Adjuvant Therapy Research Articles

DESTINY-Breast07: Dose-expansion interim analysis of T-DXd monotherapy and T-DXd + pertuzumab in patients with previously untreated HER2+ mBC.

1009 Background: Trastuzumab deruxtecan (T-DXd) is approved for adult patients (pts) with HER2+ advanced/metastatic breast cancer (mBC) who received a prior anti-HER2–based regimen. DESTINY-Breast07 is a Phase 1b/2 multicenter, open-label, modular study exploring the safety, tolerability, and antitumor activity of T-DXd alone or in combination with other anticancer agents (NCT04538742). These results are from an interim analysis of the dose-expansion phase assessing T-DXd ± pertuzumab (P) as first-line (1L) treatment in HER2+ mBC. Methods: Pts had locally assessed HER2+ mBC with measurable disease and no or stable brain metastases. A disease-free interval of ≥12 months from (neo)adjuvant therapy was required; no prior therapy for mBC was allowed. Pts were stratified by hormone receptor and disease status (recurrent vs de novo), and PD-L1 expression. Pts received T-DXd 5.4 mg/kg intravenously (IV) every 3 weeks (Q3W) as monotherapy or in combination with P 420 mg IV Q3W, with an 840 mg loading dose. Primary endpoints were safety and tolerability; key secondary endpoints included objective response rate (ORR) and progression-free survival (PFS), per RECIST 1.1 by investigator. Results: Seventy-five pts were treated in the T-DXd module and 50 pts in the T-DXd + P module; median follow up was 19.2 months (range 8.7–29.2) and 20.6 months (range 13.3–26.7), respectively. Median age was 57 years in both modules. As of August 1, 2023, the most common adverse event (AE) was nausea (T-DXd, 70.7% [4.0% Grade 3]; T-DXd + P, 68.0% [0% Grade 3]). Diarrhea was reported in 34.7% (2.7% Grade 3) and 60.0% (6.0% Grade 3) of pts in the T-DXd and T-DXd + P modules, respectively. There were no Grade ≥4 nausea or diarrhea events. Adjudicated drug-related interstitial lung disease (ILD) / pneumonitis was reported in six (8.0%) and five (10.0%) pts in the T-DXd and T-DXd + P modules, respectively (all Grade ≤2). One non-treatment-related AE with outcome of death was reported in the T-DXd module (post-acute COVID-19 syndrome); none with T-DXd + P. The confirmed ORR was 77.3% (80% confidence interval [CI] 70.0, 83.6) with T-DXd and 82.0% (80% CI 73.1, 88.8) with T-DXd + P. PFS rate at 12 months was 77.3% (80% CI 69.0, 83.7) with T-DXd and 89.4% (80% CI 81.9, 93.9) with T-DXd + P. Conclusions: Safety profiles were consistent with the known profiles for T-DXd and P, with no Grade ≥3 ILD events. Early data showed promising efficacy in both modules. The DESTINY-Breast07 study is ongoing; analyses from the Phase 3 DESTINY-Breast09 clinical trial will provide definitive data on TDXd ± P in 1L HER2+ mBC. Clinical trial information: NCT04538742 . [Table: see text]

Treatment patterns and outcomes in patients with early onset cholangiocarcinoma: A large database analysis.

e23294 Background: Although the average age of onset of cholangiocarcinoma (CCA) is ≥ 65 years, recent data have demonstrated an alarming rise in incidence of CCA in the United States (US) among people younger than 50 years of age. However, robust data regarding the characteristics and outcomes of CCA among young patients are lacking. Methods: We used TriNetX, a national database comprising approximately 74 million patients across 54 healthcare organizations in the US, to perform the current analysis. We retrospectively identified patients with CCA (using ICD-10 code C22.1) from Jul 2009 to Jan 2022. We then performed comparative analysis between patients ≤ 49 years (early-onset CCA or EOCCA) and ≥ 50 years old (average-onset CCA or AOCCA). We performed a comparative analysis of baseline characteristics, treatment patterns and overall outcomes. We used the Chi-square test for the comparative analysis and Kaplan-Meier estimates were plotted for survival analysis. A p-value of < 0.05 was considered statistically significant. Results: We included a total of 1,343 patients with EOCCA. Compared to AOCCA, patients in the EOCCA group were more likely to be females (51% vs 48%, p < 0.0001), African Americans (13% vs 9%, p < 0.0001) and have a history of primary sclerosing cholangitis (7% vs 1%, p < 0.0001). Patients in the EOCCA group were more likely to undergo surgical resection (9.7% vs 8%, p = 0.007), liver transplant (4.5% vs 1.6%, p < 0.0001) and adjuvant chemotherapy (39.2% vs 33.5%, p < 0.0001). Young patients were also more like to receive palliative chemotherapy (16.7% vs 12.6%, P < 0.00001) and FGFR-directed targeted therapy (1.5% vs 0.3%, p < 0.00001). Compared to older patients, we noted a significantly higher overall survival among young patients undergoing surgical resection (85 months vs 43 months, p = 0.008) and patients with advanced disease (28 months vs 15 months, p < 0.0001), however, no difference in overall survival was noted between young and older patients undergoing liver transplant (88 months vs 117 months, p = 0.6). Conclusions: We present a large real-world analysis highlighting treatment patterns and outcomes in patients with EOCCA. Young patients received more surgical resections, both adjuvant therapies and palliative therapies, and had a significantly longer overall survival than their older counterparts. Although more patients underwent liver transplant in the EOCCA group, post-transplant survival was not significantly better compared to their older counterparts. Prospective clinical studies tailored to assess surgical and systemic therapeutic approaches specific to EOCCA patients are warranted.

Novel electrical therapy to improve sleep disturbance in patients with autoimmune rheumatic diseases.

