bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical meaning of stromal tumor infiltrating lymphocytes (sTIL) in luminal early breast cancer.
Authors: García-Torralba Esmeralda , Ivars-Rubio Alejandra , Perez-Ramos Miguel , Navarro Manzano Esther , Blaya-Boluda Noel , de la Morena Barrio Pilar , Garcia-Garre Elisa , Marin Zafra Gema , Martinez-Diaz Francisco , Gomez Martinez Francisco , Lopez-Robles Javier , Alvarez Abril Beatriz , Garcia Martinez Elena , Ayala Francisco 
Published: June 2023

572 Background: Luminal breast cancer (BC) is associated with lower immune activation. Although stromal tumor infiltrating lymphocytes (sTIL) are a marker of better prognosis and response in hormone receptor (HR) negative tumors, sTIL predictive and prognostic implications are less clear in luminal BC. Further insights on the clinical correlations of immune microenvironment in luminal disease may facilitate therapeutic improvement and prognostic stratification in these patients. Methods: Observational and single-center cohort of 345 women with early luminal (HR positive, HER2 negative) BC (2012-2020) treated with chemotherapy. Pre-treatment sTIL were determined in the diagnostic biopsy following validated standard methods. The correlation between sTIL and other tumor characteristics were analyzed (Spearman's Rho and Chi-squared tests). Association of sTIL with pathologic complete response (pCR) in patients treated with neoadjuvant chemotherapy (nCT) was evaluated with logistic regression models. Prognostic value of sTIL for overall (OS) or relapse free interval (RFI) was analyzed by Cox regression models. Results: Median age: 50 (range: 24-89); 48.1% premenopausal; 91.3% infiltrating ductal carcinoma; 30.1% grade 3; 87.2% progesterone receptor (PgR)+; 67.5% treated with nCT and 32.8% with adjuvant CT (aCT); 47.6% N0, 32.8% N1, 19.6% N2-3; median ki67: 30% (82.7% >10%). A 29% of patients showed sTIL=0%. Median sTIL infiltration was 5 (Q1-Q3 range [IQR], 0-10), with higher values in premenopausal (p<0.001), grade 3 (p<0.001), N+ (p<0.001) and luminal B tumors (defined as PgR- and/or grade 3 and/or Ki67>15%) (p<0.001). Ki67 was significantly correlated with sTIL (ρ:0.39; p<0.001). The percentage of sTIL was associated with pCR after nCT (OR: 1.045, 95%Ci 1.02-1.07, p=0.001). No prognostic impact of sTIL for OS or RFI was found in luminal A tumors. In luminal B cases (n=286), any grade of lymphocytic infiltration (defined as sTIL > 0%) was associated with a shorter RFI both in univariate (p=0.01) and multivariate Cox models (HR: 4.83, 95%CI 1.28-18.21, p=0.02), with a non-significant trend for poorer OS (p=0.06). Conclusions: In luminal BC, an increased level of sTIL is associated with luminal B subtype characteristics such as higher proliferation, higher tumor grade and nodal involvement. Lymphocytic infiltration has been found to be a predictor of pCR after nCT, but, in contrast with hormone receptor-negative BC, it is also associated with a poorer prognosis for recurrence and a trend towards worse overall survival in luminal B tumors. [Table: see text]
10-year mastectomy trends among breast cancer phenotypes: A national cohort study.
Authors: Pierotti Matthew Lewis , Cruz Pico Christian X. , Hasler Jill S , Williams Austin David , Handorf Elizabeth A. , Aggon Allison A. , Pronovost Mary , Porpiglia Andrea S , Vasigh Mahtab , Bleicher Richard J. 
