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ABSTRACT Background Alcohol intake is a modifiable risk factor for breast cancer, yet patterns of alcohol intake in women with breast cancer remain underexplored. This study evaluates demographic and clinical predictors of alcohol intake in patients with breast cancer. Methods Patients at Mayo Clinic Rochester diagnosed with breast cancer (Stage 0–3) between July 2014 to March 2022 were surveyed about their average alcohol intake over the 10 years prior to their diagnosis. Alcohol intake was categorized as < 1, 1–4, 5–14, and ≥ 15 drinks per week. Demographic, behavioral, and clinical data were analyzed using univariate Fisher exact tests and multivariate multinomial logistic regression. Results Of 2030 participants (mean age at diagnosis: 59 years; 99.3% female; 95.9% White), 29% consumed < 1 drink/week, 48% reported 1–4 drinks/week, 20% consumed 5–14 drinks/week, and 3% reported ≥ 15 drinks/week. Older age at diagnosis (≥ 60 years), non‐White race, financial difficulty, and never smoking were associated with less alcohol intake. Patients who reported higher levels of mild–moderate intensity exercise reported more alcohol intake. Tumor stage, tumor receptors, and BRCA mutation status were not associated with alcohol intake. PROMIS‐10 physical health scores correlated with alcohol intake in univariate but not multivariate models. Conclusion Alcohol intake is more common prior to a breast cancer diagnosis for patients who are younger, White, financially secure, exercising, and smoking. These findings may inform alcohol intake‐related breast cancer prevention efforts and highlight patient subgroups who could benefit from targeted counseling at the time of diagnosis.

Abstract Background: Incorporation of Polygenic Risk Scores (PRS) can refine traditional breast cancer (BC) risk assessment models to provide precise estimates of BC risk. However, the impact of such an integrated model on BC risk estimates and clinical decision-making related to BC screening and preventive strategies in germline pathogenic variant (PV) carriers is not fully understood. Methods: The GENRE-2 is a prospective single-arm multisite clinical trial (NCT04474834) incorporating 313-PRS into standard BC risk assessment models to determine the impact of PRS on risk estimates and clinical decisions on prevention and screening. All women received pre- and post-PRS BC risk estimates and completed surveys on their screening and cancer prevention decisions before and after integrating PRS estimates. Herein, we report on the impact of integrating PRS into CanRisk-based BC risk estimates among women enrolled in GENRE-2 due to PVs in ATM, BRCA1, BRCA2, CHEK2, or PALB2. Women were categorized into average risk (&lt;20%), moderate risk (20-40%), or high risk (&gt;40%) for BC based on clinically relevant lifetime risk thresholds for supplemental MRI screening and risk-reducing bilateral mastectomies. Changes in categories of lifetime BC risk estimates were then evaluated before and after integration of PRS. Impact of PRS on patient decisions to undertake screening or preventive action (medication or prophylactic mastectomy) was evaluated based on pre- and post-PRS surveys. Results: Between 2020 and 2025, 933 women were enrolled, 633 received PRS results and completed a survey to date. Of those who received PRS results, 214 (33.8%) were PV carriers (ATM: 24, BRCA1: 54, BRCA2: 73, CHEK2: 54 and PALB2: 9). Among PV carriers, the CanRisk-based median 10-year and lifetime pre-PRS risk estimates were 6.0% and 23.9% for ATM, 22.5% and 77.5% for BRCA1, 17.9% and 77.6% for BRCA2, 7.1% and 26.6% for CHEK2, and 16.6% and 42.4% for PALB2, respectively. A total of 7 (29.2%) ATM PV carriers had a shift in lifetime BC risk categories after integration of PRS, with 1 (4.2%) shifting from average to moderate-risk, 3 (12.5%) shifting from moderate to average-risk category, and 3 (12.5%) shifting from moderate to high-risk category. Among CHEK2 PV carriers, 9 (16.7%) had a shift in lifetime risk categories, with 4 (7.4%) shifting from moderate to average-risk, 2 (3.7%) shifting from moderate to high-risk, and 3 (5.6%) shifting from high to moderate-risk. None of the BRCA1 and 4.1% of BRCA2 PV carriers had a shift in lifetime risk categories after PRS integration. Only 1 (11.1%) PALB2 PV carrier had a change in lifetime risk category after integration of PRS, although this was limited by a small sample. A significantly higher proportion of PV carriers with a high lifetime risk intended to take preventative action compared to the PV carriers with average lifetime risk (41.4% vs. 20.0%, p=0.007). Conclusions: Integration of PRS into BC lifetime risk estimates led to a clinically meaningful change in risk categories in 29.2% of ATM PV carriers and 16.7% of CHEK2 PV carriers, but in &lt;5% of BRCA1 or BRCA2 PV carriers. These findings suggest that PRS may be helpful for BC risk stratification in moderate-risk genes such as ATM and CHEK2 but may have limited clinical utility in high-risk genes such as BRCA1 or BRCA2. Citation Format: S. Yadav, C. Klassen, D. Stan, J. Fraker, S. Sahni, S. A. Khan, L. Khatri, C. Vachon, D. Schaid, J. P. Sinnwell, E. Carlson, L. Hasadsri, F. J. Couch, S. Pruthi. Impact of Polygenic Risk Scores on Breast Cancer Risk Assessment and Clinical Decision Making in Carriers of Germline Pathogenic Variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2: Results from the Prospective Multisite GENRE-2 Clinical Trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PD4-04.

