Breast Cancer Research Articles

Background: Cardiac resynchronization therapy (CRT) has been demonstrated to reduce both mortality and morbidity in patients with LBBB. Despite this, CRT remains underutilized in certain populations, particularly among women. Breast cancer generally has a high five-year survival rate of 91% and is commonly treated with cardiotoxic chemotherapy, which increases the risk of HFrEF. Given the risk and potential benefits of CRT, its application in breast cancer patients may be valuable. However, clinical bias or concerns regarding cancer status may contribute to its underuse. This study aims to evaluate disparities in CRT utilization among female patients with breast cancer. Research Question: To investigate the disparity in CRT utilization among female patients with breast cancer and HFrEF with LBBB compared to those without. Methods: We conducted a cross-sectional study using the National Inpatient Sample (2016-2022) to identify adult female hospitalizations with a diagnosis of HFrEF and LBBB. The history of breast cancer was determined using ICD-10-CM codes. Survey-weighted analyses were used to compare baseline characteristics and outcomes, including CRT use, in-hospital mortality, length of stay, and comorbidities. Logistic regression was performed to adjust for potential confounders. Results: A total of 47,437 adult women with HFrEF and LBBB were included in the analysis. Of these, 2,295 (1.0%) had breast cancer. Compared to non-cancer patients, those with breast cancer were younger (73.4 vs. 74.9 years, p < 0.01), had a lower prevalence of renal failure (27.7% vs. 36.6%, p < 0.01), valvular disease (28.3% vs. 35.3%, p <0.01), and anemia (10.5% vs. 7.4%, p = 0.01). No significant differences were observed in diabetes or obesity between the two groups. In-hospital mortality (5.2% vs. 4.3%, p = 0.33), length of stay (5.9 vs. 5.6 days), and arrhythmia burden (50.5% vs. 55.8%) were comparable between groups. CRT utilization was significantly lower in the breast cancer group (2.4% vs. 5.45%, p <0.01). After adjusting for age, race, comorbidities, and payer type, breast cancer remained independently associated with reduced CRT use (aOR 0.43, 95% CI 0.24–0.79). Conclusion: Women with breast cancer and HFrEF with LBBB are significantly less likely to receive CRT despite potential benefits. Given the high survivorship rates, these findings underscore the need to address disparities and optimize long-term cardiac care.

BACKGROUND: The association between breast cancer diagnosis, treatment, and the risk of incident ischemic stroke remains unclear. We aimed to investigate ischemic stroke risk among breast cancer survivors and evaluate the association by age, follow-up duration, and cancer treatments. METHODS: Using the Korean National Health Insurance Service database, we studied 113,232 women newly diagnosed with breast cancer (aged ≥18 years) without prior stroke history who underwent breast cancer surgery between January 2010 and December 2016. Each was matched 1:3 by birth year to a cancer-free female population (n=322,818). Subdistribution hazard ratios (sHRs) and 95% confidence intervals (CIs) were estimated, accounting for death as a competing risk and adjusting for sociodemographic factors and cardiovascular and noncardiovascular comorbidities. RESULTS: Over a mean follow-up of 7.2 years, ischemic stroke occurred in 1,155 (1.0%) breast cancer surgery survivors. Overall, breast cancer survivors had a slightly lower risk of stroke than cancer-free women (sHR 0.94; 95% CI 0.88–1.00). However, stroke risk was elevated in the short term following diagnosis (sHR 1.59, 95% CI 1.34–1.89 at 1 year; sHR 1.17, 95% CI 1.05–1.30 at 3 years) across all age groups, with stronger associations observed at 3 and 6 months post-diagnosis. A reduced risk was observed after 1 year in a landmark analysis that included only individuals event-free at the 1-year follow-up (sHR 0.87, 95% CI 0.81–0.93). Among breast cancer survivors, treatment with anthracycline (sHR 1.25) and the combination of tamoxifen and aromatase inhibitors (sHR 1.49) were associated with increased stroke risk, whereas radiation therapy was associated with decreased risk (sHR 0.84). These associations weakened and became nonsignificant after 1 year. Stroke risk was also higher in breast cancer survivors with low income, hypertension, diabetes, or current smoking. CONCLUSION: The association between breast cancer and ischemic stroke risk is time-dependent, with increased short-term risk post-diagnosis and treatment, followed by a decline over time. These findings highlight the importance of proactive stroke risk management, including baseline cardiovascular assessments and ongoing monitoring for thromboembolic events.

