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Importance Inherited pathogenic variants (PVs) in known predisposition genes can greatly increase breast cancer risk, but the combined impact of PV status, family history, and other factors on breast cancer risk in the general US population has not been well described. Objective To evaluate population-based breast cancer risk estimates for those with established PVs overall and stratified by first-degree family history of breast cancer and other factors. Design, Setting, and Participants This study used pooled data from 13 US-based breast cancer case-control studies participating in the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. Enrollment for individual studies occurred between 1976 and 2013, and results are based on data released March 2023, with analyses conducted from June 2022 to July 2025. Exposures PVs, breast cancer family history, self-reported race and ethnicity, and established risk factors. Main Outcomes and Measures Breast cancer rate ratios for PVs in 7 genes were estimated from the CARRIERS consortium. PV status and incidence and mortality statistics were combined using the Individualized Coherent Absolute Risk Estimation (iCARE) model to estimate conditional cumulative breast cancer risks and 95% CIs, stratified by family history and standardized to the US population. Models that incorporated population-based data and published estimates for established epidemiologic risk factors were also evaluated. Results A total of 67 692 women were studied, including 33 841 who were diagnosed with breast cancer. PVs in ATM , BRCA1 , BRCA2 , CHEK2 , and PALB2 were strongly associated with breast cancer risk, with BRCA1 and PALB2 PVs showing evidence of heterogeneity by family history. In models considering PVs, family history, and established risk factors, the estimated cumulative risks of breast cancer by age 50 years ranged from 2.4% (95% CI, 2.4-2.4) in women with no PVs and no family history to 35.5% (95% CI, 21.6-55.1) in PALB2 PV carriers with a family history. Among women who have not been diagnosed with breast cancer by age 50 years, the cumulative risk of breast cancer by age 80 years ranged from 11.1% (95% CI, 11.0-11.2) in noncarriers with no family history to 70.5% (95% CI, 52.8-83.5) for PALB2 carriers with a family history. PV-specific cumulative risk estimates varied across subgroups defined by race and ethnicity and potentially modifiable epidemiologic risk factors. Conclusions and Relevance In this study, population-based estimates of cumulative breast cancer risk for established PVs, as informed by the CARRIERS case-control sample, varied by family history and potentially modifiable risk factors. These estimates provide guidance for identifying individuals who will most benefit from enhanced screening and prevention strategies.

572 Background: Neoadjuvant endocrine therapy (NET) is sometimes used to shrink hormone receptor-positive (HR+) breast cancers to improve breast conservation rates and reduce axillary nodal burden. At the beginning of the COVID-19 pandemic, several organizations endorsed NET use to mitigate the harm of surgery delay when cancer operations were less available due to infection transmission concerns. However, the real-world patterns of NET during this period are understudied. This study investigated the alteration of NET utilization patterns during the COVID-19 pandemic in the United States using the National Cancer Database (NCDB). Methods: We identified patients diagnosed with stage I-III invasive HR+/human epidermal growth factor receptor 2-negative (HER2-) breast cancer between 2018-2022 in the NCDB. Estrogen receptor and/or progesterone receptor positivity was required for inclusion in the cohort. Receipt of NET was defined as initiation of endocrine therapy ≥ 14 days before the patient’s first surgical procedure. The study cohort generation and statistical analysis were conducted using Stata and R 4.4.3. A two-tailed p value < 0.05 was considered statistically significant. Results: 495,098 patients were included in the cohort, 195,371 in 2018-2019 (pre-pandemic), 91,686 in 2020 (early pandemic), 106,157 in 2021 (mid-pandemic), and 101,884 in 2022 (late pandemic). NET utilization was increased in the early pandemic compared to the pre-pandemic (seen in 5.8% vs 2.4% of the cohort, Chi-square p value < 0.001), but this use fell back to 3.4% in the mid-pandemic and 3.5% in the late-pandemic. The median (IQR) duration of NET was 15.7 (6.4-26.6) weeks in the pre-pandemic, 9.3 (5.4-18.7) weeks in the early pandemic, 13.2 (5.8-25.7) weeks in the mid-pandemic, and 12.0 (6-24.6) weeks in late pandemic (Kruskal-Wallis p value = 0.001). The transient increase in NET utilization during the early pandemic was more pronounced among patients with tumors < 5 cm and node-negative disease. Conclusions: Our study identified a significant shift in the utilization of NET for HR+/HER2- breast cancer during the COVID-19 pandemic. Pandemic-era NET policies produced a short-lived practice change that was only partially sustained once surgical access normalized. NET utilization (%) by subgroup and year for stage I-III HR+/HER2- breast cancer. Variable Category 2018-2019 2020 2021 2022 Overall NET Use 2.4 5.8 3.4 3.5 Age Group (years old) <50 2.2 4.9 3.9 4.0 >=50 2.4 6.0 3.3 3.4 Tumor Size <5 cm 2.0 5.5 2.9 3.1 >=5 cm 9.0 9.7 11.2 11.6 Histology Subtype Ductal 2.2 5.5 3.3 3.4 Lobular 3.6 7.1 4.4 4.8 Ductal/Lobular 2.6 6.2 4.3 3.6 Other 1.9 6.7 2.5 2.6 KI67 <20% 2.5 6.4 3.4 3.3 >=20% 2.3 5.5 3.5 3.7 Tumor Grade Well differentiated 1.9 5.8 2.4 2.6 Moderately differentiated 2.7 6.1 3.9 3.9 Poorly differentiated/undifferentiated 2.9 4.8 4.3 4.8 Node Positivity Positive 5.2 5.6 9.3 9.5 Negative 2.0 5.8 2.6 2.7

