Citations

e13036 Background: In January 2023, the FDA approved elacestrant for ESR1-mutated, ER+/HER2- MBC based on a companion diagnostic cell free (cf)DNA test (Guardant Health). In this study, we analyze the trends of liquid biopsy utilization at Mayo Clinic (MC) over a 3 year period to understand the impact of this drug approval on testing patterns and identify emergent alterations in patients (pts) with MBC. Methods: We extracted clinically performed Guardant 360 and Guardant 360 CDx ordered at MC sites in Rochester (MN), Florida (FL), Arizona (AZ), and across 9 additional Mayo Clinic Health System (MCHS) sites. Pts with MBC were identified using the EMR and analyzing visit diagnosis codes and staging information. Shifts in testing patterns were analyzed over a 3 year period from January 1, 2021 - December 31, 2023. Data was collected on the number of tests, serial testing, frequency of pathogenic mutations, and emergent mutations in ESR1 and PIK3CA. Chi-square test was used to compare the categorical values. Results: Between 2021-2023, 2,741 pts with MBC were seen across all sites. A total of 408 cfDNA tests were performed in 370 unique patients with MBC. Most pts (90%) had 1 test performed. The proportion of pts with MBC tested was 85/1350 (6.3%) in 2021, 77/1495 (5.2%) in 2022, and 208/1558 (13.4%) in 2023. The increased proportion of pts tested in 2023 was statistically significant compared to prior years (p<0.0001), while no difference was observed between 2021 and 2022 (p 0.19). Testing patterns varied by site, with FL ordering the highest number of tests, followed by MN and AZ. Of the 34 providers practicing during the entire period seeing more than 10 MBC pts, the number of providers ordering Guardant testing increased from 15/34 (2021) and 14/34 (2022) to 20/34 (2023), though not statistically significant (p 0.15). Of the 41% with EMR-documented staging available, testing was highest in the ER+/HER2- (81.3%) subtype, followed by TNBC (13.6%) and then HER2+ (5.2%). The most commonly identified mutations identified in the first testing were PIK3CA (41.1%), TP53 (40.5%), ESR1 (30.5%), and ATM (13.2%). D538G (8.0%), Y537N (4.4%), and Y537S (3.5%) were frequent emergent mutations seen in ESR1. Conclusions: We observed an increase in cfDNA testing at the start of 2023 which aligns with the FDA approval of elacestrant. We observed variation by site and individual providers that warrants further exploration to improve cfDNA testing in MBC pts at Mayo Clinic.

1105 Background: Approximately 2-5% of breast cancers harbor HER2 mutations, often occurring in hormone receptor-positive (HR+) disease. There are currently no approved treatment options for patients (pts) with HER2-mutated metastatic breast cancer (HER2-mut MBC). Tucatinib (TUC) is a tyrosine kinase inhibitor highly selective for HER2 and is approved for previously treated HER2+ MBC with or without brain metastases in combination with trastuzumab (Tras) and capecitabine. Here, we report the efficacy and safety results of TUC combined with Tras in pts with previously treated HER2-mut MBC. Methods: SGNTUC-019 (NCT04579380) is an open-label phase 2 basket study evaluating efficacy, safety, and tolerability of TUC and Tras in pts with metastatic HER2-altered solid tumors. Pts in the HER2-mut MBC cohort must have HER2 mutations determined locally by tissue- or blood-based next-generation sequencing, not be HER2+ per local testing, been previously treated with ≥1 systemic therapy in the locally advanced, unresectable, or metastatic setting, and if HR+, have received a CDK4/6 inhibitor. Pts were treated in 21-day cycles with TUC (300 mg orally twice a day) and Tras (8 mg/kg IV followed by 6 mg/kg every 3 wks). Pts with HR+ disease also received fulvestrant (F; 500 mg IM once every 4 wks starting from cycle 1 day 1, and cycle 1 day 15). Disease status was determined based on RECIST v1.1 with assessments performed every 6 wks for 24 wks and every 12 wks thereafter. The primary endpoint is cORR per investigator assessment. Secondary endpoints include OS, DCR, DOR, PFS, and safety. Results: As of Nov 1, 2023, 31 pts were enrolled in the HER2-mut MBC cohort. The median duration of follow-up for OS was 15.0 months. Twenty-seven (87%) pts had HR+ disease and 18 (58%) had lobular histology. The pts received a median of 4 prior lines of systemic therapy in any setting. cORR was 41.9% (90% CI, 26.9-58.2) with 13 responses including 2 complete responses. Median DOR was 12.6 months (90% CI, 4.7, not estimable), DCR was 80.6% (n=25; 90% CI, 65.3-91.2), median PFS was 9.5 months (90% CI, 5.4-13.8), and median OS was 20.1 months (90% CI, 15.9 to not estimable). The most common treatment-emergent adverse events (TEAEs) reported were diarrhea (64.5%) and nausea (35.5%). The most common grade ≥3 TEAEs reported were diarrhea (13%), alanine aminotransferase increase (10%), and hypertension (10%). Two (6.5%) pts discontinued TUC due to TEAEs, but these pts continued Tras. No deaths were due to TEAEs. Additional biomarker analyses will be included in the presentation. Conclusions: The investigational combination of TUC and Tras, plus F in pts with HR+ disease, was well tolerated and had clinical activity in pts with previously treated HER2-mut MBC. The results support further evaluation of the combination of TUC and Tras as a potential treatment option for this pt population. Clinical trial information: NCT04579380 .

