Cathcart-Rake, Elizabeth

Abstract In the United States, over 2 million individuals openly identify with a gender that differs from their sex assigned at birth. A cancer diagnosis is physically and psychologically taxing—and, in some, traumatic. However, for transgender and gender‐diverse (TGD) people, many of whom have experienced discrimination in myriad health care settings, the challenges may be even greater. These recommendations focus on how best to deliver quality cancer care to transgender men (individuals who identify as men but were assigned female sex at birth), transgender women (individuals who identify as women but were assigned male sex at birth), and people who identify somewhere beyond this gender spectrum as nonbinary or using other terms, based on the available, albeit sparse, literature. This review broaches: (1) the epidemiology of cancer in TGD individuals, including the incidence of cancer and cancer‐related mortality; (2) cancer center practices that are welcoming and affirming to TGD patients; (3) the need for awareness and intentionality in the spaces of diagnosis and treatment for cancer; (4) the inevitable conclusion that gender differences exist but much more needs to be learned about the impact of gender‐affirming therapy, consisting of gender‐affirming surgeries and gender‐affirming hormone therapy, on cancer therapy; and (5) the efficacy and perceived safety of antineoplastic therapy and gender‐affirming hormone therapy.

Background: Physical function (PF) is an important outcome that can inform cancer treatment tolerability from a clinical and regulatory perspective. PF can be assessed through different modalities: patient-reported (PRO), clinician-reported (ClinRo), performance tests (PerfO), and digital sensors (wearables). No standard approach for PF measurement has been defined, and each modality bears unique implementation challenges. The Integrating 4 Measures to Assess Physical Function study (In4M, NCT05214144) characterized the performance of these PF modalities in patients receiving cytotoxic chemotherapy, with a goal of guiding an assessment strategy in future cancer trials. Here we present feasibility results of the In4M study in patients with lymphoma. Methods: In4M is a prospective observational study with longitudinal PF assessment of PROs, ClinRo, PerfO, and wearable sensor data for over 9 months in patients initiating chemotherapy for lymphoma or breast cancer at Mayo Clinic and Yale University. Patient-reported PF was assessed using several validated ePRO instruments, ClinRo utilized clinician-reported Eastern Cooperative Oncology Group (ECOG) performance status, PerfO was measured via 6-minute walk test (6MWT), and digital sensor data was obtained from a wearable (Fitbit) provided to all participants. We evaluated the feasibility of implementing these PF modalities through compliance outcomes and a study-specific exit survey. Descriptive statistics included medians and interquartile ranges (IQR) for continuous variables and frequencies for categorical variables. We used a mixed model to estimate mean number of Fitbit compliant days per week. Results: Among 66 patients with lymphoma in the study (median age was 57 years; 52% were male), 90% self-reported as White, 4.9% as Black, 1.6% as Asian, 1.6% as American Indian or Alaska Native, and 1.6% as multiple races. Ethnicity was reported as non-Hispanic/Latino by 93% of patients. Education status was reported as more than high school by 92% of patients, and 49% reported full-time employment at time of enrollment. The overall ePROs completion rate was 80.7% for the entire study period. Baseline ePRO completion rate was 93.9%. Completion rate while undergoing chemotherapy was 91.3% and 75.4% in the post-treatment follow-up. The median time to complete ePROs was 4.1 minutes (IQR 2.8-5.9), ranging from 3.1 minutes for surveys with 37 questions to 5.6 minutes for surveys with 55 questions (survey length varied by timepoint). The baseline 6MWT was completed by 91% of patients. The most common reasons for not completing the baseline 6MWT were: patient refusal (50%, 3/6), patient not physically present (33%, 2/6), and unable to complete due to fatigue (17%, 1/6). The 3-month 6MWT was completed by 66% (40/61) of patients, with the most common reasons for missingness being: patient not physically present (38%, 8/21) and unable to complete due to fatigue (14%, 3/21). When considering the days when Fitbit was used, the median wear time was 21.3 hours (IQR 18.9-22.5) per day. The proportion of compliant days (>10 hours of wear time during waking hours) was 53% (IQR 20-84). The median of participants' average compliant days per week was 5.4 (IQR 4.3-6.1) days/week after enrollment, with a slight downward trend over time (-0.017 compliant days per week [95% CI: -0.021, -0.012, p <0.001] over each consecutive week in the study). The exit survey was completed by 39 (59%) patients. Most participants (85%) indicated they did not find the ePRO surveys burdensome to complete. Using the Fitbit (charging and syncing) was found to be manageable by most patients (87% and 84%, respectively). 60.8% of patients did not find the wearable bothersome to use, while the main themes reported by the remaining patients were related to the operation of the wearable itself (functions, small text size, forgetting login information) or discomfort (band material, wearing at night). Conclusion: Multi-modal assessment of PF with PRO, ClinRo, PerfO and wearable sensor data in patients with lymphoma undergoing treatment is feasible. Designing lymphoma therapeutic trials that incorporate at least one PF assessment modality, or assessment with a parsimonious combination of modalities, is achievable and may yield valuable insights into treatment tolerability for clinical and regulatory purposes.