Published: June 2023

584 Background: Breast cancer tumor phenotype has prognostic value with triple negative (TN) cancers having higher rates of distant metastases early. While tumor phenotypes are prognostic, published data demonstrates that the choice of local therapy does not affect this predisposition or affect survival. This study was performed to determine whether mastectomy is being performed more frequently for TN or HER2+ phenotypes, relative to hormone receptor positive (HR+) phenotypes despite the lack of benefit this should provide. Methods: Data from the National Cancer Database (NCDB) was analyzed from 2010 through 2019 to assess mastectomy trends and associations with patient and tumor characteristics. Women with invasive breast cancer were included. Women with Stage IV disease were excluded. Patients were categorized as mastectomy or breast conservation surgery. Patient and tumor characteristics were compared across groups using chi-square and Wilcoxon rank sum tests, and a multivariable logistic regression model was fit to assess the association between mastectomy and tumor phenotype controlling for patient and tumor characteristics. Results: 543,590 patients were evaluated. 173,380 (31.9%) patients underwent mastectomy, and 370,210 (68.1%) patients underwent breast conservation surgery. Mean age at diagnosis was 56. There were 425,174 HR+, 64,960 HER2+, and 53,456 TN tumors. The proportion of patients undergoing mastectomy peaked in 2013 at 36.14% before declining. Compared to HR+, HER2+ patients were more likely to undergo mastectomy, OR 1.39 p < 0.0001 (95% CI 1.35 – 1.43); however, there was no significant difference in mastectomy between HR+ patients and TN patients. Compared to whites, black patients were less likely to undergo mastectomy, OR 0.71 p < 0.0001 (95% CI 0.69 – 0.74), and individuals of Hispanic ethnicity less likely to undergo mastectomy, OR 0.92 p < 0.0001 (95% CI 0.89 – 0.95). Compared to private insurance, Medicare had a greater association with mastectomy, OR 1.2 p < 0.0001 (95% CI 1.18 – 1.23). There was no significant difference between other forms of insurance (Medicaid, other government insurance, no insurance) and private insurance. Education and income were not associated with different frequencies of mastectomy. Patients with higher comorbidity scores were more likely to undergo mastectomy. Conclusions: Mastectomy rates have been declining since 2013 at CoC centers. While TN breast cancer is not associated with increased mastectomy percent, mastectomy continues to be performed more frequently for HER2+ positive phenotype when adjusting for tumor and patient characteristics. These data suggest a need for education about HER2 positive phenotype due to a possible lack of understanding about the why such tumors pose a risk, and the role of local therapy in treating them.
Racial/ethnic and socioeconomic differences in breast cancer surgery performed and delayed surgical treatment: Mediating impact on mortality.
Authors: Bangolo Ayrton , Fwelo Pierre , Nwosu Kenechukwu O.S. , Adekunle Toluwani E. , Afolayan Oladipo , Ahaiwe Onyekachi , Ojaruega Akpevwe A. , Nagesh Vignesh , Jarri Amer , Dey Shraboni , Chacko Angel Ann , Gupta Bhavna , Atoot Adam 
Published: June 2023

585 Background: Breast cancer is the most common malignancy affecting women of all racial and ethnic backgrounds in the United States (US). Although Socioeconomic status (SES), race/ethnicity, and surgical type/delays are associated with breast cancer mortality outcomes, studies on these associations have been contrasting. This study examined the racial/ethnic and SES differences in surgical treatment types and delays. Also, we quantified the extent to which these differences explained the racial/ethnic disparities in breast cancer mortality. Methods: We studied 290,066 women 40+ years old diagnosed with breast cancer between 2010 and 2017 identified from the Surveillance, Epidemiology, and End Results database. We performed logistic regression models to examine the association of SES and race/ethnicity with surgical treatment type and delays. We performed mediation analysis models to quantify the extent to which mortality differences were mediated by treatment, sociodemographic, and clinicopathologic factors. The study subjects were de-identified, and there was no patient contact; thus, the study was exempted from an Institutional Review Board's (IRB) approval. A p-value less than 0.05 indicated significant associations for the descriptive statistics, logistic and Cox proportional hazard regressions, and mediation analysis. We used Stata 17 to perform