Introduction: Women treated for breast cancer (BC) often experience declines in exercise capacity and cardiac function which increases their heart failure risk. Physical activity (PA) participation during BC treatment may prevent these declines, but the long-term impacts of PA on exercise capacity and cardiac function in BC survivors are unknown. Research Question: This study evaluated PA participation prior to initiating BC treatment through 24-month follow-up and tested if women who reported being physically active had better exercise capacity and cardiac function relative to inactive women. Methods: Women with stage I-III BC (n=236) were enrolled in a multi-site prospective cohort study conducted through the Wake Forest NCORP Research Base (NCT02791581). Participants were categorized as active, moderately active, or inactive from self-reported PA surveys. Exercise capacity was determined by 6-minute walk distance (6MWD) and cardiac function [left ventricular ejection fraction (LVEF) and LV mean circumferential strain, LV strain] was measured by cardiac magnetic resonance imaging prior to BC treatment and then at 3-, 12- and 24-month follow-up. Analyses were adjusted for age, BMI, race, fatigue, comorbidities, and BC treatment. Results: Participants average (±SD) age was 56±11 years, 76% were White, and 52% were diagnosed with stage II BC. PA participation declined from baseline to 3-month follow-up but increased to baseline levels at 12- and 24-month follow-up. At baseline, active and inactive participants had similar exercise capacity (mean difference ± SE=17.4±10.4 m, p=0.21), LVEF (0.76±0.60, p=0.41), and LV strain (-0.71±0.87, p=0.69). 6MWD declined from baseline to 3-months among inactive participants only (-21.9±8.5 m, p=0.01). Active participants had higher exercise capacity relative to inactive participants at 3-months (42.5±11.3 m, p<0.001), 12-months (39.2±10.3 m, p<0.001), and 24-months (31.2±10.9 m, p=0.01) follow-up. LVEF and LV strain were similar between active and inactive participants throughout follow-up. Conclusions: Over 24 months, physically active women with BC maintained a higher submaximal exercise capacity compared to inactive individuals while cardiac function was similar between the groups. These data suggest that maintaining PA during BC treatment is important for preserving submaximal exercise capacity long-term, which reflects the ability to perform activities of daily living in BC survivors.

Background: Heart failure (HF) significantly impacts mortality among breast cancer patients. Studies indicate that breast cancer patients aged 65+ with HF have reduced long-term survival as HF poses a greater mortality risk than the cancer itself. Research Question: What are the trends and disparities in HF mortality among US women with breast cancer, and how do these patterns vary by race, age group, and region? Methods: We used the CDC WONDER mortality database to extract age-adjusted mortality rates (AAMRs) per 100,000 US women aged ≥25 years for breast cancer and HF mortality from 1999 to 2020. The Joinpoint Regression Program calculated the average annual percentage change (AAPC) in AAMRs. Results: From 1999 to 2020, HF caused 56,006 deaths in US breast cancer women, showing a decreasing trend with AAPC of -1.16% (95% CI: -1.5 to -0.86). The overall AAMR was 1.94 (1.93 – 1.96). Older adults (≥65 years) showed a significantly higher AAMR [8.88 (8.80 – 8.96)] with an AAPC of -1.17% (-1.45 to -0.93) than younger adults (25-64 years) [0.26 (0.25 – 0.27)] with an AAPC of -1.24% (-2.37 to -0.36). Among the racial and ethnic groups, the highest AAMR was observed in non-Hispanic (NH) Blacks [2.37 (2.31 – 2.43)], followed by NH Whites [2.03 (2.01 – 2.05)], Hispanics [0.98 (0.94 – 1.03)], and NH Asians or Pacific Islanders [0.66 (0.61 – 0.72)]. NH Blacks not only showed the highest mortality burden, but also exhibited a slight increase in AAMRs [AAPC: 0.15% (-0.48 to 0.66)]. NH Asians or Pacific Islanders showed the lowest mortality burden with the highest decline in AAMRs [AAPC: -1.47% (-2.71 to -0.28)], followed by Hispanics or Latinos (-1.27%) and NH Whites (-1.01%). Regionally, the Midwest showed the highest AAMR [2.25 (2.21 – 2.29)], followed by the West [1.95 (1.92 – 1.99)], the Northeast [1.85 (1.81 – 1.88)], and the South [1.81 (1.78 – 1.83)]. The Northeast showed the highest decline in AAMRs [AAPC: -1.48% (-2.06 to -0.98)], and the South showed the lowest [-0.59% (-0.99 to -0.20)]. Women in non-metropolitan areas had higher AAMRs [2.36 (2.32 – 2.41)] than those in metropolitan areas [1.87 (1.85 – 1.88)]. Metro and non-metropolitan areas showed a similar decline in AAMRs over the study period (-1.05% vs. -1.20%). Conclusion: HF mortality in US breast cancer females declined over the past 22 years; however, older adults, NH Blacks, the Midwest, and non-metropolitan areas experienced higher mortality burdens, highlighting the need for targeted interventions.

To investigate the value of quantitative parameters derived from triple-phase dual-energy CT (DECT) for the discrimination of immunohistochemical biomarkers in invasive breast cancer. From March 2022 to May 2023, 41 participants with breast cancer who underwent contrast enhanced (arterial, venous, and equilibrium phase) chest DECT were enrolled in this prospective study. DECT quantitative parameters were measured and compared with the immunohistochemical biomarkers [oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2)] status. Receiver operating characteristic curve analysis was used to determine the diagnostic performance of parameters. Arterial enhancement fraction (AEF) was significantly higher in the ER-negative group than in the ER-positive group (p = 0.030) with an AUC of 0.786. AEF was identified as an independent predictor for distinguishing PR-negative from PR-positive tumours (AUC = 0.857; OR = 1/e10.515, 95% CI: 0.000-0.205, p = 0.021). Enhancement ratio between venous phase and equilibrium phase (ERVE) was significantly higher in the HER2-positive group in contrast to the HER2-negative group (p = 0.037) with an AUC of 0.781. Triple-phase DECT-derived parameter AEF was identified as a useful negativity predictor for ER and PR levels, while ERVE was demonstrated as a positivity predictor of HER2 status in invasive breast cancer.