Sleep disturbance is common in autoimmune rheumatism diseases (ARD) and it plays an important role in activating disease and affects the quality of life. This study aims to evaluate the efficacy and acceptability of the novel electrical therapy on sleep disturbance in ARD patients and its effect on immunologic factors. A total of 51 ARD patients (26 treatment group and 25 control group) with sleep disturbance were enrolled in this study. Sleep parameters and immunological indicators (serum level of 12 cytokines and immune function) were collected. The novel electrical therapy was prescribed for 15-30 min 3-6 times a day. The Pittsburg Sleep Index (PSQI) was assessed before and after 3 months' treatment by Mi Energy equipment. Immune function and serum levels of cytokines of all participants at baseline and after treatment were tested with flow cytometry and flow immunofluorescence, respectively. Correlation analysis was used to analyze the relationship between sleep disturbance and immunologic factors. Multiple linear regression analysis was employed to investigate the risk of sleep disturbance in ARD. The global score of PSQI (Baseline: 12.81 ± 4.07, After novel electrical therapy: 4.88 ± 2.76) was effectively improved after 3 months of adjuvant therapy by electrical therapy. We also found that serum levels of IL-8 and IL-1β statistically significantly decreased after novel electrical therapy. This adjuvant therapy can also significantly decrease the percentage of CD4 + CD8 + T cell, effector memory CD8 + T cell, Memory CD8 + T cell, Th17 cell, and plasma cell and significantly can increase the percentage of naïve CD8 + T cell, Th2 cell, and Tfh2 cell. Nevertheless, all serum level of 12 cytokines and the percentage of immune cells did not correlate with the PSQI global score except the Tc17 cell. Furthermore, age is an independent risk factor influencing PSQI scores (OR = 1.15, p < 0.05) in patients with autoimmune diseases through multiple linear regression analysis. Novel electrical therapy can effectively improve sleep disturbance in patients with ARD. It can also change the serum level of some cytokines (IL-8 and IL-1β) and percentage of immune cells (CD4 + CD8 + T cell, effector memory CD8 + T cell, Memory CD8 + T cell, Th17 cell, naïve CD8 + T cell, Th2 cell, Tfh2 cell, and plasma cell).

A pilot study of early PET and biomarker dynamics in patients with stage 2 and 3 triple negative breast cancer treated with neoadjuvant response-adapted chemotherapy with pembrolizumab (NeoADAPT).

TPS624 Background: In patients with triple negative breast cancer (TNBC) the addition of pembrolizumab to neoadjuvant chemotherapy has improved pathologic complete response rates (pCR) and 5-year event free survival (EFS). Patients with TNBC who achieve a pCR have a significantly lower risk of recurrence compared to those with residual disease (RD). However, pCR can only be assessed at the time of surgery after completion of 6 months of intensive chemo-immunotherapy, associated with up to 77% high-grade treatment-related toxicity. Identifying pCR early on is imperative in developing optimized and individualized treatments, however, there are no predictive biomarkers. Studies in HER2-positive breast cancer have shown that early fluorodeoxyglucose positron emission tomography (FDG-PET) changes soon after initiation of neoadjuvant treatment can help predict the pathological outcomes at the time of surgery and also the risk of recurrence. Emerging data also support that clearance of circulating tumor DNA (ctDNA) during neoadjuvant treatment may be associated with higher rates of pCR. We thus designed a study to determine the association of early FDG-PET changes and ctDNA clearance with pCR in early-stage TNBC. Methods: NeoADAPT is a phase 2, open label, single center clinical trial including adult patients with previously untreated clinical stage 2 or 3 TNBC. Participants will receive 4 cycles of neoadjuvant paclitaxel/carboplatin with pembrolizumab (TC/pembro), per standard-of-care (SOC). An FDG-PET will be performed at baseline and after 1 cycle. A breast MRI will be performed at baseline and after completion of 4 cycles of treatment. Patients with a complete clinical response (cCR) will proceed to surgery and will forgo more neoadjuvant treatment. Patients with clinical RD on MRI will complete SOC neoadjuvant therapy with 4 cycles of doxorubicin/cyclophosphamide (AC) with pembro prior to surgery. If RD is identified after surgery, adjuvant therapy will be determined by the treating oncologist, which may include pembro with AC (if not given prior), capecitabine, etc. The primary objective is to evaluate if lack of decrease in maximum FDG-PET standard uptake value of lean body mass (SULmax) by less than 40% after 1 cycle of neoadjuvant treatment correlates with RD at the time of surgery (i.e. determining the negative predictive value of FDG-PET). Additional key endpoints include ctDNA clearance, evaluation of pCR and cCR rates in the treatment population and EFS. Distributions of percent reduction in SULmax will be compared between pCR and no-pCR groups using the Wilcoxon rank sum test. Receiver operating characteristic (ROC) curve analysis will be performed to estimate the ability of FDG-PET SULmax reduction and cCR by MRI in predicting pCR at surgery. Clinical trial information: NCT06245889 .

Detection of contralateral breast cancer in patients with primary breast cancer through AI-assisted mammography.

