Imlunestrant plus abemaciclib versus fulvestrant plus abemaciclib in estrogen receptor–positive (ER+), human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer (ABC): an indirect treatment comparison (ITC) of three Phase 3 trials. In the EMBER-3 trial, combination therapy with imlunestrant and abemaciclib was shown to improve progression-free survival (PFS) compared to imlunestrant monotherapy in patients with estrogen receptor–positive (ER+), human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer following progression on prior endocrine therapy with or without a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor. In this study, researchers conducted an indirect treatment comparison (ITC) study to compare the efficacy of imlunestrant plus (+) abemaciclib and fulvestrant+abemaciclib. Data from the EMBER-3 trial and pooled data from the MONARCH 2 and postMONARCH trials were analyzed. Three ITC methods were utilized: the Bucher method, which does not include population adjustment, and matching-adjusted indirect comparison (MAIC) and propensity score matching (PSM) methods, which include population adjustment. Following MAIC and PSM, baseline characteristics were comparable between patient populations. This study was not powered for formal hypothesis testing, but PFS favored imlunestrant+abemaciclib over fulvestrant+abemaciclib. Hazard ratios (HRs) (95% confidence intervals [CIs]) for imlunestrant+abemaciclib versus fulvestrant+abemaciclib were 0.77 (0.58–1.04), 0.77 (0.55–1.06), and 0.83 (0.56–1.22) for Bucher, MAIC, and PSM methods, respectively. These findings suggest that imlunestrant+abemaciclib could result in improved PFS compared to fulvestrant+abemaciclib in patients with ER+, HER2– advanced breast cancer with prior ET with or without CDK4/6 inhibitor treatment.
Exploring the hormone–brain–emotion axis in early luminal breast cancer: a cross-sectional evaluation of cognitive and affective outcomes. In this cross-sectional study, researchers assessed the relationship between ET and perceived cognitive and emotional wellbeing in patients with breast cancer. Among 126 postsurgery patients who received adjuvant ET, median age was 55.5 years. Fifty-eight percent of patients received aromatase inhibitors and 42 percent received tamoxifen. Median ET duration was 37 months. Cognitive complaints were prevalent among patients, and mean Functional Assessment of Cancer Therapy–Cognitive Function (FACT-Cog) score was 47.6 out of 148. Functional interference and frequent disruption were reported in 72 and 21 percent of patients, respectively. Mean Psychosocial Distress Questionnaire–Breast Cancer (PDQ-BC) score was 20.5 out of 50, with 27 percent of patients exceeding clinical cutoff. Fatigue was common among patients, and it showed strong correlation with distress (r=0.81) and moderate correlation with cognition (r=0.58). Patients who received ET for more than three years reported significantly fewer cognitive complaints, compared to those who did not (p<0.01). Additionally, there was a link between depressive symptoms and greater emotional and cognitive burden. Fatigue (β=0.57), distress (β=0.55), and shorter ET duration (β=–1.84/year) were significant, independent predictors of worse cognitive function (all p<0.01), according to multivariate analysis. Furthermore, distress was driven by fatigue (β=0.76); there was a weak connection between distress and cognitive complaints (β=0.11).
Real-world study on the significance of next-generation sequencing testing for ESR1 in ER+/HER2: metastatic breast cancer patients after endocrine therapy progression. Testing for ESR1 mutation is recommended for patients with breast cancer progression following prior ET. In this study, researchers assessed ESR1 testing patterns among patients with ER+, HER2– metastatic breast cancer. Data on patients who initiated a subsequent line of therapy (LOT) after prior ET from February 1, 2023, and December 31, 2024, were included for analysis. ESR1 testing and positivity were assessed at 60 days or fewer before or 30 days or fewer after initiating first LOT (Group 1), more than 30 days after first metastatic LOT but more than 60 days before second metastatic LOT (Group 2), 60 days or fewer before second metastatic LOT (Group 3), and 60 days or fewer before third metastatic LOT. A total of 621 patients with a median age of 69 years were included in this study. Overall, 78 percent of patients received ESR1 testing. In Group 1, 27 percent of patients (166/621) received ESR1 testing, of whom eight percent (n=13) had ESR1 positivity. The rate of ESR1 testing was highest for Group 2, at 41 percent (251/357), and 11 percent of tested patients (n=27) were ESR1-positive. Twenty-eight percent of patients (164/581) received testing in Group 3, and the rate of ESR1 positivity was 32 percent (n=53). The rate of ESR1 testing was lowest in Group 4, at 15 percent (35/232), but ESR1 positivity rate was high, at 37 percent (n=13).
