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Purpose: This study aimed to assess whether physical functional decline in older women with early-stage breast cancer is driven by cancer, chemotherapy, or a combination of both., Methods: We prospectively sampled three groups of women aged ≥ 65: 444 with early-stage breast cancer receiving chemotherapy (BC Chemo), 98 with early-stage breast cancer not receiving chemotherapy (BC Control), and 100 non-cancer controls (NC Control). Physical function was assessed at two timepoints (T1 [baseline] and T2 [3, 4, or 6 months]) using the Physical Functioning Subscale (PF-10) of the RAND 36-item Short Form. The primary endpoint was the change in PF-10 scores from T1 to T2, analyzed continuously and dichotomously (Yes/No, with "yes" indicating a PF-10 decline > 10 points, i.e., a substantial and clinically meaningful difference)., Results: Baseline PF-10 scores were similar across all groups. The BC Chemo group experienced a significant decline at T2, with a median change in PF-10 of -5 (interquartile range [IQR], -20, 0), while BC Control and NC Control groups showed a median change of 0 (IQR, -5, 5; p < 0.001). Over 30% of BC Chemo participants had a substantial decline in PF-10 vs. 8% in the BC Control and 5% in the NC Control groups (p < 0.001)., Conclusion: In this cohort of older adults with early-stage breast cancer, the combination of breast cancer and chemotherapy contributes to accelerated functional decline. Our findings reinforce the need to develop interventions aimed at preserving physical function, particularly during and after chemotherapy., Implications for Cancer Survivors: The high prevalence of accelerated functional decline in older women undergoing breast cancer chemotherapy underscores the urgency to develop interventions aimed at preserving physical function and improving health outcomes., Clinical Trial: NCT01472094, Hurria Older PatiEnts (HOPE) with Breast Cancer Study., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Colorectal cancer (CRC) screening utilization is low among low-income, uninsured, and minority populations that receive care in community health centers (CHCs). There is a need for evidence-based interventions to increase screening and follow-up care in these settings., Methods: A multilevel, multi-component pragmatic cluster randomized controlled trial is being conducted at 8 CHCs in two metropolitan areas (Boston and Los Angeles), with two arms: (1) Mailed FIT outreach with text reminders, and (2) Mailed FIT-DNA with patient support. We also include an additional CHC in Rapid City (South Dakota) that follows a parallel protocol for FIT-DNA but is not randomized due to lack of a comparison group. Eligible individuals in participating clinics are primary care patients ages 45-75, at average-risk for CRC, and overdue for CRC screening. Participants with abnormal screening results are offered navigation for follow-up colonoscopy and CRC risk assessment., Results: The primary outcome is the completion rate of CRC screening at 90 days. Secondary outcomes include the screening completion rate at 180 days and the rate of colonoscopy completion within 6 months among participants with an abnormal result. Additional goals are to enhance our understanding of facilitators and barriers to CRC risk assessment in CHC settings., Conclusions: This study assesses the effectiveness of two multilevel interventions to increase screening participation and follow-up after abnormal screening in under-resourced clinical settings, informing future efforts to address CRC disparities., Trial Registration: NCT05714644., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Folasade P. May: Exact Sciences: Advisory Board Sapna Syngal: inventor of the PREMM model (the intellectual property of which is owned by Dana-Farber Cancer Institute); research funding by Exact Sciences, Biological Dynamics, Inc.; consultant for Natera, Inc., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The antibody-drug conjugate (ADC) sacituzumab govitecan (SG) comprises the topoisomerase 1 (TOP1) inhibitor (TOP1i) SN-38, coupled to a monoclonal antibody targeting trophoblast cell surface antigen 2 (TROP-2). Poly(ADP-ribose) polymerase (PARP) inhibition may synergize with TOP1i and SG, but previous studies combining systemic PARP and TOP1 inhibitors failed due to dose-limiting myelosuppression. Here, we assess the proof-of-mechanism and clinical feasibility for SG and talazoparib (TZP) employing an innovative sequential dosing schedule., Patients and Methods: In vitro models tested pharmacodynamic endpoints, and in a phase 1b clinical trial (NCT04039230), 30 patients with metastatic triple-negative breast cancer (mTNBC) received SG and TZP in a concurrent (N = 7) or sequential (N = 23) schedule. Outcome measures included safety, tolerability, preliminary efficacy, and establishment of a recommended phase 2 dose., Results: We hypothesized that tumor-selective delivery of TOP1i via SG would reduce nontumor toxicity and create a temporal window, enabling sequential dosing of SG and PARP inhibition. In vitro, sequential SG followed by TZP delayed TOP1 cleavage complex clearance, increased DNA damage, and promoted apoptosis. In the clinical trial, sequential SG/TZP successfully met primary objectives and demonstrated median progression-free survival (PFS) of 7.6 months without dose-limiting toxicities (DLT), while concurrent dosing yielded 2.3 months PFS and multiple DLTs including severe myelosuppression., Conclusions: While SG dosed concurrently with TZP is not tolerated clinically due to an insufficient therapeutic window, sequential dosing of SG followed by TZP proved a viable strategy. These findings support further clinical development of the combination and suggest that ADC-based therapy may facilitate novel, mechanism-based dosing strategies., (©2024 The Authors; Published by the American Association for Cancer Research.)