e13645 Background: Survivors of breast cancer are at an elevated risk for developing contralateral breast cancer (CBC), a risk that surpasses the incidence of initial primary breast cancer within the general population. Consequently, annual mammography screenings are advocated to monitor for ipsilateral recurrence and the emergence of CBC. However, the sensitivity of surveillance mammography exhibits considerable variation, ranging between 45% and 90%, with notably lower detection rates in younger individuals and those with dense breast tissue. This study explores the efficacy of an artificial intelligence (AI) detection algorithm in mammography for the early identification of CBC prior to the official diagnosis. Methods: A retrospective analysis was conducted on patients treated for primary breast cancer from 2000 to 2021 at Seoul National University Hospital. This involved reviewing serial mammograms post-surgery and adjuvant therapy from 460 patients who subsequently developed CBC (CBC group) and 469 patients who did not (control group). These mammograms were evaluated using the Lunit INSIGHT mammogram AI system, which provides a pixel-level abnormality score between 0 and 100, with higher scores indicating increased abnormality. Scores exceeding 10 were considered indicative of CBC, reflecting a 90% sensitivity based on the AI software's tuning dataset. The diagnostic accuracy of AI-assisted mammography was then juxtaposed with that of specialist radiologists' evaluations. Results: At the point of CBC diagnosis, the median AI abnormality score was markedly higher in the CBC group (22.9 [IQR, 2.1-81.1]) compared to the control group's final follow-up mammogram (0.4 [IQR, 0.1-1.5], p&lt;0.001). The AI system's sensitivity for CBC detection paralleled that of radiologist assessments (59.6% for AI vs. 56.5% for radiologists out of 460 detected cancers), with the AI method achieving an AUROC of 0.836 and a specificity of 91.0%. Notably, AI detected 84 cases (30.7%) at least six months and 59 cases (21.5%) more than a year before the official CBC diagnosis. Conclusions: The application of AI in mammography screening has demonstrated significant potential for the early detection of CBC, identifying cases up to a year before formal diagnosis. This underscores the value of integrating AI tools in mammography to enhance early detection rates of CBC among primary breast cancer patients.

Clinical differences and management trends of localized breast cancer in the advanced geriatric population.

e12543 Background: Breast cancer remains the most common cancer diagnosis in women and, with the aging Baby Boomer population, is poised to represent an even larger volume of oncologic care in the United States over the coming decades. Combined with limited evidence-based guidelines for geriatric patients, particularly those above the age of 80, there exists the potential for unnecessary morbidity and mortality. This study aims to shed light on the characteristics of this population, including disparities, with an aim to identify subsets of patients who may benefit from more aggressive treatment. Methods: This was a retrospective cohort study to examine key clinical differences between the advanced geriatric breast cancer population (≥80 years) and those of younger age, comparing comorbidities, tumor characteristics, and management trends. The Charleston Area Medical Center cancer registry was queried from 2009-2022 for females diagnosed with invasive breast cancer who had surgery for localized disease, excluding those with previous malignancies. Data were analyzed with SAS 9.4 using student’s t-test for continuous variables, Chi-square or Fisher’s exact for categorical variables, and 5-year survival rates attained via Cox regression models. Results: The analysis involved 1041 female patients, divided into two age groups: 969 who were &lt; 80 years old and 72 who were ≥80 years old at time of breast cancer diagnosis. The ≥80 group had significantly more individuals with hypertension, 83.3% v 63.7% (p &lt; .001), osteoporosis, 26.8% v 9.5% (p &lt; .001), cardiac arrhythmia, 18.1% v 7.3% (p = .001), and CVA, 11.1% v 4.5% (p = .014), than the &lt; 80 group. Looking at overall trend, tumor grade was significantly (p = .040) lower in the ≥80 group than the &lt; 80 group, G1 34.7% v 24.9%, G2 44.4% v 45.4%, G3 20.8% v 29.7%, respectively. Her2neu positivity was significantly (p = .010) lower in the ≥80 group at 0.0% compared to the &lt; 80 group at 8.4%. There was no difference in the rate of endocrine therapy between the two groups (p = 0.320). Only 26.4% of the ≥80 group received radiotherapy compared to 79.0% of the &lt; 80 group (p &lt; .001). None of the ≥80 group received chemotherapy compared to 22.5% of the &lt; 80 group (p &lt; .001). Overall, 5-year survival for those &lt; 80 and ≥80 was 92% and 84%, respectively (p &lt; .001). Conclusions: In summary, patients 80 years of age or older were more likely to have hypertension, osteoporosis, cardiac arrhythmia, and history of CVA. Regarding tumor characteristics, both grade and Her2neu positivity were significantly higher in the &lt; 80 group. There was no difference in the administration of endocrine therapy. Radiotherapy and chemotherapy, however, were used at significantly lower rates in the advanced geriatric population, likely in adherence with current NCCN guidelines for adjuvant therapy in patients ≥70. Further investigation may help to elucidate subgroups amenable to more aggressive adjuvant therapies.

Adjuvant Therapy in Stage I Testicular Cancer: Surveillance for All

Given the remarkably high cure rates for clinical stage (CS) I testicular cancer, the toxicities and risks of adjuvant treatments, the cost effectiveness of surveillance, and the lack of reliable biomarkers to predict relapse, surveillance should be recommended for all patients with CS I testicular cancer.

A first-in-human study to evaluate a personalized neoantigen-based mRNA-loaded dendritic cell vaccine, in combination with ablation, in patients with hepatocellular carcinoma.

e14513 Background: Local recurrence of Hepatocellular Carcinoma (HCC) following potentially curative resection or ablation is an inevitable risk. T cells recognizing neoantigens are present in most cancers including HCC and offer a specific and highly immunogenic target for the personalized vaccination as an adjuvant therapy. The purpose of this study is to evaluate the safety and T cell immune response of a personalized neoantigen-based mRNA loaded dendritic cell (DC) vaccine (LK101) combined with regular ablation in patients with HCC (NCT03674073). Methods: Each patient’s fresh tumor biopsy and matched peripheral blood sample were subjected to whole-exome sequencing and RNA-sequencing. Following determination of somatic mutations and gene expression, up to 30 in silico–predicted potential neoantigens were selected with bioinformatic tool. DCs were generated from the monocytes enriched by leukapheresis, followed by transfection with neoantigen-encoding mRNA through electroporation. In total, 7 doses of LK101 were administered at 1.5×107 cells/injection intradermally with 4-dose priming weekly and 3 boosters in 4-week intervals. The primary endpoint of the clinical study was safety, and key secondary endpoints were immunogenicity, overall survival and recurrence. 24 HCC patients at HKLC stage IIa were enrolled 1:1 to ablation control arm and ablation combined with DC (LK101) arm. Results: The study was completed, patients were followed up for a median of 48.4 months and 38.8 months in vaccination arm and control arm. All of adverse events were Grade 1-2. Most frequent treatment-related adverse events are injection site reactions, inclusive of local pain (63.6%), itch (27.3%) and others (27.3%), such as redness and edema. 3 patients in ablation control arm died, whereas all vaccinated patients survived. The 1-year and 2-year recurrence rates in vaccination arm compared with control arm are 18.2%, respectively. LK101 induced neoantigen-specific T cell responses were investigated by ELISpot analysis. Overall, all patients elicited at least one measurable response. Immune responses to 60-90% of neoantigen peptides were seen post vaccination across patients. Both preexisting immune response and De Novo immune response that targeted neoantigens were observed in vaccinated patients. Moreover, both CD4 and CD8 positive effector memory T cells showed the trend of increase, and PD-1 positive T cells reduced in peripheral blood of patients after vaccination. Conclusions: Combination of LK101 with ablation therapy has a manageable safety profile, showing the evidence of immune activation and potential of prolonged survival. In combination with regular ablation, neoantigen based mRNA loaded DC vaccine is a promising immunotherapy for the treatment of HCC. Clinical trial information: NCT03674073 .