Based on the latest clinical research evidence and domestic practical experience, the Breast Cancer Committee of the Chinese Society of Clinical Oncology has systematically sorted out the core points regarding human epidermal receptor 2 (HER2) testing standardization, neoadjuvant therapy, adjuvant therapy, treatment of relapsed and metastatic breast cancer, and diagnosis and treatment of populations with HER2 low expression/ultra-low expression. The Chinese experts' consensus on the diagnosis and treatment of HER2-targeted breast cancer 2025 edition was updated. Combining with key clinical issues, this article further interprets the key points of the Expert Consensus and proposes that precise HER2 testing should focus on spatiotemporal heterogeneity, and clarify the definitions and testing standards for low expression and ultra-low expression; it also summarizes clinical key points according to different stages, and puts forward that for neoadjuvant therapy, the trastuzumab combined with pertuzumab regimen is preferred, and specific regimens should be selected according to patient characteristics, and adjuvant strategies should be formulated based on pathological complete response status; in adjuvant therapy, dual-targeted therapy is the standard regimen for high-risk patients, while low-risk and special populations require individualized selection; the treatment of relapsed and metastatic breast cancer should be formulated according to the degree of trastuzumab sensitivity, trastuzumab treatment failure, and characteristics of special populations; populations with HER2 low expression/ultra-low expression can benefit from new antibody-drug conjugates, and standardized testing and treatment selection are required. In conclusion, the diagnosis and treatment of HER2-related breast cancer should be based on precise testing, combined with patients' clinical characteristics and follow the consensus recommendations, so as to achieve individualized treatment and improve prognosis.

Background: CV mortality (CVM) is a critical competing risk in breast cancer (BC). How therapy type affects CVM by stage and receptor subtype remains incompletely defined. Objective: Compare CVM risk across treatment modalities: chemotherapy alone (C), radiotherapy alone (R), or both (C + R), in BC stages I–IV (2010–2015), stratified by receptor subtype (Luminal A (LA), Luminal B (LB), Her2-enriched, triple negative BC (TNBC)). Methods: Among 282,991 SEER patients (2010–2015), multivariable Cox models (adjusted for age, race, and laterality) and stratified by stage and receptor status estimated adjusted hazard ratios (AHRs) for CVM: C vs R and C + R vs R. Receptor-specific temporal CVM trends are shown in Figure 1. To account for baseline CV comorbidity, 1555 patients from Georgia Cancer Center (2010–2015) were analyzed, adjusting for age, receptor status, stage, hypertension, diabetes, and hyperlipidemia. Results: For the SEER cohort, there was an overall downward trend of CVm across stages 1, 2, and 3. In stage II breast cancer, both LA and LB subtypes showed significant reductions in cardiovascular mortality with C or C + R compared to R. For LA, the AHR was 0.75 (95% CI: 0.59–0.95) for C vs R and 0.75 (95% CI: 0.61–0.93) for C + R vs R. For LB, AHRs were 0.54 (95% CI: 0.33–0.90) for C vs R and 0.44 (95% CI: 0.27–0.74) for C + R vs R. In stage III disease, patients with LA who received C + R had a significantly lower risk (AHR 0.49, 95% CI: 0.35–0.68), as did those with TNBC receiving C + R (AHR 0.33, 95% CI: 0.13–0.82). There were no significant associations for other stage-receptor subgroups (p > 0.05). In the Georgia cohort, neither C nor C + R was associated with lower cardiovascular mortality compared to R (p > 0.05). Conclusions: In stages I–III, Patients selected to receive C (± R) has lower CVM vs R alone in LA (stage II–III), LB (stage II), and TNBC (stage III). CVM did not decline in stage IV (AHR ~1.0), possibly due to expanding use of newer systemic therapies. Temporal trend analysis (Figure 1) suggests broader improvements in CV risk management perhaps due to improvement of cardiac care of BC patients; aligning FDA approval timelines with CVM in BC may further elucidate therapy-related CV risks.

In stages II and III hormone receptor positive (HR+) breast cancer, selecting patients for primary surgery (PS) or neoadjuvant therapy remains challenging. This study assessed the occurrence of minimally invasive surgery in the case of PS, neoadjuvant endocrine therapy (NET), and neoadjuvant chemotherapy (NACT). This cohort study included women diagnosed with stages II and III, HR+ breast cancer in 2020-2022 in the Netherlands. Women with positive human epidermal growth factor receptor 2 (HER2+) cancer were excluded. Outcomes focused on surgical techniques and additional treatment. Of the 7809 patients, 4046 (51.8%) underwent PS, 956 (12.2%) received NET and 2807 (35.9%) NACT. NET patients were older (median: 71 years [33-94]), while NACT patients had larger tumors and more lymph node involvement (p < .001). Breast-conserving surgery (BCS) was the first procedure in 2153 (53.2%) PS women, in 694 (72.6%) NET women and 1564 (55.7%) NACT cases. There was no difference regarding free surgical margins in NET versus NACT patients (p = .421). After adjusting for T-stage, BCS occurred significantly more frequently after NET (p < .001). Minimal invasive surgery on the axilla was common after NET (83.9%) and NACT (81.5%). In the PS group, 85% received adjuvant systemic therapy. Optimizing patient selection for neoadjuvant strategies could reduce surgical morbidity. NET was frequently associated with BCS, showed comparable surgical margin outcomes to NACT, and contributed to reduced axillary surgery. These findings suggest that NET is an effective strategy, compared to PS, to facilitate less invasive surgery on the breast and axilla, in HR+/HER2-, stages II and III breast cancer.

