Recurrence Score Research Articles

Differentiating HER2-low and HER2-zero tumors with 21-gene multigene assay in 2,295h + HER2- breast cancer: a retrospective analysis.

HER2-positivity is an essential marker for therapeutic decisions, while HER2 expression is heterogenous. In recent years, there has been increasing recognition of a subgroup of breast cancer patients who have low levels of HER2 expression, also known as HER2-low because trastuzumab deruxtecan offers clinical benefit for patients with HER2-low metastatic breast cancer. Despite the growing interest in HER2-low breast cancer, there is limited research on how multigene assays can help differentiate between HER2-low and HER2-negative breast cancer. Among HR + HER2- breast cancer, we compared genomic characteristics between HER2-low and HER2-zero using the 21-gene assay. A retrospective review of clinical records was performed in 2,295 patients who underwent Oncotype DX® test in two hospitals between 2013 and 2020. Patients were classified into two groups as the HER2-zero and HER2-low based on HER2 immunohistochemistry. In cases with HER2 2+, no amplification of HER2 gene was confirmed by silver in situ hybridization. High genomic risk was defined as cases with 21-gene recurrence score (RS) > 25. Multivariable binary logistic-regression analysis was performed. Of these, 944 (41.1%) patients were assigned to the HER2-zero group, while 1351 (58.9%) patients were assigned to the HER2-low group. The average Recurrence Score (RS) was found to be 17.802 in the HER2-zero breast cancer group and 18.503 in the HER2-low group, respectively (p-value < 0.005). When comparing the proportion of high RS between the two groups, the HER2-zero group had a high RS rate of 12.4% (117 out of 944), while the HER2-low group had a high RS rate of 17.0% (230 out of 1351) (p = 0.002). The HER2 score identified by qRT-PCR was 8.912 in the HER2-zero group and 9.337 in the HER2-low group (p < 0.005). In multivariable analysis, HER2-low status was found to be an independent factor for high RS, with an odds ratio of 1.517 (1.172-1.964), independent of ER, PR, and Ki67. Within the subgroup of patients with invasive ductal carcinoma, the high RS rates were 19% in the HER2-low group and 14% in the HER2-zero group. However, when considering all patients, there were no significant differences observed in recurrence-free survival and overall survival between the HER2-low and HER2-zero groups. Within HR + HER2- breast cancer, HER2-low tumors are associated with high RS, especially for histologically invasive ductal carcinoma. A prognostic influence of HER2-low expression among HR + HER2- breast cancer remains as an area that requires further study.

Recurrence score-predicted value derived from estrogen receptor, tumor-infiltrating lymphocytes, progesterone receptor, and Ki-67 may substitute for the Oncotype DX recurrence score in estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)− breast cancer

Recurrence score-predicted value derived from estrogen receptor, tumor-infiltrating lymphocytes, progesterone receptor, and Ki-67 may substitute for the Oncotype DX recurrence score in estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)− breast cancer

Ventral hernia repair with permanent mesh for non-Hispanic black versus white patients: access and post-operative outcomes in the era of robotic surgery.

Robotic ventral hernia surgery may provide better patient outcomes. Whether it is provided equitably based on race remains unknown. We examined whether patients from the Abdominal Core Health Quality Collaborative who were Black had equitable access to robotic surgery for ventral hernia repair with permanent mesh compared to white counterparts from 2013 to 2023. We performed propensity-score matching to address confounding and then chi-squared testing to examine access to robotic, laparoscopic, and open approaches. Secondary outcomes included 30-day readmissions, complications, and death and 1- and 2-year hernia recurrence and quality of life measured by HerQLes Summary and PROMIS Pain T-Scores analyzed with chi-squared, Fisher exact, and Wilcoxon testing. 2397 patients identified as Black, and 21,900 identified as white. Our propensity-score matched cohort included 2374 Black patients and 7122 white. Black and white groups had the same rates of laparoscopy (15% vs 15%). Patients who identified as Black were more likely to undergo robotic surgery (36% vs 32%). Open approach was 49% for Black and 53% for white (p = 0.005). For 30-day complications, we found Black patients were more likely to experience reoperation (2% vs 1%, p = 0.005) and less likely surgical site infection (1% vs 2%, p < 0.001). Hernia recurrence scores and perceived abdominal health based on HerQLes were not statistically significantly different. At 2years, absolute reported T-Scores were higher for Black patients (median 40 (IQR 31-49) vs 36 (31-46), p = 0.031). This is the first large-scale study examining access to robotic surgery, complications, and quality of life measures. We found patients who identified as Black were more likely than white counterparts to undergo robotic surgery, but they were more likely to require reoperation and had higher pain scores. Our data suggest equitable access still may not translate to equitable patient outcomes.

A multi-model approach integrating whole-slide imaging and clinicopathologic features to predict breast cancer recurrence risk.

