bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical-pathological characteristics associated with multigene assay risk scores, and prognostic impact of multigene risk scores in patients with invasive lobular carcinoma.
Authors: Lee Young-Won , Kim Jisun , Lee Sae Byul , Chung Il Yong , Yoo Tae-Kyung , Kim Hee Jeong , Ko Beom Seok , Lee Jong Won , Son Byung Ho , Lee Hee Jin , Gong Gyungyub , Jeong Hyehyun , Jeong Jae Ho , Ahn Jin-Hee , Jung Kyung Hae , Kim Sung-Bae 
Published: May 2024

546 Background: Invasive Lobular Carcinoma (ILC), a unique breast cancer subtype, exhibits distinct clinical and pathological features. Multigene assays, notably the Oncotype DX (ODX) test, provide personalized prognostic insights in breast cancer. However, a research gap exists for clinical-pathological characteristics affecting multigene assay risk scores in ILC. This study aims to address this gap, investigating factors specific to ILC, distinct from those in invasive ductal carcinoma (IDC), contributing to refined risk stratification and personalized treatment decisions for ILC patients. Methods: Retrospective analysis was conducted on 238 ILC type breast cancer patients who underwent surgery at AMC between 2012 and 2022 and had undergone the ODX test. The ODX test assessed the Recurrence Score (RS) with defined categories: low (0-15), intermediate (16-25), and high (26 or above). Additionally, binary analysis categorized patients into low and high-risk groups using a cutoff of 25. The cutoffs were determined based on existing research findings. Results: Among patients undergoing ODX testing, the distribution of RS differed significantly between ILC and invasive ductal carcinoma (IDC) patients. Notably, the percentage of high-risk cases was higher in ILC (4.2%) compared to IDC (16.9%). Examination of patient characteristics revealed a prevalence of younger individuals, premenopausal status, and those undergoing breast-conserving surgery (BCS) among the low-risk binary group. In multivariate logistic regression analysis, PR negativity emerged as a significant factor influencing ODX high risk across the entire cohort (OR 23.224, 95% CI 3.732-144.527, p=0.001). Subgroup analysis by age identified specific risk factors, including PR negativity in younger patients (OR 11.896, 95% CI 1.247-113.523, p=0.031), larger tumor size (more than 2cm) (OR 4.180, 95% CI 1.229-14.214, p=0.022), and PR negativity in older patients (OR 25.030, 95% CI 3.505-178.756, p=0.001). Conclusions: In ILC, factors predicting ODX differ from IDC, emphasizing the need for tailored risk prediction models. PR negativity emerged as a consistent predictor of ODX high risk, warranting attention in risk stratification models. Recognizing this distinction is crucial for enhancing precision in prognostic assessments and optimizing patient management in ILC.
Adjunctive statistical standardization of quantitated adjuvant ER and PgR in CCTG MA.27.
Authors: Chapman Judy-Anne Williams , Bayani Jane , SenGupta Sandip , Battlett John MS , Piper Tammy , Quintayo Mary Anne , Virk Shakeel , Goss Paul E , Ingle James N. , Ellis Matthew James , Sledge George W. , Budd George Thomas , Rabaglio Manuela , Stearns Vered , Perez Edith A. , Gelmon Karen A. , Whelan Timothy Joseph , Shepherd Lois E. , Chen Bingshu E. , Taylor Karen J 
Published: May 2024

567 Background: We proposed adjunctive statistical standardization of quantitated ER and PgR to improve inter-laboratory comparability of biomarker results and therapeutic management of breast cancer. Methods: We utilized CCTG MA.27 (NCT00066573), an adjuvant phase III trial of exemestane versus anastrozole in postmenopausal women with ER+ and/or PgR+ tumours. IHC ER and PgR HSCORE and % positivity (%+) were centrally assessed by machine image quantitation, and each statistically standardized to mean of 0, standard deviation of 1 following Box-Cox variance stabilization transformations of square for ER; for PgR, 1.) natural logarithm (0.1 added to 0 HSCOREs and 0 %+), 2.) square root. The primary endpoint was STEEP distant disease-free survival (DDFS) at the longest trial follow-up of median 4.1 years; a secondary endpoint was event-free survival (EFS). Survival was described with Kaplan-Meier plots and tested with the univariate Wilcoxon (Peto-Prentice) test statistic. We