Survival Outcomes In Patients Research Articles

Optimizing pediatric liver transplantation: Evaluating the impact of donor age and graft type on patient survival outcome.

We examined the combined effects of donor age and graft type on pediatric liver transplantation outcomes with an aim to offer insights into the strategic utilization of these donor and graft options. A retrospective analysis was conducted using a national database on 0-2-year-old (N = 2714) and 3-17-year-old (N = 2263) pediatric recipients. These recipients were categorized based on donor age (≥40 vs <40 years) and graft type. Survival outcomes were analyzed using the Kaplan-Meier and Cox proportional hazards models, followed by an intention-to-treat (ITT) analysis to examine overall patient survival. Living and younger donors generally resulted in better outcomes compared to deceased and older donors, respectively. This difference was more significant among younger recipients (0-2 years compared to 3-17 years). Despite this finding, ITT survival analysis showed that donor age and graft type did not impact survival with the exception of 0-2-year-old recipients who had an improved survival with a younger living donor graft. Timely transplantation has the largest impact on survival in pediatric recipients. Improving waitlist mortality requires uniform surgical expertise at many transplant centers to provide technical variant graft (TVG) options and shed the conservative mindset of seeking only the "best" graft for pediatric recipients.

Longitudinal tracking of circulating rare events in the liquid biopsy of stage III–IV non-small cell lung cancer patients

In the United States, lung cancer is the second most common type of cancer with non-small cell lung cancer (NSCLC) encompassing around 85% of total lung cancer cases. Late-stage patients with metastatic disease have worsening prognosis, highlighting the importance of longitudinal disease monitoring. Liquid biopsy (LBx) represents a way for physicians to non-invasively track tumor analytes, such as circulating tumor cells (CTCs), and understand tumor progression in real-time through analyzing longitudinal blood samples. CTCs have been shown to be effective predictive biomarkers in measuring treatment efficacy and survival outcomes. We used the third-generation High-Definition Single Cell Assay (HDSCA3.0) workflow to analyze circulating rare events longitudinally during treatment in a cohort of 10 late-stage NSCLC patients, identifying rare events including circulating cancer cells (i.e., CTCs), and oncosomes. Here, we show (1) that there is a cancer specific LBx profile, (2) there is considerable heterogeneity of rare cells and oncosomes, and (3) that LBx data elements correlated with patient survival outcomes. Additional studies are warranted to understand the biological significance of the rare events detected, and the clinical potential of the LBx to monitor and predict response to treatment in NSCLC patient care.

The efficacy and safety of continuous intravenous infusion of rh-endostatin combined with platinum-based doublet chemotherapy for advanced non-small-cell lung cancer.

Platinum-based doublet chemotherapy is commonly used in the treatment of non-small cell lung cancer (NSCLC). A growing body of evidence indicates that incorporating antiangiogenic agents into platinum-based chemotherapy may enhance the survival outcomes for NSCLC patients. However, the optimal administration protocol for intravenous recombinant human endostatin (rh-endostatin), an antiangiogenic agent, remains uncertain at present. This study aims to investigate the efficacy and safety of 5-d continuous intravenous infusion of rh-endostatin in combination with chemotherapy for patients with advanced NSCLC. The predictive biomarkers for this treatment regimen were further probed. This prospective, single-arm multicenter study enrolled a total of 48 patients with advanced NSCLC who were histologically or cytologically confirmed but had not received any prior treatment from January 2021 to December 2022. Prior to the chemotherapy, these patients received a continuous intravenous infusion of rh-endostatin (210mg) over a period of 120h, using an infusion pump. The chemotherapy regimen included a combination of platinum with either pemetrexed or paclitaxel, given in 21-day cycles. The primary endpoint of the study was median progression-free survival (mPFS), and the secondary endpoints included median overall survival (mOS), objective response rate (ORR), disease control rate (DCR), and assessment of adverse events (AEs). The mPFS was 6.5 months (95% confidence interval (CI): 3.8-9.1m) while the mOS was 12.3 months (95% CI: 7.6-18.5m). The ORR and DCR was 52.1% and 75.0%, respectively. Leukopenia (52.1%), anemia (33.3%), and thrombocytopenia (20.8%) were the most common adverse effects and these toxicities were deemed acceptable and manageable. In addition, a correlation was noted between elevated serum carcinoembryonic antigen (CEA) levels and decreased PFS and OS. The incorporation of a 5-day continuous intravenous infusion of rh-endostatin into platinum-based doublet chemotherapy has demonstrated both safety and efficacy in the treatment of advanced NSCLC. Furthermore, the baseline serum levels of CEA may potentially function as a predictor for the efficacy of rh-endostatin when combined with chemotherapy in NSCLC patients. GOV: NCT05574998.

Abstract PO3-06-04: Clinical Features and Survival Outcomes of Oligometastatic Breast Cancer Patients: The Mayo Clinic Experience

Abstract Background The current definition, prognosis, and optimal treatment (tx) for oligometastatic breast cancer (OMBC) are not fully known. With advances in multimodality breast cancer (BC) tx and overall improvement in patient (pt) outcomes, it is important to identify baseline pt factors that confer better prognosis in OMBC and assess the impact of local/regional tx and metastasis (mets)-directed tx on survival outcomes. Methods We reviewed 105 Mayo Clinic pts with OMBC (up to 5 mets) from 2003 to 2021. Pts were excluded from analysis if they were misidentified as having OMBC (n=6), did not have a primary breast mass (n=1), developed de novo BC during tx (n=1), or were lost to follow up (n=2). Categorical variables were summarized as counts. Continuous variables were reported as medians. Kaplan-Meier method was used to estimate survival and the time from diagnosis to next tx at 1, 3, and 5 years. Log-rank test was used to compare survival rates between baseline factors. Univariate Cox proportional hazards models were performed on both baseline and time-dependent factors. All tests were two-sided with p-value &amp;lt; 0.05 considered statistically significant. Results Total pts included were 95. Median age was 49 (range, 26-86), most (93.6%) pts were White, and 46.8% were postmenopausal. Invasive ductal carcinoma (89.5%) was the most common BC type. Median survival was 10.8 years; 1-, 3-, and 5-year survival rates were 98.9%, 87.7%, and 81%, respectively. 58 pts (61.1%) required a change in tx due to disease progression. No significant survival difference was observed in pre- vs. postmenopausal pts (p=0.71) or in groups based on hormone receptor and/or human epidermal growth factor receptor 2 status. 47 pts (49.5%) received local/regional tx; no significant difference in survival (HR 0.57, 95% CI 0.23-1.40; p=0.217) or time to next tx (HR 0.67, 95% CI 0.39-1.15; p=0.144) was seen in this subgroup. Of these pts, 36 (76.6%) received neoadjuvant chemotherapy and/or immunotherapy, 5 of whom (10.6%) also started endocrine tx preoperatively. Overall, 11/47 pts (23.4%) received neoadjuvant endocrine tx. 20 pts received systemic tx without eventual surgery, and 5 pts got palliative radiation (RT). Biopsy-confirmed mets were noted in 76 pts (80%), with bone-only mets in 50%, 30 pts (31.6%) with viscera-only mets and 7 pts (7.4%) with both bone and visceral mets. 18 pts had suspected mets on imaging but did not undergo biopsy. The hazard of death was 6.34 times higher in pts with both bone and visceral mets than those with bone-only mets (p=0.008). Pts with viscera-only mets had higher survival at 2 and 3 years than pts with bone-only or both bone and visceral mets (p=0.093). Pts with 3 mets (7/76, 7.4%) had decreased survival at 1, 2, and 3 years compared to pts with 1-2 (65/76, 85.5%) mets (p=0.6). 67 pts (70.5%) received mets-directed tx; RT alone was the most common modality (52/67, 77.6%), followed by surgery (6/67, 9%), RT plus surgery (5/67, 7.5%), and ablation alone (3/67, 4.5%). There was no significant difference in survival (HR 1.27, 95% CI (0.53, 3.07), p=0.589) or time to next tx (HR 0.95, 95% CI (0.56, 1.63), p=0.856) in pts who received mets-directed tx. Multivariate analysis was not performed because most findings were not statistically significant in univariate analysis. Conclusions We did not find any significant differences in survival based on characteristics like menopausal status or site or number of mets in pts with OMBC. There was a trend toward improved survival in pts with viscera-only mets, but this finding requires validation. Local/regional and mets-directed tx did not improve survival; however, survival at 1, 3, and 5 years was excellent in this OMBC pt population. Our study was limited by low pt numbers and heterogeneity in the pt population. Findings need validation in larger studies. Citation Format: Tanmayi Pai, Raza Zarrar, Zhongwei Peng, Zhuo Li, Lauren Cornell, Kostandinos Sideras, Rohit Rao, Alvaro Moreno-Aspitia, Saranya Chumsri, Sarah McLaughlin, James Jakub, Emmanuel gabriel, Sanjay Bagaria, Laura Vallow, Santo Maimone, Pooja Advani. Clinical Features and Survival Outcomes of Oligometastatic Breast Cancer Patients: The Mayo Clinic Experience [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-06-04.

