Citations

1564 Background: Adolescent and young adult (AYA) females with early-stage ER-negative and/or HER2-positive breast cancer commonly receive chemotherapy to reduce risk of recurrence. Fertility concerns, counseling, and preservation may influence chemotherapy decisions and time to chemotherapy (TTC) initiation. Methods: We surveyed AYA survivors of stage I–III premenopausal ER-negative and/or HER2-positive breast cancer treated at Kaiser Permanente Northern and Southern California (2013-2022). Fertility concerns were defined as not having completed desired family size or being unsure about having completed desired family size at diagnosis. We summarized receipt of fertility counseling, receipt of chemotherapy, and use of oocyte/embryo cryopreservation for fertility preservation (FP). Among fertility-concerned patients who received chemotherapy, TTC (days from diagnosis) was assessed separately for neoadjuvant chemotherapy (NAC) vs for adjuvant chemotherapy (AdjC). Time to NAC was natural log–transformed and modeled with multivariable log-linear regression to estimate relative differences in TTC, adjusting for stage, study site, ER, HER2, age, and diagnosis year. Results: Of 363 respondents, 197 (54%) had fertility concerns at diagnosis; 183/197 (93%) received chemotherapy, similar to 153/166 (92%) among those without concerns (p=0.7). Of the concerned chemotherapy recipients, 45 (25%) saw a fertility specialist but did not pursue FP while 55 (30%) underwent FP. For the 112 fertility-concerned NAC recipients, FP was associated with longer TTC than no fertility specialist counseling (mean=41 vs. 30 days; adjusted ratio=1.39; 95% CI 1.15–1.69), whereas fertility specialist counseling without FP was not (mean= 31 vs. 30 days, adjusted ratio=1.04; 95% CI 0.86–1.25). For the 71 fertility-concerned AdjC recipients, TTC was similar for patients who did not see a fertility specialist (mean=63 days), those who froze oocytes/embryos (mean=65 days), and those who saw a fertility specialist but did not pursue FP (mean=69 days). Conclusions: In this AYA breast cancer cohort, there was no evidence that fertility concerns led patients to decline chemotherapy. FP was associated with a modest delay in NAC initiation (<2 weeks on average). Time to chemotherapy (TTC) among 183 AYA patients with ER− and/or HER2+ breast cancer and fertility concerns. Fertility-focused care N (n=183) Neoadjuvant chemotherapy (n=112) Mean TTC, days Relative difference in TTC, adjusted ratio (95%CI) Adjuvant chemotherapy (n=71) Mean TTC, days No fertility counseling from a specialist 83 (45%) 55 (49%) 29.6 Reference 28 (39%) 62.6 Received fertility counseling from a specialist No fertility preservation 45 (25%) 28 (25%) 30.7 1.04 (0.86,1.25) 17 (24%) 68.6 Fertility preservation 55 (30%) 29 (26%) 41.2 1.39 (1.15,1.69) 26 (37%) 64.6

