High 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.

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.

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

Given 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. We 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%. Overall, 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. Neoadjuvant 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.

Attempt to Substitute the Oncotype DX Breast Recurrence Score® Test by Histopathological Factors and MUC1 Protein Expression.

Oncotype DX Breast Recurrence Score® test (ODx) is a gene profiling assay predicting the benefit of adjuvant chemotherapy for early-stage hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Meanwhile, to avoid unnecessary financial burden on the patient, many studies have attempted to establish alternatives to ODx using conventional clinicopathological factors, but these have not yet been successful. Thus, we retrospectively investigated clinicopathological factors to establish alternatives to ODx. Data from 114 Japanese women who underwent ODx were retrospectively examined to investigate the relationship between ODx recurrence score (RS) and clinicopathological features, including MUC1 staining patterns on immunohistochemical assessment. An RS of 0-25 was defined as low, and 26-100 as high. Ninety patients (79%) had low RS and 24 patients (21%) had high RS. Univariate analysis revealed that low tumor grade, high progesterone receptor (PgR) expression, and low Ki67 labeling index (LI) were significantly associated with low RS (p=0.025, p<0.001, and p<0.001, respectively). Tumors with an apical pattern of MUC1 staining also frequently had a low RS (p=0.024). In multivariate analysis, PgR expression and Ki67 LI were independent factors associated with RS (p<0.001, for both). When the ODx results were categorized with a combination of these two factors, only 2% of the PgR-high and Ki67-low group (one in 51 cases) had a high RS. PgR expression and Ki67 LI were independent factors correlated with RS. MUC1 staining pattern also has the potential to be a useful marker. We believe that it is crucial to continue attempts to identify patients who are unlikely to benefit from ODx.

Prognostic value of the 21-Gene Breast Recurrence Score® assay for hormone receptor-positive/human epidermal growth factor 2-negative advanced breast cancer: subanalysis from Japan Breast Cancer Research Group-M07 (FUTURE trial).

This study aimed to determine whether the 21-Gene Breast Recurrence Score® assay from primary breast tissue predicts the prognosis of patients with hormone receptor-positive and human epidermal growth factor 2-negative advanced breast cancers (ABCs) treated with fulvestrant monotherapy (Group A) and the addition of palbociclib combined with fulvestrant (Group B), which included those who had progression in Group A from the Japan Breast Cancer Research Group-M07 (FUTURE trial). Progression-free survival (PFS) and overall survival (OS) were compared using the log-rank test and Cox regression analysis based on original recurrence score (RS) categories (Low: 0-17, Intermediate: 18-30, High: 31-100) by treatment groups (A and B) and types of ABCs (recurrence and de novo stage IV). In total, 102 patients [Low: n = 44 (43.1%), Intermediate: n = 38 (37.5%), High: n = 20 (19.6%)] in Group A, and 45 in Group B, who had progression in Group A were analyzed. The median follow-up time was 23.8months for Group A and 8.9months for Group B. Multivariate analysis in Group A showed that low-risk [hazard ratio (HR) 0.15, 95% confidence interval (CI) 0.04-0.53, P = 0.003] and intermediate-risk (HR 0.22, 95% CI 0.06-0.78) with de novo stage IV breast cancer were significantly associated with better prognosis compared to high-risk. However, no significant difference was observed among patients with recurrence. No prognostic significance was observed in Group B. We found a distinct prognostic value of the 21-Gene Breast Recurrence Score® assay by the types of ABCs and a poor prognostic value of the high RS for patients with de novo stage IV BC treated with fulvestrant monotherapy. Further validations of these findings are required.

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

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

Evaluating Ki67 and Oncotype DX Breast Recurrence Score during neoadjuvant treatment with letrozole/abemaciclib or chemotherapy in patients with highly proliferative HR+/HER2- breast cancer participating in the GEICAM CARABELA trial.