Introduction: Anthracyclines (AC), a class of chemotherapeutic drugs, are used to treat various cancers, including breast cancer (BC). However, AC cause dose-dependent cardiac toxicity. Practice guidelines list pre-existing cardiomyopathy as a risk factor for cancer therapy-related cardiac dysfunction (CTRCD), but there is a lack of data on cardiotoxicity risk in patients with left ventricular (LV) hypertrabeculation without LV hypertrophy/dilation. We present a patient with LV hypertrabeculation who developed LV dysfunction after AC chemotherapy for BC. Description of Case: A 55-year-old woman diagnosed with multicentric invasive ductal carcinoma (IDC) of the right breast, stage IIA (cT3 cN1 cM0), grade 2, ER+/PR+/HER2-, was treated with neoadjuvant Paclitaxel for 3 months. Before AC-based chemotherapy, stress cardiac MRI due to residual post-COVID-19 dyspnea showed LV hypertrabeculation with a non-compacted/compacted ratio of 2.3, LVEF 56%, and no delayed enhancement. Transthoracic echocardiography (TTE) reported an LVEF of 52% with GLS of -17%. The patient's electrocardiogram (ECG) showed normal sinus rhythm, and NT-pro BNP levels were <20 pg/mL. Genetic testing identified a rare variant in MYH7-encoded myosin heavy chain 7 (p.Arg941Leu-MYH7). She had no cardiovascular (CV) risk factors or family history of CV disease. She then underwent 4 cycles of Doxorubicin (cumulative dose 232.2 mg/m2) and Cyclophosphamide, followed by bilateral mastectomy and adjuvant radiotherapy (5000 cGy in 25 fractions). One year after chemotherapy, follow-up TTE showed LVEF decreased to 45% with GLS of -17%. The patient’s ECG remained normal, and NT-pro BNP levels were <36 pg/mL. Despite an LVEF decline, not all criteria for CTRCD were met, suggesting a gene-environment interplay between her chemotherapy and pre-existing MYH7-mediated non-dilated LV cardiomyopathy (NDLVC) with hypertrabeculation. The patient has remained without symptoms of heart failure and is currently taking Letrozole 2.5 mg daily. Discussion: This case offers a unique perspective on a BC patient treated with AC chemotherapy, who has a possible MYH7-mediated NDLVC with hypertrabeculation, and who experienced an LVEF decline of indeterminate significance. While the association of her possible NDLVC with hypertrabeculation is uncertain, the safety of AC in patients with isolated hypertrabeculation or NDLVC with hypertrabeculation, as introduced by the 2023 ESC cardiomyopathy guidelines, remains to be defined.

Abstract BACKGROUND Meningiomas are the most common primary intracranial tumors, typically managed with surgical resection and/or radiation therapy. Systemic therapy options are limited and reserved for cases refractory to conventional interventions. Cyclin dependent kinase (CDK) proteins are key cell cycle regulators. CDK inhibitors are clinically available, approved for treatment of breast cancer and in clinical trials for meningioma. METHODS We present a case where a patient with incidentally-discovered intracranial meningioma undergoing CDK inhibitor therapy with ribociclib for breast cancer experienced a radiographic response. RESULTS A 73-year-old female was diagnosed with estrogen receptor (ER) positive, progesterone receptor (PR) positive, HER2 negative metastatic invasive ductal carcinoma of the breast. She was treated with estrogen receptor antagonist fulvestrant and CDK 4/6 inhibitor ribociclib. MRI of the brain performed for disease staging demonstrated an extraaxial, dural-based, homogenously enhancing mass along the left posterior petrous ridge consistent with a meningioma. Two-month interval scan demonstrated a marginal decrease in size of the mass (15.6x18.3 mm to 15.4x17.5 mm). Systemic disease related to breast cancer concurrently improved. Two years later, with ongoing fulvestrant and ribociclib therapy, a repeat MRI brain demonstrated further decrease in size of the meningioma (13.4x16.8 mm). CONCLUSIONS Hormonally-directed therapies previously demonstrated limited benefit for meningiomas despite PR/ER positivity reported for these tumors. However, CDK 4/6 inhibitors abemaciclib and ribociclib have demonstrated activity in treatment of recurrent grade 2/3 meningiomas. The radiographic response noted in our case suggests there may be a role for systemic therapy even in treatment-naive cases that may not be amenable to surgical resection or radiation therapy.