PURPOSE Given the extended survivorship of young adults with breast cancer, characterizing health care utilization and adherence to surveillance guidelines can inform gaps in care. PATIENTS AND METHODS Patients age 40 years and younger at diagnosis of stage 0-III breast cancer enrolled in a prospective cohort study completed a survey 7 years after diagnosis assessing receipt of care and surveillance. We evaluated factors associated with transition to a primary care provider (PCP) for cancer-related follow-up and adherence to mammography and bone density scans. RESULTS Among 660 women, 92% reported having a PCP, although for cancer-related follow-up, 57% saw only an oncology provider, 29% saw both a PCP and oncology provider. In the past 2 years, 68% reported getting a flu shot, 76% a pap test/pelvic examination, 56% cholesterol screening, and 42% (n = 232 endocrine therapy [ET] users) a bone density scan. Among women who had a unilateral mastectomy or lumpectomy (n = 356), 82% reported a mammogram in the past year. In multivariate analyses, those with stage 0 ( v I disease) were more likely to see a PCP for follow-up ( v PCP + oncology provider); ET users and those more concerned about recurrence were less likely. Patients with human epidermal growth factor receptor 2-positive (HER2) disease were more likely to adhere to mammography; those with a BRCA mutation and those with a unilateral mastectomy were less likely. Patients with a BRCA mutation and who had chemotherapy were more likely to report a bone density scan. CONCLUSION Although most have a PCP, over half of young survivors continue to see an oncology provider for follow-up in long-term survivorship. Mammography uptake was high; uptake of other health maintenance practices was lower. Identification of barriers/facilitators to receipt of guideline-concordant care may inform strategies to optimize survivorship.