examined cut-points at standard deviations about mean of 0 (<-1; (-1,0]; (0,1]; >1) and explored single cut-points. Cox multivariate regressions were adjusted for age, T and N stage, grade, lymphovascular invasion, treatment, and baseline patient demographics; 2-sided Wald tests had nominal significance if p<0.05. Results: Of the 7576 women accrued, 3048 women had machine-quantitated image analysis results: 2900 (95%) for ER; 2726 (89%) for PgR. Statistically standardized HSCORE and %+ units differentiated both univariate DDFS and EFS; DDFS was significantly different by ER levels (p<0.001) and PgR levels (p<0.001). In multivariable assessments, ER HSCORE and %+ were not significantly associated (p=0.52-0.88) with the DDFS primary endpoint in models with PgR, while higher PgR HSCORE and %+ had significantly better DDFS (p=.001, in all instances) in models with ER. Conclusions: DDFS was superior for patients with higher ER and PgR standardized units compared with those with HSCOREs and %+ <-1. The adjunctive statistical standardization of ER and PgR performed here is similar to that mandated for clinical practice by the World Health Organization for BMD. [Table: see text]
Systemic inflammatory markers in neoadjuvant pembrolizumab therapy for triple-negative breast cancer: Prognostic insights and nomogram construction.
Authors: Giovanardi Filippo , Casartelli Chiara , Di Cicilia Roberto , Bologna Alessandra , Gasparini Elisa , Moretti Gabriella , Degli Esposti Claudia , Bisagni Giancarlo , Pinto Carmine 
Published: May 2024

e12649 Background: Systemic inflammatory markers derived from peripheral blood cells, such as the neutrophils and lymphocytes ratio (NLR), derived neutrophil lymphocyte ratio (dNLR), platelet-lymphocyte ratio (PLR), and lymphocyte–monocyte ratio (LMR), have shown promise as prognostic markers. Currently, neoadjuvant treatment (NACT) for early triple-negative breast cancer (eTNBC) involves the addition of an immune therapy, and little is known about the variation of these markers in this specific context. Methods: This study evaluated two groups who received NACT for eTNBC in a single third-level cancer center. The first received NACT with EC X4 and a weekly paclitaxel regimen, the second pembrolizumab and NACT. A total of 70 patients were included, 37 patients in the pembrolizumab group. NLR was defined as the absolute blood neutrophil count (N) divided by the absolute lymphocyte count (L), dNLR was defined as the N divided by the derived L (absolute leukocyte count — N), PLR was defined as the absolute platelet count divided by the L, LMR was defined as the L divided by the absolute monocyte count. Association between systemic inflammatory markers and pathological complete response (pCR) was analyzed using statistical tests. Inflammatory markers were evaluated at the time of diagnosis, at the time of chemotherapy regimen change, and 1 week before surgery. The χ2 test or Fisher’s exact test was used for correlation and Student’s t-test to compare different groups. Results: The pCR rates were 60,6% in the standard therapy and 77,8% in the pembrolizumab. There were no significant differences in clinical characteristics between the two groups. NLR, dNLR, PLR and LMR at 6 months showed significant differences compared to baseline levels. dNLR in the immunotherapy group, at the end of therapy, showed statistical significance with the Welch Two Sample t-test with p-value = 0.001. Variables were weighted with respect to the type of treatment and the outcome was assessed as pCR. On the basis of these data, a nomogram was constructed to predict the likelihood of achieving pCR in patients undergoing neoadjuvant pembrolizumab therapy. Conclusions: This study highlights the potential of systemic inflammatory markers as prognostic indicators in patients with eTNBC undergoing NACT. dNLR is a novel biomarker associated with clinical outcome in solid tumors. In this study, for the first time, a correlation was found between the use of pembrolizumab and the change in dNLR and consequently its impact on pCR. A nomogram was constructed to predict the outcome of pCR. [Table: see text]
Predicting pathological response in early-stage triple-negative breast cancer: Exploring the role of BRCA gene mutations—A retrospective single-institution study.