The role of 18F-fluoroestradiol (18F-FES) PET/CT has been investigated in breast cancer recurrence identification and noninvasive hormone receptor profiling. The detection of distant metastasis, however, lacks high quality evidence comparing FES to standard imaging protocols. Additionally, if 18F-FES PET/CT is to become one of the first-line exams in ER positive breast cancer patients, obtaining its maximum utility will be beneficial and this includes prognosis prediction. Here, we address these issues by analyzing literature on diagnostic accuracy comparisons and reconstructing progression-free survival data to investigate the ideal PET parameter for predicting survival. A systematic review was conducted on PubMed, Scopus and Embase to identify studies assessing survival or diagnostic outcomes on breast cancer patients undergoing 18F-FES PET/CT for metastasis detection. Random-effects inverse variance meta-analyses were conducted for summarizing hazard ratios, sensitivity, specificity and likelihood ratios. Meta-regressions were conducted to compare 18F-FES PET/CT and 18F-FDG PET/CT; and to evaluate the impact of clinical covariates on the survival prediction potential of 18F-FES PET/CT. Risk of bias was assessed using the QUADAS-2 and QUADAS-C tools, for diagnostic studies; and the Evidence Project risk of bias tool for the survival trials. 19 papers were included. 10 studies had survival outcomes, and 9 had diagnostic endpoints. Overall, patients with higher 18F-FES SUVmax, complete lesion concordance or no complete lesion discordance had significantly longer PFS (HR:0.29 [0.16-0.54]). Stratification by complete lesion concordance had numerically longer PFS than stratification by 18F-FES SUVmax. Out of the 9 metastasis detection studies, 3 were pooled in the bivariate model, resulting in overall estimates for 18F-FES PET/CT and 18F-FDG PET/CT or CT, respectively, of 87.9% [82.6-91.7%] and 83.4% [80-87%] for sensitivity; and 97.1% [85.4-99.5%] and 45.5% [4.8-93.2%] for specificity. For confirmation, 6 studies had their sensitivities meta-analyzed in a univariate approach, with similar results. A bivariate meta-regression showed a significant difference in sensitivity between modalities. Patients with higher 18F-FES SUVmax or full lesion concordance on 18F-FES/FDG PET/CT have significantly longer PFS. Lesion concordance approaches were associated with longer PFS. 18F-FES PET/CT has slightly higher sensitivity than 18F-FDG PET/CT for metastasis detection in the ER+/HER2- metastatic breast cancer setting. Cost-benefit analysis will be essential in the development of guidelines to integrate its clinical applicability, on a case-by-case basis.

Background: Anthracyclines are highly effective, yet cancer therapy-related cardiac dysfunction (CTRCD) and heart failure are known adverse effects. Elevations in hsTnT and NT-proBNP may predict CTRCD but the optimal timing of testing is not defined. Research Question: What are the longitudinal cardiac biomarker trends with anthracycline treatment and do biomarker values differ pre and post anthracycline infusion? Methods: Participants 18+ with planned treatment with doxorubicin for breast cancer or lymphoma were enrolled in a prospective cohort study at 3 hospitals in a single health system. Biomarkers including hsTnT (normal &lt;12 ng/L) and NT-proBNP (normal 0-125 pg/mL) were collected prior to and immediately after each anthracycline infusion and every 6 months for 24 months. Echocardiograms were conducted prior to doxorubicin treatment in all participants and 6-12 months after doxorubicin in the majority. Patients were followed for 24 months. Baseline cardiovascular risk was determined using the Heart Failure Association-International Cardio-Oncology Society (HFA-ICOS) algorithm. Change in biomarkers over time was analyzed using generalized estimating equations and the linear mixed effect model. Results: We enrolled 43 participants (mean age 50, 51% female) with lymphoma (n=33) or breast cancer (n=10). The baseline mean hsTnT was 9 (SD 18) and NT-proBNP 384 (SD 741). HFA-ICOS risk was low in 21 (49%), moderate in 11 (26%), high in 9 (21%) and very high risk in 2 (4%) Pre-anthracycline infusion hsTnT level trends increased significantly with each cycle while patients were on chemotherapy and trended downwards after completion of chemotherapy (p&lt;0.001) (Fig. A). NT-proBNP did not change (p=NS) (Fig. B). Among the 36 participants with pre and post anthracycline infusion biomarkers, there was a decrease in post-infusion hsTnT levels (p=0.018) and no difference in pre and post NT-proBNP (p=0.10). Of the 32 patients with follow-up echocardiograms, 2 patients developed moderate asymptomatic and 2 developed moderate symptomatic CTRCD. Higher peak troponin level was associated with CTRCD (p=0.051). Conclusions: In this small study, there was a broad representation of cardiovascular risk among breast cancer and lymphoma patients. HsTnT, but not NT-proBNP, significantly increased with anthracycline chemotherapy. Peak troponin was associated with CTRCD. Further studies with larger sample size are needed to assess the effect of changes in biomarkers on CTRCD.