Background Older LGBTQIA+ patients face discrimination in healthcare and therefore are sometimes reluctant to engage and interact with healthcare providers. This report explores whether a large medically-based internet platform can be used to engage these patients and describes preferable methods for doing so. Methods This study used Mayo Clinic Connect, a continuously monitored, internet-based social media platform of 100,000-plus users. Participants completed a brief on-line survey to ensure their study eligibility. No patient-identifying data was asked. Participants then were to call in by phone during specified day time hours for a 45-minute qualitative interview. Alternatively, as a second subsequent option, they were to complete an on-line typed response to 4 questions about their health and healthcare. No temporal overlap occurred between the availability of the phone interview option and the typed-in response option. Results For the phone interviews, 17 of 64 individuals were deemed eligible, but no individual called in to be interviewed. In contrast, for the typed-in response option, 20 of 37 individuals were eligible and provided comments. Conclusion A large medically-based internet platform can be used to engage older LGBTQIA+ patients, but the use of typed-in comments appears more successful, presumably because of greater anonymity and convenience.

1564 Background: Physical function (PF) is a core outcome in cancer trials that can inform treatment tolerability. PF can be assessed across modalities including by patient (pt) report, clinician (clin) report, performance tests and digital sensors. The optimal approach for PF measurement has not been defined. Methods: In4M is a prospective observational study evaluating PF in pts initiating chemotherapy for breast cancer or lymphoma followed over 9 months. We used an electronic platform (Hugo) to aggregate serially assessed pt-reported PF, clin- and pt-reported ECOG performance status (PS), 6-minute walk test (6MWT) and wearable (Fitbit) data. We evaluated feasibility in all pts; associations among PF measures and the ability of PF measures to detect change were evaluated in pts with both baseline (BL) and 3-month (3M) data. We used Pearson correlations to assess the relationship of average daily steps with measures of PF. To assess change, we compared each PF measure from BL to 3M using a 2-sided α=.05 paired t-test. Results: Of the208 pts enrolled, 193 (93%) and 159 (76%) completed surveys, and 121 (58%) and 124 (60%) provided wearable data (evaluable: ≥1 day data) at BL and 3M, respectively. When requiring a stringent BL with 4+ days of data with ≥1 weekend day to be evaluable, 88 (42%) and 120 (58%) provided wearable data at BL and 3M. At both BL and 3M, pt-reported PF was generally more highly correlated with wearable-derived daily steps than clin-reported PF and 6MWT were (Table). Significant declines in PF were observed for pt- and clin-reported PF (all p<0.05), but not other modalities. Conclusions: Longitudinalassessment of multi-modal PF data including pragmatic wearable data collection was feasible in pts receiving chemotherapy. Pt-reported PF was the only modality that was both correlated with step count and able to detect change. Additional wearable metrics, correlations among PF measurements and outcomes, and clinically meaningful change scores will be reported. Optimal PF measurement may improve future reporting of treatment tolerability. Clinical trial information: NCT05214144 . [Table: see text]