Authors: Eldib Howide , Nwanwene Kemnasom , Kachynski Yury , Wright Thomas , Abdallah Mahmoud , Kumar Love , Mahdi Ahmad , Alhusari Leena , Shenouda Mina , Tirona Maria Tria 
Published: May 2024

e12656 Background: Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer, constituting approximately 15-20% of all breast cancer cases. While less than 10% of all breast cancer patients harbor BRCA1/2 mutations, ~20% of TNBC patients carry these mutations. Notably, at least one-third of BRCA1 carriers develop TNBC. This study aimed to investigate the association between BRCA mutation status and pathological response (PR) in early-stage TNBC patients, specifically, the impact of BRCA positivity on achieving pathological complete response (pCR), and identify other potential predictors of PR. Methods: We conducted a retrospective cohort study of patients with early-stage (Stage I-III) triple-negative breast cancer diagnosed and treated at our institution between January 2012 and June 2022, following Institutional Review Board (IRB) approval. Patients were identified from our Institutional Cancer Registry based on complete data availability (including other inclusion criteria) excluding patients who did not receive neoadjuvant chemotherapy. Data on demographics, tumor characteristics, treatment regimens, and pathological response (assessed according to [specified criteria]) were extracted from the charts. Results: Out of 228 patients diagnosed with early-stage triple-negative breast cancer, 54.6% had no genetic mutations, while 7.9%, 4.9%, and 8.4% harbored BRCA1, BRCA2, and other mutations, respectively. Notably, 23.4% did not receive genetic counseling or testing at our institution. Patients with BRCA2 mutations had a 100% pathological response rate, of which 57.14% had pCR, compared to 85.7% for BRCA1, of which 71.43% had pCR. Furthermore, 93.8% of patients with other genetic mutations had pathological response, of which 56.25% had pCR, as compared to 68.42% in non-mutated cases of which 26.7% had pCR ( P=0.038). Analysis of other variables revealed no significant impact of age, BMI, performance status, or neoadjuvant chemotherapy regimen on pathological response. Conclusions: This retrospective study suggests a trend towards higher complete pathological responses in early-stage triple-negative breast cancer patients with BRCA and other genetic mutations compared to those without. These findings were statistically significant, indicating a potential clinical trend that specific genetic mutations may be associated with improved response to neoadjuvant chemotherapy in early-stage triple-negative breast cancer. Further research is needed to confirm these findings and guide the development of personalized treatment strategies based on a patient's genetic profile. Additionally, our findings highlight the importance of genetic testing for all patients with early-stage triple-negative breast cancer, regardless of age or family history.
Treatment outcomes of the KEYNOTE-522 regimen in an ethnically diverse patient population: A real world experience.
Authors: Ng'ang'a Mukuhi , Burdette-Radoux Susan , Borgen Patrick I. , Kodali Abhigna , Andaz Charusheela , Urazov Anna , Sobol Gene , Silver Michael , Feinberg Joshua 
Published: May 2024

e12663 Background: Pembrolizumab (pembro) in combination with neoadjuvant chemotherapy (NACT) became standard of care for high risk, early stage TNBC on July 26, 2021, as a result of the KEYNOTE-522 trial. Black women are disproportionately affected by TNBC with more advanced stage at diagnosis, however the KEYNOTE-522 did not collect data on race. This retrospective review evaluates response to pembro plus NACT in a racially diverse population to assess the generalizability of the trial findings to potentially under-represented patient populations. Methods: This is a single center, retrospective review of patients with stage II/III TNBC diagnosed between 08/2020 to 08/2023, treated with pembro plus NACT at Maimonides Medical Center, a safety-net hospital in Brooklyn, New York serving a diverse patient population. Exclusion criteria included age < 18 years, ER/PR/Her2 positivity, NACT without pembrolizumab and unreported race. Data were collected from electronic health records and analyzed using SPSS Statistics. Results: 50 patients met inclusion criteria, among whom 40 patients had complete information available for review. 52.5% (95% CI: 38% - 69%) of patients had a pCR. Nearly half of the patient population (47.5%) were African American. Subgroup analysis of ethnicity demonstrated a lower pCR amongst African American women, but this was not statistically significant (table). 5 patients had progression of disease with the development of distant metastasis (2 whilst on treatment and 3 following completion of therapy). 3 patients had grade 3/4 adverse events (pembro associated endocrine and cardiac dysfunction). Notably, lack of complete imaging response to treatment was significantly associated with lack of pCR (p=0.003). Conclusions: In this retrospective review of a racially diverse patient population, the pembrolizumab-NACT regimen was well tolerated with an acceptable side effect profile. While our rate of pCR is lower than the findings of the Keynote-522 trial; 52.5 % (95% CI: 38% - 69%) vs. 64.8% (95% CI: 59.9%-69.5%), our sample size is not large enough to detect a statistically significant difference. Sub-analysis of patient ethnicity demonstrated varying rates of pCR, however findings are limited by a small sample size. Additional data collection is in progress and future analysis will provide insight into a potential correlation between race and therapy response. [Table: see text]
Optimizing colorectal cancer screening outreach: A probability-based strategy by Temple University Hospital.