12007 Background: YAs with cancer, defined as those diagnosed prior to the age of 40, may experience greater symptom burden compared to those diagnosed at older ages. We evaluated the impact of an ePROM-triggered, CC-based, supportive care intervention on symptom burden in YAs with cancer. Methods: The Enhanced, Electronic Health Record-facilitated Cancer Symptom Control (E2C2) trial was a cluster-randomized, pragmatic trial (NCT03892967) that enrolled oncology patients seen at Mayo Clinic Rochester and within the Mayo Clinic Health System (sites in Minnesota and Wisconsin) between March 2019 and January 2023. Patients routinely reported the severity of six SPPADE symptoms (Sleep deficit, Pain, Physical function impairment, Anxiety, Depression, and Energy deficit/fatigue) on 11-point numerical rating scales. Symptom severity was classified as none to mild (0-3), moderate (4-6), or severe (7-10). Those with moderate or severe symptoms were offered symptom management education, while those with severe symptoms were also offered the option to work virtually with a symptom care manager. In this post hoc analysis, we examined the effects of the intervention on change in symptom scores among YAs and time to improvement to a mild/moderate level in those with at least one severe symptom. Results: Among 40,659 patients who responded to at least one survey, 2,598 were YAs and 38,061 were adults ≥ 40 years. Among YAs, 10.7%, 24.3%, and 65.1% were 18-24 years, 25-31 years, and 32-39 years, respectively. A greater proportion of YA patients were female (61.5% vs 57.0%), of a non-white race (12.4% vs 5.3%), living in an urban setting (65.7% vs 55.1%), single (36.4% vs 9.6%), on non-government insurance (78.1% vs 36.6%), employed (72.6% vs 37.4%), and had a Bachelor’s degree or greater (37.8% vs 28.3%, p < 0.001 for all). Fewer YA patients had metastatic disease compared to older patients (24.2% vs 35.2%, p < 0.001). Compared to a pre-intervention baseline, the mean change in symptom score for YA patients following the intervention demonstrated improvements in anxiety (-0.195) and depression (-0.168, p < 0.0001 for both), while physical function impairment worsened over the intervention period (0.101, p = 0.014). Compared to adults ≥ 40 years, YAs experienced greater intervention effects for management of depression ( p < 0.001), fatigue ( p = 0.01), pain ( p < 0.0001), and physical function impairment ( p < 0.0001). Among YAs with a severe symptom during the intervention period, median time to improvement to a mild/moderate level was longer for anxiety compared to those ≥ 40 years (3.5 vs 2.7 months, p = 0.009). Conclusions: Routine ePROM surveillance, coupled with CC-based symptom management, led to improvements in anxiety and depression among YAs with cancer, although, time to improvement was longer for anxiety compared to adults ≥ 40 years.

11025 Background: Adjuvant endocrine therapy (AET) improves outcomes in HR+ breast cancer. Nonadherence to AET is common, but manual screening for nonadherence is fraught. High-specificity structured cancer electronic health record (EHR) data, particularly if it includes key variables like stage, could streamline these steps for both clinical care and research purposes. We conducted an analysis of approaches to identifying patients as eligible for a multi-site AET adherence study to understand how variation in structured data informatics-supported screening impacts coordinator time. Methods: Mayo Clinic implemented a two-step identification: (1) EHR structured data (diagnosis date, stage, ER/PR/HER2 positivity, medication script) to prescreen for eligibility; (2) SureScripts fills to flag nonadherence using proportion of days covered < 80% across early fills. Medical College of Wisconsin (MCW) implemented a more manual screening process for Step 1 using only medication scripts. Coordinators at both sites then conducted a medical record review to assess if the resulting list of patients had a plan to continue AET for at least two additional years. Opt-out clinician permission preceded patient contact; pharmacists delivered a patient reported outcome (PRO)-guided intervention and documented encounters. Results: At Mayo, 829 patients were prescreened for study eligibility through informatics workflow; 120 (14.5%) met eligibility criteria. At MCW, 1,763 patients were prescreened; 168 (9.5%) were eligible. EHR filters included non–breast cancer encounters (50% at MCW) and ineligible based on time since cancer (36% at Mayo; 26% at MCW). At Mayo, screening required 5.6 minutes/patient for experienced coordinators. At MCW, experienced coordinators averaged 6.67 minutes/patient and inexperienced coordinators averaged 9.33 minutes/patient. Conclusions: Structured EHR data, pharmacy-fill information, and standardized workflows allowed consistent prescreening, intervention and recruitment processes across sites. Higher-specificity informatics-supported screening reduced the percentage of patients requiring manual review and reduced coordinator screening time. It also supported timely provider-permission steps and patient outreach. These workflows were feasible to implement at both institutions, and study enrollment is ongoing. Clinical trial information: NCT06765707 .