Immuno-related cardiac toxicity in patients with cancer: A prospective study applying multiparametric cardiac MRI.

e24014 Background: Since Immune checkpoint inhibitor (ICI) immunotherapy has emerged as a cornerstone of modern oncology, oncologists are facing a new spectrum of ‘immune-related adverse events’ (irAEs), potentially affecting every tissue and organ. ICI-induced symptomatic myocarditis occurs only in around 1% of ICI-treated patients (pts), but is fatal in 50% of cases. Methods: Pts undergoing ICI therapy at the Humanitas Cancer Center from May 2021 to December 2023 were prospectively recruited and assigned to three study groups: 1) ICI given as monotherapy (Mono) 2) ICI given in combination (Combo) 3) history of cardiac disease or two cardiological risk factors other than smoke (Cardio). Exclusion criteria were: previous exposure to any immunotherapy, combination with other cardiotoxic therapies, and acute (in the last 3 months) cardiac events. All pts underwent a complete cardiological assessment with clinical visit, 12-lead ECG, and multiparametric cardiac MRI (cMRI) at two time-points: prior initiation of the ICI therapy, and around 8 weeks later. Peripheral blood samples for immunophenotyping analyses were collected at the same time-points. cMRI scans were performed using a 1.5 Tesla scanner. Chi-square, Fisher exact and paired t-test were used to compare groups; all analyses were performed using SAS v9.4. Objectives of the study were: detection of subclinical cardiac damage and identification of groups of patients at major risk, who may benefit from cardiological pre- or/and on-treatment assessment. Results: We present data on the first 47 pts enrolled, diagnosed with a wide range of solid tumors, including 16 renal carcinoma, 11 melanoma and 3 NSCLC; 15 (32%), 16 (34%) and 16 (34%) pts were assigned to the Mono, Combo and Cardio group, respectively. Most pts (42, 89%) were treated with ICI for locally advanced/metastatic disease (26 as first-line therapy, 16 from second-line on), while 5 (11%) as adjuvant therapy. All pts received an anti-PD-(L)1, either as single agent (25, 53%) or in combination, with ICI plus a TKI being the most frequent combinatorial strategy (16; 34%). Overall, the cMRI analysis showed a statistically significant left ventricle ejection fraction (LVEF) reduction pre- versus post-ICI treatment (p &lt; 0.001), with 18 (38%) pts experiencing a loss of &gt; 3 points of LVEF. No statistically significant differences in LVEF reduction were observed considering the three different groups (p = 0.6), tumor types (p = 0.2), or occurrence of any grade non-cardiological irAEs (p = 0.6). Conclusions: Our study was able to show a statistically significant reduction in LVEF, with more than 3% LVEF loss in a clinically significant proportion of ICI-treated patients (18; 38%), not selected for suspected cardiac symptoms, warranting prospective evaluation to eventually identify pts at higher risk. The trial is continuing prospective enrollment and immunophenotyping analyses are ongoing.

Global trends and hotspots on recurrent respiratory papillomatosis: A 20-year bibliometric analysis.

Recurrent respiratory papillomatosis (RRP) is the most common benign laryngeal tumor in children. It can cause serious psychological and mental burden on patients since RRP requires repeated surgical treatment. This study aims to delineate the global trends and identify hotspots related to RRP over the past two decades. We systematically gathered research findings on RRP from 2004 to 2023, utilizing the Web of Science as our data source. Subsequently, we performed a comprehensive bibliometric analysis of the literature using Vosviewer, CiteSpace, and Bibliometrics online analysis platform. A total of 839 publications were finally identified on RRP from 2004 to 2023. The United States has the largest number of publications (392), accounting for 46.7%. The Capital Medical University is the most productive organization (24), followed by the Centers for Disease Control and Prevention (18). The most productive journal was the Laryngoscope, with 86 publicatios. Comparatively, Vaccine is the most cited journal (2297). Craig S. Derkay ranked highest among all authors in publication (16). Burst detection shows onset, adjuvant therapy, management, juvenile-onset RRP, systemic bevacizumab, avastin, human papillomavirus vaccine are recent keywords of great interest to researchers. Research on RRP has progressed significantly over the past two decades, especially in terms of therapeutic strategies. We strongly believe that this article will provide new research directions for other researchers and may contribute to future breakthroughs in the field.