Breast cancer is the most common malignancy affecting women worldwide and is notable for its morphologic and biologic diversity, with varying risks of recurrence following treatment. The Oncotype DX Breast Recurrence Score test is an important predictive and prognostic genomic assay for estrogen receptor positive/HER2 negative breast cancer that guides therapeutic strategies; however, such tests can be expensive, delay care, and are not widely available. The aim of this study was to develop a multi-model approach integrating the analysis of whole-slide images and clinicopathologic data to predict their associated breast cancer recurrence risks and categorize these patients into two risk groups according to the predicted score: low-risk and high-risk. The proposed novel methodology uses convolutional neural networks for feature extraction and vision transformers for contextual aggregation, complemented by a logistic regression model that analyzes clinicopathologic data for classification into two risk categories. This method was trained and tested on 956 hematoxylin and eosin-stained whole-slide images of 950 ER+/HER2- breast cancer patients with corresponding clinicopathological features that had prior Oncotype DX testing. The model's performance was evaluated using an internal test set of 192 patients from Dartmouth Health and an external test set of 405 patients from the University of Chicago. The multi-model approach achieved an AUC of 0.91 (95% CI: 0.87-0.95) on the internal set and an AUC of 0.84 (95% CI: 0.78-0.89) on the external cohort for predicting low- and high-breast cancer recurrence risk categories based on the Oncotype DX recurrence score. With further validation, the proposed methodology could provide an alternative to assist clinicians in personalizing treatment for breast cancer patients and potentially improving their outcomes.

Erratum: Development and validation of a REcurrent Liver cAncer Prediction ScorE (RELAPSE) following liver transplantation in patients with hepatocellular carcinoma: Analysis of the US multicenter HCC transplant consortium.

Erratum: Development and validation of a REcurrent Liver cAncer Prediction ScorE (RELAPSE) following liver transplantation in patients with hepatocellular carcinoma: Analysis of the US multicenter HCC transplant consortium.

IMPACT OF DNA METHYLATION PROfiLING IN REfiNING MENINGIOMA RECURRENCE RISK STRATIfiCATION AND CLINICAL FOLLOW UP

Abstract AIMS To assess clinical impact of the additive information gained from Integrated Meningioma Risk Score on the risk of meningioma recurrence. METHOD DNA methylation (Illumina EPIC Array) analysis was performed on all recurrent meningioma tumours, primary tumours CNS5 WHO grade 2, 3 and grade 1 with unusual morphological features from Dec 2021 to Jan 2024. DNA methylation analysis was performed, and data files were processed on the DKFZ Heidelberg Classifier v12.5/6 (molecularneuropathology.org). The output from the classifier including methylation class combined with WHO Grade and chromosomal loss (1p, 6q,14q) was used to produce an integrated meningioma risk score for recurrence. RESULTS 70 meningioma cases were profiled. This included 68 cranial meningiomas, ((WHO grade 1, n=19; recurrences=7), (grade 2, n=47; recurrences =9), (grade 3 n=2; recurrences=1)) and 2 spinal meningiomas (grade 1 n=1, grade2 n=1). 3 tumours were excluded due to poor calibration scores. Of the 67 cases the diagnosis was revised in 1 case following DNA methylation analysis due to presence of CDKN2A/B loss. Molecular-morphologic integrated risk score was calculated for all 67 cases. In 10% of overall patients the predicted risk of meningioma recurrence was increased to either intermediate or high, whilst 32% had the risk lowered mainly from intermediate to low. Interestingly, 1 patient who underwent a gross total resection of a WHO Grade 2 meningioma, experienced recurrence with the integrated meningioma risk score indicating low risk of recurrence, which is contrary to the clinical aggressiveness of the tumour. CONCLUSION Meningioma integrated risk stratification by DNA methylation profiling has shown concordance of integrated risk score with WHO Grade in 58% of cases. In 42% of cases the predicted risk was altered when compared to the WHO Grade alone. These results need to be further validated with long term data on patient outcomes.

Real-World Implications of the SOUND Trial.

The SOUND trial demonstrated that omission of sentinel lymph node biopsy (SLNB) is noninferior to axillary staging in patients with early-stage breast cancer (BC) and negative axillary ultrasound (AxUS). We examined the generalizability of these findings in patients with hormone receptor (HR)+HER2- disease. Patients with cT1N0M0, HR+HER2- BC and negative AxUS undergoing breast conservation with SLNB from 2016 to 2023 were identified from a prospectively maintained database. Clinicopathologic characteristics, disease burden, adjuvant treatment, and oncologic outcomes were examined and compared with the SLNB arm of the SOUND trial. In postmenopausal patients, the impact of nodal status and 21-gene recurrence score on chemotherapy recommendations were also examined. Of 3972 patients with cT1N0M0 HR+HER2- breast cancer, 544 underwent AxUS; 312 met SOUND eligibility criteria. Median age was 57 (interquartile range [IQR] 48-64) years, and 199 (63.8%) were postmenopausal. Median (IQR) tumor size was 1.3 (0.9-1.7) cm, and 260 (83.3%) tumors were grade 1 or 2. Sentinel lymph node biopsy was positive in 38 (12.2%) patients. Only three (0.4%) had ≥ 4 positive lymph nodes. At a median follow-up of 26.2 (IQR 10.8-38.2) months, there were no axillary recurrences and one (0.3%) distant recurrence. Among postmenopausal women with recurrence score ≤ 25, chemotherapy recommendations were not associated with nodal status. Examination of our real-world HR+ HER2- "SOUND-eligible" population suggests that nodal disease burden and oncologic outcomes are similar to the SOUND trial population, supporting careful implementation of trial results into multidisciplinary practice. In postmenopausal patients, omission of SLNB does not appear to impact adjuvant chemotherapy recommendations.