the analyses. Results: Non-Hispanic (NH) Black [Odds ratio (OR) = 1.16, 95% CI: 1.13-1.19] and Hispanic women [OR = 1.27, 95% CI: 1.24-1.31] were significantly more likely to undergo mastectomy compared to NH White women. Similarly, NH Black and Hispanic women had higher odds of delayed surgical treatment than NH Whites. Patients in the highest SES quintile, compared to those in lowest the lowest, were less likely to experience breast cancer-specific mortality (BCSM). Variations in treatment, SES, and clinicopathological factors significantly explained 70% of the excess BCSM among NH Blacks compared to their NH White counterparts. Conclusions: In conclusion, health disparity continues to be a major societal concern in the US. It affects people of all ages, socioeconomic classes, and ethnic/racial backgrounds. The findings of this study showed that racial and ethnic minorities, the majority of whom have a lower socioeconomic position, are significantly disadvantaged regarding the evaluation, quality, cost, and duration of medical care. Future studies can assess the multifactorial effects of sociodemographic factors like SES, access to health care assessment, and educational background amidst other variables as a multidimensional predictor of treatment delay and overall survival of breast cancer and other health issues among minoritized populations.
Disease outcomes by race in patients with high-risk triple negative breast cancer with residual disease after neoadjuvant chemotherapy: A post-hoc analysis of the EA1131 randomized clinical trial.
Authors: Kantor Olga , Newman Lisa A. , Anderson Lauren K , Glass Charity , Mayer Erica L. , Ogayo Esther R. , Chavez-MacGregor Mariana , Freedman Rachel A. , King Tari A. , Mittendorf Elizabeth A. 
Published: June 2023

586 Background: Black women with breast cancer have the highest breast cancer mortality (BCM) rates of any racial and ethnic group. The higher burden of triple negative breast cancer (TNBC) in Black women contributes to disparities in BCM, but the extent to which disparate outcomes exist in patients with similar tumor biology is uncertain. The objective of this study was to examine racial differences in disease outcomes and BCM between Black and White patients in a clinical trial population of high-risk TNBC with residual disease after neoadjuvant chemotherapy (NAC). Methods: From 2015-2021, the ECOG-ACRIN EA1131 clinical trial randomized 415 clinical stage II-III TNBC patients with residual disease after NAC to either adjuvant capecitabine or platinum. For this analysis, 366 patients with known self-reported Black or White race and follow-up data were included. The aim of this unplanned exploratory analysis was to examine locoregional recurrence (LRR), distant recurrence (DR), and BCM by race using Kaplan-Meier curves for unadjusted estimates and Cox modeling for adjusted analyses. Results: Racial distribution of the analysis population included 66 (18.0%) Black and 300 (82.0%) White patients. 239 (65.3%) patients presented with clinical stage II and 127 (34.7%) with stage III disease. All patients had residual pathological disease after NAC: 86 (23.5%) stage I, 176 (48.1%) stage II, and 102 (27.9%) stage III (n=2 unknown). Median age was 49 years in Black and 54 years in White patients, p=0.003. Disease presentation, response to chemotherapy, and treatment arm were similar by race. Median follow up was 20 months. 2-year estimated LRR occurred in 31.6% of Black and 18.6% of White patients although this was not statistically significant (p=0.387), and 2-year estimated DR and BCM were similar by race. Estimated 2-year outcomes are outlined. Models adjusted for race, age, stage, grade, treatment arm, and locoregional therapy did not identify race as an independent predictor of LRR, DR, or BCM. Higher pathologic stage was the only consistent independent predictor of recurrent disease or BCM (stage III with HR 6.14 for LRR; HR 5.16 for DR; HR 6.84 for BCM; all p<0.001). Conclusions: In this population of high-risk patients with residual TNBC after NAC with similar tumor biology treated on a clinical trial, there was a trend towards increased LRR in Black patients and similar DR and BCM between Black and White patients at 2 years of follow-up. This suggests that differences in BCM in other breast cancer populations may be at least partially driven by differences in tumor biology. Clinical trial information: NCT02445391 . [Table: see text]
Association of minimizing the false negative rate of axillary staging surgery in patients with cN1 breast cancer after neoadjuvant chemotherapy with surgical overtreatment.