Mitochondrial metabolism blockade nanoadjuvant reversed immune-resistance microenvironment to sensitize albumin-bound paclitaxel-based chemo-immunotherapy

Currently, the efficacy of albumin-bound paclitaxel (PTX@Alb) is still limited due to the impaired PTX@Alb accumulation in tumors partly mediated by the dense collagen distribution. Meanwhile, acquired immune resistance always occurs due to the enhanced programmed cell death-ligand 1 (PD-L1) expression after PTX@Alb treatment, which then leads to immune tolerance. To fill these gaps, we newly revealed that tamoxifen (TAM), a clinically widely used adjuvant therapy for breast cancer with mitochondrial metabolism blockade capacity, could also be used as a novel effective PD-L1 and TGF-β dual-inhibitor via inducing the phosphorylation of adenosine 5ʹ-monophosphate-activated protein kinase (AMPK) protein. Following this, to obtain a more significant effect, TPP-TAM was prepared by conjugating mitochondria-targeted triphenylphosphine (TPP) with TAM, which then further self-assembled with albumin (Alb) to form TPP-TAM@Alb nanoparticles. By doing this, TPP-TAM@Alb nanoparticles effectively decreased the expression of collagen in vitro, which then led to the enhanced accumulation of PTX@Alb in 4T1 tumors. Besides, TPP-TAM@Alb also effectively decreased the expression of PD-L1 and TGF-β in tumors to better sensitize PTX@Alb-mediated chemo-immunotherapy by enhancing T cell infiltration. All in all, we newly put forward a novel mitochondrial metabolism blockade strategy to inhibit PTX@Alb-resistant tumors, further supporting its better clinical application.

Impact of semaglutide and tirzepatide administration on weight in women with stage I-III breast cancer.

e24140 Background: Weight gain and obesity are significant problems for women receiving adjuvant therapy for breast cancer and obesity is associated with adverse breast cancer outcomes. In addition, obesity is associated with negative impact on overall physical and mental health. The GLP-1 agonists, semaglutide (S) and tirzepatide (T), are effective in achieving weight loss and have been associated with decreased incidence of diabetes, stroke and overall mortality in the non-diabetic as well as diabetic populations. There are limited data on the efficacy and safety of GLP1 agonists in women with breast cancer. Methods: We performed a retrospective analysis of the association of S and T use with weight loss in patients with stage I-III breast cancer diagnosed and treated at the Yale Cancer Center/Yale New Haven Health Network between 2017 and 2022. After institutional review board approval, a database including 7149 patients including 92,989 office visits was constructed. Maximal weight loss after S/T prescription as well as mean weight loss were calculated. S and T treated patient’s stage distribution and rates of recurrence were compared to untreated patients. For patients without metastatic disease, repeated measures regression analysis was utilized to evaluate changes in weight and BMI. Results: Of the 5430 evaluable patients with non-metastatic disease, 70 (1.3%) were prescribed S or T. Mean age was 58 (41-78). 74% received endocrine therapy. Mean pretreatment weight was 95.8 kg and BMI was 35.9 kg/m2. Mean weight loss for S/T treated patients was 3.03 kg (3.9-2.13, p &lt; .0001) corresponding to reduction in BMI of 1.1 kg/m2 (0.7-1.5 p &lt; .0001). We also calculated maximal weight loss after S/T prescription. Mean maximal weight loss was 8.89 kg (6.71-10.98 P &lt; .0001) corresponding to a mean maximal reduction in BMI of 3.2 kg/m2 (2.3-4.2 P &lt; .0001). Rates of local, locoregional, and distant breast cancer recurrence were 1.5%, 0%, 1.5% in the S/T treated patients and 1.3%, 4.7% and 3.3% in the untreated patients. None of these differences were statistically significant. Conclusions: In this retrospective analysis, GLP-1 agonist are associated with clinically meaningful weight loss in overweight and obese women with early breast cancer. Recurrence risk did not appear to be preliminarily impacted by treatment. Additional research is needed on long term safety as well as weight loss maintenance with these drugs in breast cancer survivors.

Disparities in patients with HER2-positive breast cancer receiving optimal treatment: Analysis of the real-world ASCO CancerLinQ dataset.

e13739 Background: Racial/ethnic disparities in locoregional second breast cancer events (SBCE) in patients (pts) with HER2-positive (HER2+) breast cancer (BC) are not well defined. We examined rates of SBCE and overall survival (OS) by race and ethnicity in the ASCO CancerLinQ Discovery (CLQD) real-world dataset in HER+ BC pts receiving optimal and not-optimal treatment. Methods: CLQD was used to identify pts undergoing surgery for stage I-III HER2+ BC from 2005-2022. Race/ethnicity were self-reported. Optimal treatment was defined as HER2-directed therapy for stage II-III HER2+ BC starting in 2008, adjuvant endocrine therapy for hormone-receptor positive (HR+) HER2+ BC, radiation after lumpectomy, and regional nodal irradiation for N2-N3 disease. The primary endpoint was SBCE defined as a second event in the ipsilateral or contralateral breast or axilla, with OS as a secondary endpoint. Kaplan-Meier analysis was used to estimate SBCE-free survival and OS. Results: Of 8,795 stage I-III HER2+ BC pts, 5,487 (62.4%) were Non-Hispanic White (NHW), 1,083 (12.3%) Non-Hispanic Black (NHB), 418 (4.7%) Hispanic, 323 (3.7%) Asian or Pacific Islander (API), and 1,484 (16.9%) other/unknown. Overall, 39.2% had HR-HER2+ and 60.7% had HR+HER2- BC. NHW pts were the most likely to present with stage I disease (40.2% vs 31.9%, 29.0%, and 30.3% of NHB, Hispanic, and API pts, respectively, p&lt;0.01) and less likely to be age &lt;50 at diagnosis (26.1% vs 32.3%, 41.0%, and 36.6% in NHB, Hispanic, and API, p&lt;0.01). Overall, 54.2% of HER2+ BC pts received optimal treatment: 54.1%, 60.2%, 60.5%, and 58.8% of NHW, NHB, Hispanic, and API pts (p&lt;0.01). Neoadjuvant HER2-therapy was given in 42.4%, 46.3%, 53.8%, and 51.2% of NHW, NHB, Hispanic, and API pts (p&lt;0.01) and endocrine therapy in 64.7%, 56.8%, 59.3%, and 54.7%, respectively (p&lt;0.01). 5-yr SBCE-free survival and OS are shown (Table). SBCE-free survival was not statistically different by race and ethnicity in optimally or non-optimally treated pts. Optimal treatment increased OS by 4.1% and 0.9% in NHW and NHB pts with HR-HER2+ BC and 2.4% and 8.9% in NHW and NHB pts with HR+HER2+ BC. Conclusions: Differences in OS, but not SBCE, were seen by race/ethnicity in HER2+ BC. OS differences were not completely mitigated by receipt of optimal treatment. [Table: see text]