12048 Background: Playing music has been an important part of human culture for millennia. Today more than half of American households have at least one person who plays music, and in the UK 43% of adults play an instrument. Despite the overlap between musicians and people diagnosed with cancer, the effect of cancer treatment on musicianship has not been well-studied. We previously reported that 26% of a musician breast cancer survivor cohort reported difficulty with musicianship after treatment, and here we conduct further analysis to identify treatment and disease factors associated with this difficulty, termed acute musical toxicity (AMT). Methods: The Musical Toxicity Questionnaire was distributed to participants who had previously enrolled in the Mayo Clinic Breast Cancer Registry. PROMIS (Patient-Reported Outcomes Measurement Information System) scores were available through the Registry and treatment details were collected retrospectively. Due to the inter-dependency and high correlation between treatment and disease-related variables, a classification tree analysis (CTA) was performed to identify the combination of variables that most accurately classified patients by AMT. Sixteen variables were analyzed by the algorithm. Logistic regression was utilized for examining associations between AMT and continuous variables. Results: Of the 4075 surveys distributed, 1871 were returned and 535 respondents identified as musicians. Median time from diagnosis was 5.2 years, respondents were mostly stage I or II (71%), and 32% were node positive (N+). Over a quarter (26% or 144 respondents) reported AMT. In the final CTA model, being N+ was strongly associated with AMT (42% of those N+ had AMT, 20% of those not N+ had AMT). For respondents who were N+, those who received endocrine therapy were more likely to have AMT than those who did not (46% vs 21% respectively). Subsequent leaves identified not undergoing axillary lymph node dissection (ALND) and receiving chemotherapy as associated with AMT. For respondents who did not receive chemotherapy, breast reconstruction was associated with AMT (60% vs 19%). Variables such as mastectomy, radiation volume, specific chemotherapies, and stage of disease were not selected by the algorithm. The odds of having AMT decreased by 9.7% and 17% with each additional point in the composite mental health (p=0.003) and physical health (p<0.001) PROMIS scores, respectively. The odds of having AMT increased by 3.5% with each lymph node removed (p=0.001). Conclusions: The final model suggests that the group with the largest proportion of AMT was N+, received endocrine therapy, did not have ALND, and received chemotherapy. Both physical and mental health PROMIS scores were associated with AMT, although the directionality of this relationship requires more study. Care teams should counsel patients on potential musical toxicity and engage in shared decision making with musical patients.

11145 Background: T-DXd is increasingly used in mBC. A T-DXd toxicity of special interest is interstitial lung disease/pneumonitis (ILD), occurring in 10-15% of pts in the DESTINY-Breast trials, and with potential lower incidence/severity in earlier line settings [Krop et al, ASCO 2023]. However, in routine practice, T-DXd may be used in pts with more heavily pre-treated mBC and previously exposed to other antibody-drug conjugates (ADC) [Premji et al SABCS 2023]. We evaluated the incidence/severity of T-DXd related ILD in mBC at Mayo Clinic. Methods: We retrospectively identified pts with mBC who received ≥1 dose of T-DXd at Mayo Clinic, Rochester, MN, between July 2022-December 2023. Demographic, mBC, and pulmonary clinical variables were abstracted from the clinical records. Data was summarized using descriptive statistics. Diagnosis of ILD was determined by treating clinicians, and severity to CTCAE V5 based on clinical documentation. Results: 77 pts with mBC received T-DXd during the study period. All were female, the majority (70, 91%) were Caucasian, and median age was 58. 53 (69%) had HER2-low mBC (37 HR+, 16 HR-) and 24 (31%) had HER2+ mBC (17 HR+, 7 HR-). 31 (40%) were active or former smokers. 11 (14%) had pulmonary comorbidities, including 6 (7.8%) with asthma, 2 (2.6%) with prior pneumonitis, and 3 (3.9%) with other pulmonary comorbidities. They had previously received a median of 1 line of endocrine therapy, and 4 lines of chemotherapy, with 20 (26%) having received another ADC. 17 (22%) developed any grade ILD [G1: 3 (4%), G2: 7 (9%), G3: 2 (3%), G4: 1 (1%), G5: 4 (5%)]. Among pts with ILD of any grade, 13 (76.5%) presented with at least 1 symptom (cough/SOB). The median number of T-DXd cycles prior to onset of any grade ILD was 6 (range 2-13), or 18 (range 6-39) weeks. 5 (29%) pts with any grade ILD received a prior ADC. Of pts with ≥G3 ILD (n=7), all were Caucasian, 2 (30%) were prior smokers, none had prior lung disease, and had received a median of 5 prior lines of chemo, with 4 (57%) having received a prior ADC. All grade ≥2 ILDs were treated with systemic steroids, and 1 also received IVIG. CT chest was used for diagnosis of all ILD. 7 pts (41%) required hospitalization, all of whom had bronchoscopy, with 5 (29%) requiring intubation. All pts with G1 ILD (3, 18%) restarted T-DXd without ILD recurrence. Conclusions: In this case series,22% of ps treated with T-DXd experienced ILD (5% G5), higher than the rate observed in the pivotal DESTINY-Breast trials, possibly due to real-world use of T-DXd in more heavily pre-treated pts and in pts with pulmonary comorbidities.