Abstract Purpose To evaluate alcohol intake trends and identify demographic, clinical, lifestyle and socioeconomic factors associated with alcohol consumption in late survivorship among breast cancer survivors. Methods Individuals diagnosed with stage 0–3 breast cancer enrolled in the Mayo Clinic Breast Disease registry between 2014 to 2022 reported their average weekly alcohol intake at baseline (time of diagnosis) and at approximately four years post-diagnosis. Alcohol intake was divided into four categories and cross-sectional associations with demographic, clinical, and lifestyle factors were examined using Monte Carlo-based Fisher exact tests and multivariable multinomial logistic regression. Changes in alcohol consumption from baseline to Year 4 were evaluated using Bowker’s test of symmetry and multinomial models. Results Among 719 participants, alcohol intake 4 years post diagnosis closely resembled baseline patterns, with 30.2% of patients reporting no alcohol use and 48.8% of patients consuming 1–4 drinks per week. Younger age and current smoking status were strongly associated with higher intake at Year 4. Exercise and better physical health were associated with higher alcohol intake in univariable models, however not in adjusted models. From time of diagnosis to Year 4, 15.6% of patients decreased their alcohol intake, 10.2% increased alcohol intake, and 74.3% reported no change. Higher levels of mild intensity exercise were associated with an elevation in alcohol intake over time. Conclusion Alcohol consumption remained stable in late survivorship, in contrast to the initial decline in alcohol use during early survivorship seen in this cohort. Younger age and smoking were key associations with higher alcohol intake.

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.

11114 Background: Advances in early detection and treatment of breast cancer (BC) have significantly improved survival outcomes. In this growing survivor population, addressing modifiable lifestyle factors such as alcohol intake (AI), a known risk factor for BC and BC recurrence, is critical to improving prognosis and health-related quality of life (HRQoL). This study examines AI patterns and their associations with mental and physical HRQoL in early BC survivorship. Methods: Adult patients newly diagnosed (≤1 year) with stage I–III BC at Mayo Clinic Rochester were invited to enroll in the Mayo Clinic Breast Disease Registry. Of the 3252 patients who consented, 1997 completed surveys approximately one-year post-diagnosis, capturing weekly AI, demographic factors, and PROMIS-10 scores. PROMIS-10 (a 10-item measure of health, well-being, and distress) physical and mental health T-scores (mean = 50, SD = 10) are standardized to the U.S. population. Weekly AI was categorized as minimal/none (<1 drink), mild (1–4 drinks), moderate (5–14 drinks), or high (≥15 drinks). Univariate analyses were performed with Monte Carlo-based Fisher exact tests. Multivariate multinomial logistic regression models using a glogit link function assessed AI as the outcome and PROMIS-10 scores as independent variables, adjusting for financial status, smoking, chemotherapy, and moderate exercise because those were associated with AI at year 1 in prior analyses. Results: Univariate analyses revealed statistically significant associations between AI and PROMIS-10 scores (Table 1). Adjusted multivariate analyses identified that patients with better physical health were more likely to drink 1–4 or 5–14 drinks/week and less likely to abstain (<1 drink/week) than those with poorer physical health (p=0.027). There was no statistically significant association between AI and mental health QoL after adjustment for covariates. Conclusions: Better physical HRQoL during early survivorship was associated with higher AI, suggesting that patients who are feeling physically unwell may be less likely to drink alcohol. Additional public health messaging about the relationship between AI and breast cancer risk and recurrence may be needed, especially for those who are feeling well enough to consume alcohol. Univariate analyses of year 1 PROMIS-10 scores with year 1 alcohol consumption using Monte Carlo-based Fisher exact test. Alcoholic drinks per week at year 1 < 1(N=1204) 1-4(N=600) 5-14(N=175) 15+(N=18) Total(N=1997) P-value PROMIS global mental health T score, Year 1, n (%) 0.008 < 50 466 (63.8%) 200 (27.4%) 54 (7.4%) 10 (1.4%) 730 (37.1%) 50+ 718 (57.9%) 394 (31.8%) 120 (9.7%) 7 (0.6%) 1239 (62.9%) Missing 20 6 1 1 28 PROMIS global physical health T score, Year 1, n (%) <0.001 < 50 440 (66.5%) 165 (24.9%) 50 (7.6%) 7 (1.1%) 662 (33.6%) 50+ 740 (56.7%) 432 (33.1%) 124 (9.5%) 10 (0.8%) 1306 (66.4%) Missing 24 3 1 1 29