Factors associated with benefit of adjuvant chemotherapy in patients with T1b/T1c HR-positive/HER2-negative breast cancer and high multigene recurrence score.

e12540 Background: Patients diagnosed with early-stage HR-positive/HER2-negative Breast Cancer (BC) and high Oncotype DX Recurrence Score (RS ≥26) are offered adjuvant chemotherapy and endocrine therapy compared (CET) to endocrine therapy alone (ET). We sought to investigate if additional clinical factors that could further determine benefit from chemotherapy in patients with T1b/T1c and N0 tumors with high Oncotype DX to help deescalate treatment by avoiding chemotherapy induced toxicity. Methods: The purpose of this study is to determine the clinical factors associated with a survival difference from CET compared to ET alone in T1b/T1c and N0 BC. We analyzed the record of patients diagnosed with T1b/T1cN0M0 HR-positive/HER2-negativeBC and RS ≥26 between 2006 and 2020 from the National Cancer Database. Patients were separated into two groups based on their treatment: CET or ET and the following characteristics were assessed: age, grade, histology, and RS (26-30, 31-40, 41-100) to determine overall survival differences among the two groups. Chi-square was performed to evaluate the association between baseline categorical characteristic variable and chemotherapy treatment. Survival analysis of treatment modalities using Kaplan Meier curves and univariate Cox regression. Multivariate Cox regression with backwards elimination was performed for subgroup analyses. Results: A total of N=19,373 eligible patients were identified, n=14,422 (74.4%) received CET and the rest ET alone. The mean age at diagnosis was 59.6 years (SD=10.3); 86.6% presented with invasive ductal carcinoma and 83.3% had a Charlson-Deyo Comorbidity Score of 0. In the overall group, patients who received CET had a higher median overall survival than endocrine therapy alone (65.7 versus 52.1 months, log-rank p-value&lt;.0001). However, further analysis noted that treatment with CET showed better outcome compared to ET alone in the following subgroups of patients: invasive ductal histology (95% OS 65.5 versus 52.7 months, log-rank p-value&lt;.0001) and RS &gt;30 (95% OS 63.6 versus 40.5 months, log-rank p-value&lt;.0001). Importantly, multivariable cox regression subgroup analysis revealed no significant overall survival difference among the subgroup of patients with T1b/T1c and low grade (p=0.286) or RS 26-30 (p=0.200) with CET compared to ET alone. Conclusions: This large database confirms the heterogeneity of BC in patients with low burden disease despite high Oncotype.While patients diagnosed with T1b/T1cN0M0 and high RS (&gt;30) could benefit from CET compared to ET alone as per standard practice, additional criteria could be considered in this group including low grade or RS 26-30 to better determine which population of patients do not benefit from the addition of chemotherapy and accordingly individualized chemotherapy decision might be made to minimize toxicity.

Male Breast Cancer: Two Case Studies and Review of the Literature

Male breast cancer (MBC) is a rare disease, accounting for 1% of all breast cancers and 0.5% of all malignancies in men. While long considered stable, MBC incidence has increased 26% over the past 25 years. Despite this rise, MBC remains poorly recognized by the public and sometimes clinicians, risking delayed diagnosis and poor prognosis cases. This rarity also impacts treatment, as men have received little research attention and management largely relies on evidence from women. Currently, MBC has become a topic of interest to uncover similarities between males and females to better tailor therapeutic approaches. We present two cases - a 56-year-old man with a 2-year history of a 2cm retroareolar left breast mass, diagnosed as grade III invasive ductal carcinoma, and a 38-year-old man with a 4cm retroareolar left breast mass complicated by bloody nipple discharge, diagnosed as grade II invasive ductal carcinoma. Both underwent mastectomy and axillary dissection followed by adjuvant radiation and hormonal therapy. MBC diagnosis relies on triple assessment like female breast cancer. While rare, raising MBC awareness is crucial for timely diagnosis and management per evidence-based guidelines, warranting further research into this malignancy affecting men.

Phase III study to evaluate the efficacy and safety of GLSI-100 (GP2 + GM-CSF) in patients with breast cancer with residual disease or high-risk PCR after both neo-adjuvant and postoperative adjuvant anti-HER2 therapy: Flamingo-01.

TPS617 Background: GP2 is a biologic nine amino acid peptide of the HER2/ neu protein delivered in combination with Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) that stimulates an immune response targeting HER2/neu expressing cancers, the combination known as GLSI-100. Of the 146 patients that have been treated with GLSI-100 over 4 clinical trials, GLSI-100 was well-tolerated and no serious adverse events observed were considered related to the immunotherapy. Methods: This Phase III trial is a prospective, randomized, double-blinded, multi-center study. After 1 year of trastuzumab-based therapy, 6 intradermal injections of GLSI-100 or placebo will be administered over the first 6 months and 5 subsequent boosters will be administered over the next 2.5 years for a total of 11 injections over 3 years. The participant duration of the trial will be 3 years treatment plus 1 additional year follow-up for a total of 4 years following the first year of treatment with trastuzumab-based therapy. Patients will be stratified based on residual disease status at surgery, hormone receptor status and region. Study size, interim analysis: Approximately 498 patients will be enrolled. To detect a hazard ratio of 0.3 in invasive breast cancer free survival (IBCFS), 28 events will be required. An interim analysis for superiority and futility will be conducted when at least 14 events have occurred. This sample size provides 80% power if the annual rate of events in placebo patients is 2.4% or greater. Up to 100 non-HLA-A*02 subjects will be enrolled in an open-label arm. The patient population is defined by these key eligibility criteria: HER2/neu positive and HLA-A*02; residual disease or high risk pCR (Stage III at presentation) post neo-adjuvant therapy; exclude Stage IV; completed at least 90% of planned trastuzumab-based therapy. Trial objectives: To determine if GP2 therapy increases IBCFS; to assess the safety profile of GP2; and to monitor immunologic responses to treatment and assess relationship to efficacy and safety. Study status: The study has been initiated at a number of sites in the US. The study is also expected to be opened in Spain, France, Germany, Italy, and Poland. Clinical trial information: NCT05232916 .