e12641 Background: Many promising agents or combinations regimens relevant to breast cancer lack sufficient clinical information for use in the neoadjuvant setting. To enable acceleration of drug development by reducing time and cost of clinical trial planning and conduct, the Phase I initiative PRE-ISPY Program was created. Methods: The PRE-ISPY Program is built within the I-SPY network, with the overall aim to streamline the regulatory pathway and the processes of trial design, contracting, activation, enrollment, execution, data gathering and analysis, as well as reporting of new therapeutic agents or combinations of relevance to breast cancer. Results: The PRE-ISPY trial is an open-label platform phase IB study designed to evaluate compelling single agent or combination regimens with the overall goal of moving promising drug regimens into I-SPY2 Trial and/or into other oncology-based trials in a timely manner. Graduation of a PRE-ISPY regimen to I-SPY2 is not mandatory. The primary objectives in each study Arm are to determine safety and to obtain preliminary efficacy data of the new regimen in patients with metastatic cancer, including a cohort of breast cancer patients. Each Arm may contain a Part 1 (dose finding) and a Part 2 (dose expansion). The new treatment can be tested also in patients with other solid malignancies than breast cancer, in which the treatment may be applicable, as specified in the design of the Arm. A breast cancer specific cohort is required in Part 2. Candidate treatment regimens are selected with advice from the I-SPY2 Agent Selection Working Group. The PRE-ISPY/Phase IB trial has multiple ongoing drug regimen Arms subsequently added as new protocol appendices through amendments to a Master protocol. There is no randomization; participants are enrolled, and treatment selected according to the relevance of therapy to their disease. Prospective companion biomarkers are evaluated. The current arms under study are PRE1: ALX-148 combined with trastuzumab deruxtecan; PRE2: tucatinib combined with zanidatamab; and PRE3: vidutolimod combined with cemiplimab. Selected agents or therapeutic combinations are tested through this protocol in the I-SPY Network Centers that participate in the PRE-ISPY Program. Toxicities are graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE). Clinical responses are evaluated based on RECIST v1.1 criteria. Conclusions: Once safety is established, promising regimens can be rapidly transitioned to I-SPY 2.2 or other phase 2/3 trials. The first patient was enrolled on 2/1/2023. Clinical trial information: NCT05868226 .

Abstract To address acute vaso-occlusive episodes (VOEs), the leading cause of emergency department (ED) visits among individuals with sickle cell disease (SCD), we conducted the clinical study, ALIGN (An Individualized Pain Plan with Patient and Provider Access for Emergency Department care of SCD), across 8 sites. We hypothesized an improvement of 0.5 standard deviations in perceived quality of ED pain treatment of a VOE after implementing individualized pain plans (IPPs) accessible to both patients and providers. Patients with SCD were aged 18 to 45 years, owned a cell phone, and had an ED VOE visit within 90 days prior. Patients completed the perceived quality of care surveys at baseline and within 96 hours after an ED VOE visit. Providers completed surveys regarding comfort managing VOEs at baseline and after managing an enrolled patient. Most of the 153 patients were African American (95.4%), female (64.7%), and had Hb SS/Sβ0 genotype (71.9%). The perceived quality of ED pain treatment was high at both baseline and after implementation of IPPs; our primary outcome hypothesis was not met, because no statistically significant change in the patient-perceived quality of ED treatment occurred. A total of 135 providers completed baseline and follow-up surveys. On a scale of 1 to 7, with 7 being extremely comfortable managing VOEs, 60.5% reported a score ≥6 after IPP implementation vs 57.8% at baseline. Almost all (97.6%) ordered the recommended medication, and 94.7% intended to use IPPs. In this implementation protocol, all sites successfully implemented IPPs. Patients and ED providers both endorsed the use of IPPs. This trial was registered at www.ClinicalTrials.gov as # NCT04584528.