Authors: Laws Alison , Leonard Saskia , Vincuilla Julie , Parker Tonia , Kantor Olga , Mittendorf Elizabeth A. , Weiss Anna , King Tari A. 
Published: June 2023

587 Background: Efforts to minimize the false negative rate (FNR) of axillary staging in cN1 breast cancer patients (pts) treated with neoadjuvant chemotherapy (NAC) have received much attention since the publication of ACOSOG Z1071. We first adopted sentinel node biopsy (SNB) with a requirement of retrieving ≥3 nodes, and later transitioned to targeted axillary dissection (TAD) with a requirement of retrieving the biopsy-proven clipped node (CN) and ≥3 nodes overall. Group consensus was to perform axillary lymph node dissection (ALND) if these technical requirements were not met. This study evaluates likelihood of surgical overtreatment with ALND due to technical failures of SNB or TAD in cN1 pts who converted to ypN0 status, and reports oncologic outcomes with each approach. Methods: Among 598 cN1 breast cancer pts treated with NAC from 2017-2022 in our prospective institutional database, we included 191 (31.9%) with attempted SNB or TAD and ypN0 status. We used descriptive statistics and chi-squared tests to compare technical complications of SNB vs. TAD resulting in requirement for ALND per group consensus despite ypN0 status. Kaplan Meier methods were used to determine oncologic outcomes in those treated with SNB or TAD alone. Results: Planned axillary surgery was SNB in 77 (40.3%) pts and TAD in 114 (59.7%). The CN was not visualized for seed localization in 14 pts (12.2% of planned TAD) and the seed was not found to be within the CN intra-operatively in 20 pts (20.0% of those with seed placed). Technical failures resulting in requirement of ALND per group consensus criteria occurred in 14 (18.2%) pts with planned SNB and 17 (14.9%) with planned TAD. Among planned TAD pts, the rate of not retrieving the CN did not change over time (p=0.52). Median follow-up in those treated with SNB alone (n=79) was 3.5 years with 1 (1.3%) axillary recurrence as well as 2 local and 2 distant recurrences and 1 non-breast cancer death. 3-yr recurrence-free survival was 90.4% (95%CI: 79.5-95.7%). Median follow-up in those with TAD alone (n=92) was 1.8 years with no recurrences or deaths. Conclusions: This study contributes to a growing body of literature supporting the oncologic safety of omitting ALND in cN1 ypN0 pts treated with NAC, irrespective of the axillary staging approach. Technical limitations in identifying ≥3 nodes or localizing and retrieving CNs resulted in overtreatment with ALND in a significant proportion (≥15%) of ypN0 pts, without significant differences between SNB vs. TAD approaches. These data support consideration of re-evaluating NCCN guidelines recommending retrieval of ≥3 nodes and localization of the CN to minimize risk of overtreatment. [Table: see text]
A phase II randomized clinical trial to assess toxicity and quality of life of patients with breast cancer with hypofractionated versus conventional fractionation radiotherapy with regional nodal irradiation.