Abstract PO4-16-06: From Real-World Data to Improved Outcomes: Examining the Impact of Trastuzumab Disparities on Pathological Complete Response and Long-Term Survival in HER-2 Positive Breast Cancer Patients within the Brazilian Public Health System

Abstract Introduction: Equitable access to healthcare is a fundamental principle of public health, aiming to ensure that all individuals have the opportunity to receive effective treatments. However, disparities in access to healthcare still persist in many countries, including Brazil. These disparities can have significant impacts on the health and well-being of patients, particularly in the case of breast cancer treatment. Neoadjuvant chemotherapy (NAC) has been increasingly used for the treatment of breast cancer, encompassing conditions ranging from locally advanced tumors to early-stage triple-negative and HER-2 positive tumors. Objectives: The aim of this study is to evaluate the impact of disparities in the use of trastuzumab (Herceptin) within the Brazilian public health system on pathological complete response (pCR), overall survival (OS), and disease-free survival (DFS). We aim to investigate whether variations in access to trastuzumab treatment influence the achievement of pCR and impact long-term survival outcomes in breast cancer patients. Methods: This retrospective, multicenter cohort study included female patients over 18 years of age with a diagnosis of non-metastatic breast cancer undergoing NAC. pCR was defined as the absence of residual invasive or in situ tumor in the breast and axilla. As an exploratory real-world data study, no confirmatory hypothesis was established, thus no corrections for multiple comparisons were necessary. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method, calculated at five years. The study was approved by the Research Ethics Committee with registration number CAAE 64633422.4.0000.5463. Results: Between 2011 and 2020, a total of 1,891 patients were included in the study, of whom 454 (22.9%) were HER-2 positive. The pCR rate was 25.7%. Trastuzumab was accessed by 291 (64.1%) patients (p &amp;lt; 0.001). Among those who received trastuzumab, pCR was observed in 105 (36.1%) patients, compared to 12 (7.6%) in those who did not have access to trastuzumab (p &amp;lt; 0.001). OS in HER-2 positive patients was 90.1% with pCR and 64.5% without pCR (log-rank p &amp;lt; 0.001), while DFS was 89.2% with pCR and 68.2% without pCR (log-rank p = 0.003). Evaluating OS and DFS in patients who received trastuzumab versus those who did not, OS with trastuzumab and pCR was 94.3% and without pCR was 89.5% (log-rank p &amp;lt; 0.001); OS without trastuzumab and pCR was 83.3% and without pCR was 58.2% (log-rank p &amp;lt; 0.001). DFS in patients who received trastuzumab and achieved pCR was 94.5% and without pCR was 90.5% (log-rank p = 0.05), whereas without trastuzumab and pCR was 79.9% and without pCR was 62.1% (log-rank p = 0.001). Conclusion: These findings underscore the significant impact of disparities in trastuzumab utilization within the Brazilian public health system on pCR rates and long-term survival outcomes in HER-2 positive breast cancer patients. Access to trastuzumab was associated with higher pCR rates and improved overall and disease-free survival rates. Ensuring equitable access to targeted therapies is crucial for improving treatment response and long-term outcomes in breast cancer patients. Table 1 Clinicopathological characteristics of patients Legend: AJCC, American Joint Committee on Cancer; IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma; HR hormonal receptor. Table 2 - NAC schemas and correlation with pCR. AC-T, doxorubicin + cyclophosphamide – taxane; AC-TH, doxorubicin + cyclophosphamide – taxane+herceptin. Citation Format: Marcelo Antonini, Andre Mattar, Gabriel Pannain, Fernanda Grace Bauk Richter, Andressa Amorim, Marina Diogenes, Odair Ferraro, Luiz Gebrim, Reginaldo Coelho Lopes, Juliana Real. From Real-World Data to Improved Outcomes: Examining the Impact of Trastuzumab Disparities on Pathological Complete Response and Long-Term Survival in HER-2 Positive Breast Cancer Patients within the Brazilian Public Health System [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-16-06.

KDM7A-DT induces genotoxic stress, tumorigenesis, and progression of p53 missense mutation-associated invasive breast cancer