The preoperative recurrence score: Predicting early recurrence in peri-hilar cholangiocarcinoma

IntroductionDespite advances in surgical techniques, the rate of early recurrence in perihilar cholangiocarcinoma (PCC) remains high. We sought to develop the Preoperative Recurrence Score (PRS), a model to estimate the risk of early recurrence after resection based on preoperative radiological characteristics. Materials and methodsData of patients who underwent surgery for PCC were retrospectively collected, and preoperative imaging was reviewed to assess tumor characteristics. A model to assess the risk of early recurrence based on preoperative radiologic characteristics was internally developed and externally validated on two cohorts of patients from two European major hepatobiliary surgery referral centers. ResultsA total of 215 patients among three different patient cohorts were included in the study. Tumor size ≥18 mm (HR 2.70, 95 % CI 1.48–4.92, p = 0.001), macroscopic portal vein involvement (HR 2.28, 95%CI 1.19–4.34, p = 0.013), hepatic arteries involvement (HR 2.44, 95%CI 1.26–4.71, p = 0.008), and presence of suspicious lymph nodes (HR 1.98, 95%CI 1.02–3.83, p = 0.043) were significantly associated with recurrence-free survival (RFS). The model showed excellent discrimination both on the internal (AUC 0.83) and external validation cohorts (external 1: AUC 0.84; external 2: AUC 0.70). High PRS was associated with worse RFS among all three cohorts, with a 1-year recurrence probability of 80.1 %, 100.0 %, and 54.2 % in the internal and external validation cohorts 1 and 2, respectively. ConclusionsThe PRS is a simple tool that can accurately assess the risk of early recurrence in patients with PCC. Up-front surgery should be carefully evaluated in patients with high PRS, as it could result in a futile resection.

Irish national real-world analysis of the clinical and economic impact of 21-gene oncotype DX® testing in early-stage, 1-3 lymph node-positive, oestrogen receptor-positive, HER2-negative, breast cancer.

The treatment landscape of Oestrogen receptor-positive (ER-positive) breast cancer is evolving, with declining chemotherapy use as a result of Oncotype DX Breast Recurrence Score® testing. Results from the SWOG S1007 RxPONDER trial suggest that adjuvant chemotherapy may benefit some premenopausal women with ER-positive, HER2-negative disease with 1-3 positive lymph nodes (N1), and a Recurrence Score® (RS) of ≤ 25. Postmenopausal women with similar characteristics did not benefit from adjuvant chemotherapy. We examine the clinical and economic impact of Oncotype DX® testing on treatment decisions in patients with N1 disease in Ireland using real world data. From March 2011 to October 2022, a retrospective, cross-sectional observational study was performed of patients with ER-positive, HER2-negative N1 breast cancer, who had Oncotype DX testing across 5 of Ireland's largest cancer centres. Patients were classified into low risk (RS 0-13), intermediate risk (RS 14-25) and high risk (RS > 25). Data were collected via electronic patient records. Information regarding costing was provided primarily by pre-published sources. A total of 828 N1 patients were included in this study. Post Oncotype DX testing, 480 patients (58%) were spared chemotherapy. Of the patients who had a change in chemotherapy recommendation based on Oncotype DX testing, 271 (56%), 205 (43%), 4 (1%) had a RS result of 0-13, 14-25 and > 25 respectively. Use of Oncotype DX testing was associated with a 58% reduction in chemotherapy administration overall. This resulted in estimated savings of over €6 million in treatment costs. Deducting the assay cost, estimated net savings of over €3.3 million were achieved. Changes in the ordering demographics of Oncotype DX tests were identified after RxPONDER data were presented, with increased testing in women ≥ 50years and a reduction in proportion of tests ordered for women < 50years. Between 2011 and 2022, assay use resulted in a 58% reduction in chemotherapy administration and net savings of over €3.3 million.