Importance Little is known about how factors external to the workplace, such as spousal support, influence physician attrition. Objectives To explore associations of spousal support among married/partnered physicians with both ‘hard’ attrition ((HA), considering leaving academic medicine within 2 years) and ‘soft’ attrition ((SA), having ever considered part-time work), before and after adjusting for demographic variables, burnout and satisfaction with work-life integration (WLI). Design This cross-sectional survey study was conducted among faculty physicians employed at Mayo Clinic. Outcomes and measures Survey items measured demographics, spousal support (five items), HA, SA, satisfaction with WLI (single-item measure) and burnout (two-item measure). Check-all-that-apply questions explored reasons for considering attrition. We investigated associations of spousal career support with attrition consideration using logistic regression analyses, adjusting for demographic variables then for WLI satisfaction and burnout. Results 739/2103 physicians responded (response rate 35.1%); 666 (90.1%) were married or partnered and responded to the HA question. 42.5% (283/666) reported considering HA and 60.9% of full-time employees (288/473) had ever considered SA. 65.5% (437/666) considered any attrition (AA). Respondents reporting more frequent spousal career support had lower odds of HA (OR 0.80, 95% CI 0.68 to 0.94, p=0.006), though this was not significant when considering AA (OR 0.85, 95% CI 0.71 to 1.01, p=0.07). Neither association was significant after adjusting for WLI satisfaction and burnout (OR 1.01, 95% CI 0.80 to 1.29, p=0.91 (HA), OR 1.10, 95% CI 0.86 to 1.37, p=0.45 (any attrition)). Conclusions While spousal support was no longer significantly associated with attrition after adjusting for WLI satisfaction and burnout, it may mitigate attrition.

Abstract Background Whether outcomes of germline BRCA1/2 (gBRCA1/2)-associated breast cancer differ compared with sporadic tumors is controversial. We explored the impact of gBRCA1/2 pathogenic variant (PV) status beyond established prognostic features. Methods We conducted 2 retrospective, matched cohort studies comparing gBRCA1/2 PV carriers and noncarriers with HER2-negative, stage I-III breast cancer (Clinical Outcomes Quality Database [COQD] cohort: 185 carriers, 555 noncarriers; Young Women’s Breast Cancer Study [YWS] cohort: 113 carriers, 226 noncarriers). Matching factors were age, stage, hormone receptor status, and year of diagnosis. Clinicopathological features, treatments, and survival outcomes were compared between carriers and noncarriers. Results Most patients in COQD had stage I-II disease (87.2%), and more carriers than noncarriers had genetic testing before diagnosis (33% vs 5.6%, P &lt; .001). In YWS, 22.7% of patients had stage III tumors, and few were tested before diagnosis (14.8% of carriers vs 1.7% of noncarriers; P &lt; .001). Carriers in COQD received chemotherapy more often than noncarriers (81.1 vs 67.0%, P &lt; .001), including platinum (P = .010); the proportion was similar for carriers and noncarriers in YWS. After adjusting for chemotherapy, relapse-free survival was longer in carriers than noncarriers in COQD (adjusted hazard ratio = 0.48 [95% CI = 0.26 to 0.87], P = .016), and a favorable trend was observed for other survival outcomes in both cohorts. Triple-negative tumors appeared to drive the differences. Conclusions We observed a trend toward improved outcomes in gBRCA1/2 PV carriers compared with noncarriers. These findings suggest that carriers should not receive more aggressive treatment solely based on their germline mutation status. Prospective clinical trials in this population are warranted.

Abstract Background Breast cancer (BC) diagnosed during pregnancy or postpartum often presents with aggressive features, potentially influenced by hormonal, immunological, and tissue remodeling changes. Studies have suggested that postpartum BC may be associated with worse outcomes, though most evidence is retrospective and constrained by methodological limitations. This study evaluated associations between pregnancy history, recency of childbirth, and long-term outcomes in a prospective cohort of young patients with early-stage BC. Patients and Methods Patients aged ≤40 years with stage I–III BC enrolled in the Young Women’s Breast Cancer Study were categorized at diagnosis as nulligravid, nulliparous, pregnant, or parous (≤5 vs 5 to 10 years postpartum). Analyses were stratified by BC subtype (estrogen receptor-positive [ER+]/HER2−, HER2+, and triple-negative [TNBC]), with distant recurrence-free survival (DRFS) as the primary endpoint. Results Among 859 patients, 257 (29.9%) were nulligravid, 50 (5.8%) nulliparous, 37 (4.3%) pregnant, and 515 (60.0%) parous. Pregnant patients had proportionally more TNBC, nodal involvement, T3/T4, and grade 3 tumors. After 11.1 years median follow-up, pregnancy or postpartum status was not independently associated with DRFS in multivariable models adjusted for age, tumor characteristics, and treatment, with consistent findings across ER+/HER2−, HER2+, and TNBC subtypes. Sensitivity analyses, including further categorization of postpartum diagnoses (&lt;2 vs 2 to 5 years), yielded consistent results. Conclusions Pregnancy history and recency of childbirth were not independently associated with long-term DRFS. Despite more aggressive features at diagnosis, patients diagnosed during or after pregnancy had comparable outcomes after adjustment, suggesting no adverse prognostic impact. Clinical trial registration NCT01468246 (https://clinicaltrials.gov/study/NCT01468246? term=NCT01468246&rank=1).