Effects of plant-based diet (PBD) and exercise therapy (Ex) on weight and body composition in patients with primary hormone receptor (HR) positive breast cancer: A phase 2 randomized controlled trial.

548 Background: Obesity increases breast cancer recurrence and mortality. Strategies that induce weight loss may improve clinical outcomes. We investigated the feasibility and efficacy of personalized energy restricted PBD plus Ex on weight and body composition in primary HR-positive breast cancer (NCT04298086). Methods: Postmenopausal women with body mass index (BMI) ≥ 27 kg/m2 on adjuvant endocrine therapy were randomized (1:1) to PBD plus Ex or attention control for 24 weeks. PBD plus Ex received individualized caloric goals adjusted weekly to target 1.5 lbs/week weight loss. PBD targeted 500 kcal/day goal deficit achieved via nutrition coaching and meal delivery. Ex sessions targeted 250 kcal goal expenditure via remotely delivered treadmill walking 3-5 days/week with real-time monitoring. Attention control received a home treadmill and monthly check-in calls. Baseline to post-intervention changes in weight and body composition, measured by dual energy X-ray absorptiometry (DXA), were compared between arms using linear mixed models. Results: 43 women were randomized between 8/2020 and 4/2023. Weight data was available for all participants (35 measured at follow-up, 8 abstracted from clinical documentation); 37 completed post-intervention DXA. At baseline, mean BMI was 34 (SD 4) kg/m2. Intention-to-treat results are presented in the Table. Mean weight loss in PBD plus Ex was –13% (SD 6%) compared with –5% (SD 6%) in attention control (mean between group difference –8 kg, 95% CI –11, –4). Mean fat loss in PBD plus Ex was –6 kg compared with –2 kg in attention control (mean between group difference –4 kg, 95% CI –6, –2). Lean mass increases were greater in PBD plus Ex (P&lt;0.001). Weekly energy deficit goal compliance was 95% in month 1 and 64% in month 6. No serious adverse events were observed. Baseline and post-intervention tissue samples were available on 37 (86%) patients, which will undergo biologic correlative analysis. Conclusions: Personalized PBD plus Ex led to substantial weight loss and favorable changes in body composition during endocrine therapy for HR-positive breast cancer. Clinical trial information: NCT04298086 . [Table: see text]

Baseline (BL) characteristics and efficacy endpoints for patients (pts) with node-negative (N0) HR+/HER2− early breast cancer (EBC): NATALEE trial.

512 Background: NATALEE assessed ribociclib (RIB) + non-steroidal aromatase inhibitor (NSAI) vs NSAI alone in pts with HR+/HER2− EBC at increased risk of recurrence, including pts with N0 disease, and showed a statistically significant invasive disease-free survival (iDFS) benefit. We report BL characteristics, efficacy, and safety for the N0 subgroup. Methods: Pts with stage II/III HR+/HER2− EBC were randomized (R) 1:1 to RIB 400 mg/d (3 wk on/1 wk off for 36 mo) + NSAI (letrozole or anastrozole for ≥60 mo) or NSAI alone. Men and premenopausal women received goserelin. Pts could receive any standard (neo)adjuvant endocrine therapy (ET) ≤12 mo before randomization. In the intent-to-treat (ITT) population, 78% of pts completed 3y of RIB treatment (tx) or discontinued early with 21% still on tx at the time of this analysis (data cutoff: July 21, 2023; median follow up, 33 mo). The N0 subgroup included pts with T2N0 (stage IIA; with grade [G]3, or G2 disease and Ki-67 ≥20% or high genomic risk [HGR]), T3N0 (stage IIB), and T4N0 (stage IIIB); T1N0 was excluded. Results: Of 2549 pts R to RIB + NSAI and 2552 to NSAI alone, 285 (11%) and 328 (13%) had N0 disease, respectively. BL characteristics for the N0 subgroup were balanced across arms. Most pts were premenopausal (RIB + NSAI: 67% vs NSAI alone: 63%). Pts with N0 disease had anatomic stage IIA (RIB + NSAI: 74% vs NSAI alone: 73%), stage IIB (17% vs 13%), or stage IIIB (9% vs 12%) disease (Table). Most pts received prior chemotherapy (RIB + NSAI: 72% vs NSAI alone: 71%); prior ET was received by 59% vs 62% of pts with RIB + NSAI vs NSAI alone. For pts with T2N0 disease treated with RIB + NSAI vs NSAI alone, 49% vs 45% had G3 disease and 49% vs 53% had G2 disease (54% vs 56% with T2N0, G2 &amp; Ki-67 &gt; 20%; 13% vs 23% with T2N0, G2, Ki-67 ≤20%/missing &amp; HGR). Consistent with the ITT population, RIB + NSAI improved iDFS (HR, 0.72; 95% CI, 0.41-1.27; 3y rate with RIB + NSAI vs NSAI alone, 93.2% vs 90.6%), distant disease–free survival (DDFS; HR, 0.70; 95% CI, 0.38-1.29; 3y rate, 94.3% vs 91.5%), and distant recurrence–free survival (DRFS; HR, 0.58; 95% CI, 0.29-1.17; 3y rate, 96.3% vs 92.5%) in pts with high-risk N0 disease. The safety profile of RIB in the N0 subgroup was consistent with the ITT population. The rate of discontinuation due to all grade adverse events was 24% vs 8% with RIB + NSAI vs NSAI alone. Conclusions: This analysis showed a consistent efficacy benefit and manageable safety profile of RIB + NSAI vs NSAI alone in pts with N0 disease in NATALEE. The 3y iDFS, DDFS, and DRFS rates in the control arm at this early follow-up underscore the risk of recurrence for the N0 subgroup. These findings support the use of RIB in pts with HR+/HER2− EBC at increased risk of recurrence, including pts with N0 disease. Clinical trial information: NCT03701334 . [Table: see text]