PURPOSE Routine collection of sexual orientation (SO) and gender identity (GI; collectively SOGI) in cancer clinics advances cancer care equity. METHODS In 2022, NCI Community Oncology Research Program (NCORP) practice groups were asked about routine collection of SOGI data in the electronic health record. The proportions of practice groups reporting collection of SO and/or GI data were calculated, and practice group characteristics were assessed for associations. RESULTS Of 271 practice groups nationwide, 42% (n = 112) collect SO data, 58% (n = 157) collect GI data, and 35% (n = 96) collect both. In multivariate analyses, SO data collection was associated with practice groups having minority outreach staff (odds ratio [OR], 2.07 [95% CI, 1.12 to 3.81]; P = .02); GI data collection was associated with practice groups located in the Northeastern United States (OR, 2.08 [95% CI, 0.73 to 5.91]; P = .045), and those with a higher proportion of new patients who were White (OR, 1.02 [95% CI, 1.01 to 1.04]; P < .001). Practice groups in the South were least likely to collect SOGI data (OR, 0.49 [95% CI, 0.26 to 0.94]; P = .004). There were no statistically significant differences in SO and/or GI collection on the basis of the practice group's proportion of Medicaid/Medicare patients, number of new patients with cancer per year, or practice ownership. CONCLUSION Slightly over one third of NCORP practice groups report routinely collecting SOGI data. There are regional differences in data collection, underscoring the need to craft targeted, region-specific interventions focused on boosting the capture and recording of SOGI data in an affirming manner.

Abstract Background: Eyebrow and eyelash loss, known as madarosis, can occur secondary to breast cancer-directed therapy. However, the incidence and predictors of this phenomenon are not well-known. The purpose of this study is to ascertain the proportion of breast cancer survivors who experience madarosis, potential contributing factors to eyebrow and eyelash loss, and associations between this symptom and mental health. Methods: Breast cancer survivors were invited to participate in an ongoing longitudinal cohort study, the Mayo Clinic Breast Disease Registry (MCBDR), after having been seen at least once for breast cancer at Mayo Clinic in Rochester, MN. Those who consented were mailed a survey approximately one year after diagnosis. Respondents were asked to report their degree of eyebrow and eyelash loss experienced since their diagnosis on a 4-point scale of “no loss” (0) to “complete loss” (3). The proportions of participants who reported eyebrow and eyelash loss were evaluated overall and according to treatment type by descriptive statistics. Relationships between eyebrow and eyelash loss and mental health scores collected using the PROMIS-10 project scales (ranging from 0-20), with the poorest mental health indicated by scores under 8, were explored. Results: 838 registry participants responded to the year 1 survey’s alopecia questions. The median age of breast cancer survivors was 59.4 years (range 22-100 years). The majority were diagnosed at stage I-II (69%). 315 (37%) had received chemotherapy (+/- endocrine therapy), 415 (50%) had received endocrine therapy only, and 108 (13%) had received neither. Nearly half reported eyebrow loss (49%) or eyelash loss (49%). Eyebrow loss was reported by 89% of chemotherapy recipients, 27% of endocrine therapy only recipients, and 19% of those not treated with chemotherapy or endocrine therapy. 102 (32%) of those with chemotherapy-associated eyebrow loss reported that it was complete. Eyelash loss was reported by 274 (87%) of chemotherapy recipients, 112 (27%) of endocrine therapy only recipients, and 23 (21%) of those who received neither. Although no formal statistical testing was performed, there was a numerically higher proportion of patients with eyebrow and/or eyelash loss who reported poor mental health. Conclusions: Madarosis is a bothersome symptom in cancer survivors, particularly after chemotherapy. Future investigation into the incidence, predictors, and treatment of anti-neoplastic medication-related madarosis is needed. Table. Global mental health scores on PROMIS scale for eyebrow and eyelash loss Citation Format: Sarah Premji, Kathryn Ruddy, Nicole Larson, Charles Loprinzi, Brittany Dulmage, Maryam Lustberg, Fergus Couch, Janet Olson, Elizabeth Cathcart-Rake. Eyebrow and eyelash loss in breast cancer survivors [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 PO5-12-10.