Authors: Grivas Christopher , Vallabhaneni Manasa , Ifrah Abraham , Gillow Gabrielle , Graham Brianna , Dahake Nikita , McNeilly Shelby , Khatri Rishabh , Raab Claire 
Published: May 2024

e13502 Background: Temple University Hospital has created an initiative to increase colorectal cancer (CRC) screening to a historically underserved population in Northern Philadelphia through the administration of Fecal Immunochemical Tests (FIT). FIT testing possesses the advantage of being inexpensive and easy to use. Moreover, FIT testing serves as an additional opportunity for underserved patients to be integrated into a health network to receive lifesaving care when utilized by a large health system such as Temple Health. This study demonstrates how healthcare institutions, such as Temple Health, can employ probability-based modeling created from empiric data to navigate uncertainty and establish goals for the number of colonoscopies they aim to perform per a specific quantity of FIT tests distributed within the community. By doing so, they can significantly enhance the overall screening efforts in Northern Philadelphia and provide an essential service to those who need it most. Methods: FIT tests were distributed to the participants at community engagement events. FIT response rates, positivity rates, and progression to colonoscopy rates were determined and fit to a binomial distribution in Palisades @Risk software and underwent a Monte Carlo simulation of 10,000 iterations to determine the different probabilities of response rates, positivity rate, and colonoscopies performed per 1000 FIT tests distributed. Results: A total of 292 tests were distributed with a response rate of 56.5% (165 patients) and a positivity rate of 8.9% (26 patients). Out of 292 patients, 2.4% (7 patients) have had a colonoscopy or are scheduled to have a colonoscopy at Temple University Hospital. Probability curves were created to demonstrate the probability of number of responses, number of positive tests, and number of colonoscopies performed per 1000 FIT tests administered to the community. Lastly, we modeled the number of FIT tests that need to be administered to the community to perform at least 100 colonoscopies with different levels of certainty (Table). Conclusions: Here we show how hospital systems, like Temple Health, can use probability distributions based on empiric data to set tangible goals regarding their community engagement efforts to increase access to CRC screening. Through the utilization of probability distributions, healthcare organizations can gain deeper insights into resource allocation needs and strategically direct their initiatives, ultimately fostering a more inclusive and equitable approach to population-based CRC screening. [Table: see text]
Association between patient tumour characteristics and five-year survival in Nigerian patients with breast cancer.