Abstract Background Opioid stewardship policies could adversely affect pain management for patients with cancer. Yet patients with cancer are also at risk for opioid‐related harms. This study sought to determine trends in opioid prescribing by clinical stratum and pain for patients with cancer from 2016 to 2020. Methods A retrospective study was conducted of opioid‐naive adults with newly diagnosed cancer from 2016 to 2020 ( N = 10,232) in a large Connecticut health system. Logistic regression was used to calculate changes in the predicted probability of opioid prescribing from 2016 to 2020. Two subpopulations were examined: patients treated surgically ( n = 4405) and patients with metastatic cancer ( n = 2158). Flowsheet pain scores for patients with metastatic cancer were used to stratify by no pain (all scores, 0) versus any pain. The main outcomes were new (≥1 prescription in the 0–6 months after diagnosis) and additional (0–6 and 7–9 months) opioid prescriptions. Results A decline was observed in the predicted probability of new (71.1% to 64.6%; p < .001) and additional prescribing (27.2% to 24.2%; p = .07 [not significant]) declined. Among surgical patients, the predicted probability of new opioid prescribing fell (96.0% to 88.6%; p < .001), whereas additional prescribing was stable (13%). For patients with metastatic cancer with pain, new opioid prescribing was stable (56%). For those reporting no pain, the predicted probability of new opioid prescribing declined from 61.6% to 36.1% ( p < .001). Conclusions In the context of widespread policy changes, this study showed a modest decline in new and additional opioid prescribing for patients with cancer. In metastatic cancer, prescribing remained stable for patients reporting pain and declined steeply for those reporting no pain.

Abstract Background Breast cancer (BC) survivors frequently experience sleep disturbances, which may persist for many years after treatment. This study aimed to describe trends in sleep-related symptoms over time and identify factors that may be associated with sleep disturbances in BC survivors. Patients and Methods Adult patients from the Mayo Clinic Breast Disease Registry were surveyed annually for up to 7 years post-diagnosis. Sleep disturbance severity was assessed using numeric rating scales for difficulty falling and staying asleep. Data from 3354 unique patients were analyzed, excluding those with metastatic disease or recurrence. Univariable and multivariable analyses were performed at the 1-year survey timepoint to evaluate disease and patient-related factors that were associated with increased sleep-related symptoms, and these factors were also assessed in relationship to sleep-related symptoms over time. Results In multivariable analyses, more trouble falling asleep was associated with financial insecurity, higher clinical stage, more cigarettes smoked per day, and less weekly exercise. More trouble staying asleep was associated with older age, race, advanced education, financial insecurity, and higher clinical stage. Over time, there was a nonsignificant trend toward increased trouble falling asleep and fluctuations in trouble staying asleep. Higher clinical stage and receipt of radiotherapy were associated with decreased severity in trouble falling asleep over time, while more cigarettes smoked per day was linked to increased severity in trouble staying asleep. Conclusions These findings highlight the complex interplay of clinical, lifestyle, and demographic factors in sleep disturbances among BC survivors, underscoring the need for tailored sleep management strategies.

Background/Objectives: This study aims to evaluate the quality of life (QoL) and oncological outcomes in premenopausal women diagnosed with hormone receptor-positive breast cancer who are receiving either bilateral oophorectomy (BO) or gonadotropin-releasing hormone agonist (GnRH) therapy. Both methods serve to inhibit ovarian function, which is essential for the management of estrogen-dependent tumors; however, their effects on QoL have yet to be fully clarified. Methods: Data were analyzed from the Mayo Clinic Breast Disease Registry, focusing on women under 55 diagnosed with estrogen receptor-positive breast cancer who received either BO or GnRH within one year of diagnosis. QoL was assessed using the Patient-Reported Outcomes Measurement Information System Global-10 (PROMIS-10) at baseline and annually for five years. Results: A total of 181 patients were enrolled in the study; 40 into the BO group and 141 to the GnRH group. Both groups exhibited similar levels of sexual dysfunction after a one-year period; however, the BO group stated a higher frequency of hot flashes. PROMIS-10 scores improved in both mental and physical health over time, with no significant differences between the groups. Within the BO group, one recurrence was observed, in contrast to the GnRH group, which had six events. Nonetheless, the difference in recurrence rates did not reach statistical significance. Conclusions: The long-term QoL and oncologic outcomes for premenopausal women with hormone receptor-positive breast cancer were similar for BO and GnRH therapy. These findings emphasize the need for individualized treatment decisions, considering patient preferences and side effects.