Background/Objectives. Decades of research have failed to uncover effective approaches to prevent chemotherapy-induced peripheral neuropathy (CIPN), a common side effect of neurotoxic chemotherapy. Increased interest in placebo response as a potentially under-recognized confounder in CIPN trials was recently sparked by the results of a multisite NCI-funded phase II-III CIPN prevention study of duloxetine, a promising serotonin–norepinephrine reuptake inhibitor that enhances pain-inhibitory mechanisms within the central nervous system. Study findings revealed high and nearly equivalent response rates in three randomized treatment groups—little to no CIPN was reported by 65.2%, 66.0%, and 68.0% of study participants who received duloxetine 30 mg, 60 mg, or placebo treatment, respectively. Methods. We performed a meta-analysis of placebo response rates from seven randomized, double-blinded, placebo-controlled trials conducted over the past 20 years and comprising 191 placebo participants that were specifically testing interventions for oxaliplatin- and paclitaxel-induced peripheral neuropathy and that serially collected patient responses on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Chemotherapy-Induced Neuropathy questionnaire. Additionally, we sought to identify trial- and patient-specific factors that predicted higher placebo response rates from a participant-level pooled analysis. Results. The placebo response rate was 10.0% [95% CI: 5.8%, 16.6%] when response was defined more conservatively as patients reporting no neuropathy at all. When the placebo response was defined more broadly based on patients reporting no or a little neuropathy, the placebo response rate was higher (39.6% [95% CI: 27.4%, 53.2%]). Male participants, receipt of oxaliplatin, and a 2:1 randomization ratio favoring the intervention arm were individually associated with a higher placebo response. Conclusions. High placebo response rates can threaten scientific progress toward identifying effective treatments for cancer treatment-associated side effects, like CIPN. Careful attention to study design factors, participant eligibility, and patient and research staff expectations may help to minimize placebo response rates in future CIPN intervention studies.

ABSTRACT Aims Exercise capacity is a powerful predictor of cardiovascular risk. In patients unable to exercise, body composition analysis can potentially be used to estimate cardiorespiratory fitness. We developed a body composition “fitness” score, then validated its utility in two external populations. Methods and Results We included patients from four sites undergoing single photon emission computed tomography (SPECT) and twelve sites undergoing positron emission tomography (PET). We quantified body composition using deep learning. We evaluated associations between body composition and good exercise capacity (defined as completing ≥7 minutes on a Bruce protocol) then developed a body composition “fitness” score. We then assessed the associations of “fitness” score with exercise capacity and all-cause mortality in external populations. In total, 36471 patients were included with median age 67 (interquartile range 58 – 74). Median skeletal muscle density was higher among patients with good exercise capacity. In the external SPECT population, the body composition “fitness” score had higher prediction performance for good exercise capacity (AUC 0.771, 95% CI 0.752 – 0.789) than age (AUC 0.717, p<0.01). In the external PET population, high body composition “fitness” score was associated with lower cardiovascular death (adjusted hazard ratio 0.70, 95% CI 0.62 – 0.79, p<0.001). Conclusions We demonstrated that a comprehensive body composition “fitness” score could identify patients with good cardiorespiratory fitness. This approach transforms routinely acquired CT data into a surrogate marker of fitness which can be applied in patients undergoing PET, or other CT imaging, where exercise testing is not performed. Graphical Abstract Overview of study design. The overall population (n=36471) was split as outlined above. Body composition was analyzed from available computed tomography imaging. The distribution of body composition measures were analyzed in the combined single photon emission computed tomography (SPECT) populations. A body composition “fitness” score was derived to predict good exercise capacity in the internal population, with associations assessed in the two external testing populations.