576 Background: CARABELA (NCT04293393) is a phase 2 randomized trial comparing 12 months of neoadjuvant letrozole/abemaciclib (let/abema) vs. 6 months of neoadjuvant chemotherapy (CT) for stage II-III, Ki67≥20%, HR+/HER2- breast cancer patients. Let/abema failed to show similar residual cancer burden (RCB) 0-I rates compared to CT (13% vs. 18%), highlighting the need to identify response biomarkers to CDK4/6 inhibitors and to determine which patients cannot avoid CT. Methods: We explored the predictive role of baseline (BL) Ki67 and Recurrence Score (RS) in tumor samples, and their changes during treatment. Ki67 was centrally determined using a standardized assay (Ki67 MIB-1 pharmDx, Dako Omnis, Agilent Technologies) at BL, 2 weeks (2w), and surgery. RS result was assessed at BL and at surgery (Exact Sciences), in the case of RCB=0, RS and Ki67 was assigned a value of 0. We examined the association of BL Ki67 and RS with RCB 0-I rates as independent variables, by logistic regression (adjusting by disease stage and cN), checking for treatment interaction. Results: BL Ki67 and RS showed similar distributions between arms; median Ki67: let/abema 38% vs CT 36% ( P=0.528); median RS: let/abema 27 vs CT 30 ( P=0.188). Although we could not detect a differential treatment effect based on BL Ki67 or RS, rates of RCB0-I were higher in the CT arm both for high Ki67 (≥40%) and high RS (&gt;25) (table 1). In addition, BL Ki67 as a continuous variable was associated to RCB 0-I only in the CT arm (OR 0.954; 95%CI 0.922-0.988, P=0.006), with an interaction P=0.05. Ki67 suppression was higher in let/abema arm, with a lower median Ki67 at 2w: let/abema 0% vs. CT 21.7% ( P&lt;0.0001), but not at surgery: let/abema 0% vs. CT 2.25% ( P=0.157). In addition, rates of Ki67 &lt;2.7% were higher with let/abema compared to CT at 2w (68% vs. 6%, P&lt;0.0001), but not at surgery (53% vs. 45%, P=0.157). Moreover, 17% of patients in the let/abema arm shifted from 2w Ki67&lt;2.7% to surgery Ki67≥2.7%, while only 2% did so with CT ( P&lt;0.0001). Median RS at surgery was higher in let/abema arm (22 vs. 19 in CT, P=0.028), and CT induced higher downstaging from BL high (&gt;25) to low (≤25) RS at surgery (36% vs. let/abema 20%, P=0.024). Conclusions: Highly proliferative tumors Ki67 (≥40%) or those with high Recurrence Score (&gt;25) exhibited higher rates of RCB 0-I when treated with chemotherapy, than when treated with letrozole/abemaciclib. This suggests that relying solely on letrozole/abemaciclib as systemic treatment for these tumors may be insufficient. Clinical trial information: NCT04293393 . [Table: see text]

Prediction of Oncotype DX Recurrence Score Based on Systematic Evaluation of Ki-67 Scores in Hormone Receptor-Positive Early Breast Cancer.

Oncotype DX (ODX) predicts the risk of recurrence and benefits of adding chemotherapy for patients with estrogen receptor positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-) early-stage breast cancer. We aimed to develop a simplified scoring system using readily available clinicopathological parameters to predict a high-risk ODX recurrence score (RS) while minimizing reproducibility issues regarding Ki-67 index evaluation methods. We enrolled 300 patients with ER+/HER2- early breast cancer, for whom ODX RS data were available in the test set. Using the QuPath image analysis platform, we systematically evaluated the average, hotspot, and hottest spot Ki-67 scores in the test set. Logistic regression analyses were conducted to establish a predictive scoring system for high-risk ODX RS. An independent validation set comprising 117 patients over different periods was established. Factors such as age ≤ 50 years, invasive ductal carcinoma tumor type, histologic grade 2 or 3, tumor necrosis, progesterone receptor negativity, and a high Roche-analyzed Ki-67 score (> 20) were associated with high-risk ODX RS. These variables were incorporated into our scoring system. The area under the curve of the scoring system was 0.8057. When applied to both the test and validation sets with a cutoff value of 3, the sensitivity of our scoring system was 92%. We successfully developed a scoring system based on the systematic evaluation of Ki-67 scoring methods. We believe that our user-friendly predictive scoring system for high risk ODX RS could help clinicians in identifying patients who may or may require additional ODX testing.

Combination of predicted sensitivity to endocrine therapy (SET2,3 index) and the Recurrence Score in node-positive breast cancer: Independent validation in the PACS-01 trial.