Stress-induced promoter-associated and antisense lncRNAs (si-paancRNAs) originate from a reservoir of oxidative stress (OS)-specific promoters via RNAPII pausing-mediated divergent antisense transcription. Several studies have shown that the KDM7A divergent transcript gene (KDM7A-DT), which encodes a si-paancRNA, is overexpressed in some cancer types. However, the mechanisms of this overexpression and its corresponding roles in oncogenesis and cancer progression are poorly understood. We found that KDM7A-DT expression is correlated with highly aggressive cancer types and specific inherently determined subtypes (such as ductal invasive breast carcinoma (BRCA) basal subtype). Its regulation is determined by missense TP53 mutations in a subtype-specific context. KDM7A-DT transcribes several intermediate-sized ncRNAs and a full-length transcript, exhibiting distinct expression and localization patterns. Overexpression of KDM7A-DT upregulates TP53 protein expression and H2AX phosphorylation in nonmalignant fibroblasts, while in semi-transformed fibroblasts, OS superinduces KDM7A-DT expression in a TP53-dependent manner. KDM7A-DT knockdown and gene expression profiling in TP53-missense mutated luminal A BRCA variant, where it is abundantly expressed, indicate its significant role in cancer pathways. Endogenous over-expression of KDM7A-DT inhibits DNA damage response/repair (DDR/R) via the TP53BP1-mediated pathway, reducing apoptosis and promoting G2/M checkpoint arrest. Higher KDM7A-DT expression in BRCA is associated with KDM7A-DT locus gain/amplification, higher histologic grade, aneuploidy, hypoxia, immune modulation scores, and activation of the c-myc pathway. Higher KDM7A-DT expression is associated with relatively poor survival outcomes in patients with luminal A or Basal subtypes. In contrast, it is associated with favorable outcomes in patients with HER2+ER- or luminal B subtypes. KDM7A-DT levels are coregulated with critical transcripts and proteins aberrantly expressed in BRCA, including those involved in DNA repair via non-homologous end joining and epithelial-to-mesenchymal transition pathway. In summary, KDM7A-DT and its si-lncRNA exhibit several intrinsic biological and clinical characteristics that suggest important roles in invasive BRCA and its subtypes. KDM7A-DT-defined mRNA and protein subnetworks offer resources for identifying clinically relevant RNA-based signatures and prospective targets for therapeutic intervention.

Abstract PO1-05-11: Efficacy of metformin as adjunctive therapy in patients with de novo metastatic breast cancer: a retrospective cohort study

Abstract Background: Metformin, an oral biguanide used for the treatment of type-2 diabetes mellitus (DM), has been shown in a considerable number of studies to have an anti-tumorigenic impact against breast cancer cells through several mechanisms,thereby improving breast cancer outcomes. However, the impact of metformin treatment on survival outcomes in patients with non-diabetic breast cancer is still under debate, with very few data available regarding metformin administration in de novo metastatic breast cancer (dnMBC). This study was conducted to investigate and evaluate the impact on survival outcomes of patients with dnMBC treated with metformin as adjunctive therapy at our institutes. Methods: All dnMBC women who received chemotherapy-based systemic therapy or combined with metformin administered orally in our hospitals between March 2007 and November 2016 were enrolled in the study. Data were retrospectively extracted from the patients’case records. Data were analyzed according the clinicopathological features and treatment outcomes. All specimens were rechecked for the purpose of the research. Overall survival (OS), as the study endpoint, was defined as the time from pathologically confirmed diagnosis to all-cause death or end of the follow-up time.Kaplan-Meier estimate was used to calculate the survival rates.The difference between metformin and non-metformin groups was compared by the log-rank method.Cox regression analysis (uni-and multivariate analysis) was used to assess the effect of variables on survival outcomes.Analyses were performed by Stata 17 software for windows version. Results: A total of 252 women with dnMBC were included with an average age of 54.41±11.61 years. Among them, 97 patients (including 11 DM patients) received chemotherapy-based systemic therapy plus oral administration of metformin 850-1000mg twice daily (metformin group), and 155 patients received chemotherapy-based systemic therapy (non-metformin group). There was no significant difference in body mass index, age, N-stage, P53 index, ER/PR status, HER-2 expression and initial metastatic sites between metformin group and non-metformin group. But there were differences in T-stage and Ki67 index between the two groups (Table 1). The median follow-up was 70 months.The median OS was 24 months.The 3-year and 5-year OS rates for all patients were 29.8% (95% CI:24.2% to 35.4%) and 11.6% (95% CI:7.5% to 16.7%),respectively; Log-rank test showed that the metformin group had a significant advantage over the non-metformin group in OS rates(p=0.0002).The 3-year and 5-year OS rates in the metformin group were 42.3% (95% CI:32.4% to 51.8%) and 21.2% (95% CI:12.8% to 31.1%), respectively; the same rates for non-metformin group were 21.9% (95% CI: 15.8% to 28.7%) and 5.6% (95% CI: 2.4% to 11.1%), respectively. Results of proportional hazards model, after adjustment for T-stage and Ki67 index, depicted an independent prognostic value of metformin use with multivariate hazard ratio of 0.61 (95% CI: 0.45 to 0.81) for OS compared to non-metformin group (p=0.001).No survival advantage was found for DM patients (0.59;95% CI:0.29 to 1.22; p=0.159). Conclusions: Our data support a favorable outcome for survival associated with metformin use in dnMBC patients. However, the retrospective nature and small sample size of the current study are major limitations to reliable conclusions about metformin's potential to improve OS in patients. Therefore, prospective evidence from phase-3 randomized controlled trials on the feasibility of metformin use in dnMBC is required before its routine use can be recommended. Keywords: Metformin; De novo metastatic breast cancer; Adjunctive therapy; Survival outcomes Citation Format: Ren Chongxi, Sun Jianna, Kong Lingjun, Hongjun Yu. Efficacy of metformin as adjunctive therapy in patients with de novo metastatic breast cancer: a retrospective cohort study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-05-11.

Abstract PO3-05-09: The impact of body mass index on CDK4/6 inhibitor treatment survival outcomes in metastatic breast cancer

Abstract Introduction: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) are important in the treatment of hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (MBC). Previous studies have shown that CDK4/6is affect metabolic processes and cell metabolism, including adipogenesis, lipid synthesis, and glucose regulation. Obesity has been associated with worse survival in breast cancer. We aimed to assess the effect of body mass index (BMI) on survival outcomes in patients treated with CDK4/6is for MBC. Methods: Patients diagnosed with metastatic HR+/HER2-negative BC and who were treated with palbociclib, ribociclib, or abemaciclib from 6/10/2015 to 12/28/2022 were selected from the Montefiore Health system database and followed until 3/24/2023. The patients were divided into three groups according to BMI level as follows; normal: 18.5-24.9 kg/m2, overweight: 25-29.9 kg/m2 and obese: ≥ 30 kg/m2. Patients were also stratified by BMI measured after 3 months of therapy. Characteristics of the patients and tumors in the subgroups were compared using chi-squared/Fisher’s exact test for categorical data and Kruskal-Wallis/Wilcox signed rank tests for continuous data. Kaplan-Meier and Cox proportional hazards analysis were used to compare overall survival (OS) and progression free survival (PFS). Results: Among 221 patients, 66 were normal weight, 78 were overweight, and 77 were obese. There was no statistically significant difference in clinicopathological characteristics among the cohorts. Neither BMI measured at baseline nor after 3 months of therapy had any association with OS (P = 0.8 at baseline and P = 0.1 after 3 months) or PFS (P = 0.4 at baseline and P = 0.6 after 3 months). Multivariable analysis showed no statistically significant association between BMI and worse OS (HR: 1.1 for overweight, P = 0.7; and 0.96 for obese, P = 0.9) or worse PFS (HR: 0.9 for overweight, P = 0.8; and 0.76 for obese, P = 0.5). Multivariate analysis revealed a significant effect of obese BMI after 3 months of treatment on OS (HR: 0.48, P = 0.035) but not on PFS (HR: 0.88, P = 0.8). Overweight BMI after 3 months of treatment was not found to have a significant effect on OS (HR: 0.49, P = 0.063) or PFS (HR: 0.89, P = 0.9). Conclusion: The clinical effectiveness of CDK4/6is was not found to be influenced by BMI measured prior to therapy; however, there may be an association between improved OS and obese BMI after 3 months of treatment. Median OS and PFS in patients with MBC comparing different BMI groups (normal, overweight, and obese) at baseline prior to therapy and after 3 months of therapy. Table 1 Baseline characteristics of patients with MBC comparing different BMI groups (normal, overweight, and obese) at baseline prior to therapy and after 3 months of therapy. Table 2 Table 3 Multivariable analysis of OS and PFS for patients with MBC comparing different BMI groups (normal, overweight, and obese) at baseline prior to therapy and after 3 months of therapy. Citation Format: Frank Zhang, Jesus Anampa Mesias. The impact of body mass index on CDK4/6 inhibitor treatment survival outcomes in metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-05-09.