Neoadjuvant letrozole and palbociclib in patients with HR-positive/HER2-negative early breast cancer and Oncotype DX Recurrence Score ≥18: DxCARTES study

The effect of the addition of cyclin-dependent kinases 4 and 6 inhibitors to endocrine therapy in terms of molecular downstaging remains undetermined. Switching from a high-risk to a low risk Recurrence Score (RS) group could provide useful information to identify patients who might not require chemotherapy. The purpose of this study was to assess the biological and clinical activity of letrozole plus palbociclib as neoadjuvant treatment for patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative early breast cancer with an initial Oncotype DX RS ≥18. Participants were women aged ≥18 years with HR-positive/HER2-negative, Ki67 ≥ 20%, stage II-IIIB early breast cancer with a baseline RS ≥18. Eligible patients with a pretreatment RS 18-25 (cohort A) and 26-100 (cohort B) received six 28-day cycles of letrozole (2.5 mg per day; plus goserelin if pre- or perimenopausal) plus palbociclib (125 mg per day; 3/1 schedule) before surgery. The primary endpoint for both cohorts was the proportion of patients who achieved an RS ≤25 at surgery or a pathological complete response (pCR). A total of 67 patients were enrolled, among which 65 were assessable for the primary endpoint (32 patients in cohort A and 33 in cohort B). At surgery, 22 (68.8%) patients in cohort A and 18 (54.5%) patients in cohort B had an RS ≤25 or a pCR [only 1 (3.0%) patient in cohort B], meeting the primary endpoint in cohort B (P < 0.01), but not in cohort A (P= 0.98). No new safety signals were identified. The efficacy of neoadjuvant treatment with letrozole plus palbociclib does not seem to depend on pretreatment RS for patients with RS ≥18. However, around half of patients with HR-positive/HER2-negative early breast cancer with an RS 26-100 at baseline achieved molecular downstaging with this regimen.

Outcomes of Ponseti Method for the Treatment of Clubfeet in Children With Spina Bifida.

While the Ponseti method is the primary treatment for idiopathic clubfoot, its application in treating myelodysplastic clubfeet is less certain. Myelodysplastic clubfoot tends to be more severe and difficult to treat. Although the Ponseti method can initially correct these cases, there is conflicting evidence about recurrence rates and the need for additional treatment. This study aims to assess the effectiveness of the Ponseti method in treating myelodysplastic clubfeet compared with idiopathic clubfeet over a 20-year period. The study conducted a retrospective review of medical records from patients treated for clubfoot at a single institution (2002 to 2021), comparing children with myelodysplastic and idiopathic clubfoot. Included patients were under 18, initially treated with Ponseti-casting, and had a minimum 2-year follow-up. Data on demographics, treatment details, recurrence, and Patient-reported Outcomes Measurement Information System (PROMIS) scores were analyzed. Forty-nine myelodysplastic and 512 idiopathic clubfeet in 366 patients met the inclusion criteria. Myelodysplastic cases had a median age of 5 months at presentation versus 2 months for idiopathic cases ( P =0.002). Initial correction was achieved in 95% of idiopathic and 87.8% of myelodysplastic feet ( P =0.185). Recurrence rates were higher in the myelodysplastic cohort, 65.3% versus 44.1% ( P =0.005). Surgery was necessary to treat recurrence in 59.2% of myelodysplastic and 37.7% of idiopathic cases, P =0.003. Follow-up was 3.9±1.8 years for myelodysplastic and 3.3±1.5 years for idiopathic feet, P =0.030. Myelodysplastic feet had lower PROMIS mobility scores; 31.94±7.56 versus 49.21±8.64, P <0.001. To the best of our knowledge, we report the largest series of myelodysplastic clubfeet treated by Ponseti casting and the first to assess PROMIS data. Overall, the Ponseti method is as effective in obtaining initial correction in myelodysplastic clubfoot as it is in idiopathic clubfoot. However, myelodysplastic clubfeet has a higher risk of relapse and increased need for surgical interventions. Children with spina bifida may need closer follow-ups and more stringent adherence to bracing. Level III-therapeutic studies-investigating the results of treatment.

Medical misinformation and fear of recurrence in patients with breast cancer.