565 Background: SET2,3 index measures hormone receptor-related transcriptional activity (SETER/PR) adjusted for a baseline prognosis index (BPI) derived from tumor size, nodes involved and a 4-gene molecular subtype (RNA4). SET2,3 added prognostic information to the 21-gene Breast Recurrence Score (RS) in the SWOG 8814 trial (1). To confirm this, we independently evaluated both tests performed on node-positive, hormone receptor-positive (HR+) cancers from the PACS-01 trial (Roche et al, JCO 2006, PMID: 17116941) that evaluated the addition of adjuvant docetaxel to anthracycline-based chemotherapy. Adjuvant endocrine therapy became standard for premenopausal patients during PACS-01, justifying a sensitivity analysis in the population who received adjuvant endocrine therapy. Methods: SET2,3 was measured with the QuantiGene Plex bead-based hybridization assay (ThermoFisher) using an aliquot of residual RNA from prior RS testing in 791 HR+ tumor samples. Pre-defined cut points defined higher risk if RS &gt;25 or SET2,3 &lt;2.10. SETER/PR index and BPI, individual components of SET2,3 index, were evaluated as continuous variables. The primary endpoint was distant recurrence-free interval (DRFI). Multivariable Cox proportional hazards models were used to calculate hazard ratios with 95% confidence interval (HR, 95%CI) adjusted for treatment arm, and the likelihood ratio (LR) of benefit from addition of SET2,3 to RS with LR test for significance at p &lt;0.05. Results: Of 791 tumor samples, 760 (96.1%) passed quality control (QC) for the SET assay; 724 had pathologic information to calculate SET2,3 index; and 659 had results for RS and SET2,3. At a median follow-up of 8 years, distant recurrence occurred in 144 of 659 (21.9%) patients overall, and 94 of 490 (19.2%) patients in the sensitivity population. Overall, high RS status (HR 2.33, 1.60-3.39) and high SET2,3 (HR 0.43, 0.30-0.62) were independently prognostic. SET2,3 was high in 303/377 (80.4%) patients with RS ≤25, with 5-year DRFI of 93.7% [95%CI 90.2;95.9]; and SET2,3 was low in 171/282 (60.6%) patients with RS &gt;25, with 5-year DRFI 64.6% [95%CI 56.9;71.3]. SETER/PR index of endocrine transcriptional activity and the BPI, each contributed additional prognostic information to RS status in the sensitivity population (Table). Conclusions: SET2,3 index added prognostic information to the Recurrence Score in this independent blinded validation study of the PACS-01 trial for node-positive breast cancer. 1. Speers et al, JCO 2023, PMID: 36649570. [Table: see text]

Abstract PO4-20-03: HIPEx: Adjuvant palbociclib plus endocrine therapy in ER-positive HER2-negative early breast cancer with high recurrence score according to GenesWellTM BCT; a multi-center single arm phase II clinical trial (KCSG BR 19-13)