Authors: Gil Gabriel Oliveira Bernardes , Andrade Warne Pedro , Costa Diniz Paulo Henrique , Cantidio Farley Soares , Vieira Gil Maria Luisa , Queiroz Izabella Nobre , Almeida Conceição Aparecida Mediros , Caldeira Paola Palmer Reis , Regalin Marcos , Silva-Filho Agnaldo Lopes 
Published: June 2023

588 Background: The primary aim was comparing acute toxicity between conventional fractionated radiation therapy (CF-RT) and hypofractionated radiation therapy (HF-RT) for patients undergoing breast-conserving surgery or mastectomy with breast or chest wall and regional nodal irradiation (RNI). The secondary endpoints were acute and subacute toxicity, cosmesis, quality of life, and lymphedema features. Methods: Unblinded randomized trial with total of 86 patients treated with CF-RT (n = 33; 50 Gy/25 fractions ± sequential boost [10 Gy/5 fractions]) versus HF-RT (n = 53; 40 Gy/15 fractions ± concomitant boost [8 Gy/15 fractions]). Toxic effects and cosmesis evaluation used the Common Terminology Criteria for Adverse Events version 4.03 (CTCAE) and the Harvard/NSABP/RTOG scale. Patients-reported QoL was determined using European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30) and the breast cancer-specific supplementary questionnaire (QLQ-BR23). Lymphedema determination compared volume differences between the affected and contralateral arms using the Casley-Smith volume formula. Results: Grade 2 and grade 3 skin rash dermatitis were lower with HF-RT than with CF-RT (28% vs. 52%, 0% vs. 6%; p = 0.022, respectively). HF-RT vs. CF-RT had lower rate of grade 2 hyperpigmentation (23% vs. 55%; p = 0.005). No differences in overall rates of any physician-assessed grade 2 or higher and grade 3 or higher acute toxicity between HF-RT vs. CF-RT were registered. There was no statistical difference between the CF-RT and the HF-RT regarding cosmesis, lymphedema rate (13% vs. 12% HF-RT vs. CF-RT; p = 1.000, respectively), and functional and symptom scales during irradiation and after six months of treatment. Conclusions: HF-RT showed lower rates of acute toxicity, with no changes in quality-of-life outcomes. Clinical trial information: NCT04015531 .
Use of PLR and NLR to evaluate the efficacy and prognosis of neoadjuvant chemotherapy with lobaplatin in triple-negative breast cancer.
Authors: Wang Cheng , Shi Qiyun , Zhang Guozhi , Yan Wenting , Wu Xiujuan , Wan Andi , Xiong Siyi , Yuan Long , Tian Hao , Ma Dandan , Jiang Jun , Zhang Yi , Qi Xiaowei 
Published: June 2023

594 Background: Previously, we showed that addition of lobaplatin (L) to taxane (T) combined with anthracycline (E) could improve the pathological complete response (pCR) rate of neoadjuvant therapy for triple-negative breast cancer (TNBC) and lengthen long-term survival significantly, but the therapeutic markers of this regimen are not known. We investigated if the platelet/lymphocyte ratio (PLR) and neutrophil/lymphocyte ratio (NLR) could be used to predict the efficacy of the TEL regimen. Methods: Eighty-three patients with TNBC (stage I–III) who received TEL (docetaxel (T) at 75 mg/m2, epirubicin (E) at 80 mg/m2, and lobaplatin (L) at 30 mg/m2) from January 2014 to August 2019 were recruited. They received four cycles before surgery and two cycles after surgery. Patients were divided into four groups according to the mean values of the PLR (145.71) and NLR (2.74): high PLR (PLR+), low PLR (PLR−), high NLR (NLR+), and low NLR (NLR−). Differences in the total pathologic complete response (tpCR) rate, event-free survival (EFS), and overall survival (OS) were analyzed in different groups of patients using the TEL protocol. Results: The tpCR rate in the PLR− group was 49.0% (25/51), which was significantly higher than that in the PLR+ group (25.0% (8/32); odds ratio (OR) = 2.885, 95% confidence interval (CI) = 1.093–7.612, P = 0.032). The tpCR rate in the NLR− group was 49.1% (26/53), which was significantly higher than that in the NLR+ group (23.3% (7/30); OR = 3.164, 95% CI = 1.161–8.626, P = 0.024). The tpCR rate of the PLR−NLR− group was 53.7% (22/41), which was significantly higher than that of the PLR+/NLR+ group (26.1% (11/42), with a high proportion of any index (OR = 3.263, 95% CI = 1.298–8.204, P = 0.012). The median duration of follow-up was 69 months. EFS and OS in the NLR− group were significantly longer than those in the NLR+ group (hazard ratio (HR) = 5.946, 95% CI = 1.526–23.169, P = 0.010 for EFS; HR = 7.803, 95% CI = 1.565–38.907, P = 0.012 for OS). Five-year EFS was 95.1% for the PLR−NLR− group, 91.0% for the PLR+NLR− group, 76.0 for the PLR+NLR+ group, and 59.1% for the PLR−NLR+ group. Compared with the PLR+/NLR+ group, patients in the PLR-NLR- group had the longest EFS (P = 0.002). Conclusions: PLR and NLR could be used to predict the efficacy of neoadjuvant therapy with taxane, anthracycline, and lobaplatin regimen in TNBC, and the low-proportion group had a higher tpCR rate and a better long-term prognosis. Clinical trial information: ChiCTR-TRC-14005019 .