Subtype evolution in luminal breast cancer following neoadjuvant therapy: clinical relevance of receptor changes. In this retrospective study, researchers aimed to identify factors associated with biological subtype conversion following neoadjuvant therapy in patients with ER/PR+, HER2– breast cancer. A total of 661 patients were included for analysis, and median age was 61 years. Most patients had breast cancer of no special type (NST; 82.2%) and Stage II disease (64.4%), and 68.7 percent had luminal A-like tumors. Forty patients (6.1%) experienced subtype conversion; 20 patients converted to triple-negative breast cancer (TNBC), and 20 converted to HER2+ disease. Following neoadjuvant therapy, PR became undetectable in 23.3 percent of patients. A total of 3.2 percent of tumors experienced ER loss, and this was significantly more common in patients with 10-percent or lower baseline ER expression compared to those with higher baseline ER expression (odds ratio [OR]: 59.7, p<0.001). Additionally, patients with G3 tumors versus those with G1/2 tumors (OR: 25.5, p<0.001) and those with baseline HER2-zero status (OR: 4.41, p=0.0027) had significantly higher odds of ER loss. Tumors with baseline expression of ER of 10 percent or less (OR: 8.77, p=0.002) and PR of 10 percent or less (OR: 3.59, p<0.001) had significantly greater odds of PR loss. Furthermore, PR loss occurred more frequently in G2/3 tumors versus G1 tumors (OR: 2.43, p<0.003) and after neoadjuvant ET (OR: 5.03, p<0.001). Conversion to HER2+ disease was significantly more common in G3 tumors compared to G1/2 tumors (OR: 4.95, p<0.001).
Real-world application of 18F-FES PET/CT on patients with HR+ breast cancer with brain metastases. Researchers retrospectively analyzed real-world data to determine the role of 18F-fluoroestradiol positron emission tomography/computed tomography (18F-FES PET/CT) in detecting intracranial disease in hormone receptor–positive (HR+) breast cancer. Twenty-three patients with HR+ breast cancer who had intracranial metastases detected via 18F-FES PET/CT were included for analysis. Seven patients (30.4%) experienced intracranial symptoms. Sixteen patients (69.6%) received ET-based treatment, and 12 (52.2%) underwent radiotherapy or surgery. 18F-FES PET/CT showed 100-percent concordance with pathology and 80-percent concordance with magnetic resonance imaging (MRI). Intracranial PFS was significantly longer in patients with FES maximum standardized uptake value (SUVmax) of 1.8 or higher compared to those with SUVmax below 1.8, with median PFS of not reached and 3.75 months, respectively (p=0.002). According to receiver operating characteristic (ROC) curve analysis, FES SUVmax was a significant predictor of intracranial progress, with an area under the curve (AUC) of 0.742 (95% CI: 0.556–0.928); additionally, multivariate analysis identified FES SUVmax classification as a significant predictor of intracranial PFS (HR: 7.985, 95% CI: 1.214–52.506, p=0.031), as well as disease-free interval.
Lymphedema in the upper extremity in patients with breast cancer: an NIS analysis. Analyzing 2022 National Inpatient Sample (NIS) data, researchers assessed risk factors associated with upper limb lymphedema in patients with breast cancer. A total of 17,850 of 1,176,749 patients (1.51%) had upper limb lymphedema. Prevalence was highest in African American patients (1.8%), followed by White (1.54%), Native American (1.29%), Hispanic (1.12%), and Asian/Pacific Islander (0.8%) patients. Lymphedema was more common in patients who had a history of radiation exposure (1.26%) compared to those without radiation exposure (0.74%). Obesity was more frequently reported in patients with lymphedema compared to those without lymphedema (32.66% vs. 14.19%); other comorbidities that were more common in the lymphedema group included chronic heart failure (29.02% vs. 18.79%), cerebrovascular insufficiency (5.77% vs. 0.63%), diabetes (28.26% vs. 26.33%), and chronic kidney disease (10.36% vs. 9.06%). Prevalence of lymphedema was similar across private nonprofit, private investor-owned, and government nonfederal hospitals (range: 1.35–1.55%). Additionally, lymphedema prevalence was comparable across urban teaching, urban nonteaching, and rural hospitals (range: 1.42–1.56%).
Assessment of TROP2 and PD-L1 expression on circulating tumor cells (CTCs) of patients with triple-negative breast cancer (TNBC). In this study, researchers evaluated the expression of trophoblast cell surface antigen 2 (TROP2) and programmed death-ligand 1 (PD-L1) on circulation tumor cells (CTCs) in TNBC. Peripheral blood samples from 65 patients with early-stage TNBC and 29 patients with metastatic TNBC. CTCs, which included CK+/CD45– cells, were found in seven patients (10.8%) with early-stage TNBC and eight patients (27.6%) with metastatic TNBC. TROP2+ CTCs were detected in 85.7 percent of patients with early-stage disease and 87.5 percent of those with metastatic disease. PD-L1+ CTCs were detected in 50 percent of patients with metastatic disease, whereas no patients with early-stage disease exhibited PD-L1+ CTCs. A total of 37.5 percent of patients with metastatic disease had TROP2/PD-L1 co-expression. When comparing Ficoll- and Parsortix-enriched samples, CTCs were detected in 25 and 35.7 percent of patients, respectively. TROP2+ and PD-L1+ CTCs were each identified in 90 percent of Parsortix-enriched samples. Ficoll-enriched samples detected TROP2+ CTCs in 87.5 percent of patients, while PD-L1+ CTCs were not detected.