AbstractElectronic patient-reported outcome measures (ePROMs) can improve care for people with cancer, but effectiveness hinges on well-supported integration in clinical settings.We evaluated clinician use of specific clinical decision support (CDS) tools in the electronic health record (EHR) designed to facilitate timely, clinically appropriate responses to ePROM scores for six symptoms commonly experienced by cancer patients.The parent pragmatic trial, which took place at Mayo Clinic (Rochester, Minnesota, United States) and its affiliated community health care system between March 2019 and January 2023, evaluated the population-level effectiveness and implementation of an ePROM surveillance and EHR-facilitated collaborative care symptom management intervention. The present evaluation used a case study approach with four data sources: (1) clinician interactions with CDS tools abstracted from the EHR; (2) clinician notes identified with an institution-specific textual search tool; (3) qualitative interviews and group discussions with care teams; and (4) administrative records reviewed to identify training and outreach to care teams.EHR metrics showed very low adoption of CDS tools including alerts and symptom-specific order sets, despite educational outreach and information technology support provided to clinical care teams. Qualitative findings revealed that CDS use was not easy to integrate into busy clinical workflows and highlighted clinician perceptions that the collaborative care intervention provided additional patient support that reduced clinicians' need to utilize CDS tools. They also highlight the importance of contextual factors, including institutional priorities and EHR changes.This pragmatic clinical trial case study found limited adoption of EHR CDS tools that had been developed to increase clinicians' awareness of and responses to ePROM data. Findings suggest the need to align clinician and organizational implementation strategies, simplify CDS tools to fit practice expectations, and identify and address contextual factors that could undercut strategies like education and peer support. This may be especially important for teams who aim to iteratively evaluate and refine CDS and implementation strategies for multicomponent interventions or introduce new strategies that are responsive to barriers while maintaining scalability.

This cross-sectional study analyzes patient-reported outcome findings from the Enhanced, Electronic Health Record–Facilitated Cancer Symptom Control (E2C2) trial to investigate level of symptom burden in adolescents and young adults with cancer.

Abstract Background Endocrine therapy has been the mainstay treatment for metastatic hormone receptor-positive / HER2-negative (HR+/HER2-) breast cancer. Given that cell cycle dysregulation and consequent uncontrolled cellular proliferation is a key mechanism behind cancer growth, agents targeting this pathway have been of major therapeutic interest.[1] The cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors palbociclib, ribociclib, and abemaciclib have shown a synergistic effect in combination with endocrine therapy.[2-3] Despite favorable results, post-approval studies have revealed potential concerns for cardiotoxicity. [4] Given this, we sought to characterize the incidence and outcomes of atrial arrhythmia among metastatic HR+/HER2- breast cancer patients who were treated with CDK 4/6 inhibitors at our institution. Purpose To investigate the incidence and risk factors of atrial arrhythmia among hormone receptor-positive/HER2-negative breast cancer patients treated with CDK4/6 inhibitors at our institution. Methods A retrospective cohort study was conducted among 2754 patients ≥18 years of age who received treatment with CDK4/6 inhibitors (palbociclib, ribociclib, or abemaciclib) for an established diagnosis of hormone receptor-positive, HER-2 negative breast cancer between 2015-2024. Patients with new onset atrial fibrillation and/or flutter were identified through chart review. The cumulative incidence of new-onset atrial arrhythmia was estimated using the Kaplan-Meier method. Univariable and multivariable Cox regression analyses were performed to identify predictors of atrial arrhythmia. Results A total of 2754 patients was included in the study; 97.3% were female and mean age was 61 years (13). Among these, 101 (3.6%) had a prior history of atrial arrhythmia. The 1-year and 5-year cumulative incidence of new-onset AA were 1.1% and 2.8% respectively (Figure 1). When stratified by specific CDK4/6 inhibitor agents, there was no statistically significant difference. On univariable analysis, age at treatment, hypertension, coronary artery disease, and peripheral vascular disease were associated with new-onset atrial arrhythmia. However, following multivariable adjustment, only age at treatment was statistically significant. Conclusions New-onset atrial arrhythmias may occur during or after CDK4/6 inhibitor use. Older patients appeared to have a higher risk. There were no clear differences in atrial arrhythmia risk between the three CDK4/6 inhibitors.