Association between genomic alterations and response of triple-negative breast cancers (TNBC) to talimogene laherparepvec (TVEC) in combination with neoadjuvant chemotherapy (NACT).
Authors: Soliman Hatem Hussein , Han Hyo S. , Mooney Blaise , Costa Ricardo L , Lee Marie Catherine , Niell Bethany , Chau Alec , Falcon Shannon , Soyano Muller Aixa Elena , Armaghani Avan J. , Khakpour Nazanin , Weinfurtner Robert J , Hoover Susan , Kiluk John , Laronga Christine , Rosa Marilin , Khong Hung T. , Czerniecki Brian J. 
Published: June 2023

598 Background: TVEC is an engineered oncolytic virus (OVs) approved for the treatment of melanoma. We published a phase 1/2 trial combining TVEC with NACT in early stage TNBC demonstrating increased pathologic complete response (pCR) compared to expected rates with NACT. RNAseq was performed on 37 pretreatment samples from enrolled patients to identify potential predictive genomic alterations. Methods: Transcriptomic RNA sequencing analysis was performed on macrodissected tumor tissue through the Moffitt Molecular Genomics core using Illumina Truseq RNA exome kits. Read adapters were detected using BBMerge (v37.88) and removed with cutadapt (v1.8.1). For gene expression analysis, processed raw reads were aligned to human genome HG19 using STAR (v2.5.3a). Gene expression was evaluated as read count at gene level with HTSeq (v0.6.1) and Gencode gene model v19. Gene expression data were normalized and differential expression between experimental groups were evaluated using DEseq2 (v 1.38.2). Ensembl was used for SNP data search. Results: Tumor mutation burden was not significantly different between pCR and non-pCR samples (median 227 vs 222 mut/MB, p = .11). Top 5 upregulated non-immunoglobulin genes associated with pCR in baseline samples were MYBL1, DNAH8, NR2E1, FGFR2, and SLC12A1 (FDR < 1%). A single nucleotide polymorphism (SNP) of the EIF2A gene (c.C290G, p.T97S) was the top variant associated with response present in 21/37 samples (non-pCR = 17/21 vs. pCR = 4/21, FDR = < 1%). This exon 4 coding region SNP is present in 17% of Black, 35% of White, and 46% of Asian individuals but its biologic or clinical significance is unknown. Lower EIF2A pathway activation was associated with inferior response to therapy. Additional data will be presented at the meeting. Conclusions: Genomic alterations including a EIF2A SNP were correlated with response to OV plus NAC in TNBC. EIF2A is an important mediator of cellular responses to OV and may play a role in susceptibility to oncolysis. Additional investigation and validation of these variations in experimental models of OV susceptibility may provide predictive biomarkers for TNBC patients treated with OV plus NAC therapy. Clinical trial information: NCT02779855 .