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Background Sexual and gender diverse (SGD) individuals comprise nearly 10% of the United States’ population but remain underrepresented in cancer research, particularly in intimate partner violence (IPV) studies. Although IPV rates are comparable or higher in SGD individuals than in non-SGD individuals, the literature on IPV in SGD patients with cancer remains sparse. Methods This qualitative study was conducted within a Mayo Clinic IRB-approved parent database on SGD patients with cancer. Eligible patients were adults who self-identified as non-heterosexual or non-cisgender, had an invasive cancer diagnosis, and reported IPV via a four-question screening tool. A detailed medical review was performed to extract qualitative data related to IPV and other violence. Two investigators employed thematic analyses to understand these qualitative data. Results Among 258 SGD patients whose medical records were screened, 13 (5%) reported IPV. Six key themes emerged: (1) IPV co-occurred with other violence (childhood, workplace, sexual violence); (2) IPV was associated with mental health conditions (depression, PTSD, suicidality); (3) Unhealthy coping mechanisms (substance use, risky behaviors) were common; (4) Social isolation and lack of support exacerbated challenges; (5) Internalized stigma influenced self-perception, relationships, healthcare experiences; (6) Chronic stress from cumulative trauma negatively impacted cancer care. Conclusion IPV was reported by a small proportion of SGD cancer patients, and cause and effect associations been IPV and the above themes have not been demonstrated. These findings suggest a need for trauma-informed, culturally competent interventions to address IPV and its broader psychosocial effects in these underserved populations.

Background: Gender-affirming hormone therapy (GAHT) may increase multiple sclerosis (MS) risk, yet MS disease course among transgender and gender-diverse (TGD) individuals remains understudied. We aimed to evaluate the disease course in TGD individuals with MS (TGD-MS). Methods: Seventeen TGD-MS were identified. Ten TGD-MS on GAHT (five transgender women with MS (TW-MS) and five transgender men with MS (TM-MS)) were investigated further for MS outcomes of symptomatic (clinical)/asymptomatic (radiological) disease activity and progressive MS (PMS) onset. Results: TW-MS (mean = 54.5 years, range = 35.1–66.3) were older than TM-MS (39.2 years, range = 29.6–47.2) at last follow-up. MS onset was later in TW-MS (31.5 years, range = 25.1–39.1) than in TM-MS (21.0 years, range = 15.0–29.8). Three patients (one TW-MS, two TM-MS) experienced symptomatic activity after GAHT initiation (8–10 months); in two patients (one TW-MS, one TM-MS), this marked symptomatic MS onset. Seven patients (four TW-MS, three TM-MS) had ⩾1 clinical/radiological disease activity. Four had PMS; all were TW-MS. In three, GAHT initiation preceded PMS onset (1–5 years). Disability was higher in TW-MS than in TM-MS. Conclusion: MS disease course may be modified by GAHT and may differ between TW-MS and TM-MS, highlighting the need for larger long-term studies to overcome disparities in MS care. Comprehensive GAHT history, timely management, and closer follow-up are warranted in TGD-MS.

The NCCN Guidelines for Survivorship include screening, evaluation, and treatment recommendations for common physical and psychosocial problems resulting from adult-onset cancer and its treatment and provide a framework for coordination of survivorship care. They also include recommendations to help cancer survivors enhance their wellness and maintain a healthy lifestyle. These NCCN Guidelines Insights summarize the panel’s current recommendations and recent updates regarding physical activity, nutrition, and weight management for cancer survivors.