Background: Anthracycline cardiotoxicity increases breast cancer morbidity and mortality. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve cardio-renal outcomes in diabetes, but their effect during anthracycline therapy is unknown. Objectives: To determine whether adding GLP-1RAs to anthracycline-based therapy reduces mortality and major cardio-renal events compared to anthracycline alone. Methods: We conducted a retrospective propensity-score–matched cohort study within the TriNetX Global Collaborative Network (146 health-care organizations) of adult females with breast cancer who received anthracyclines between 2005-2024. Cohort A received ≥1 GLP-1a (n = 1691); Cohort B did not (n = 1691). Outcomes were captured 1-1095 days after index and analyzed with Kaplan–Meier survival and Cox proportional-hazards models. Significance was defined as log-rank P &lt; 0.05 with 95 % confidence intervals (CIs) excluding 1. Cohorts were also matched for medication use [ACE inhibitors, Angiotensin receptor blockers, Sodium glucose transporter -2 reuptake inhibitors, Furosemide, and Spironolactone use]. Results: Mean follow-up: 625 ± 379 vs 728 ± 398 days. GLP-1RA therapy lowered risk of all-cause death (HR 0.19, 0.148-0.247, P &lt; 0.01), cardiac arrest (0.335, 0.12-0.92, P=0.03), atrial fibrillation (0.40, 0.22-0.73, P &lt; 0.01), hospitalization (0.478, 0.39-0.59, P &lt; 0.001), emergency-department visit (0.67, 0.54-0.84, P &lt; 0.001), and progression to stage 4 or 5 chronic kidney disease (eGFR &lt;30 mL/min 1.73 m2; 0.41, 0.29-0.56, P &lt; 0.001) (Table 1). Conclusions: The findings suggest that GLP-1a medications may offer protective benefits beyond glucose control, potentially improving cardiovascular, renal, and overall survival outcomes in breast cancer patients undergoing anthracycline chemotherapy. These real-world data support prospective trials of GLP-1a agents as cardio-renal protective adjuncts in oncology domains. Next steps include conducting prospective clinical trials, exploring mechanisms of action, stratifying patient populations, and expanding research into other cancer types or therapies.

Background: Breast cancer survivors face an increased risk of cardiovascular disease (CVD) due to shared risk factors and cardiotoxic treatments such as anthracyclines and trastuzumab. The performance of CVD risk prediction models among breast cancer survivors is understudied. Goals: To evaluate the performance of the American Heart Association PREVENT equations in breast cancer survivors and determine if recalibration or inclusion of cardiotoxic treatment enhances prediction while considering the effect of age at breast cancer diagnosis. Methods: We included 10,403 women diagnosed with first primary unilateral breast cancer between 2002 and 2019 within the NCI-Kaiser Permanente (KP) Breast Cancer Survivors Cohort (KP Colorado, Georgia, and Washington members aged 30-79 years, survived ≥1 year without second cancer or prevalent CVD). PREVENT risks for total CVD, heart failure (HF), coronary heart disease (CHD), and stroke were calculated using CVD risk factors at breast cancer diagnosis. The primary outcome was total CVD; deaths from other causes were treated as competing events. Discrimination was evaluated using time-dependent area under the receiver operating characteristic curve (AUC t ). Calibration was assessed by the estimated-to-observed risk ratio (E/O). We evaluated the performance of 3 models: PREVENT, recalibrated PREVENT and modified PREVENT which included age and chemotherapy. Results: Over a median follow-up of 4.5 years, 734 women developed CVD events. The AUC t (95% CI) of PREVENT equations were 0.74 (0.71-0.77) for CVD, 0.76 (0.73-0.79) for HF, 0.75 (0.71-0.78) for CHD, and 0.79 (0.76- 0.82) for stroke.The PREVENT equations markedly underestimated the risk of total CVD (E/O 0.56; 95%CI 0.51 to 0.61), HF (E/O 0.70; 0.62 to 0.78), CHD (E/O 0.34; 0.30 to 0.38), and stroke (E/O 0.40; 0.35 to 0.45). As shown for total CVD (Figure), recalibration to the baseline risk of the study population improved calibration, but underestimation persisted in patients aged &lt;45 years (E/O 0.47; 0.31 to 0.72) and those treated with anthracyclines and/or trastuzumab (E/O 0.71; 0.61 to 0.82). The modified PREVENT (Figure) was well calibrated. Conclusion: The PREVENT equations underestimate CVD risk in breast cancer survivors, especially in young patients and those treated with anthracyclines and/or trastuzumab. Our findings have important implications for tailored CVD prevention in breast cancer survivors.

Background: Breast cancer (BC) is the most common cause of cancer-related mortality among women. Despite advancements in treatment and longer survival, BC patients are at a higher risk of heart failure (HF) with an increased relative risk of 20% as compared to the general population. This has been attributed to cardiotoxicity from BC treatment and shared pathophysiological mechanisms. However, there is a need for more data on the outcomes of BC patients admitted with acute heart failure (AHF). Aim: To evaluate clinical outcomes, including in-hospital mortality, cardiogenic shock, respiratory failure, and length of stay (LOS), across different subtypes of AHF in BC patients. Methods: We analyzed the National Inpatient Sample database (2019-2022) to identify BC patients admitted with a primary diagnosis of AHF. AHF subtypes were classified into acute systolic heart failure (ASHF), acute diastolic heart failure (ADHF), combined ASHF/ADHF, and acute right heart failure (ARHF) based on ICD codes. Demographic information and clinical outcomes were collected and compared across AHF subtypes. Results: We identified 50,623 hospitalizations for AHF in patients with BC. The majority had ADHF only (55.6%), followed by ASHF (27.8%), combined ASHF/ADHF (16.1%), and ARHF (0.6%). The mean age across all groups was 77.8 years (SD ±10.2). In terms of racial distribution, most patients were White (73.6%), followed by Black (15.3%) and Hispanic (5.1%). The overall in-hospital mortality rate was 4.4%, with ARHF had the highest mortality at 12.2%, followed by ASHF (4.9%), combined ASHF/ADHF (4.5%), and ADHF (4.1%). Cardiogenic shock occurred in 2.6% of all AHF cases, most frequently in ARHF (8.2%) and ASHF (5.0%), and least in ADHF (1.0%). Respiratory failure was seen in 46.2% of all AHF patients—highest in ARHF (59.9%) and ADHF (50.3%). Mean LOS for AHF admissions was 6.11 days, ranging from 6.0 days in ASHF to 6.59 days in ARHF. Conclusion: Patients with ARHF had the highest rates of mortality, cardiogenic shock, respiratory failure, and the longest hospital stays, likely indicating a more severe clinical course. ADHF was the most common subtype but was associated with the lowest mortality and complication rates. These findings highlight the importance of recognizing AHF subtype in this population, as it may have significant implications for prognosis, management strategies, and healthcare resource allocation.