10544 Background: Incorporation of Polygenic Risk Scores (PRS) can refine traditional breast cancer risk assessment models to provide precise estimates of breast cancer risk. However, the impact of such an integrated model on clinical decision-making related to breast cancer surveillance and preventive strategies is not fully understood. Methods: The GENRE-2 is a prospective single-arm multisite clinical trial (NCT04474834) incorporating PRS into standard breast cancer risk assessment models to determine the impact of PRS on clinical decisions on breast cancer prevention and surveillance. Women at high risk of breast cancer due to NCI-BCRAT 5-year risk of ≥ 3%, or IBIS (Tyrer-Cuzik) 10-year breast cancer risk of ≥5%, biopsy-proven high-risk breast lesion, or a pathogenic variant (PV) in ATM , BRCA1, BRCA2, CHEK2 or PALB2 , were enrolled from five sites in the United States. All women were invited to complete surveys on their breast surveillance and cancer prevention decisions based on pre-PRS standard risk models and post-PRS risk estimation, and further annual surveys are planned for 10 years. Results: Among 902 women enrolled in the study, 605 (median age: 52 years) received PRS results and completed a survey to date. Of those who received PRS results,195 (32.2%) were PV carriers. Among non-carriers, the median 10-year and lifetime pre-PRS IBIS-based risk was 10.0% and 28.7%, respectively. Among PV carriers, the CanRisk-based 10-year and lifetime pre-PRS risk estimates were 6.3% and 25.2% for ATM , 22.3% and 77.6% for BRCA1 , 18.5% and 77.7% for BRCA2 , 7.1% and 25.7% for CHEK2 , and 16.8% and 38.0% for PALB2 PV carriers, respectively. After the incorporation of PRS, the lifetime risk of breast cancer increased by at least 10% in 31% of non-carriers and 7.7% of PV carriers and decreased by at least 10% in 10.7% of non-carriers and 7.7% of PV carriers. The proportion of non-carriers with lifetime risk < 20% or > 40% changed from 17.3% and 22.0%, respectively, in the pre-PRS evaluation to 24.4% and 32.9%, in the post-PRS evaluation. A higher lifetime post-PRS score was associated with intent to take preventive action (surgery or endocrine agents). In non-carriers, the proportion of women with a lifetime risk < 20% with intent to take preventive action was 11%, compared to 36.8% of those with a lifetime risk > 40% (p < 0.001). Similarly, in PV carriers, the proportion of women with lifetime risk < 20% with intent to take preventive action was 20.8% compared to 41.1% of those with lifetime risk > 40% (p = 0.015). Conclusions: The GENRE-2 trial demonstrates that the incorporation of PRS into breast cancer risk assessment models in high-risk women is feasible and leads to clinically meaningful changes in breast cancer risk estimates and decision-making regarding preventive strategies. Evaluation of the implementation of breast cancer risk management strategies in study participants is ongoing and will be reported. Clinical trial information: NCT04474834 .