AbstractINTRODUCTIONWhile Latin America (LatAm) is facing an increasing burden of dementia due to the rapid aging of the population, it remains underrepresented in dementia research, diagnostics, and care.METHODSIn 2023, the Alzheimer's Association hosted its eighth satellite symposium in Mexico, highlighting emerging dementia research, priorities, and challenges within LatAm.RESULTSSignificant initiatives in the region, including intracountry support, showcased their efforts in fostering national and international collaborations; genetic studies unveiled the unique genetic admixture in LatAm; researchers conducting emerging clinical trials discussed ongoing culturally specific interventions; and the urgent need to harmonize practices and studies, improve diagnosis and care, and use affordable biomarkers in the region was highlighted.DISCUSSIONThe myriad of topics discussed at the 2023 AAIC satellite symposium highlighted the growing research efforts in LatAm, providing valuable insights into dementia biology, genetics, epidemiology, treatment, and care.

Background: Despite growing interest in delivering high-value orthopaedic care, the costs associated with hip arthroscopy remain poorly understood. By employing time-driven activity-based costing (TDABC), we aimed to characterize the cost composition of hip arthroscopy for labral pathological conditions and to identify factors that drive variation in cost. Methods: Using TDABC, we measured the costs of 890 outpatient hip arthroscopy procedures for labral pathological conditions across 5 surgeons at 4 surgery centers from 2015 to 2022. All patients were ≥18 years old and were treated by surgeons who each performed ≥20 surgeries during the study period. Costs were normalized to protect the confidentiality of internal hospital cost data. Descriptive analyses and multivariable linear regression were performed to identify factors underlying cost variation. Results: The study sample consisted of 515 women (57.9%) and 375 men (42.1%), with a mean age (and standard deviation) of 37.1 ± 12.7 years. Most of the procedures were performed in patients who were White (90.6%) or not Hispanic (93.4%). The normalized total cost of hip arthroscopy per procedure ranged from 43.4 to 203.7 (mean, 100 ± 24.2). Of the 3 phases of the care cycle, the intraoperative phase was identified as the largest generator of cost (>90%). On average, supply costs accounted for 48.8% of total costs, whereas labor costs accounted for 51.2%. A 2.5-fold variation between the 10th and 90th percentiles for total cost was attributed to supplies, which was greater than the 1.8-fold variation attributed to labor. Variation in total costs was most effectively explained by the labral management method (partial R 2 = 0.332), operating surgeon (partial R 2 = 0.326), osteoplasty type (partial R 2 = 0.087), and surgery center (partial R 2 = 0.086). Male gender (p < 0.001) and younger age (p = 0.032) were also associated with significantly increased costs. Finally, data trends revealed a shift toward labral preservation techniques over debridement during the study period (with the rate of such techniques increasing from 77.8% to 93.2%; P trend = 0.0039) and a strong correlation between later operative year and increased supply costs, labor costs, and operative time (p < 0.001 for each). Conclusions: By applying TDABC to outpatient hip arthroscopy, we identified wide patient-to-patient cost variation that was most effectively explained by the method of labral management, the operating surgeon, the osteoplasty type, and the surgery center. Given current procedural coding trends, declining reimbursements, and rising health-care costs, these insights may enable stakeholders to design bundled payment structures that better align reimbursements with costs. Level of Evidence: Economic and Decision Analysis Level IV . See Instructions for Authors for a complete description of levels of evidence.