Introduction: Gastric sleeve stenosis (GSS) is an increasingly common adverse event following sleeve gastrectomy for which objective diagnostic criteria are lacking. Impedance planimetry measurements show promise in characterizing GSS, though normal and abnormal benchmark values have never been established., Methods: This was a retrospective analysis of upper endoscopies performed with impedance planimetry for suspected GSS. A bariatric endoscopist, blind to impedance planimetry measurements, assessed gastric sleeve anatomy and graded GSS severity. Impedance planimetry of diameter and distensibility index (DI) were obtained using 3 different balloon volumes (30, 40, and 50 mL)., Results: A total of 110 upper endoscopies were included. Distribution of GSS was graded as none, mild, moderate, and severe in 19 (17%), 27 (25%), 34 (31%), and 30 (27%) procedures, respectively. In normal gastric sleeve anatomy, mean (±SD) diameter and DI measurements using consecutive balloon volumes ranged from 19.1 (±5.5) to 23.2 (±1.7) and 16.8 (±4.9) to 23.1 (±10.9), respectively. In severe GSS, mean diameter and DI measurements ranged from 10.3 (±3.0) to 16.6 (±2.1) and 7.5 (±2.4) to 7.7 (±2.4), respectively. When stratified by severity, impedance planimetry measurements of diameter and DI were significantly lower with each subsequent increase in GSS grade regardless of balloon fill volumes ( P ≤ 0.001)., Discussion: Impedance planimetry measurements provide objective assessment in the diagnosis of GSS and correlate with luminal narrowing. A diameter ≥20 mm and a DI ≥15 mm 2 /mm Hg, as measured by impedance planimetry, are predictive of normal gastric sleeve anatomy. This study provides new benchmark values for the diagnosis and severity of GSS., (Copyright © 2024 by The American College of Gastroenterology.)

Background: Older women with breast cancer frequently experience toxicity-related hospitalizations during adjuvant chemotherapy. Although the geriatric assessment can identify those at risk, its use in clinic remains limited. One simple, low-cost marker of vulnerability in older persons is fall history. Here, the authors examined whether falls prechemotherapy can identify older women at risk for toxicity-related hospitalization during adjuvant chemotherapy for breast cancer., Methods: In a prospective study of women >65 years old with stage I-III breast cancer treated with adjuvant chemotherapy, the authors assessed baseline falls in the past 6 months as a categorical variable: no fall, one fall, and more than one fall. The primary end point was incident hospitalization during chemotherapy attributable to toxicity. Multivariable logistic regression was used to examine the association between falls and toxicity-related hospitalization, adjusting for sociodemographic, disease, and geriatric covariates., Results: Of the 497 participants, 60 (12.1%) reported falling before chemotherapy, and 114 (22.9%) had one or more toxicity-related hospitalizations. After adjusting for sociodemographic, disease, and geriatric characteristics, women who fell more than once within 6 months before chemotherapy had greater odds of being hospitalized from toxicity during chemotherapy compared to women who did not fall (50.0% vs. 20.8% experienced toxicity-related hospitalization, odds ratio, 4.38; 95% confidence interval, 1.66-11.54, p = .003)., Conclusions: In this cohort of older women with early breast cancer, women who experienced more than one fall before chemotherapy had an over 4-fold increased risk of toxicity-related hospitalization during chemotherapy, independent of sociodemographic, disease, and geriatric factors., (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Exploration is an important feature for successfully learning motor skills. However, game rules such as one attempt to serve in volleyball could discourage exploration due to an individual's fear of making a mistake and forfeiting a point. The constraints-led approach is a coaching methodology that encourages exploration by selectively manipulating task constraints such as rules. Therefore, the aim of this study was to examine whether the addition of the task constraint of a second serve would encourage volleyball players to use their first serve to explore their action capabilities. Forty male high school students competed in two volleyball games; a regulation (single serve) game and a modified (2-serve) game. Participants reported that having a second chance at serving allowed them to feel more confident and relaxed which facilitated the exploration of their serving capability. In the 2-serve game, participants attempted a more powerful ( M  = 60.3 km/hr), and complex ( M  = 44.5% jump topspin serves) first serve, compared to the regulation game ( M  = 55.6 km/hr; M  = 25.2% jump topspin serves). Findings suggest that to facilitate learning of motor skills, it is important to manipulate the practice environment using task constraints to address the factors that restrict exploration.