354 Background: Fear of recurrence is a common yet underappreciated burden patients experience during and after cancer treatment. Medical misinformation about factors that influence risk of cancer progression/recurrence is also common. Little is known about the spread of medical misinformation and how it affects fear of cancer recurrence. Methods: From 7/2023 to 8/2023 patients completed an anonymous online survey administered by Breastcancer.org. Surveys were available in English and Spanish with eligibility: US resident, age ≥18 years, and breast cancer diagnosis within 10 years. Surveys assessed patient awareness of various factors purported to increase or decrease risk of cancer progression/recurrence and fear of recurrence (via validated FCRI-SF, scored 0-36, higher scores indicate greater fear, score ≥22 indicate clinical relevance). Multivariate analysis (MVA) assessed awareness of misinformation after controlling for age, race and ethnicity, marital status, and level of education. Chi-square assessed association between misinformation exposure and fear of recurrence. Results: Overall, 997 completed the survey. Median age was 62 (IQR 53-69), 86% were White, 5% Black, 4% Hispanic, and 3% Asian. 76% were married and 77% had completed a college or advanced degree. 52% were undergoing active cancer treatment at the time of assessment. Most (65%) reported hearing misinformation regarding factors that may INCREASE risk of cancer progression/recurrence. Specifically, patients heard that sugar (61%), deodorant (22%), vaccines (8%), cell phones (8%), and bra type (8%) could increase risk. Half (54%) reported hearing misinformation regarding factors that may DECREASE risk of cancer progression/recurrence. Specifically, patients heard that eating organic food (41%), oral vitamins/supplements (29%), alkaline diet/alkalized water (12%), vitamin infusions (7%), cleanses (5%), essential oils (5%), and oxygen therapy (4%) could decrease risk. Overall, 76% had reported at least one incorrect factor influencing risk of cancer progression/recurrence. On MVA, younger age (OR 0.99/year of age, 95%CI 0.97-1.00, p=0.044) and Hispanic ethnicity (OR 2.98, 95%CI 1.02-8.25, p=0.047) were associated with hearing misinformation. Fear of recurrence score was available for 695 (70%) patients. Median score was 19 (IQR 13-24), 38% had a clinically significant level of fear (≥22). Awareness of medical misinformation was not associated with clinically significant fear (38% vs. 35%, χ 2 0.53, p=0.469). Conclusions: In a large cohort of patients with breast cancer, medical misinformation about risk of progression/recurrence was common. Fear of recurrence was high in over a third of surveyed patients, but was not associated with awareness of false information. Further understanding of how patients perceive and process medical misinformation is essential, especially in populations at highest risk for misinformation spread.

Improving the OncotypeDX ordering process in patients with ER+ HER2- early-stage breast cancer: A longitudinal QI project.

292 Background: Use of the 21-gene recurrence score assay, OncotypeDX, is an NCCN category 1 recommendation to define adjuvant treatment planning for patients with hormone receptor positive (HR+), HER2 negative (HER2-) early-stage breast cancer. The assay is a key part of the decision-making process to define who may benefit from adjuvant chemotherapy with delays in testing that may impact patient care and loss of trust between oncologists and patients. Methods: We first created a comprehensive process map of the system in place to order OncotypeDX and met with an interdisciplinary team to determine the best area of intervention. A nurse coordinator from medical oncology took over OncotypeDX ordering in September 2023. To determine impact, we obtained data on OncotypeDX orders (N=473) sent by medical oncologists at Washington University in St. Louis between 9/2022 and 4/2024. We determined the delay between specimen collection and OncotypeDX order and the time from order to delivery of the report in the electronic medical record system. We then assessed our outcome measure, the date of the first office visit after surgery and whether patients had an OncotypeDX test result at that visit for 270 consecutive orders spanning pre- and post-intervention (6/2023 – 4/2024). Results: We used a p-chart to assess our outcome measure of OncotypeDX availability at the time of office visit with medical oncology, a key metric for both treatment planning and patient trust. We observed a positive trend of seven data points in the most recent data when mapping the 270 patients by consecutive groups of 10. In our most recent data pull from April 2024, 85% (22/26) of patients who required an OncotypeDX had one completed at the time of office visit, in comparison to 50% (20/40) in August 2023, the month prior to the intervention. We used XmR and S charts to determine impact on delay from specimen collection to OncotypeDX order, which showed increased precision and a trend of decreased delay after implementing the nurse coordinator. The overall delay decreased from an average of 28 days pre-intervention (9/2022-9/2023) to 24 days in the most recent post-intervention data (3/2024). Average time between order and delivery, our balancing measure, decreased during these time periods from 16 days to 13 days. Conclusions: Implementing a nurse coordinator improved delays in specimen collection to order and order to receipt. This intervention increased the percentage of patients who had an OncotypeDX result at the time of office visit with medical oncology after surgery.

Identifying High Recurrence Risk in Breast Carcinoma Patients Through Spatial Transcriptomic Analysis.

Comparing gene expression profiles according to recurrence risk using spatially resolved transcriptomic analysis has not been reported. This study aimed to identify distinct genetic features of breast carcinoma associated with a high Oncotype DX Recurrence Score (ORS). Patients were categorized into two groups, ORS-high (ORS-H; two patients) and ORS-non-high (ORS-NH; five patients). We performed digital spatial profiling and bioinformatic analyses to investigate the spatial transcriptomic profiles. Lysozyme (LYZ), complement C1q C chain (C1QC), and complement C1q B chain (C1QB) exhibited the highest fold changes in the stromal compartment of the ORS-H group. Gene ontology enrichment analysis of the ORS-H group revealed significant up-regulation of genes associated with immune response in the stromal compartment, including lymphocyte-mediated immunity, adaptive immune response related to the immunoglobulin superfamily, and leukocyte-mediated immunity. Gene set enrichment analysis showed significant positive enrichment of gene sets associated with interferon (IFN) response and complement pathways in the stromal compartment. This study highlights significant differences in gene expression profiles and spatially resolved transcriptional activities between ORS-H and ORS-NH breast carcinomas. The significant up-regulation of genes and pathways associated with cell-mediated immunity, IFN response, and complement C1q in the stromal compartment of the ORS-H group warrants further evaluation with larger population cohorts.