Background: Novel antibody-drug conjugates (ADCs) such as trastuzumab-emtansine (T-DM1) and trastuzumab-deruxtecan (T-DXd) have shown efficacy in treating HER2-positive breast cancer (BC) that has progressed on prior HER2-targeted therapy. We aimed to compare the incidence of cardiotoxicity of these novel ADCs to standard-of-care chemotherapy regimens containing trastuzumab for HER2-positive locally advanced/metastatic BC. Methods: We searched PubMed, ScienceDirect, Cochrane Library, and clinicaltrials.gov to identify phase III clinical trials that investigated patients with locally advanced/metastatic HER2-positive BC treated with either T-DM1, T-DXd, trastuzumab + chemotherapy (TC), or trastuzumab + pertuzumab + chemotherapy (TPC). We performed a single-arm meta-analysis that compared the pooled incidence of LVEF decrease across the four chemotherapy regimens. Results: All analyses accounted for publication bias if present. In the 5 studies that included 3531 patients who received T-DM1, a pooled analysis demonstrated a 0.94% [95% CI: 0.56 – 1.57] incidence of LVEF decrease. In the 2 studies that included 667 patients who received T-DXd, a pooled analysis demonstrated a 4.20% [95% CI: 2.91 – 6.01] incidence of LVEF decrease. In the 12 studies that included 2929 patients who received TC, a pooled analysis demonstrated a 4.85% [95% CI: 3.73 – 6.28] incidence of LVEF decrease. In the 5 studies including 2411 patients who received TPC, a pooled analysis demonstrated a 5.52% [95% CI: 3.41 – 8.83] incidence of LVEF decrease. Conclusion: In our single-arm meta-analysis indirectly comparing the incidence of LVEF decrease across four chemotherapy regimens containing trastuzumab, we found that T-DM1 had the lowest incidence of LVEF decrease, and T-DXd, TC, and TPC had similar incidences of LVEF decrease. While T-DM1 and T-DXd have shown promise in treating HER2-positive metastatic BC that has progressed, there is a paucity of data comparing the cardiotoxicity between ADCs, of ADCs vs. the standard of care trastuzumab-containing chemotherapy regimens, and of the potential of ADCs as first-line therapy for metastatic BC.

Background: Echocardiography (TTE) is used for cardiac surveillance in patients with breast cancer (BC) receiving potentially cardiotoxic therapies. There is significant variability in the assessment of TTE parameters which reduces diagnostic accuracy and may adversely affect patient care. Artificial intelligence (AI) tools have shown promise in improving TTE measurement standardization and reproducibility. Research Question: We conducted a proof-of-concept study in patients with BC who underwent serial TTEs to 1) assess the agreement between AI-generated and clinical readers’ (human) measures of left ventricular ejection fraction (EF) and global longitudinal strain (GLS), and 2) analyze differences in meeting criteria for cancer therapy-related cardiac dysfunction (CTRCD) on follow-up TTE. Methods: Using the medical record, we identified patients with BC who underwent baseline and surveillance TTE (within 6 months) from 2019 to 2024. DICOM images were analyzed using Us2.ai software. We compared Us2.ai (AI) measured EF and GLS with previously reported clinical results (human). Descriptive statistics included agreement rate, unweighted Cohen’s Kappa, Bland-Altman statistics. CTRCD was determined using the published ICOS criteria based on EF and GLS change. Results: With 162 TTE studies in 81 patients (mean age 54±4), the overall rates of agreement between AI and human for EF and GLS were 83% and 66%, respectively (Bland-Altman, p&lt;0.00). The unweighted Cohen’s Kappa for baseline EF was 0.29 (95% CI 0.07-0.50, fair) and for GLS 0.07 (95% CI -0.08-0.22, slight). By the human read, the mean EF was 63±5% at baseline and 61±6% at surveillance. By AI read, the mean EF was 61±5% at baseline and 60±6% at surveillance (Figure). Mean GLS was 20.9±2.1% at baseline and 20.3±2.6% at surveillance by human and 18.9±2.4% at baseline and 18.7±2.5% at surveillance by AI. The per-patient interval changes in EF and GLS from baseline to surveillance TTE by human and AI are shown in the Figure. Based on the human read, 9 patients (11.1%) met CTRCD criteria (mild N=6, moderate N=3) compared to 16 patients (19.8%) by AI read (mild N=14, moderate N=2). Conclusion: In this proof-of-concept study in patients with BC undergoing surveillance TTE, automated AI measurement of EF and GLS was feasible and showed fair to slight agreement with the human read. More studies met CTRCD criteria by AI compared to human, highlighting the need for research into AI’s ability to predict outcomes.