529 Background: Neoadjuvant chemotherapy (NAC) is commonly administered to patients (pts) with estrogen receptor alpha (ER) negative (immunohistochemistry [IHC] 0%) and ER-low (IHC 1-10%) breast cancer (BC). For pts without pathological complete response (pCR), ER expression may differ between baseline and residual BC following NAC. We previously demonstrated adjuvant endocrine therapy (ET) omission in ER-low early-stage BC was associated with significantly worse overall survival (OS); however, this effect was restricted to pts with residual BC following NAC and those with higher baseline ER levels (IHC 6-10%) (Choong et al., ASCO 2024). Here, we assessed how often ER was expressed in residual invasive BC for pts treated with NAC for ER-negative and ER-low BC. Methods: Weidentified pts with pre-treatment (tx) ER-negative and ER-low (regardless of HER2 expression) stage I-III BC treated with NAC who underwent BC surgery at Mayo Clinic Rochester between 2009 and 2023. ER IHC was performed in a CAP/CLIA laboratory. We evaluated ER expression in residual invasive BC for pts without pCR. The percent of pts with a post-tx change in ER status was estimated and reported with 95% Wilson confidence intervals. Results: 955 pts (838 [88%] pre-tx ER-negative; 117 [12%] pre-tx ER-low) met inclusion criteria, of whom 69% had HER2-negative and 31% HER2-positive BC. The median age at diagnosis was 52 (range: 24-86). 496 (52%) had residual BC. Residual BC was more common in HER2-negative versus (vs) positive tumors (56% vs 42%, p < 0.001) but did not differ significantly by ER status (ER-negative 51% vs ER-low 57%, p = 0.22). Of those with residual BC, 277/496 (56%) had ER re-testing. Rates of ER re-testing did not vary for pre-tx ER-negative vs -low (57% vs 51%, p = 0.37) but were significantly lower for HER2-positive vs HER2-negative tumors (39% vs 62%, p < 0.001). Among those with post-tx testing, 31/277 (11%, 95% CI: 8-15%) had an increase in ER expression from pretreatment levels (defined as ER IHC < 1% to either 1-10% or > 10%; or ER IHC 1-10% to > 10%). In these 31 pts, the original NAC was for either TNBC (21/31; 68%) or HER2+ BC (10/31; 32%). In pts with pre-tx ER-negative BC, 27/243 (11%, 95% CI: 8-16%) had ER expression in the residual BC including 14/243 (6%, 95% CI: 3-9%) with ER > 10% and 13/243 (5%, 95% CI: 3-9%) with ER 1-10%. For pts with baseline ER-low BC, 4/34 (12%, 95% CI: 5-27%) had ER > 10% in the residual BC. Among the 31 pts where ER increased following NAC, 21/31 (68%) received adjuvant ET, including 17/18 if ER was > 10% in the residual disease and 4/13 in those with ER 1-10%. Conclusions: In pts treated with NAC for ER-negative or ER-low BC not achieving pCR, we identified higher ER expression in the residual breast cancer in > 10% of pts. Given that omission of ET in ER-low BC with residual cancer following NAC is associated with worse survival, repeat biomarker testing should be considered in those without pCR, and ET individualized according to ER expression.

1530 Background: Regular breast cancer screening reduces mortality. The American College of Radiology (ACR) recommends annual screening mammography for asymptomatic, average risk 1) transgender and gender diverse (TGD) men (individuals assigned female sex at birth but identify as men) age 40+ and with residual breast tissue and 2) TGD women (individuals assigned male sex at birth but identify as women) age 40+ and on gender-affirming hormone therapy for 5+ years. This nationwide study investigated screening mammography in TGD individuals. Methods: Four cohorts were identified with complex algorithms of medical and pharmacy data in the OptumLabs Data Warehouse, a longitudinal, administrative insurance claims database that includes patients with commercial insurance and Medicare Advantage: 1) TGD men, 2) TGD women, 3) individuals with gender dysphoria not meeting other TGD criteria (NMOT), and 4) cisgender women -- all of whom met ACR screening criteria. The primary endpoint was the percentage of individuals with high adherence, defined as completing >75% of recommended screenings; comparisons were made across the cohorts (Chi-square test). Multivariable logistic regression was used to compare adherence between TGD men and cisgender women with adjustment for demographics and with 1:4 matching (on race/ethnicity, age group, year of healthcare plan enrollment, and duration of follow-up). Results: 10,478 TGD individuals (3,778 TGD men; 1,294 TGD women; and 5,406 with gender dysphoria NMOT) and 6,218,369 cisgender women were identified. For TGD men, TGD women, individuals with gender dysphoria NMOT, and cisgender women, high adherence was observed in 41.1% (95% confidence interval (CI): 39.5, 42.6%); 7.4% (95% CI: 6.0, 8.8%); 11.9% (95% CI: 11.0, 12.7%); and 38.3% (95% CI: 38.3, 38.4%), respectively, p < 0.0001. No screening ever in these same populations was observed in 23.6% (95% CI: 22.2, 24.9%); 81.3% (95% CI: 79.2, 83.4%), 72.8% (95% CI: 71.6, 74%), and 35.9% (95% CI: 35.8, 35.9%), respectively, p < 0.0001. When TGD men were matched and compared to 15,112 cisgender women, a differential association was observed between gender and high adherence by age group (p < 0.0001); compared to cisgender women, the likelihood of high adherence in TGD men ages 40-49 (n = 2,472), 50-59 (n = 852), 60-69 (n = 320), and 70+ (n = 134) were as follows: odds ratios (OR‘s): 1.38 (95% CI: 1.28, 1.50), p < 0.0001; 1.57 (95% CI: 1.35, 1.81), p < 0.0001; 0.812 (95% CI: 0.619, 1.065), p = 0.1316; and 1.277 (95% CI 0.835, 1.951), p = 0.2595, respectively. Conclusions: This study found that TGD men manifest relatively high adherence to screening mammography, whereas TGD women and individuals with gender dysphoria NMOT manifest low adherence. Future research should focus on improving breast cancer screening in these underserved populations.