Abstract PO1-01-08: The impact of drug-drug interactions between palbociclib and proton pump inhibitors on clinical outcomes of patients with hormone receptor positive, HER2-negative, early breast cancer: an exploratory analysis of the PALLAS study

Abstract Background: Data suggest that concomitant intake of proton pump inhibitors (PPI) may create drug-drug interactions, potentially impacting efficacy of agents including palbociclib, which is widely used in the treatment of metastatic hormone-receptor-positive/HER2-negative (HR+/HER2-) breast cancer. In the open label, randomized, phase 3 PALLAS trial, the addition of palbociclib for two years to standard adjuvant endocrine therapy (ET) in patients with HR+/HER2- early breast cancer (EBC) did not improve invasive disease-free survival (IDFS) compared to adjuvant ET alone. We explored whether concomitant use of PPIs could have affected clinical outcomes in patients treated with palbociclib in PALLAS. Methods: This is an exploratory, unplanned analysis of the PALLAS trial (AFT-05/ABCSG-42/PrE0109/BIG-14-13, NCT02513394), which enrolled 5796 patients with stage II-III HR+/HER2- EBC. Patients were randomized to receive either 2 years of palbociclib (125 mg oral capsules once daily on days 1-21 of a 28-day cycle) with adjuvant ET or ET alone. Primary endpoint was IDFS in the intention-to-treat population. The present exploratory analysis included patients who received at least one dose of palbociclib. Definitions of IDFS, distant relapse-free survival (DRFS) and overall survival (OS) were according to the PALLAS protocol (STEEP criteria), using first day of palbociclib intake as start date. Only PPI concomitant intake during palbociclib treatment was considered. To determine the association of concomitant PPI use with IDFS, DRFS, and OS, uni- and multivariable Cox models with time-dependent PPI (the latter adjusted for age, prior chemotherapy, progesterone receptor, grade, tumor stage, nodal stage, body mass index (BMI)) were used. Also, the association between PPI use and neutropenia was investigated in patients initiating PPI prior to randomization vs never. Odds ratios (OR) unadjusted and adjusted for age and BMI estimated with logistic regression models are reported. Results: Of 2840 patients treated with palbociclib + ET, 533 (18.8%) had concomitant PPI and palbociclib intake. Median duration of PPI intake was 10.8 months (interquartile range 2.3-22.3). Most patients received omeprazole as PPI (n=265, 49.7%). PPI intake was significantly associated with older age, post-menopausal status, use of aromatase inhibitors as ET, higher BMI, and worse ECOG status (all p&amp;lt; 0.001). Concomitant PPI intake was not significantly associated with survival outcomes (Table 1). Unadjusted all grade neutropenia rates were slightly lower in patients who initiated PPI prior study start vs patients never initiating (79% vs 85%, unadjusted OR 0.66, 95%CI 0.50-0.88). After adjustment for BMI and age, the difference between the groups decreased (adjusted OR = 0.77, 95%CI 0.57-1.04). Similar effect sizes were found for grade 3/4 neutropenia rates (54% vs 64%, unadjusted OR 0.66, 95%CI 0.52-0.83, adjusted OR 0.81, 95%CI 0.64-1.03). Conclusions: Our exploratory analysis did not demonstrate a statistically significant relationship between concomitant use of PPIs and palbociclib and survival outcomes of patients in the PALLAS trial. Nonetheless, careful consideration of concomitant medications and of drug-drug interactions is important when studying novel agents in the adjuvant breast cancer setting. Support: AFT, Pfizer; https://acknowledgments.alliancefound.org Table 1. Association between PPI intake and survival outcomes. Citation Format: Elisa Agostinetto, Georg Pfeiler, Dominik Hlauschek, Erica Mayer, Matteo Lambertini, Evandro de Azambuja, Meritxell Bellet- Ezquerra, Jane Meisel, Gabor Rubovszky, Nicholas Zdenkowski, Yelena Novik, Manuel Ruíz - Borrego, Karen Gelmon, Eleftherios Mamounas, Hiroji Iwata, Dongrui Lu, Lidija Sölkner, Christian Fesl, Michael Gnant, Angela DeMichele. The impact of drug-drug interactions between palbociclib and proton pump inhibitors on clinical outcomes of patients with hormone receptor positive, HER2-negative, early breast cancer: an exploratory analysis of the PALLAS study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-01-08.

Abstract PO5-05-01: ASSESING THE CLINICAL AND SURVIVAL RESULTS OF PATIENTS WITH HR-POSITIVE, HER2 NEGATIVE ADVANCED BREAST CANCER TREATED WITH CDK 4/6 INHIBITORS IN A SPANISH COHORT

Abstract BACKGROUND First line treatment of HR-positive, HER2 negative advanced breast cancer is based on endocrine therapy plus CDK 4/6 inhibitors (CDK 4/6i). Recently, there has been published in ASCO 2023 results from SONIA trial, which explores the use of CDK 4/6i in second-line treatment after monotherapy with endocrine therapy. This trial have shown using a CDK4/6i in the first-line setting did not significantly prolong the time from random assignment to progression on second-line therapy (PFS2) or overall survival (OS) when compared with deferred use until the second-line setting. METHODS We conducted a descriptive, observational and retrospective analyses of patients treated in our centre with CDK4/6i, comparing demographic, clinical and survival results. We also analysed different outcomes between first versus second line CDK4/6i. RESULTS A cohort of 153 patients were included, treated between January 2018 and June 2023, with a median age of 50 years. At diagnosis, 49% were stage I-II and 31% stage IV. 59% had visceral metastases at the start of CDK4/6i treatment. Palbociclib was the most commonly CDK4/6i used (55%), followed by Ribociclib (32%) and Abemaciclib (12.5%). The most widely endocrine therapy used was letrozole (60%), followed by fulvestrant (38%). 58% received CDK4/6i in first-line setting while 9% received them in second-line. The overall median progression-free survival (mPFS) was 18 months. In a subgroup analysis, the mPFS was 19 months with Palbociclib, 26 months with Ribociclib, and 31 months with Abemaciclib. Baseline characteristics were similar between subgroups of CDK4/6i. Better survival data were obtained with letrozole than with fulvestrant (not reached versus 29 months OS respectively). After CDK4/6i disease progression the most common subsequent treatment was chemotherapy (capecitabine, 23%). The median OS with palbociclib and abemaciclib was 37 months, while not reached with ribociclib. We analysed PFS2 using CDK4/6i in the first-line setting compared with deferred use until the second-line. The use of CDK4/6i in second-line showed a PFS2 of 45 months, while first-line PFS2 was 26 months. CONCLUSIONS Our study results are consistent with previous studies assesing the efficacy of cyclin inhibitors in first and second-line setting. Palbociclib seems to have a lower PFS rate. Patients treated with letrozole had a stadistically significant benefit in survival outcomes. Our data continue the trend observed in the SONIA trial in terms of PFS2. Using endocrine therapy as first-line monotherapy may be a valid treatment option. However, larger sample sizes are required to draw definitive conclusions. The identification of potential predictors of treatment response may help in the selection of the most effective treatment for patients with HR-positive HER2 negative advanced breast cancer. Citation Format: Alicia Cano-Jimenez, Rocio Urbano-Cubero, Ruben Garcia-Muñoz, Ana Maria Jaen-Morago, Maria Lomas-Garrido, Pedro Sánchez-Rovira. ASSESING THE CLINICAL AND SURVIVAL RESULTS OF PATIENTS WITH HR-POSITIVE, HER2 NEGATIVE ADVANCED BREAST CANCER TREATED WITH CDK 4/6 INHIBITORS IN A SPANISH COHORT [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-05-01.