Purpose: To guide clinicians and policymakers in three global resource-constrained settings on treating patients with metastatic breast cancer (MBC) when Maximal setting-guideline recommended treatment is unavailable., Methods: A multidisciplinary, multinational panel reviewed existing ASCO guidelines and conducted modified ADAPTE and formal consensus processes., Results: Four published resource-agnostic guidelines were adapted for resource-constrained settings; informing two rounds of formal consensus; recommendations received ≥75% agreement., Recommendations: Clinicians should recommend treatment according to menopausal status, pathological and biomarker features when quality results are available. In first-line, for hormone receptor (HR)-positive MBC, when a non-steroidal aromatase inhibitor and CDK 4/6 inhibitor combination is unavailable, use hormonal therapy alone. For life-threatening disease, use single-agent chemotherapy or surgery for local control. For premenopausal patients, use ovarian suppression or ablation plus hormone therapy in Basic settings. For human epidermal growth factor receptor 2 (HER2)-positive MBC, if trastuzumab, pertuzumab, and chemotherapy are unavailable, use trastuzumab and chemotherapy; if unavailable, use chemotherapy. For HER2-positive, HR-positive MBC, use standard first-line therapy, or endocrine therapy if contraindications. For triple-negative MBC with unknown PD-L1 status, or if PD-L1-positive and immunotherapy unavailable, use single-agent chemotherapy. For germline BRCA1 / 2 mutation-positive MBC, if poly(ADP-ribose) polymerase inhibitor is unavailable, use hormonal therapy (HR-positive MBC) and chemotherapy (HR-negative MBC). In second-line, for HR-positive MBC, Enhanced setting recommendations depend on prior treatment; for Limited, use tamoxifen or chemotherapy. For HER2-positive MBC, if trastuzumab deruxtecan is unavailable, use trastuzumab emtansine; if unavailable, capecitabine and lapatinib; if unavailable, trastuzumab and/or chemotherapy (hormonal therapy alone for HR-positive MBC).Additional information is available at www.asco.org/resource-stratified-guidelines. It is ASCO's view that healthcare providers and system decision-makers should be guided by the recommendations for the highest stratum of resources available. The guideline is intended to complement but not replace local guidelines.

Purpose: There is a demand for improved care delivery surrounding genomic testing and clinical trial enrollment among patients with metastatic breast cancer (MBC). We sought to improve the current process via real-time informal consultation and prescreening assessment for patients with MBC treated by community and academic medical oncologists by implementing a virtual molecular and precision medicine (vMAP) clinic., Methods: The vMAP program used a virtual referral system directed to a multidisciplinary team with precision medicine expertise. Providers contacted vMAP regarding patients with MBC, and on receipt of referral, the vMAP team engaged in discussion to identify if further diagnostics were needed (including genomic testing) and to identify potential clinical trials or standard treatment options. Recommendations were then sent to the referring provider within 72 hours. Pre-/postsurveys were issued to network physicians to assess for barriers, clinical trial access, and vMAP referral experience. Program implementation was evaluated with the Squire 2.0 reporting guidelines for quality improvement in health care as a framework., Results: Eighty-one cases from 22 providers were referred to vMAP over a 26-month period. The average response time to the referring provider with a finalized recommendation was 1.90 ± 1.82 days. A total of 86.4% of cases had clinical trial options on vMAP prescreen, with 40.7% initiating formal screening assessments and 27 patients (33.3%) ultimately enrolling on trials. On resurvey, 92% of survey responses across community oncology referring providers said that they were very likely to use vMAP again., Conclusion: In the initial 2-year period, vMAP demonstrated an efficient means to offer real-time interpretation of genomic testing and identification of clinical trials for patients with MBC, with effective clinical trial enrollment and high rates of referring provider satisfaction.