Background: Breast and prostate cancer survivors are at high risk of cardiovascular events due to cardiotoxic therapies. Physical activity is associated with better outcomes in these patients, but most do not meet targets. Black and Hispanic cancer survivors are at higher risk for cardiovascular events and are less active than non-Hispanic White survivors. Methods: This was a pragmatic randomized controlled trial evaluating the effectiveness of a remotely delivered gamification intervention to increase daily physical activity in Black and Hispanic breast and prostate cancer survivors who had received cardiotoxic therapy and had at least 1 additional cardiovascular risk factor. Patients were mailed a wearable device to track daily steps, established a baseline daily step count, set a goal to increase daily step count by 1500-3000/day, and were randomized to control (n=76) or gamification (n=74). The gamification group was entered into a 24-week game designed using insights from behavioral economics with points and levels for achieving step goals. The intervention included a 12-week follow-up period to evaluate sustainability of behavior. The control group received feedback from the wearable device but no other interventions for 36 weeks. The primary outcome was change from baseline in daily steps through the end of the 24-week intervention period. Results: A total of 150 patients (mean age, 64 years; 81% female, 64% Black, 35% Hispanic, 60% hypertension, 51% hyperlipidemia, 44% obesity, 28% diabetes; mean time since cancer diagnosis, 7.8 years) were enrolled from 2 health systems. Mean±SD daily step count increase from baseline through the end of the intervention period was 983±1539 in the control arm and 1757±1921 in the gamification arm ( Figure ). Compared with controls, gamification participants had a significantly greater increase from baseline in mean daily steps during the intervention period (+770, 95% CI 217 to 1323, P = 0.006), which persisted during follow-up (+596, 95% CI -30 to 1223, P = 0.06). Gamification also increased weekly minutes of moderate to vigorous physical activity more than control (intervention period: +16, 95% CI 4 to 29, P =0.01; follow-up: +11, 95% CI 0 to 21, P = 0.05). Conclusion: Remotely delivered gamification increased daily physical activity from baseline more than control in breast and prostate cancer survivors, and may represent a scalable intervention to reduce cardiovascular risk in this high-risk population.

Breast cancer is the leading cancer type that is reported in women worldwide, with its 2.3million annual incidence and 685,000-related deaths (WHO, 2023). Although genetic mutations have proven to be major driving agents of tumorigenesis, the tumor microenvironment (TME) is increasingly being considered as the definitive indicator of disease progression, metastasis, immune evasion and therapeutic resistance. It is an active, diverse cellular webwork of substances cancer-related fibroblasts, (CAFs), tumor-related macrophages, (TAMs), regulatory T cells, (Tregs), myeloid-derived suppressor cells (MDSCs), and cancer-related adipocytes; (CAAs). These cellular processes interact reciprocally with not only malignant cells through paracrine communication but also through the composition of the extracellular matrix, (ECM). Recent research indicates that CAFs produce pro-invasive factors i.e. TGF-B and HGF whereas TAMs tend to be M2-like and secret VEGF and IL-10 to encourage angiogenesis and immune subversion. Cytokines, chemokines, ECM proteins, and tumor-derived EVs are non-cellular factors serving to alter cellular phenotypes and facilitate construction of metastatic niche. Besides oncogenic microRNAs (e.g., miR-21, miR-10b) that is released in exosome, hypoxia-mediated activation of HIF-1a induces both neovascularization and metabolic reprogramming. The repolarization of TAM (e.g. CSF1R inhibitors) and depletion of CAF and inhibition of EV pathway are also being explored as therapeutic mechanisms against TME resistance and are in preclinical and clinical development. In particular, the combination procedures with immunomodulation and TME disruption have demonstrated some success in conquering resistance in TNBC models. Therefore, it is paramount to understand how the surrounding tissue, the immune system, the immune system, and other elements behave over time and space as cofounding partners of tumors, in a way that would create better precision and clinical outcomes in breast cancer patients.

Poly(ADP-ribose) polymerase inhibitors (PARPi) have survival benefits for patients with high-risk (High-risk disease is defined per the phase III OlympiA trial as follows: for triple-negative breast cancer, residual disease after neoadjuvant chemotherapy or node-positive or ≥2 cm tumors after adjuvant chemotherapy; for hormone receptor-positive disease, four or more positive nodes after adjuvant chemotherapy or a CPS + EG score ≥3 after incomplete response to neoadjuvant chemotherapy. The CPS + EG score accounts for clinical/pathologic stage, ER status, and grade (Giaquinto et al. in CA Cancer J Clin 72:524-541, 2022)), human epidermal growth factor receptor 2 (HER2)-negative early breast cancer (eBC) with germline BReast CAncer gene mutations (gBRCAm). However, many patients are unaware of their gBRCA status; this can impact eligibility for targeted treatment. We sought to evaluate patient preferences for BRCA testing and treatment decision-making as they relate to HER2-negative eBC. We conducted an online survey, including a best-worst scaling exercise (BWS) and discrete-choice experiment (DCE), among patients with self-reported HER2-negative eBC residing in the USA who were either untested, unsure if they were tested, or tested positive for the gBRCAm. The BWS generated a rank ordering of 16 barriers and facilitators to BRCA testing. The DCE evaluated patient preferences for adjuvant therapies versus no treatment based on seven treatment attributes: invasive disease-free survival, targeted treatment, nausea risk, risk of serious side effects, regimen, treatment duration, and cost. BWS and DCE exercises were analyzed using hierarchical Bayesian models. Among the 359 women included in our sample, the top facilitators for BRCA testing were determining eligibility for targeted therapy that may prevent or delay metastasis, a physician's recommendation, and absence of out-of-pocket costs (OOPC). In contrast, the top barriers were an OOPC of $250, potential anxiety from test results, and the possibility of a 3- to 4-week delay in treatment. The DCE showed that most participants preferred adjuvant treatment (77.6%) over no treatment, and reducing treatment OOPC from $900 to $0, reducing the risk of serious side effects from 77 to 24%, and having a BRCA-targeted treatment influenced treatment choice most. Individuals reported that a key benefit of BRCA testing was the insight it provided into their treatment options, allowing for more personalized care. However, OOPC was a barrier to testing. Their choice to receive adjuvant therapy was most influenced by OOPC, followed by the tolerability of the treatment and the ability to receive a targeted therapy.