Deciphering the role of apoptosis signature on the immune dynamics and therapeutic prognosis in breast cancer: Implication for immunotherapy

Background: In breast cancer oncogenesis, the precise role of cell apoptosis holds untapped potential for prognostic and therapeutic insights. Thus, it is important to develop a model predicated for breast cancer patients’ prognosis and immunotherapy response based on apoptosis-related signature.Methods: Our approach involved leveraging a training dataset from The Cancer Genome Atlas (TCGA) to construct an apoptosis-related gene prognostic model. The model’s validity was then tested across several cohorts, including METABRIC, Sun Yat-sen Memorial Hospital Sun Yat-sen University (SYSMH), and IMvigor210, to ensure its applicability and robustness across different patient demographics and treatment scenarios. Furthermore, we utilized Quantitative Polymerase Chain Reaction (qPCR) analysis to explore the expression patterns of these model genes in breast cancer cell lines compared to immortalized mammary epithelial cell lines, aiming to confirm their differential expression and underline their significance in the context of breast cancer.Results: Through the development and validation of our prognostic model based on seven apoptosis-related genes, we have demonstrated its substantial predictive power for the survival outcomes of breast cancer patients. The model effectively stratified patients into high and low-risk categories, with high-risk patients showing significantly poorer overall survival in the training cohort and across all validation cohorts. Importantly, qPCR analysis confirmed that the genes constituting our model indeed exhibit differential expression in breast cancer cell lines when contrasted with immortalized mammary epithelial cell lines.Conclusion: Our study establishes a groundbreaking prognostic model using apoptosis-related genes to enhance the precision of breast cancer prognosis and treatment, particularly in predicting immunotherapy response.

Abstract PO1-09-11: Racial Differences in Pathologic Complete Response Rate and Overall Survival Following Neoadjuvant Chemotherapy for Breast Cancer

Abstract Background: Neoadjuvant chemotherapy (NAC) is increasingly used in the treatment of breast cancer and has been utilized in multiple clinical trials assessing the efficacy of novel therapies. Pathologic complete response (pCR) following NAC is associated with improved survival outcomes in breast cancer and pCR is a commonly used endpoint in clinical trials. Despite improvements in breast cancer survival using modern treatment regimens, Black women continue to experience worse survival outcomes as compared to White women. The objective of this study was to evaluate the association between race and clinical outcomes, specifically pCR rate, recurrence free survival and overall survival, in patients undergoing neoadjuvant chemotherapy at our institution. Methods: We conducted a retrospective review of patients who completed at least 75% of the recommended cycles of neoadjuvant chemotherapy for breast cancer between 2010 and 2016 and underwent surgery. Receptor subtypes were defined as HR+/HER2-negative, HER2+ or triple-negative. The association between race and pCR, defined as ypT0/ypTis ypN0, and survival endpoints of overall survival and recurrence free survival were analyzed using multivariable logistic regression and Cox proportional hazard models. Results: A total of 532 women met the inclusion criteria, 323 (60.7%) were White, 188 (35.3%) were Black and 21 (3.9%) were other/unknown. Median follow-up was 65 months. The receptor subgroups consisted of 195 (36.7%) HR+/HER2-negative cancers, 193 (36.3%) HER2+ cancers and 144 (27.1%) triple-negative cancers. No significant association between race and receptor subtype (p=0.55) or pre-treatment clinical stage (p=0.96) was observed. The overall observed pCR rate was 19% for Black patients and 27% for White patients, demonstrating a significantly different pCR rate by race in multivariate analysis (odds ratio of pCR White vs Black of 1.75; p=0.02). The largest discrepancy in pCR rate between White and Black patients was within subjects with triple-negative disease (pCR rate 44% White patients vs 27% Black patients, p=0.03). There was no association between recurrence free survival and race in univariate analysis (p=0.15). A significant difference in overall survival by race was observed using multivariable Cox proportions hazard model (hazard ratio Black vs White 1.77; p=0.03). Conclusions: In this retrospective analysis of patients receiving neoadjuvant chemotherapy, Black patients experienced a significantly lower pCR rate compared to White patients, with the biggest gap identified within triple-negative breast cancers. During the study period, Black patients also experienced a lower overall survival rate compared to White patients. Differences in the ability to achieve a pCR may be a contributing factor to the worse survival outcomes of Black patients. Citation Format: Chad Livasy, Erin Donahue, Brittany Neelands, Lejla Hadzikadic-Gusic, Terry Sarantou, Mckenzie Needham, Alicia Patrick, Arielle Heeke, Antoinette Tan, Richard White. Racial Differences in Pathologic Complete Response Rate and Overall Survival Following Neoadjuvant Chemotherapy for Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-09-11.

Abstract PO5-05-05: Clinical outcomes of CDK4/6 inhibitors in patients with bone only metastatic breast cancer