12038 Background: CIPN, primarily associated with sensory neuropathy rather than motor or autonomic dysfunction, is a potentially long-term complication of cancer treatment including taxanes and platinums (T/Ps), and can negatively impact quality of life for breast cancer (BC) survivors. This project aims to quantify the severity of neuropathic symptoms at one and three years after diagnosis in BC survivors, comparing recipients of T/P to non-recipients. Methods: In the Mayo Clinic Breast Registry (MCBDR), a longitudinal cohort, surveys and medical record data from patients with stage 1-3 BC were used to understand the burden of neuropathic symptoms at 1- and 3-years post-diagnosis (denoted as Y1 and Y3). Y1 and Y3 raw scores from The Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 (CIPN20) composite (CIPN20-C) and sensory subscale (CIPN-S) were converted to a 0-100 point scale, with lower scores corresponding to worse symptoms. Patients with BC recurrence prior to Y3 or incomplete surveys were excluded. We used two sample t-tests and multivariable linear regression modeling to compare recipients of T/P to non-recipients of T/P (with threshold for statistical significance p <0.05). Results: 786 patients were included, 112 of whom (14.2%) received T/P. T/P recipients were younger (p<0.001), more likely to have Stage II/III disease (p<0.001), and less likely to have received endocrine therapy (p<0.001). Univariate analyses revealed worse CIPN20-C score at Y1 (p=0.02) and worse CIPN20-S scores (p=0.004) at Y1 and Y3 in T/P recipients compared to non-recipients (Table). However, differences between the groups were no longer statistically significant after adjustment for age, stage and endocrine therapy. Conclusions: In this cohort, neuropathic symptom severity at Y1 and Y3 after a breast cancer diagnosis did not differ between recipients of taxane and/or platinum agents and nonrecipients after adjustment for age, stage, and endocrine therapy. These data may reassure patients and clinicians who are concerned about CIPN and considering use of these chemotherapies in this setting. Patient demographics and CIPN20 results. Clinical characteristic T/P recipients Non-recipients of T/P Age at diagnosis, mean (SD) 55.3 (11.6)* 59.8 (11.9) White race, N (%) 108 (96.4%) 660 (97.9%) Clinical stage II/III, N (%) 76 (68.5%)* 250 (37.5%) Endocrine therapy, N (%) 73 (65.2%)* 636 (94.4%) Diabetes mellitus, N (%) 9 (8.9%) 52 (8.6%) Y1 CIPN20-C score, mean (SD) 89.6 (10.9)* 92.0 (9.7) Y3 CIPN-C score, mean (SD) 89.4 (11.4) 91.1 (9.7) Y1 CIPN20- S score, mean (SD) 87.3 (15.1)* 91.3 (13.0) Y3 CIPN20-S score, mean (SD) 88.2 (14.1)* 91.1 (11.7) *Statistically significant (p <0.05) on univariate analysis.

Background: Patients who experience homelessness manifest poor cancer outcomes, often because of treatment delays. Few studies have used mixed methods to learn what happens at the patient and health care staff level to explain these delays. Methods: This single-institution, multi-site study interrogated the entire medical record system (thousands of patients annually) for homelessness and cancer diagnoses from January 1, 2019, through October 10, 2023. Records were abstracted for relevant quantitative and qualitative data; rigorous methods were used to analyze, integrate, and report findings. Results: Forty-three patients with a median age of 58 years (range: 32, 73 years) and 34 (79%) assigned male sex at birth are the focus of this report. The most common cancers include hematologic (n = 8), gastrointestinal (n = 8), and genitourinary (n = 8). Thirty-five patients (81%) initiated cancer therapy, and 27 (63%) manifested treatment delay (>4 weeks post-diagnosis). The median time to cancer therapy was 9 weeks (95% confidence interval: 4.6, 12 weeks). Qualitative themes that explain delays are as follows: (1) logistical challenges in communication between the patient and health care team (“lack of a cell phone”); (2) patient reluctance to receive care (“patient elected to leave Against Medical Advice”); and (3) medical challenges in providing care (“he was hospitalized after being found down and hypotensive”). Conclusions: This study confirms that initiation of cancer therapy is often delayed in patients who experience homelessness. It sheds light on reasons for delay – for example, lack of phone access, an observation which suggests that perhaps provision of a burner phone might help some patients.