Abstract Background: In estrogen receptor (ER)-positive human epidermal growth factor receptor2 (HER2)-negative early breast cancer (EBC) patients, NCCN treatment guideline recommend 21-gene tests for decision of adjuvant chemotherapy if tumor size is over 0.5cm or node positive disease. In addition, GenesWellTM BCT is a prognostic assay that predict the risk of recurrence in patients with ER-positive HER2-negative and nodal stage 0-1 EBC. According to gene tests, EBC patients with high recurrence risk would have help from adjuvant chemotherapy to increase the rate of disease free survival but toxicities of chemotherapy are not negligible. Therefore, the effort for escaping adjuvant chemotherapy has been performed and currently CDK4/6 inhibitor would be considered as the substitute for cytotoxic chemotherapy in ER-positive HER2-negative EBC patients. Methods: HIPEx trial is a multi-center, phase II clinical trial to determine the efficacy of adjuvant palbociclib plus endocrine therapy in ER-positive HER2-negative EBC with high recurrence score according to GenesWellTM BCT (NCT04247633). Eligible patients are women who received curative surgery and diagnosed as ER-positive, HER2-negative and pathologic stage T1b-T2 and/or N0-1. Clinical recurrence risk is high according to the modified Adjuvant! Online guideline and GenesWellTM BCT score is 4 or more which being genomic high risk. Other criteria include ECOG performance status ≤1, adequate organ functions and availability of an archival surgical specimens. Patients receive palbociclib 125mg once daily for 21 days of 28-day cycle plus tamoxifen or aromatase inhibitor (anastrozole, letrozole or exemestane) once daily for every day. Palbociclib would be taken for two years and endocrine therapy for five years or more. If adjuvant radiotherapy is required, palbociclib should be taken two weeks after the end date of radiotherapy. If patients are premenopausal status, GnRH agonist is allowed. Primary endpoint is 3-year event free survival (EFS) rate of high clinical and genetic risk ER-positive EBC. Secondary endpoints include 3-year overall survival, quality of life, safety and tolerability of palbociclib with endocrine therapy as an adjuvant setting, exploratory analysis of predictive and prognostic biomarkers and the performance of GenesWellTM BCT for 3-year EFS rate. In total, 578 patients would be enrolled in this trial. Based on the previous results of GenesWell™ BCT in Korea, the 3-year EFS rate for the past control group (chemotherapy followed by endocrine therapy) is 87.0% and the treatment group in this clinical trial is assumed to be 90.5%.(hazard ratio for EFS = 0.717). Null hypothesis is the 3year-EFS rate in patients received adjuvant palbociclib and endocrine therapy is not less than that of the past control group. Alternative hypothesis is the 3year-EFS rate of this trial is less than that of the past control group (one-sided). Significance level is 0.025, power is 0.80. Considering 10% drop out rate, 4-years of accrual patient enrollment and 3-years of follow up period, 578 patients were required in this clinical trial. Citation Format: Ji-Yeon Kim, Sung Hoon Sim, Jieun Lee, In Hae Park, Kyong Hwa Park, Seock-Ah Im, Jee Hung Kim, Kyoung Eun Lee, Jeong Eon Lee, Jai Min Ryu, Young Kee Shin, Yeon Hee Park. HIPEx: Adjuvant palbociclib plus endocrine therapy in ER-positive HER2-negative early breast cancer with high recurrence score according to GenesWellTM BCT; a multi-center single arm phase II clinical trial (KCSG BR 19-13) [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 PO4-20-03.

Abstract PO2-15-01: EZH2 protein expression in early hormone receptor positive HER2 negative breast cancer with high recurrence score

Abstract Background: The 21 gene recurrence score assay (RS) is both prognostic and predictive of chemotherapy benefit in hormone receptor positive (HR+) HER2 negative (HER2-) breast cancer (BC). While patients (pts) with RS&amp;gt;26 benefit from chemoendocrine therapy, they remain with poorer outcomes than pts with lower RS. Overexpression of the enhancer of zeste homolog 2 oncoprotein (EZH2) is linked to poor prognosis in multiple cancers, and is associated with resistance to endocrine therapy in HR+/HER2- BC. We evaluated association between EZH2 expression and distant metastases in a single institution cohort of pts with HR+/HER2- BC and RS&amp;gt;26. Methods: Pts with ER+/HER2- BC and RS&amp;gt;26 who underwent surgery at our institution between 2011 and 2017 were identified from pathology database. All pts with available tumor specimens were included in analysis. Immunohistochemistry was performed to evaluate EZH2 protein expression within invasive tumor cells and quantified as follows: nuclear staining intensity was scored as 3 (strong), 2 (moderate), 1 (weak), and 0 (no stain). Percentage of positive nuclei at each intensity was multiplied, and all values were added to arrive at a final EZH2 score multiplied by 100, ranging from 0 (no nuclei staining) to 300 (strong nuclear staining in 100% of cells). The investigator scoring EZH2 staining was blinded as to pts clinical outcomes. EZH2 score was both evaluated as a continuous variable and dichotomized at a score of 140. Associations between EZH2 score and age at diagnosis, progesterone receptor (PR) status, tumor size, grade, node involvement, RS, and metastatic recurrence were determined by Kruskal-Wallis or Wilcoxon rank-sum tests for categorical variables and Spearman correlation coefficients for continuous variables. Results: 45 pts were included. Median (IQR) age was 60 (55, 69). 32 (71.1%) pts received chemotherapy. 37 (82.2%) pts received endocrine therapy. Tumor size was ≤2 cm in 26 pts (57.8%), and &amp;gt;2 cm but ≤5 cm in 19 pts (42.2%). 7 pts (15.6%) had involved axillary nodes. Median RS was 31 (28, 37). Median EZH2 score was 120 (90, 170). With median follow-up of 7.6 (5.7, 9.2) years, 4 pts (8.9%) developed distant metastatic disease. EZH2 score was significantly associated with development of metastatic disease, both when EZH2 was expressed as a continuous variable (p=0.040) and when dichotomized at 140 (p=0.015). EZH2 score was positively associated with RS (r = 0.37; p=0.013) and negatively associated with age at diagnosis (r = -0.44; p=0.002), but was not associated with clinicopathologic features such as tumor size, grade, node involvement, and PR status. Younger age was also associated with development of metastatic disease (p=0.023), whereas tumor size, grade, node involvement, PR status, RS, and receipt of chemotherapy were not. Conclusion: In this single institution cohort of pts with early HR+/HER2- BC and high RS, EZH2 protein expression and younger age were associated with development of distant metastases. This preliminary data suggests that determination of EZH2 expression levels may assist in risk stratification of pts with high RS. This should be investigated in a larger data set. Citation Format: Shuwen Lin, Yungtai Lo, Della Makower, Jinyu Lu, Susan Fineberg. EZH2 protein expression in early hormone receptor positive HER2 negative breast cancer with high recurrence score [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 PO2-15-01.