Abstract C022: Pathomics-based classifiers for inferring breast cancer genomic assays and prognosis in sub-Saharan Africa: Results from the Ghana Breast Health Study

Abstract Background: Although several gene expression-based assays are validated for informing prognosis and treatment decision-making for breast cancer (BC) patients, their uptake has been hampered by technical complexities and cost, particularly in underrepresented and low-resource settings. Here, we explored whether machine learning-based features on standard hematoxylin and eosin (H&amp;E)-stained images can be used in conjunction with routinely available pathology data (pathomics) to infer clinically relevant tumor genomic assays among BC patients from a sub-Saharan African population. Methods: This study comprised 563 BC patients with diagnostic H&amp;E-stained images, clinicopathological data, and Nanostring gene expression data from the Ghana Breast Health Study (GBHS), a population-based case-control study that recruited BC patients between 2013 and 2015. H&amp;E images were analyzed using high-accuracy machine learning algorithms to extract data on several, prospectively selected, human interpretable imaging features. The assessed features encompassed characteristics of the tumor (e.g., average nuclear size, nuclear optical density, nuclear roundness, etc.) and stroma (e.g., degree of stromal cellularity, stromal cell phenotype, extent of stromal desmoplasia, remodeling, necrosis, etc.). Nanostring technology was used to generate data on PAM50 subtype [luminal (A and B), non-luminal (HER2-enriched and Basal), normal-like], 21-gene recurrence score (RS), and TP53 pathway function. Multivariable logistic regression models were fitted to luminal (vs other subtypes), non-luminal (vs other subtypes), TP53 mutant-like (vs wildtype-like), and RS (4th vs 1st quartile) data to develop predictive classifiers in a discovery set (60% of the data). The performance of the classifiers was then tested in a held-out internal validation set (40% of the data). Results: In the discovery set, the pathomics-based classifiers achieved varying but excellent discriminatory accuracy [AUROC = 0.90 (0.86-0.94), 0.94 (0.91-0.97), 0.95 (0.91-0.98), and 0.96 (0.94-0.99) for TP53, non-luminal, RS, and luminal classification, respectively]. In the held-out (validation) set, the corresponding AUROC values were 0.82 (0.75-0.88), 0.87 (0.81-0.92), 0.85 (0.77-0.92), and 0.88 (0.83-0.93) for TP53, non-luminal, RS, and luminal classification. The TP53 classifier was correlated with the luminal (R=-0.73), non-luminal (R=0.80), and RS (R=0.77) classifiers. The distribution of the pathomics-based TP53 probability score varied considerably between PAM50 subtypes (P&amp;lt;0.0001), and according to RS categories within both ER+ (P=0.009) and ER- (P=0.006) BC subtypes in the validation set. Conclusion: H&amp;Es are cost-effective and routinely performed as part of the diagnostic workup for BC patients. Accordingly, the results open promising avenues for the use of interpretable, machine learning-based, H&amp;E imaging and pathology data to infer breast tumor genomic signatures and prognosis in low-resource settings. Further work is required to validate findings in independent populations.: Citation Format: Mustapha Abubakar, Amber N. Hurson, Thomas U. Ahearn, Ebonee N. Butler, Alina M. Hamilton, Maire A. Duggan, Scott M. Lawrence, Ernest Adjei, Joe-Nat Clegg-Lamptey, Joel Yarney, Beatrice Wiafe-Addai, Baffour Awuah, Seth Wiafe, Kofi Nyarko, Francis Aitpillah, Daniel Ansong, Stephen Hewitt, Louise A. Brinton, Melissa A. Troester, Lawrence Edusei, Nicolas Titiloye, Jonine D. Figueroa, Montserrat Garcia-Closas. Pathomics-based classifiers for inferring breast cancer genomic assays and prognosis in sub-Saharan Africa: Results from the Ghana Breast Health Study [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C022.