Abstract Background: CDK4/6 inhibitors (CDK 4/6i) have significantly advanced the treatment of hormone receptor-positive (HR+) metastatic breast cancer in the last decade. Several clinical trials including PALOMA, MONALEESA, and MONARCH have shown improved progression-free survival (PFS) rates when CDK4/6i were combined with endocrine therapy (ET). These results led to recommending their use in combination with ET as the first line of therapy in the metastatic settings. Bone metastasis is the most common site of disease in patients with HR+ metastatic breast cancer, about 40% of whom have bone as the only site of metastasis (bone-only disease [BoD]). While previous studies have shown that BoD can have a unique clinical course and a more favorable prognosis compared to non-BoD metastasis, most of the aforementioned CDK 4/6i clinical trials have not shown significant improvements in PFS in BoD subset of patients. Here we aimed to investigate the survival outcomes of BoD patients at a single institution center and evaluate CDK 4/6i activity in preclinical models of bone metastasis in breast cancer. Patients and methods: Patients with HR+, HER2-negative metastatic breast cancer from a retrospective CDK4/6i study at Washington University School of Medicine were included in this analysis. We selected all the patients who received CDK4/6i in the first- or second-line settings from June 2014 to March 2020. Outcomes were collected through June 10, 2023. The Kaplan-Meier method with log rank test and multivariable cox model were used for survival analysis. Results: 114 female patients (n=75 first line, n=39 second line, n=20 African American, n=94 Caucasian) were included in this study. All patients received Palbociclib as the first exposure to CDK4/6 inhibitor in combination with ET for at least two months. Median age was 60 years (range, 28-87) and forty-seven patients (41%) were in the BoD group. Survival outcomes for BoD group were compared to the rest of patients who had either bone and visceral or visceral only metastatic lesions (BV group). Our results demonstrated a significantly reduced median PFS in BoD group compared to BV group (13.1 months [95%CI:8-18.2] vs 19.6 months [95%CI:6.8-32.4], p=0.01) respectively. There was no significant difference in overall survival between BoD and BV groups (36.6 months [95%CI:32.2-41] vs 41.7 months [95%CI 36.1-47.2] p=0.74) respectively. In multivariate analysis regarding the associated risk factors with PFS, after adjusting for age and race, BoD had a HR of 1.62 (95%CI:1.04-2.54) for PFS. Among the 75 patients who received CDK4/6i as their first line of therapy, BoD (n=32 patients [42.7%]) also showed an inferior (p=0.05) median PFS (20 months [95%CI 12.9-27]) compared to BV group (n=43 patients [57.3%], median PFS=28.4 months [95%CI: 16.3-40.4]). To investigate potential treatment resistance mechanisms in bone metastases, we used the triple negative 4T1 and the ER+ luminal B PyMT Bo1 breast tumor cell line derived mammary gland models in immunocompetent mice. Single agent CDK4/6i, ribociclib, decreased primary mammary gland tumor burden. This effect was abrogated when CD8+ T-cells were depleted. In the bone colonization model using these cell lines, ribociclib had little effect on bone tumor burden. Arg1+ immune suppressive macrophages were significantly decreased in the primary mammary tumor but not in the bone tumor after ribociclib administration, suggesting a relative treatment resistance and immune suppression in the bone tumor microenvironment compared to the primary mammary gland. Conclusion: CDK4/6i play a significant role in the treatment of patients with HR+ metastatic breast cancer. Our single institution, retrospective study and preclinical data suggests that CDK4/6i may not be as effective for the treatment of tumors residing in the bone microenvironment, warranting future studies to understand the mechanisms of CDK4/6 inhibitors action in bone versus visceral metastases. Citation Format: Mahta Mardani, Suleyman Noordeen, Katherine Clifton, Cynthia Ma, Jingqin Luo, Jing Xi, Nusayba Bagegni, Foluso Ademuyiwa, Rama Suresh, Ashley Frith, Andrew Davis, Ron Bose, Lindsay Peterson, Shana Thomas, Yu Tao, Takayuki Kobayashi, Jingyu Xiang, Yalin Xu, Xinming Su, Katherine Weilbaecher. Clinical outcomes of CDK4/6 inhibitors in patients with bone only metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-05-05.

Survival After Contralateral Axillary Metastasis in Breast Cancer.

Despite stage IV categorization, survival outcomes for breast cancer patients who experience contralateral axillary lymph node metastasis (CAM) remain uncertain. This study aimed to investigate the clinical outcomes for patients with metachronous CAM to provide insights into its prognosis and treatment recommendations. This study retrospectively reviewed medical records of patients who underwent curative surgery for breast cancer and experienced CAM as the first site of distant metastasis (DM) during the follow-up period between January 2001 and April 2023. Survival outcomes of the CAM patients were compared with those of breast cancer patients with other DM via propensity score-matching (PSM). The study identified 40 breast cancer patients with metachronous CAM. The estimated 5-year overall survival (OS) was 39.6%, and the progression-free survival was 39.4%. The patients with CAM exhibited marginally better OS than the patients with DM (p = 0.071), but survival similar to that of the patients with isolated supraclavicular node recurrence (SCN) (p = 0.509). Moreover, matching of CAM with DM using two PSM models showed a consistently insignificant survival difference (hazard ratio [HR], 1.47; p = 0.124 vs. HR, 1.19; p = 0.542). Ipsilateral breast tumor recurrences (IBTRs) were experienced by 12 patients before or concurrently with the CAM. These patients exhibited significantly better survival than the remaining patients (HR, 0.28; p = 0.024). The breast cancer patients with CAM showed survival similar to that for the patients with DM, supporting the current stage IV classification of the CAM. However, CAM associated with IBTR exhibited superior survival outcomes, suggesting that this subset of CAM may benefit from treatments with curative intent.

Abstract PO3-15-10: Enhanced Cancer Cell Proliferation and Aggressive Phenotype Counterbalance in Breast Cancer with High BRCA1 Gene Expression

Abstract Introduction: It is estimated that 5–10% of all breast cancer cases have a hereditary component with BRCA1 mutation being one of the most frequently observed gene mutations in breast cancer patients. BRCA1 plays a crucial role in DNA repair, and its mutation has been extensively studied. However, the clinical significance of BRCA1 gene expression remains largely unexplored. Given that heightened DNA repair mechanisms can potentially increase cancer cell proliferation, we hypothesized that breast cancer with high BRCA1 gene expression might be associated with aggressive tumor biology and worse survival. Methods: The clinical, pathological and gene expression levels of a total of 6,245 breast cancer patients were analyzed from three large independent cohorts: METABRIC (n = 1,903), GSE96058 (n = 3,273), and The Cancer Genome Atlas (TCGA, n = 1,069). The data was retrieved through cBioPortal. The xCell algorithm was used to correlate the BRCA1 gene expression with the stromal and immune cell fractions infiltrating the tumor microenvironment (TME). Results: BRCA1 gene expression was higher in breast cancer patients without BRCA1 mutation, and it correlated with the DNA repair activity (p = 0.026 and p &amp;lt; 0.01 respectively), however, it did not correlate with BRCA2 gene expression (p = 0.38). Breast cancer with high BRCA1 gene expression was associated with cancer cell proliferation as evidenced by higher Nottingham histological grade (p &amp;lt; 0.001), Ki67 expression (p &amp;lt; 0.001), significant enrichment of cell proliferation-related gene sets such as E2F Targets, G2M Checkpoint, MYC Targets V1 and V2, Mitotic Spindle (all FDR &amp;lt; 0.25), and significantly less infiltration of stromal cells such as adipocytes, fibroblasts, microvascular and lymphatic endothelial cells, and pericytes (all p &amp;lt; 0.05). High BRCA1 gene expression was associated with higher homologous recombination deficiency, intratumor genomic heterogeneity, and fraction altered (all p &amp;lt; 0.001); however, there was no correlation observed with mutation rates or neoantigens. It was observed that breast cancer with high BRCA1 gene expression had less infiltration of CD8 T cells, dendritic cells, regulatory T cells, and B cells and had higher infiltration of Th1 cells (all p &amp;lt; 0.05). To our surprise, there was no significant difference in overall survival regardless of the subtypes (except for ER+/HER2- subtype in METABRIC cohort, p = 0.03). Breast cancer with low BRCA1 gene expression enriched cancer aggravating pathway gene sets such as Cancer Stem Cell-related signaling pathways (NOTCH and HEDGEHOG), Angiogenesis, Epithelial Mesenchymal Transition, Inflammatory Response, and TGF-beta signaling (all FDR &amp;lt; 0.25). Conclusion: Contrary to our initial hypothesis, we did not find any significant association between BRCA1 gene expression and survival outcomes in breast cancer patients. Based on the results of our study, we speculate that the interplay between enhanced cancer cell proliferation and aggressive tumor characteristics may counterbalance the effect of high BRCA1 expression in breast cancer. Citation Format: Kohei Chida, Masanori Oshi, Arya Mariam Roy, Itaru Endo, Kazuaki Takabe. Enhanced Cancer Cell Proliferation and Aggressive Phenotype Counterbalance in Breast Cancer with High BRCA1 Gene Expression [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-15-10.