524 Background: Antiangiogenic tyrosine kinase inhibitors (TKIs) play a key role in treating renal cell carcinoma and other solid organ malignancies, but TKIs cause bothersome side effects that frequently necessitate dose reductions or treatment holds. Olanzapine has been useful for palliating symptoms from classical chemotherapies and advanced cancer, but its effect on TKI-related symptoms is largely unknown. This retrospective study aimed to estimate the efficacy of olanzapine for TKI-induced nausea, vomiting, anorexia, weight loss, and insomnia. Methods: All patients prescribed olanzapine with lenvatinib, cabozantinib, axitinib, or tivozanib at Mayo Clinic between January 1, 2018, and June 30, 2024 were assessed for inclusion. For baseline symptom assessment, clinical care team notes documenting the presence or absence of symptoms and indication(s) for starting olanzapine were reviewed. For response assessment, clinical notes and patient portal messages from the first three months after starting olanzapine were evaluated for qualitative descriptions of change in symptom burden. Relevant data were extracted as direct quotations, which were reviewed by the research team and categorized as “improved,” “worsened,” “stable,” or “missing data.” Each symptom domain was analyzed independently when olanzapine was prescribed for multiple interrelated symptoms. Results: A total of 60 patients who received olanzapine for the treatment of TKI-related adverse effects were included. The most common documented indication for olanzapine was nausea without vomiting (n=35), followed by anorexia (n=25), nausea with vomiting (n=16), weight loss (n=16), and insomnia (n=11). In 32 cases (53%), olanzapine was prescribed for multiple, simultaneous symptoms. Response rates for each symptom domain are shown in the table. In addition, prior to olanzapine, 34 patients (57%) had documented weight loss. Following olanzapine, 50% (n=17) gained weight (median increase: 6.1 kg; range: 2.0 - 10.7 kg), 26% (n=9) stabilized their weight (±1 kg), and 24% (n=8) continued to lose weight. Clinicians utilized a TKI dose reduction within one week of olanzapine initiation in 5 cases (8.3%), and 3 of these patients could resume the higher dose of TKI after starting olanzapine. Only 4 patients (7%) discontinued olanzapine within 3 months due to perceived side effects. Conclusions: Olanzapine appears to be effective in treating TKI-induced nausea, vomiting, anorexia, insomnia, and weight loss. Prospective randomized placebo-controlled studies are needed to confirm these findings. Improvedn (%) Worsened n (%) Stablen (%) Missing Datan (%) Nausea without emesis 32 (84) 3 (8) 1 (3) 2 (5) Nausea with emesis 13 (93) 0 (0) 0 (0) 1 (7) Anorexia 26 (74) 2 (6) 4 (11) 3 (9) Insomnia 11 (85) 0 (0) 2 (15) 0 (0)

PURPOSE Over 50% of households in the United States have at least one musician—many musicians are also breast cancer survivors. This group has not been well studied, and given the level of fine sensory-motor skill required for musicianship, we hypothesized that musicians experience unique manifestations of breast cancer treatment toxicities. METHODS A nine-item Musical Toxicity Questionnaire (MTQ) was distributed to patients who had consented to participate in the Mayo Clinic Breast Cancer Registry. The MTQ screened participants by asking if they played a musical instrument or sang in the last 10 years: questions populated for those who answered yes. Respondents were asked if they noticed difficulty with their musical endeavor during or after breast cancer treatment, defined as acute musical toxicity (AMT). The questionnaire asked which side effect and cancer-directed therapy most influenced musical ability, what musical attributes were affected, and the timeline of resolution. Multivariable and classification tree analyses assessed relationships between AMT and treatment characteristics. RESULTS Of 1,871 survey respondents, 29% (535/1,871) self-identified as musicians. Over a quarter (27%, 144/535) reported AMT, and for 57% (82/144), AMT had not resolved at the time of survey. Of the treatments each participant received, chemotherapy was most often reported as most negatively impactful (63/89 who received chemotherapy, 71%). Decreased endurance was the most common musical difficulty (64% of those with AMT, 92/144), followed by decreased accuracy, trouble playing/singing quickly, and difficulty using proper technique. Multivariable and classification tree analyses revealed that receipt of chemotherapy was most strongly correlated with AMT. CONCLUSION These results will help oncology care teams counsel musicians, answer questions about impacts on musicality, and provide a timeline for resolution of musical symptoms.