Introduction: Cardiovascular (CV) diseases are a major cause of morbidity and mortality in breast cancer survivors. Side effects of antineoplastic agents used in treating breast cancer have been known to be a culprit for the development of CV diseases. Aromatase Inhibitors (AIs) and Selective Estrogen Receptor Modulators(SERMs) are widely used for Estrogen receptor positive breast cancer, but limited data is available on the CV risk profiles of these classes. We aimed to compare CV risk profiles of AIs and SERMs. Methods: We queried the Food and Drug Administration (FDA)’s Adverse Event Reporting System (FAERS) database for CV AEs of AIs and SERMs from 1996-2023. We included Anastrozole, Letrozole, and Exemestane for AIs and Raloxifene, Tamoxifen, Fulvestrant, and Toremifene for SERMs. The data on CV risk profiles were collected, analyzed, and compared for both classes using descriptive statistics. Reporting Odds Ratio (ROR) was calculated for all reported CV AEs and both AIs and SERMs. Fisher’s exact test was used to compare and look for differences among AIs and SERMs. Results: On the FAERS database, a total of 37,128 events were reported for AIs, while 16,616 events were reported for SERMs. 2,499 CV AEs were reported for AIs, and 865 CV AEs were reported for SERMs. Though both AIs [ROR:2.31 (2.20-2.44) P&lt;0.05], and SERMs [ROR:1.79 (1.64-1.95) P&lt;0.05], had increasingly reported CV AEs, when comparing the adjusted ratio, AIs had more reported CV AEs compared to SERMs (ROR = 2.31 vs 1.79, P&lt;0.05). On subsequent analysis, CVA (ROR = 2.62 vs 1.44, P&lt;0.05), HF (ROR = 2.16 vs 1.51, P&lt;0.05), and Arrhythmia (ROR = 1.62 vs 1.26, P&lt;0.05) were also reported more with AIs compared to SERMs. HTN was found to be equally reported among both classes. Most of these findings were supported by coinciding findings from VigiAccess and EudraVigilance databases. More cardiac AEs were seen with AIs when compared with SERMs on VigiAccess [(3.92% vs 3.44%); ROR = 1.15 (1.08-1.22, p&lt;0.05)] as well as EudraVigilance [(5.02% vs 4.07%); ROR = 1.24 (1.15-1.34, p&lt;0.05)] databases. Conclusion: AIs are observed to be associated with higher rates of CV AEs compared to SERMs. Further studies are warranted to establish the CV risk profile of these agents.

Background: Oncology rehabilitation (OR) may facilitate recovery of cardiopulmonary fitness (CRF) following cytotoxic chemotherapy in breast cancer (BC), however there is no consensus on who should be referred, or the optimal timing in relation to chemotherapy. We aimed to characterize OR utilization, timing, and efficacy among patients referred for OR within our institution. Methods: BC patients were eligible for this retrospective cohort study if they received chemotherapy, participated in OR, and underwent at least one CRF assessment. The OR program (Providence Cancer Institute (Anchorage, Alaska)) was modeled after cardiac rehabilitation, consisting of individualized exercise programs prescribed by a licensed cancer physical therapist. Metrics of OR utilization included timing of initiation (before during, or after chemotherapy) and number of therapeutic sessions. Metrics of OR efficacy included maximal oxygen consumption (VO 2 max) estimated from a sit-to-stand and/or six-minute walk test and left ventricular ejection fraction (LVEF) measured by transthoracic echocardiogram. Results: Between 2015-2024, 162 early stage BC patients participated in OR. Timing of OR initiation varied, with 31% (n=49) enrolling before chemotherapy, 26% (n=43) during chemotherapy, and 43% (n=70) after. Participants received a mean of 17 OR sessions, with patients enrolling after chemotherapy attending less sessions than those that attended before or during chemotherapy. Baseline VO 2 max was higher in patients commencing OR before chemotherapy (p&lt;0.05). However, the change in VO 2 max was greater in patients commencing OR after chemotherapy (before: 0.47; during: 0.51; after: 0.70) although not significant. and in patients that attended ≥ 10 compared to &lt;10 OR sessions (p&lt;0.01; before: 0.90 vs. -0.97, during: 1.20 vs. -0.97, after: 0.75 vs. 0.47ml/kg/min). LVEF did not differ appreciably across subgroups or following OR. Results shown in the Table. Conclusion: BC chemotherapy patients receiving OR in our institution experienced modest improvements in VO2max, with greater improvement among patients that attended ≥ 10 sessions. Timing of initiation did not influence outcomes significantly, therefore it would be reasonable to encourage OR referral either before, during, or after receipt of chemotherapy. Additional patient advocacy and research is required to increase OR utilization, determine best practices, and elucidate the benefits of OR.