Abstract PO4-02-08: Outcomes of patients treated with chemotherapy for breast cancer during pregnancy compared with non-pregnant breast cancer patients treated with systemic therapy

Abstract Introduction: Prior studies comparing outcomes of patients diagnosed with and treated for breast cancer during pregnancy (PrBC) with those of non-pregnant patients with breast cancer report mixed results. Data are sparse for PrBC patients treated with systemic therapy, who may be at risk for poorer outcomes owing to the need to modify regimens or delay initiation of teratogenic agents until the postpartum period. This study aims to compare survival outcomes of PrBC patients treated with chemotherapy during gestation versus matched non-pregnant breast cancer patients treated with systemic therapy. Methods: Pregnant women with non-metastatic, non-inflammatory breast cancer treated with chemotherapy during gestation on prospective institutional protocols from 1989-2022 were identified. Two non-pregnant patients selected from a departmental database were matched to each PrBC patient using coarsened exact matching based on age at diagnosis (&amp;lt; 30 years old, 30-35, &amp;gt;35), year of diagnosis (&amp;lt; 1997, 1997-2004, &amp;gt;2004), stage at diagnosis (I, II or III), hormone receptor (HR) status, and Human epidermal growth factor receptor 2 (HER2) status. Retrospective chart review was performed to update vital status and other clinical data. Overall survival (OS) was calculated from diagnosis until last known vital status and compared using the Kaplan-Meier method and log-rank test. Results: 167 PrBC patients were matched to 334 non-pregnant patients (Table 1). Median age at diagnosis was 33 years for both cohorts (IQR: PrBC, 6; non-pregnant 7). Other characteristics are shown in Table 1. Median time from diagnosis to initiation of chemotherapy or oncologic surgery was 25 days (IQR 27) for PrBC patients and 27 days (IQR 37) for non-pregnant patients (p=0.61). Anti-HER2 therapy was deferred to the postpartum period for PrBC patients, with median time from diagnosis to therapy initiation of 73 days (IQR 190) compared with 63 days (IQR 143) for non-pregnant patients (p=0.36). Median follow-up was 4.5 years (IQR 9.0) for PrBC patients and 5.8 years (IQR 7.5) for non-pregnant patients (p=0.27). At last follow-up, 128 PrBC patients (77%) and 222 non-pregnant patients (66%) were alive. Median OS was 24.1 years (95% CI 15.8-undefined) for PrBC patients and 14.0 years (95% CI 10.8-33.8) for non-pregnant patients. OS did not differ significantly between cohorts (p=0.12). Conclusion: This retrospective, matched cohort study suggests that PrBC patients treated with chemotherapy during gestation have comparable OS compared with non-pregnant breast cancer patients treated with systemic therapy, despite treatment modifications and delayed initiation of teratogenic agents. This is the largest reported cohort of PrBC patients treated with a standardized chemotherapy protocol during gestation and therefore adds valuable insight into outcomes of this uncommon presentation of breast cancer. Continued study is needed to determine whether longer-term outcomes are similar, particularly for patients with triple-negative breast cancer who did not receive immunotherapy during pregnancy. Table 1 Baseline characteristics Citation Format: Helen Johnson, Carla Warneke, Ashley Martinez, Jennifer Litton, Oluchi Oke. Outcomes of patients treated with chemotherapy for breast cancer during pregnancy compared with non-pregnant breast cancer patients treated with systemic therapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-02-08.

Abstract ED08-02: Next generation therapeutics in hormone positive breast cancer: balancing efficacy and tolerability

Abstract The past several years have brought a wealth of new and emerging novel agents for the management of both early and advanced hormone repcetor positive breast cancer, including inhibitors of PIK3CA, mTOR, AKT, CDK4/6, PARP, as well as oral SERDs. These agents have significantly improved survival outcomes for many patients, but progress may come at the cost of specific and sometimes challeging side effects, whcih may threaten the ability to keep a patient on a therapy that is providing benefit. We will review a spectrum of agents, the expected side effect profiles, and strategies to mitigate toxicity and maximize therapeutic index. Citation Format: E. Mayer. Next generation therapeutics in hormone positive breast cancer: balancing efficacy and tolerability [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr ED08-02.

Abstract PO4-27-03: Real-World Evidence: Impact of Margin Involvement on Overall Survival Following Breast Cancer Surgery – A Single-Center Analysis at Charité University Medical Center Berlin

Abstract Introduction: Limited data is available regarding the impact of margin involvement following surgery for early-stage breast cancer on distant recurrence and overall survival (OS). We therefore conducted a retrospective single-center analysis to provide further real-world evidence of margin status on OS. Methods: We systematically evaluated patients who underwent surgical intervention for early breast cancer or carcinoma in situ at Charité University Medical Center Berlin between 2006 and 2022. Our study cohort included individuals with a minimum follow-up period of 6 months and documented margin status. Patients with secondary tumors were excluded from this comprehensive analysis. Results: In our analysis, we included a total of 3767 patients, with a median follow-up duration of 72.2 months. Among these, 3443 patients underwent surgery for invasive breast cancer, while 324 patients underwent surgery for carcinoma in situ. The median overall survival (OS) for the entire cohort was 63.7 months. Specifically, patients who achieved clear margins after primary surgery exhibited a median OS of 63.5 months (n=3068), and those with free margins after secondary surgery had a median OS of 65.2 months (n=610). Conversely, patients with definitively involved margins experienced a shorter median OS of 58.6 months (n=89). The multivariate analysis revealed a statistical trend toward adverse survival outcomes for patients with definitive involved margins (Hazard Ratio 1.55; 95% CI: 0.93-2.56; p=0.090), with no statistically significant difference observed between clear margins following primary or secondary surgery. Notably, patients who underwent breast-conserving surgery demonstrated a significantly improved OS (HR 0.45; 95% CI 0.37-0.45; p&amp;lt; 0.001). Higher rates of margin involvement were observed in patients with hormone receptor-positive tumors and carcinoma in situ, while lower rates were noted in triple-negative breast cancer and after neoadjuvant chemotherapy. Implication: Our findings suggest that involved margins may be associated with a limited overall survival. Notably, patients who underwent breast-conserving therapy exhibited more favorable outcomes in our analysis, underscoring the oncologic safety of this procedure. Citation Format: Maximilian Heinz Beck, Karoline Weiler, Sophia Ossmann, Verena Kiver, Jens-Uwe Blohmer. Real-World Evidence: Impact of Margin Involvement on Overall Survival Following Breast Cancer Surgery – A Single-Center Analysis at Charité University Medical Center Berlin [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-27-03.