Background: Breast cancer survivors face a risk of significant psychological distress, which can persist for years after their initial diagnosis. Although numerous guidelines and tools exist to help screen for and measure distress in patients with cancer, additional longitudinal studies are needed to better characterize the trajectory of distress over time. Patients and Methods: We conducted a longitudinal study to evaluate distress and health-related quality of life in patients with breast cancer. Annual assessments included global mental and physical health scores using the Patient-Reported Outcomes Measurement Information System Global-10 (PROMIS-10), posttraumatic stress symptoms using the Impact of Event Scale-Revised (IES-R), and depressive symptoms using the Patient Health Questionnaire-2 (PHQ-2). Eligible participants had stage 0–III breast cancer, with baseline surveys administered within 1 year of diagnosis. Annual follow-up surveys were conducted through year 4 after the baseline survey. Only patients who completed the baseline survey and at least one follow-up survey were included in this analysis. Individuals with stage IV or recurrent breast cancer were excluded. Results: A total of 2,140 individuals were included. Over time, global mental health scores declined slightly, with differences in T-scores from baseline ranging from 0.4 to 0.9. In contrast, global physical health scores improved, with differences in T-scores ranging from 0.3 to 0.6. Mean scores remained in the normative range. Depressive symptoms remained stable throughout the study period, while posttraumatic stress symptoms showed improvement over time. Conclusions: This study provides important longitudinal data on distress subtypes in breast cancer survivors with nonmetastatic disease. Although global mental health declined slightly, depression symptoms remained stable, and posttraumatic stress symptoms improved. Investigation of distress subtypes over time merits further study to advance detection of significant distress across the cancer continuum.

Abstract Background Breast cancer survivorship has markedly improved in the last two decades due to improved therapies. Among these, adjuvant chest radiotherapy stands out as an integral part of the current treatment. Chest radiotherapy can trigger accelerated atherosclerosis, which, coupled with cardiovascular (CV) risk factors common to this population, can lead to increased rates of coronary artery disease (CAD). ESC 2022 guidelines have established both Exercise Stress Echocardiography (ESE) and Dobutamine Stress Echocardiography (DSE) as cost-efficient and reliable tools for screening this patient population. Recommendations include ESE or DSE 5 years after radiotherapy as a screening tool. Double product (DP), an index common to both tests, parallels myocardial oxygen consumption. It has been used to predict major adverse cardiovascular events (MACE) in other cohorts. Purpose We sought to evaluate if DP could be used as a prognostic indicator for MACE (myocardial infarction, stroke, cardiovascular death, and heart failure) in this population. Methods Breast cancer patients treated with adjuvant radiotherapy from 2000 to 2022 were included. ESE or DSE was done after a mean of 5.4 years (1Q-2.2, 3Q-7.5) post-radiotherapy. Uni and multivariable adjusted Cox regression models were performed to evaluate the association between DP quartiles achieved and the risk of MACE in DSE and ESE groups. MACE-free survival among different quartiles was plotted with the Kaplan Meier method. Results 696 patients were included, with a mean age of 65 (SD 10.0) and 72 (SD 9.4) in ESE and DSE respectively. 61% of patients had ESE. In ESE, we observed increased rates of MACE in the 1st quartile when compared to the other quartiles (Figure 1a). On the other hand, univariate and multivariate Cox models established that for every increase of 1000 units of DP achieved during ESE, there is a risk-reduction of 9% [HR=0.91 (0.86-0.95); p=&lt;0.01] in the future incidence of MACE, thus establishing DP as a protective marker. Additionally, advanced age was shown to be a major risk factor as well [HR=4.58 (1.91-10.9); p=&lt;0.01]. In the DSE cohort however, the development of MACE was equally distributed across DP quartiles even after adjusting for existing comorbidities (Figure 1b). Cox analysis did not establish DP as a prognostic tool in this cohort (Table 1). Conclusion DP is established as an excellent prognostic tool for the detection of MACE in patients who underwent ESE. Patients who achieve higher DP quartiles during these tests have lower future rates of MACE. Regarding DSE, DP is not a good prognostic tool. This could be explained by higher burden of cardiovascular risk factors in this patient population. ESE should be recommended when possible.