Abstract Background Anxiety is a common symptom experienced by patients with cancer, who are increasingly interested in non-pharmacologic symptom management. Acupressure, a noninvasive intervention thought to impact the neurohormonal axis, has shown promise in reducing anxiety. However, research on acupressure for anxiety in patients with cancer has been limited. Methods Individuals receiving chemotherapy, who reported baseline anxiety, were eligible for this study. Consenting participants received one 15-minute nurse-led acupressure session and completed pre- and post-intervention surveys. The primary endpoint was a change in anxiety. Participants were also asked about symptoms of nausea, pain, well-being, relaxation, worry, and distress. Participants were invited to learn self-acupressure techniques. These participants were asked to complete a final survey 1-week post-intervention. Results Thirty adult patients participated in this study. Mean baseline anxiety was 5 on a 0 to 10 Likert scale. Immediate post-intervention anxiety scores significantly improved for all thirty patients to an average of 2.0 (P &lt; .001). Mean nausea scores improved from 1.5 at baseline to 0 post-intervention (P &lt; .001), and pain scores improved from 2.0 at baseline to 1.0 post-intervention (P = .001). Participants reported significant improvement in sense of wellbeing (P = .0004), distress (P &lt; .001), ability to achieve relaxation (P &lt; .001), and ability to control their worries (P &lt; .001). The improvement in anxiety, well-being, and relaxation was sustained at one week. 100% of participants stated that they would recommend acupressure for symptom management. Conclusion Acupressure is a promising non-pharmacologic intervention for the management of cancer-associated anxiety.

Abstract Purpose Spatial distribution of coronary artery calcium (CAC) may provide additional prognostic value in patients undergoing SPECT and PET myocardial perfusion imaging (MPI). We aimed to automatically identify CAC in proximal segments from attenuation correction CT (CTAC) scans using artificial intelligence (AI) and to evaluate prognostic significance in two large international multicenter registries. Methods From hybrid MPI/CT imaging (N=43,099) across 15 sites, we included 4,552 most relevant patients with 1) no prior coronary artery disease; 2) AI-derived mild CAC scores (1-99); and 3) normal perfusion (stress total perfusion deficit <5%). The independent associations between AI-identified proximal CAC and major adverse cardiovascular events (MACE) and all-cause mortality (ACM) were evaluated using multivariable Cox regression, likelihood ratio test (LRT), and continuous net reclassification index (NRI). Results Among the patients with mild CAC and normal perfusion (mean age 65±12 years, 51% male), 1,730 (38%) had proximal CAC. Over 3.6 (inter-quartile interval 2.1, 5.2) years follow-up, 599 (13%) and 444 (10%) patients had MACE or ACM, respectively. Proximal CAC was associated with an increased risk of MACE (adjusted hazard ratio [HR] 1.24, 95% CI 1.03–1.48, P=0.02) and ACM (adjusted HR 1.25, 95% CI 1.01–1.53, P=0.04) after the adjustment of CAC score and density, clinical risk factors, and perfusion deficit. Proximal CAC improved the risk stratification of MACE (LRT P=0.02; NRI 12%) and ACM (LRT P=0.04; NRI 12%). Conclusion In patients with mild CAC and normal perfusion, AI detection of proximal CAC identified a higher-risk group for adverse outcomes, highlighting its prognostic utility. Graphical Abstract From patients who underwent hybrid myocardial perfusion imaging (MPI) from 15 sites, we analyzed those without prior coronary artery disease (CAD), mild coronary artery calcium (CAC) scores (1-99), and normal perfusion (stress total perfusion deficit <5%). A previously developed AI model was used to identify CAC lesions in proximal coronary segments on CT attenuation correction maps (CTAC). We evaluated associations with major adverse cardiovascular events (MACE) and all-cause mortality (ACM), showing risk stratification of proximal CAC and improvement by net reclassification index (NRI). CAC lesion color: green, left anterior descending artery (LAD) with left main artery; red, left circumflex artery (LCX); yellow, right coronary artery (RCA). Adjusted hazard ratios (HRs) are shown with 95% confidence intervals.