Objectives: In hemodialysis patients, central hemodynamics, stiffness, and wave reflections assessed through ambulatory blood pressure monitoring (ABPM) showed superior prognostic value for cardiovascular (CV) events than peripheral blood pressures (BPs). No such evidence is available for lower-risk hypertensive patients. Methods: In 591 hypertensive patients (mean age 58 ± 14 years, 49% males), ambulatory brachial and central BP, pulse wave velocity (PWV), and augmentation index (AIx) were obtained with a validated upper arm cuff-based pulse wave analysis technology. Information on treatment for hypertension (73% of patients), dyslipidemia (27%), diabetes (8%), CV disease history (25%), was collected. Patients were censored for CV events or all-cause death over 4.2 years. Results: One hundred and four events (24 fatal) were recorded. Advanced age [hazard ratio and 95% confidence interval: 1.03 (1.01, 1.05), P = 0.0001], female sex [1.57 (1.05, 2.33), P = 0.027], CV disease [2.22 (1.50, 3.29), P = 0.0001], increased 24-h central pulse pressure (PP) [1.56 (1.05, 2.31), P = 0.027], PWV [1.59 (1.07, 2.36), P = 0.022], or AIx [1.59 (1.08, 2.36), P = 0.020] were significantly associated with a worse prognosis (univariate Cox regression analysis). The prognostic power of peripheral and central BPs was lower. However, PWV [1.02 (0.64, 1.63), P = 0.924], AIx [1.06 (0.66, 1.69), P = 0.823], and central PP [1.18 (0.76, 1.82), P = 0.471], were not significant predictors in multivariate analyses. Conclusions: In hypertensive patients, ambulatory central PP, PWV, and AIx are associated with an increased risk of CV morbidity and all-cause mortality. However, this association is not independent of other patient characteristics.

Abstract Background: In patients with micro- and macrometastases in the sentinel lymph node (SLN) after neoadjuvant chemotherapy (NAC), additional positive nodes are found in &gt;60% of cases and axillary lymph node dissection (ALND) is currently considered standard of care. The likelihood of finding additional positive lymph nodes in patients with residual isolated tumor cells (ITCs) is unknown, and the benefit of ALND is unclear. As a consequence, surgical management of the axilla in these patients is not standardized. We sought to evaluate how often additional positive lymph nodes are found, to determine factors associated with ALND, and to compare oncological outcomes in patients treated with and without ALND after identification of residual ITCs in the SLN. Methods: Data were collected from 42 centers: 20 in the Oncoplastic Breast Consortium (OPBC) and EUBREAST networks, and 22 in North and South America. We included patients with cT1-4 N0-3 breast cancer at diagnosis who underwent NAC followed by axillary staging with either SLN biopsy (SLNB) or targeted axillary dissection (TAD) and were found to have residual ITCs [ypN0(i+)]. Single-tracer mapping was allowed for cN0 patients, while dual mapping or TAD was required for cN+ cases. Axillary treatment included completion ALND and/or nodal radiotherapy (RT). Competing risk analysis was performed to assess the cumulative incidence rates of any axillary recurrence (AR), locoregional recurrence (LRR), and any invasive (locoregional or distant) recurrence. Five-year cumulative incidence rates were compared between patients who underwent ALND and those who did not using the Gray’s test. Type I error rate was set to 0.05 (α). Results: We included 412 patients treated with NAC followed by surgery from 01/2009-05/2022. 146 (35.4%) had completion ALND and 266 (64.6%%) did not. Median patient age was 48 years. The majority (57%) of patients had clinical T2 tumors, and 68% had biopsy-proven N1 disease. Most were HR+/HER2- (41%) or HER2+ (39%). Most patients (80%) received anthracycline and taxane-based chemotherapy regimens. Nodal RT was administered to 83% of patients. The median number of SLNs with ITCs was 1. Patients treated with ALND were more likely to have ITCs detected on frozen section (61% v 6.7%, p&lt; 0.001), to have N2/3 disease at presentation (15.1% v 5.6%, p=0.001) and to have LVI (40% v 26%, p=0.004) (Table 1). There was no significant trend over time in the proportion of patients undergoing completion ALND during the study period (p=0.5). In the ALND group, additional positive nodes were found in 43/146 (29.5%) of cases, and consisted of macrometastases in 11/146 (7.5%), micrometastases in 9/146 (6.2%), and ITCs in 23/146 (15.8%). 5-year rates of any AR, LRR, and any invasive recurrence in the entire cohort were 2.7% (95% CI 1.2-5.4), 2.8% (95% CI 1.2-5.4) and 16% (95% CI 11-21), respectively. There was no statistical difference between patients who underwent ALND and those who did not in any of the 3 endpoints (2.2% v 3.1%, p=0.6), (2.6% v 3.0%, p=0.4) and (14% v 18%, p=0.12), respectively. Conclusion: The likelihood of finding additional positive lymph nodes in patients with ITCs after NAC is lower than in patients with residual micro- and macrometastases, and in the majority of cases, they contain ITCs. Nodal recurrence after omission of ALND is rare in this population. Overall, these results do not support routine ALND in patients with residual ITCs. Table 1. Clinicopathological Features of the Study Cohort, Stratified by Type of Axillary Surgery Frequency (row percent) reported for categorical variables, and median (IQR) reported for continuous variables. SLNB sentinel lymph node biopsy; TAD targeted axillary dissection; SLNs sentinel lymph nodes; LNs lymph nodes; pCR pathologic complete response; ACT anthracycline and taxane; AC anthracycline; H Herceptin, HP, Herceptin and Perjeta; TC taxol (or Taxotere) and carboplatinum; LVI lymphovascular invasion; BCS breast-conserving surgery. ^ Applied to HER2- tumors only (n=252). ^^ Applies to HER2+ tumors only (n=160). # LVI was present on core biopsy or final pathology. * Applies to BCS patients only (n=175). ** Applies to mastectomy patients only (n=237). Citation Format: Giacomo Montagna, Alison Laws, Massimo Ferrucci, Mary Mrdutt, Natália Polidorio, Varadan Sevilimedu, Tracy-Ann Moo, Andrea Barrio, Marissa K. Boyle, Flavia Vidal Cabero, Daniela Cocco, Fabio Corsi, Angelena Crown, Meghan R. Flanagan, Mehmet Ali Gulcelik, Callie Hlavin, Justyna Jelinska, Hasan Karanlik, Susan Kesmodel, Henry Kuerer, Sherko Küemmel, Cornelia Leo, Tehillah Menes, Melissa Pilewskie, Nina Pislar, Nicola Rocco, Jai Min Ryu, Leonardo Soares, Christoph Tausch, M. Umit Ugurlu, CICERO URBAN, Astrid Botty van de Bruele, Denise Vorburger, Fredrik Wärnberg, Anna Weiss, Austin Williams, Stephanie Wong, Steven G. Woodward, Susie X. Sun, Jennifer Q. Zhang, M. Firdos Ziauddin, Guldeniz Karadeniz Cakmak, Nuran Bese, Thorsten Kühn, Judy Boughey, Tari King, Nina Ditsch, Maggie Banys-Paluchowski, Monica Morrow, Walter Weber. Are nodal ITCs after neoadjuvant chemotherapy an indication for axillary dissection? The OPBC05/EUBREAST-14R/ICARO study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr GS02-02.