Abstract Refinement of breast cancer risk estimates with a polygenic-risk score (PRS) may improve uptake of risk-reducing endocrine therapy (ET). A previous clinical trial assessed the influence of adding a PRS to traditional risk estimates on ET use. We stratified participants according to PRS-refined breast cancer risk and evaluated ET use and ET-related quality of life (QOL) at 1-year (previously reported) and 2-year follow-ups. Of 151 participants, 58 (38.4%) initiated ET, and 22 (14.6%) discontinued ET by 2 years; 42 (27.8%) and 36 (23.8%) participants were using ET at 1- and 2-year follow-ups, respectively. At the 2-year follow-up, 39% of participants with a lifetime breast cancer risk of 40.1% to 100.0%, 18% with a 20.1% to 40.0% risk, and 16% with a 0.0% to 20.0% risk were taking ET (overall P = 0.01). Moreover, 40% of participants whose breast cancer risk increased by 10% or greater with addition of the PRS to a traditional breast cancer-risk model were taking ET versus 0% whose risk decreased by 10% or greater (P = 0.004). QOL was similar for participants taking or not taking ET at 1- and 2-year follow-ups, although most who discontinued ET did so because of adverse effects. However, these QOL results may have been skewed by the long interval between QOL surveys and lack of baseline QOL data. PRS-informed breast cancer prevention counseling has a lasting, but waning, effect over time. Additional follow-up studies are needed to address the effect of PRS on ET adherence, ET-related QOL, supplemental breast cancer screening, and other risk-reducing behaviors. Prevention Relevance: Risk-reducing medications for breast cancer are considerably underused. Informing women at risk with precise and individualized risk assessment tools may substantially affect the incidence of breast cancer. In our study, a risk assessment tool (IBIS-polygenic-risk score) yielded promising results, with 39% of women at highest risk starting preventive medication.

Abstract INTRODUCTION Accelerated atherosclerosis has been described in breast cancer patients receiving cardiac exposure from adjuvant radiotherapy (RT). As a result of multidisciplinary care, breast cancer cure rates have improved in recent decades. Therefore, evaluating radiation-induced heart disease (RIHD), especially coronary artery disease (CAD), is essential. The 2022 cardio-oncology European Society of Cardiology (ESC) guidelines recommend screening patients 5 to 10 years after RT for CAD according to cardiovascular risk factors. This screening is generally recommended with exercise stress echocardiography since it can assess the physiological functional performance. Until now, it is unknown if dobutamine stress echocardiography (DSE) is an equal screening tool and if it can predict major adverse cardiovascular events (MACE) (myocardial infarction, stroke, cardiac death, revascularization). PURPOSE Evaluate if DSE is an adequate tool to stratify and predict MACE in post-radiotherapy patients. Methods A retrospective, descriptive cohort study was conducted. Patients who had chest RT for breast cancer and underwent DSE from 2000 to 2022 were included. A bivariate analysis, including Kruskal Wallis and Pearson Chi-Squared test, was done to identify variables associated with a positive DSE. A multivariable Cox Model for MACE and a time-to-event curve for MACE were also performed. Results We identified 163 patients that underwent DSE after a median time of 5.8 years from the end of RT. The median age was 74 years, 98.2% were female, 50% had left and 45% right breast cancer, 81% had hypertension, 41% diabetes mellitus, 71% dyslipidemia, 34% were smokers, and 19% had a prior myocardial infarction. The average dose of photon RT to the chest was 55Gy in the cohort, and 40% received chemotherapy before RT. Patients were divided into two groups: positive and negative DSE. A positive DSE was seen in 19.6%. The median (Q1, Q3) regional wall motion abnormalities (RWMA) of patients with a positive DSE was 1 (1, 1.015) at baseline and 1.280 (1.190, 1.520) at peak stress, and for a negative DSE, was 1 (1, 1) at baseline and peak stress. 88.2% of negative DSE and 87.5% of positive DSE achieved the target heart rate of 85%. HTN, dyslipidemia, and prior MI were significantly associated with a positive DSE (p &lt;0.023). The cumulative incidence of MACE was higher in the group of positive DSE (p&lt;0.001), even after adjusting for hypertension, diabetes mellitus, dyslipidemia, smoking, and prior myocardial infarction, with a hazard ratio of 2.500 (1.51 – 4.13) and a p&lt; 0.001. Similar results were observed regardless of RT laterality. Conclusions In breast cancer survivors that received adjuvant radiotherapy as part of multidisciplinary care, a positive DSE was an independent predictor of MACE compared to a negative result. These results support the usefulness of dobutamine stress echocardiography as a screening tool in breast cancer survivors.Kaplan-Meier Curve for MACE