Abstract A055: Neighborhood Deprivation and Oncotype DX Recurrence Scores among Black and White Women: the interplay between race, place, and tumor biology

Abstract Background: Breast cancer (BC) mortality disparities have persisted between non-Hispanic Black (NHB) and non-Hispanic White (NHW) women, even those diagnosed with prognostically favorable BC. The Oncotype Dx Recurrence score (ODX) test is a gene expression panel that can be used to identify estrogen receptor (ER)-positive BC with aggressive tumor biology. Previous studies have found that Black women are more likely to have higher ODX scores than White women and socioeconomic factors (e.g., area-level income, urbanicity) are associated with higher ODX scores. We explored race-stratified associations of neighborhood deprivation and ODX to help elucidate the interplay between race, place, and tumor biology. Methods: Neighborhood deprivation was examined in relation to ODX scores among 7,100 NHB and NHW women diagnosed with ER-positive BC (stage I–IIIA and ≤3 lymph nodes) between 2010–2017, followed through 2022, and identified by the Georgia Cancer Registry. The neighborhood deprivation index (NDI) was used to characterize neighborhood deprivation. Principal component analysis of block group-level American Community Survey data representing six domains (poverty, income, occupation, housing, employment, and education) was used to derive the NDI composite score. NDI was assessed in quartiles and linked to patient residence at the time of diagnosis. Three cut-points were used for ODX scores (low &amp;lt;18, intermediate 18–30, high ≥31). Prevalence ratios (PR) and 95% confidence intervals (CI) were calculated to determine the prevalence of ODX scores based on NDI by race/ethnicity. Results: This study included 1651 NHB and 5449 NHW women. There were 4152 (58.5%) with a low ODX Score and 514 (7.2%) with a high ODX score; 2773 (39.1%) resided in the least deprived neighborhoods (NDI quartile 1) and 928 (13.1%) resided in the most deprived neighborhood (NDI quartile 4). Living in the most deprived neighborhood was associated with an increased prevalence of high ODX scores in models adjusted for age, race, and stage (PR=1.23, 95% CI 0.97–1.62). Stratification by race showed associations were stronger among NHW women (PR=1.41, 95% CI 1.02–1.95) but null among NHB women (PR= 0.91, 95% CI 0.59-1.39). Overall, NHB women were more likely to have a high ODX compared to NHW women. The highest prevalence of a high ODX was observed among NHB women living in the least deprived neighborhoods (PR=1.92, 95% CI 1.34–2.77). Conclusions: Findings from this study suggest that living in a deprived neighborhood increases the prevalence of high ODX among NHW women but not NHB women. NHB women in the least deprived neighborhoods had the greatest prevalence of high ODX scores. The intersection between race, neighborhood, and tumor biology needs more nuanced investigation of the social-structural drivers of disparate BC outcomes. Citation Format: Jasmine M. Miller-Kleinhenz, Lauren E. Barber, Lindsay J. Collin, Maret L. Maliniak, Demetria J. Smith-Graziani, Lauren E. McCollough. Neighborhood Deprivation and Oncotype DX Recurrence Scores among Black and White Women: the interplay between race, place, and tumor biology [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A055.

21-gene recurrence score predictive of the benefit of postoperative radiotherapy after breast-conserving surgery for elderly patients with T1N0 and luminal breast cancer.

To assess the predictive value of the 21-gene recurrence score (RS) on the survival outcomes of postoperative radiotherapy (PORT) in elderly patients with T1N0 luminal breast cancer after breast-conserving surgery. We retrospectively included patients aged ≥ 70years and diagnosed with T1N0 luminal BC between 2004 and 2015 using the data from the Surveillance, Epidemiology, and End Results. The RS groups were categorized using the TAILORx criteria as follows: low risk (RS < 11) (LR), intermediate risk (RS 11-25) (IR), and high risk (RS > 25) (HR). Kaplan-Meier analysis, propensity score matching (PSM), and Cox proportional hazards analysis were used for statistical analysis. We included 5901 patients in the analysis. Of the patients, 4492 (76.1%) underwent PORT, while 1409 (23.9%) did not receive PORT. There were 1588 (26.9%), 3613 (61.2%), and 700 (12.0%) patients classified as LR, IR, and HR, respectively. There were 1182 (74.4%), 2773 (76.8%), and 537 (76.7%) patients in the LR, IR, and HR groups receiving PORT, respectively (P = 0.182). A total of 1353 pairs of patients were completely matched using PSM. PORT was independently associated with better overall survival (OS) (P < 0.001) and breast cancer-specific survival (BCSS) (P = 0.015) in the entire cohort. The sensitivity analyses showed that the receipt of PORT was not associated with OS (P = 0.887) and BCSS (P = 0.861) in the LR group. However, the receipt of PORT was associated with OS (P < 0.001) and BCSS in the IRHR group (P = 0.026). Our study highlights the possible role of the 21-gene RS in predicting the survival outcomes of PORT following BCS in elderly patients with T1N0 luminal breast cancer.