Comprehensive clinical characteristics and ctDNA mutational profile analysis of endocrine resistance/sensitivity to adjuvant ET therapy in luminal breast cancer from the GEICAM/2014-03_RegistEM registry.

1011 Background: Patients (pts) with hormone receptor-positive (HR) early breast cancer (BC) may develop resistance to adjuvant endocrine therapies (ET), with relapse occurring months (m) to decades after surgery. Our study explores clinical characteristics, prognosis, and oncogenic drivers in circulating tumor DNA (ctDNA) at relapse in HR+ BC pts, based on their sensitivity to adjuvant ET. Methods: In the REGISTEM study, we identified 805 primary HR-positive BC pts who developed metastatic relapse. These cases were classified based on their sensitivity to adjuvant ET, according to the 5th ESO-ESMO ABC Guidelines: 1ET-resistance (1ET-R, relapse within the first 2 years of adj ET; n=138), 2ET-resistance (2ET-R, relapse after the first 2 years or &lt;12 m after completing adj ET; n=284), and ET-sensitive (ET-S, relapse after &gt;12 m of completing adj ET; n=383). Out of this cohort, 139 individuals had plasma samples obtained prior to the initiation of the first-line treatment for advanced disease, and these samples were analyzed using the AVENIO ctDNA assay. Results: Pts with 1ET-R were significantly more likely to have grade 3, stage III, and highly proliferative tumors (Ki67&gt;20%). The median time to distant relapse was 24 m for 1ET-R, 52.8 m for 2ET-R, and 124 m for ET-S cases. For first-line treatment, the median PFS was 8.1 m for 1ET-R, 13 m for 2ET-R, and 21.2 m for ET-S relapse (p&lt;0.0001). With a median follow-up in the advanced setting of 34 m, median OS was 28 m for 1ET-R, 46 m for 2ET-R, and 55 m for ET-S relapses (p&lt;0.0001). Pts with ET resistance had more mutations (mut) and higher mut allele frequency than ET-sensitive relapse. Pts with ET resistance showed higher incidence of mut in TP53, ESR1, PTEN, andhigh copy number in EGFRand ERBB2 than ET-sensitive, but similar incidence of mut in PIK3CA.Mut in ESR1 and high copy number in EGFR were correlated with poorer PFS, while ESR1 mut were additionally associated with worse OS, although these associations were not independent of the ET relapse groups (Table). Furthermore, mut in PIK3CA were associated to worse PFS only in ET-R pts. Conclusions: In HR-positive BC, both primary and secondary resistance to adjuvant ET represents a highly aggressive disease with enriched actionable genetic alterations detected at the time of diagnosis of metastatic relapse. Addressing these alterations has the potential to mitigate the unfavorable prognosis associated with these cases. Clinical trial information: NCT02819882 .[Table: see text]

Evaluation of recurrence rate in Canadian patients with stage II/III HR+/HER2- early breast cancer in the real-world setting.

e23303 Background: Breast cancer is the most prevalent cancer and second leading cause of cancer-related mortality among Canadian women. Most of cases belong to the HR+/HER2- subtype, representing approximately two-thirds of all instances. Treatment for this subtype encompasses a multifaceted approach with a curative intent. This real-world evidence study aims to comprehensively analyze the clinical outcomes of Canadian patients diagnosed with early-stage HR+/HER2- breast cancer, focusing on recurrence rates after initiation of adjuvant endocrine therapy to identify opportunities for enhancing patient care. Methods: This is a retrospective, longitudinal cohort study involving 541 patients enrolled in the pan-Canadian cancer patient registry PMT (Personalize My Treatment), with newly diagnosed or recurrent stage II or III HR+/HER2- breast cancer between January 1st, 1996, and May 31st, 2022. We evaluated disease recurrence rates, time to recurrence, and overall survival (OS). Furthermore, the study explored duration of endocrine therapy (ET) in the adjuvant setting. Results: 409 patients received adjuvant ET representing 75.6% of the total cohort, emphasizing the role of ET as standard of care for adjuvant treatment in this patient population. The median duration of adjuvant ET was 4.5 years. In the overall adjuvant patient population, recurrence rates progressively increased over time from 13.2% after 2 years, 21.4% after 3 years, 30.3% after 5 years, and peaking at 58.4% after 10 years. Median time to recurrence for the overall patient population on ET was 7.76 years. OS rate for patients on ET was 94.6% at 5 years and 78.3% at 10 years. Conclusions: This study marks a pioneering real-world analysis utilizing pan-Canadian EHR data, demonstrating increasing recurrence rates over time in HR+/HER2- early breast cancer. It highlights the high unmet need in stage II and stage III breast cancer, with 1 patient out of 3 recurring after 5 years, and more than half recurring after 10 years despites adjuvant treatment with ET alone. This indicates the need for more efficacious and tolerable treatment options to reduce short- and long-term recurrence and to prolong survival, not only in the higher risk patient population, but in the overall HR+/HER2- breast cancer patients at increased risk of recurrence.