pCR and non-pCR (mean=1.19, SD is ± 0.27 10-3 mm2/s vs mean=1.34, SD ± 0.27 10-3 mm2/s respectively, AUC=0.70, p=0.048). The kurtosis and 25th percentile of the ADC of peritumoral region were borderline significantly different between pCR and non-pCR (AUC=0.69, p=0.067; AUC=0.69, p= 0.073 respectively). Conclusion: ADC first-order radiomic features from tumor and peritumoral region in TNBC may be useful for predicting treatment response to NACT. Larger study is necessary and is currently in progress to validate these findings. Citation Format: Beatriz E. Adrada, Abeer H. Abdelhafez, Benjamin C. Musall, Kenneth R. Hess, Jong Bum Son, Mark D. Pagel, Ken-Pin Hwang, Rosalind P. Candelaria, Lumarie Santiago, Gary J. Whitman, Huong Le-Petross, Tanya W. Moseley, Elsa Arribas, Deanna L. Lane, Marion E. Scoggins, David A. Spak, Jessica W.T. Leung, Senthil Damodaran, Bora Lim, Vicente Valeo, Jason B White, Alastair M. Thompson, Jennifer K. Litton, Stacy L. Moulder, Jingfei Ma, Wei T. Yang, Gaiane M Rauch. Quantitative apparent diffusion coefficient (ADC) radiomics of tumor and peritumoral regions as potential predictors of treatment response to neoadjuvant chemotherapy (NACT) in triple negative breast cancer (TNBC) patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-02-03.

Background:Although promoted for weight loss, especially in young adults, it has yet to be determined if the physical activity energy expenditure (PAEE) and intensity of the newest active video games (AVGs) qualifies as moderate-to-vigorous physical activity (MVPA; > 3.0 METs). This study compared the PAEE and intensity of AVGs to traditional seated video games (SVGs).Methods:Fifty-three young adults (18−35 y; 27 females) volunteered to play 6 video games (4 AVGs, 2 SVGs). Anthropometrics and resting metabolism were measured before testing. While playing the games (6−10 min) in random order against a playmate, the participants wore a portable metabolic analyzer for measuring PAEE (kcal/min) and intensity (METs). A repeated-measures ANOVA compared the PAEE and intensity across games with sex, BMI, and PA status as main effects.Results:The intensity of AVGs (6.1 ± 0.2 METs) was significantly greater than SVGs (1.8 ± 0.1 METs). AVGs elicited greater PAEE than SVGs in all participants (5.3 ± 0.2 vs 0.8 ± 0.0 kcal/min); PAEE during the AVGs was greater in males and overweight participants compared with females and healthy weight participants (p’s < .05).Conclusions:The newest AVGs do qualify as MVPA and can contribute to the recommended dose of MVPA for weight management in young adults.

The purpose was to examine the effect of prior performance of dumbbell lateral squats (DBLS) on an agility movement-into-a-sprint (AMS) test. Twelve collegiate, resistance-trained, baseball athletes participated in three sessions separated by three days. Session One consisted of AMS baseline test, DBLS 5-RM test, and experimental protocol familiarization. Subjects were randomly assigned the protocol order for Sessions Two and Three, which consisted of warm up followed by 1-min sitting (no-DBLS) or performing the DBLS for 1 × 5 repetitions @ 5RM for each leg. Four minutes of slow recovery walking preceded the AMS test, which consisted of leading off a base and waiting for a visual stimulus. In reaction to stimulus, subjects exerted maximal effort while moving to the right by either pivoting or drop stepping and sprinting for 10 yards (yd). In Session Three, subjects switched protocols (DBLS, no-DBLS). Foot contact time (FCT), stride frequency (SF), stride length (SL), and 10-yd sprint time were measured. There were no differences between conditions for FCT, SF, or SL. Differences existed between DBLS (1.85 ± 0.09 s) and no-DBLS (1.89 ± 0.10 s) for AMS (p = 0.03). Results from the current study support the use of DBLS for performance enhancement prior to performing the AMS test.