Importance Observational studies of survivors of breast cancer and prospective trials of aspirin for cardiovascular disease suggest improved breast cancer survival among aspirin users, but prospective studies of aspirin to prevent breast cancer recurrence are lacking. Objective To determine whether aspirin decreases the risk of invasive cancer events among survivors of breast cancer. Design, Setting, and Participants A011502, a phase 3, randomized, placebo-controlled, double-blind trial conducted in the United States and Canada with 3020 participants who had high-risk nonmetastatic breast cancer, enrolled participants from 534 sites from January 6, 2017, through December 4, 2020, with follow-up to March 4, 2023. Interventions Participants were randomized (stratified for hormone receptor status [positive vs negative], body mass index [≤30 vs &amp;gt;30], stage II vs III, and time since diagnosis [&amp;lt;18 vs ≥18 months]) to receive 300 mg of aspirin (n = 1510) or placebo once daily (n = 1510) for 5 years. Main Outcomes and Measures The primary outcome was invasive disease–free survival. Overall survival was a key secondary outcome. Results A total of 3020 participants were randomized when the data and safety monitoring committee recommended suspending the study at the first interim analysis because the hazard ratio had crossed the prespecified futility bound. By median follow-up of 33.8 months (range, 0.1-72.6 months), 253 invasive disease–free survival events were observed (141 in the aspirin group and 112 in the placebo group), yielding a hazard ratio of 1.27 (95% CI, 0.99-1.63; P = .06). All invasive disease–free survival events, including death, invasive progression (both distant and locoregional), and new primary events, were numerically higher in the aspirin group, although the differences were not statistically significant. There was no difference in overall survival (hazard ratio, 1.19; 95% CI, 0.82-1.72). Rates of grades 3 and 4 adverse events were similar in both groups. Conclusion and Relevance Among participants with high-risk nonmetastatic breast cancer, daily aspirin therapy did not improve risk of breast cancer recurrence or survival in early follow-up. Despite its promise and wide availability, aspirin should not be recommended as an adjuvant breast cancer treatment. Trial Registration ClinicalTrials.gov Identifier: NCT02927249