Abstract PS18-07: Trends in Guideline Concordant Care for Inflammatory Breast Cancer: An analysis of the National Cancer Database

Abstract Background: Inflammatory breast carcinoma (IBC) is an aggressive form of breast cancer associated with worse survival outcomes compared with other subtypes of breast cancer. Black patients with IBC have worse survival outcomes than White patients. Trimodality treatment (TMT) which includes neoadjuvant chemotherapy (NCT) followed by modified radical mastectomy without immediate reconstruction (MRM), and postmastectomy radiotherapy (PMRT), has been associated with improved survival outcomes for patients with IBC. Whether receipt of TMT varies by race, ethnicity, and insurance status and its impact on survival is largely unknown. Methods: Adult female patients with non-metastatic IBC treated from 2010-2018 were identified from the NCDB. Guideline concordant care (GCC) was defined as TMT administered in the correct sequence. In addition, clinical tumor/nodal stage, age, race, ethnicity, facility type, patient location, insurance status, and pathologic complete response (pCR) were examined for each patient. Additional quality metrics of GCC examined included time to initiation of NACT &amp;lt; 60 days (TTNC) and proper surgical care defined as complete axillary lymph node dissection (&amp;gt;6 lymph nodes removed) at the time of MRM without reconstruction. Univariate and multivariate mixed methods were performed to determine association between patient, treatment, and facility-level factors and receipt of GCC, TTNC &amp;lt; 60 days, and proper surgical care. OS was estimated using the Kaplan-Meier method, and the log-rank test was used to compare groups. Results: 7,374 women with non-metastatic IBC were included. 78% were White, 17% Black, and 2.5% Asian/Pacific Islander patients; 7.7% identified as Hispanic and 92% as non-Hispanic. The majority had private insurance (51%), 29% Medicare, 14% Medicaid, 4.9% uninsured, and 1.3% other government insurance.Only 2,418 patients (32.7%) received GCC with only 29% undergoing MRM without reconstruction.Receipt of GCC was more common among patients age &amp;gt;50 years, patients with higher clinical nodal burden and those treated from 2010-2013 (p=0.001).Receipt of GCC did not differ by race, ethnicity, insurance status, or location.92% (6,005/7,374 patients) received NAC within 60 days of diagnosis. Both Black (OR 0.58, 95% CI 0.46-0.74, p= &amp;lt; 0.001) and Asian (OR 0.52, 95% CI 0.30-0.90, p= &amp;lt; 0.001) patients with IBC were less likely to have TTNC &amp;lt; 60 days when compared to White patients. Non-Hispanic patients (OR 2.24, 95% CI 1.65-3.03, p= &amp;lt; 0.001) and those with private insurance (OR 1.82, 95% CI 1.23-2.68, p= &amp;lt; 0.001) were more likely to have TTNC within 60 days of diagnosis. Patients with lower clinical nodal burden(cN0) were less likely to undergo proper surgery compared to patients with higher nodal burden(cN1-3) (p &amp;lt; 0.001). In addition, patients treated in a more contemporary cohort (2014-2018) were less likely to undergo proper surgery compared to patients treated earlier (2010-2013) (OR 0.82, 95% CI 0.73-0.92, p&amp;lt; 0.001).Among IBC patients receiving GCC, Black patients had significantly worse overall survival compared to White patients (p &amp;lt; 0.001) Conclusions: The majority of patients with IBC do not receive GCC and GCC has decreased since 2014 with fewer patients undergoing appropriate surgical treatment. The very low level of GCC indicates a need for multidisciplinary education, while improvement in TTNC may improve outcomes among racial/ethnic minorities. Citation Format: Brian Diskin, Audree Tadros, Varadan Sevilimedu, Amy Xu, Perri Vingan, Jonas Nelson, Yoshiko Iwai, Monica Morrow, Oluwadamilola (Lola) Fayanju. Trends in Guideline Concordant Care for Inflammatory Breast Cancer: An analysis of the National Cancer Database [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS18-07.

Abstract PO5-02-13: Distinct differences in the prognostic implication of tumor size for invasive lobular carcinoma of breast when compared to invasive ductal carcinoma

Abstract Purpose Invasive lobular carcinoma (ILC) is the second common types of breast cancer and its clinicopathological feature and outcomes differ from invasive ductal carcinoma (IDC). However, in terms of survival outcomes, there are conflicting data on the prognostic implication of the ILC when compared to that of IDC. This study aims to evaluate the survival outcomes of patients diagnosed with ILC at single center and compared them with those of IDC. Methods We reviewed the data of the 13,034 IDC patients and 935 ILC patients who were treated between January 2005 and December 2022 at Seoul National University Hospital. We investigated the overall treatment outcomes of two histologic types with a special focus on the tumor size and lymph nodes. Result ILC exhibited distinct characteristics compared to IDC, including a larger tumor size (2.6 ± 1.8 vs. 1.9 ± 1.1 cm, p &amp;lt; 0.001) and a higher hormone receptor positivity (97.4% vs. 79.3%, p &amp;lt; 0.001). Additionally, the presence of lymphovascular emboli was lower in ILC (8.0% vs. 24.6%, p &amp;lt; 0.001). While IDC patients showed slightly better overall survival (OS) than ILC (10-year OS, ILC 89.9% vs. IDC 91.1%, the difference was not statistically significant (p = 0.85). However, distant metastasis-free survival (DMFS) was significantly higher in ILC (10-year DMFS, ILC 93.2% vs. IDC 89.9%, p = 0.001). Age at diagnosis, tumor size, presence of lymphovascular emboli, high expression of Ki-67, and higher pathologic N stage were poor prognostic markers for ILC. Multivariate analysis for DMFS showed that age, high expression of Ki-67 and higher pathologic N stage were poor prognostic markers for ILC. Tumor size was not an independent prognostic factor for DMFS (HR: 0.92, 95% CI: 0.72-1.17, p = 0.491) and for OS (HR: 1.18, 95% CI: 0.99-1.41, p = 0.060) in ILC. Conclusion Our data suggest that the tumor size, which is a well-known prognostic factor in IDC, carries distinctly different prognostic implication in ILC. These observation indicate that adjuvant treatment decisions based on tumor size can be tailored to different histologic subtypes of breast cancer. Citation Format: Ik Beom Shin, Eunhye Kang, Ji-Jung Jung, Hawjeong Lee, Jin Young Byeon, Yunhee Choi, Changjin Lim, Jong-Ho Cheun, Hong-Kyu Kim, Han-Byoel Lee, Wonshik Han, Hyeong-Gon Moon. Distinct differences in the prognostic implication of tumor size for invasive lobular carcinoma of breast when compared to invasive ductal carcinoma [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-02-13.