Authors: Fatiregun Omolara Aminat A. , Lasebikan Nwamaka 
Published: May 2024

e13504 Background: Breast cancer is a heterogeneous disease. The sociodemographic features and biological profile of breast cancer differ globally, especially in women of African descent. In Nigeria, limited studies explore the impact of these breast cancer-related factors on survival. This study evaluated the association between patients' tumour characteristics and survival in breast cancer patients in three regional tertiary cancer treatment centres across Nigeria. Methods: Data were extracted from patients' case files with a histopathologic diagnosis of breast cancer from January 1, 2005 - January 1, 2019. Patients' sociodemographic and clinical features were presented, and survival probabilities were reported; the Log-rank test was used to determine the association between time to death and categorical variables. Results: The study included 1020 patients across the three centres. Five-year survival probability was 0.65; 95% C.I: 0.60- 0.69. Most patients were between ages 30 and 49, and 49% presented with left-sided breast cancer. Patients aged>70 had significantly better survival. Only 40% had Immunohistochemistry (IHC) done, out of which HR+ breast cancer accounted for 43% while triple-negative breast cancer was 30%. Patients who received Herceptin and had molecular subtyping (immunohistochemistry) done had a higher survival probability. Conclusions: Most breast cancer patients in Nigeria present at earlier ages with advanced disease. Regardless of patient tumour characteristics, 5-year survival rates are lower than global rates. Only a few patients have access to optimal breast cancer management, molecular subtyping and targeted treatment inclusive. There is an urgent need to fund the National Cancer Control program to aid in implementing its strategic framework for breast cancer screening and management to improve access to cancer care in Nigeria.
Informing optimal treatment (tx) sequences for platinum-eligible patients with locally advanced or metastatic urothelial carcinoma (la/mUC) in the United States: Results of a clinical simulation modeling exercise.
Authors: Sanchez Alvarez Javier , Benedict Agnes , Tichy Eszter , Kongnakorn Thitima , Ike Chiemeka , Kearney Mairead 
Published: May 2024

e13514 Background: Platinum-based chemotherapy (PBT) followed by avelumab (AVE) as first-line (1L) maintenance for patients with nonprogressive disease (PBT ± AVE) is the standard of care in la/mUC. This study compared the overall survival (OS) and cost-effectiveness of the tx sequence of PBT ± AVE followed by enfortumab vedotin (EV) or other therapies, including immuno-oncology (IO), in second line (2L; ie, PBT + 2L EV/IO or PBT + AVE + 2L EV/IO) vs 1L EV + pembrolizumab (PEM) for PBT-eligible patients (PBTp) from a US commercial payer perspective. Methods: A partitioned survival model compared outcomes with PBT ± AVE and EV + PEM among PBTp. Inputs included progression-free survival and OS, time to tx discontinuation, adverse event (AE) incidence, and health utilities and costs. Efficacy inputs were sourced and extrapolated from patient data in JAVELIN Bladder 100 (data cut: Jun 4, 2021), AVENANCE real-world study (1), and published data (EV-302 trial). Safety data were sourced from US prescribing information. Drug, subsequent tx, disease management, and AE management costs (2023 USD) were calculated. The optimal tx sequencing scenario assumed 80% of patients starting PBT were eligible to receive AVE (2023 Flatiron data cut; (2)), 70% of patients progressing on PBT ± AVE would start 2L, and 70% of those would be eligible for EV. Outcomes included life-years (LYs), quality-adjusted LYs (QALYs), costs, and incremental cost-effectiveness ratio (ICER). Scenarios and probabilistic sensitivity analyses (PSAs) were conducted to assess uncertainty. Results: LY, QALY, costs, and ICER modeling outcomes are shown in the Table. Use of EV in 2L after PBT ± AVE is associated with 0.76 lower QALYs, but given the large cost saving, it represents a cost-effective use of resources at the $150,000/QALY willingness to pay (WTP) threshold. PSAs showed that PBT ± AVE is likely to be more cost-effective over a broad and relevant WTP threshold range ($0-500,000/QALY). Results were sensitive to drug acquisition costs and eligibility to receive AVE and 2L EV. Conclusions: Based on this simulation exercise, the use of 2L EV after PBT ± AVE achieves considerable survival benefit at substantially lower costs vs 1L EV + PEM in PBTp with la/mUC. Given the shift toward value-based care in oncology, such analyses are becoming increasingly relevant to guide clinical decision-making. There is a need to assess tx alternatives that balance healthcare costs while optimizing outcomes in patients with la/mUC. 1. Barthélémy et al, J Clin Oncol 2024;42[suppl 4]: Abstract 561. 2. Moon et al, J Clin Oncol 2023;41[suppl 16]: Abstract 4567. [Table: see text]