Quantitative Biomarkers, Genomic Assays, and Demographics Associated with Breast-Conserving Surgery Following Neoadjuvant Therapy in Early-Stage, Hormone Receptor-Positive, HER-Negative Breast Cancer

BackgroundGiven increased neoadjuvant therapy use in early-stage, hormone receptor (HR)-positive/HER2-negative breast cancer, we sought to quantify likelihood of breast-conserving surgery (BCS) after neoadjuvant chemotherapy (NACT) or endocrine therapy (NET) as a function of ER%/PR%/Ki-67%, 21-gene recurrence scores (RS), or 70-gene risk groups.MethodsWe analyzed the 2010–2020 National Cancer Database. Surgery was categorized as “mastectomy/BCS.” Logistic regression was performed. Adjusted odds ratios (AOR) were per 10-unit increase in ER%/PR%/Ki-67%.ResultsOverall, 42.3% underwent BCS after NACT, whereas 64.0% did after NET. Increasing ER% (AOR = 0.96, 95% confidence interval [CI] 0.94–0.97) or PR% (AOR=0.98, 95% CI 0.96–0.99) was associated with lower odds of BCS after NACT. Increasing Ki-67% was associated with greater odds of BCS (AOR = 1.07, 95% CI 1.04–1.10). Breast-conserving surgery rates increased by ~20 percentage points, with Ki-67% ≥15 or RS >20. Patients with a low (43.0%, AOR = 0.50, 95% CI 0.29–0.88) or intermediate (46.4%, AOR = 0.58, 95% CI 0.41–0.81) RS were less likely than patients with a high RS (65.0%) to undergo BCS after NACT. Increasing ER% was associated with higher odds of BCS after NET (AOR = 1.09, 95% CI 1.01–1.17). Breast-conserving surgery rates increased by ~20 percentage points between ER <50% and >80%. In both cohorts, the odds of BCS were similar between 70-gene low-risk and high-risk groups. Asian or uninsured patients had lower odds of BCS.ConclusionsNeoadjuvant chemotherapy is unlikely to downstage tumors with a low-intermediate RS, higher ER%/PR%, or lower Ki-67%. Breast-conserving surgery after NET was most dependent on ER%. Findings could facilitate treatment decision-making based on tumor biology and racial/socioeconomic disparities and improve patient counseling on the likelihood of successful BCS.

UTILITY OF HALP SCORE IN PREDICTING MORTALITY IN ACUTE ISCHEMIC STROKE

Acute ischemic stroke (AIS) poses significant mortality and morbidity risks. The HALP score, integrating hemoglobin, albumin, lymphocytes, and platelets, has been proposed as a potential marker for predicting outcomes in AIS patients. This study evaluates the predictive utility of the HALP score for mortality and recurrence in these patients. Objective: To assess the predictive value of the HALP score at admission for mortality and recurrent stroke within one and six months post-admission. Methods: In this prospective hospital-based cohort study, 1206 patients presenting with AIS were included. Patients were stratified into tertiles based on their HALP score at admission. The study accounted for age, gender, medical history, and NIHSS scores at baseline. Results: The cohort's mean age was 60.55 years, with 33.8% female. Patients with lower HALP scores showed worse outcomes, with 1.5% lost to follow-up and 1.3% experiencing poor outcomes at one month. At six months, 9.2% were lost to follow-up, and 8.8% had poor outcomes. Higher HALP scores correlated with reduced risk of adverse outcomes, with adjusted hazard ratios of 0.8 (95% CI: 0.05–0.19) at one month and 0.21 (95% CI: 0.13–0.34) at six months. Sensitivity and specificity were 16.1% and 25.4%, respectively, at one month and 24.6% and 36.4% at six months. Conclusion: The HALP score at admission significantly predicts mortality and recurrent stroke within the first six months post-AIS, supporting its integration into initial assessment protocols.

Association of Oncotype-DX HER2 Single Gene Score With HER2 Expression Assessed by Immunohistochemistry in HER2-low Breast Cancer.

"HER2-low" is an emerging subtype of breast cancer, with a documented role in predicting response to treatment with novel antibody-drug conjugates. It is defined based on immunohistochemistry, but increasing evidence is challenging this approach as appropriate for identifying the HER2-low subgroup, due to both interobserver variability and limitations of the method itself. We retrospectively analyzed data from 430 patients from our departmental databases who had been subjected to an Oncotype-DX score and assessed the correlation of the Oncotype-DX HER2 single-gene score with the HER2 expression on immunohistochemistry. The Oncotype-DX Recurrence Score was also evaluated in the HER2-0 versus HER2-low subgroups. The HER2 single-gene score was found to accurately correlate with the HER2 result on immunohistochemistry, with a statistically significant difference both between HER2-0 and HER2 +1 tumors (p<0.0001), as well as between HER2 +1 and +2 tumors (p<0.0001). There was no statistically significant difference in the recurrence score between the HER2-0 and the HER2-low subgroups. Oncotype-DX single-gene scores for HER2 are a potential surrogate marker for assessing the precise HER2 status, with better reproducibility and less interobserver variance compared to immunohistochemistry. The use of rt-PCR emerges as an alternative method of assessment of the HER2-low subgroup.