Can the combination of circulating tumor cells and circulating tumor DNA predict neoadjuvant therapy response? A prospective study in patients with inflammatory breast cancer. In this prospective study, researchers assessed the utility of circulating tumor deoxyribonucleic acid (ctDNA) and CTC to predict response to neoadjuvant systemic therapy in inflammatory breast cancer. Forty-two patients with a median age of 45 years were included for analysis. Patients had undergone a total of 151 ctDNA and 47 CTC assessments. Stage III disease was reported in 54.8 percent of patients, and Stage IV disease was reported in 45.2 percent. The most common receptor subtypes were triple-negative (33.3%) and HR+, HER2– (31.0%). Baseline ctDNA samples were available for 23 patients, all of whom had ctDNA positivity, with a median 11.0 mean tumor molecules (MTM)/mL. Among 12 patients with corresponding baseline CTC assessments, seven (58.3%) had baseline ctDNA and CTC concordance. Across 26 timepoints with dual ctDNA and CTC assessments, the overall concordance rate was 73.1 percent. Clearance of ctDNA before surgery was reported in 16 of 22 patients (72.7%) with baseline ctDNA assessment at a median time of 7.5 weeks of neoadjuvant systemic therapy. Of 19 patients who have undergone surgery, seven (36.8%) experienced pathologic complete response (pCR). The rate of ctDNA clearance before surgery did not significantly differ between patients with and without pCR (87.5% vs. 70.0%, p=0.45). Median time to ctDNA clearance was 10 weeks for patients with pCR and 15 weeks for those without pCR (p=0.20).
Independent predictive role of obesity on vertebra fracture risk in breast cancer patients undergoing adjuvant aromatase inhibitor therapy. Patients with early-stage breast cancer who receive adjuvant aromatase inhibitor therapy can experience an increased risk of skeletal fragility, regardless of their bone mineral density (BMD). In this prospective cohort study, researchers assessed the relationship between adiposity and skeletal fragility in this patient population. At baseline and every 24 (±6) months, body composition and bone parameters were measured with dual-energy X-ray absorptiometry (DXA). In total, 769 patients with two DXA scans were included for analysis. Mean age was 62 years, and mean body mass index (BMI) was 25.40kg/m2. Thirty-eight percent of patients had obesity. History of bone fragility was reported in 21.3 percent of patients, and baseline vertebral fractures were present in 8.3 percent. Sixty-three percent of patients received bone-targeting agents. Fifty-seven patients (7.4%) experienced vertebral fracture progression, typically occurring within 30 months (n=33) or 31 to 60 months (n=28). According to multivariable analysis, obesity was significantly associated with vertebral fracture progression (HR: 2.05, 95% CI: 1.19–3.54, p=0.012); other factors associated with vertebral fracture progression included prior fractures (HR: 1.82, 95% CI: 1.05–3.15, p=0.036), age (HR: 1.19, 95% CI: 1.04-1.37, p=0.004), and BMD (HR: 0.77, 95% CI: 0.63–0.94, p=0.027). Trabecular bone score was not associated with vertebral fracture progression.
The innovative Lancet technique for breast-conserving oncoplastic surgery in small- to medium-sized breasts with tumors in the lower inner quadrant: a multicenter retrospective study (IOS study). Researchers developed an oncoplastic surgical approach (Lancet oncoplastic surgery technique [L-OPS]) tailored to small-to-medium-sized breasts with tumors in the lower inner quadrant. This L-OPS involves surrounding glandular tissue to fill the surgical defect to prevent visible deformity following tumor removal. In this study, researchers compared complications of L-OPS and traditional oncoplastic techniques (T-OPS). Among 1,298 patients, 217 underwent L-OPS and 1,081 underwent T-OPS. Compared to the T-OPS group, the L-OPS group had shorter mean operative time (150 vs. 106 minutes) and lower mean intraoperative blood loss (110mL vs. 90mL). Twenty patients in the L-OPS group experienced short-term complications, compared to 159 in the T-OPS group; this difference was significant (p=0.042). There was no significant difference in the incidence of long-term complications between groups (p=0.29), and the rate of re-excision did not significantly differ (L-OPS: 11.5%; T-OPS: 16.8%; p=0.064). Following propensity score matching, at eight-year follow-up, disease-free survival was comparable between groups (p=0.15). Additionally, mean cosmetic scores were similar (L-OPS: 4.8; T-OPS: 4.6).