Abstract PO5-08-04: Characteristics of breast cancer in carriers of pathogenic variant in ATM in a large academic health center

Abstract Background: Pathogenic variants (PVs) in ATM are associated with an increased risk of breast, pancreas, and other cancers. The clinical and pathological characteristics of ATM-associated breast cancers have not been well defined. Methods: Patients who underwent multigene panel testing between December 2012 and May 2023 and were identified to harbor ATM PVs were included in the study. We analyzed demographics, germline findings, histopathology, genomic recurrence score, and management of ATM PV carriers with breast cancer. Results: A total of 222 individuals were identified to have PVs in ATM, of whom 184 (83%) were female. The majority were Caucasian (n = 179, 81%) and of those, 22 (12%) had Ashkenazi Jewish ancestry. The median age at genetic testing was 52y, with a range of 20-90y. A total of 111 patients (50%) had a personal cancer diagnosis, the most common of which was breast cancer (n = 70; 63%). The median age at breast cancer diagnosis was 53y, with a range of 25-84y. The most common histopathology was invasive ductal carcinoma (74%), followed by DCIS (21%), and invasive lobular carcinoma (5%). The majority of patients had breast tumors with stage 2 or 3 (78%), grade 2 or 3 (92%), ER and/or PR positive (92%) and HER2 negative (70%). One patient had triple-negative breast cancer. Forty-four percent of breast cancers were less than two centimeters, 23% were lymph node-positive, and 29% had lymphovascular invasion. Thirty-eight percent of patients underwent bilateral mastectomy, 54% received radiation therapy, 40% received adjuvant chemotherapy, 24% received neoadjuvant chemotherapy, and 70% received hormonal therapy. Of the 15 breast cancers with known 21-gene recurrence scores, 47% were intermediate (11-26), 33% were high (&amp;gt;=26) and 20% were low (&amp;lt; =10). Other notable cancers observed were pancreas (n = 9), colorectal (n = 6), prostate (n = 5), uterine (n = 4), melanoma (n = 4), and thyroid (n = 4). Conclusion: Our study outlines the clinical and pathological characteristics of ATM-associated breast cancer in a large academic center. The majority of breast cancers were invasive ductal type, early stage, intermediate or high grade, and hormone receptor-positive with an intermediate or high recurrence score. Despite the early stage, a significant proportion of patients underwent bilateral mastectomy. Further studies are needed to better elucidate the unique characteristics of breast cancer in ATM PV carriers in order to provide tailored management guidelines for this population. Citation Format: Ujjwal Karki, Tara Rangarajan, Dana Zakalik. Characteristics of breast cancer in carriers of pathogenic variant in ATM in a large academic health center [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 PO5-08-04.

Abstract PO1-14-12: Quantitative Biomarkers and 21-Gene Assay Results Predict Breast-Conserving Surgery Following Neoadjuvant Therapy in Early-Stage, Hormone Receptor-Positive, HER2-Negative Breast Cancer

Abstract Background: Neoadjuvant chemotherapy (NACT) and neoadjuvant endocrine therapy (NET) are often used to downstage tumors and/or enable breast-conserving surgery (BCS) in patients (pts) with early-stage, hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer. Given the increasing use of neoadjuvant therapy for HR+ breast cancer, studies are needed to better quantify the success of NACT/NET in downstaging tumors as a function of estrogen (ER), progesterone (PR), and Ki-67 expression, and 21-gene recurrence score (RS) in this patient population. Methods: Data were from pts with stage I-III, HR+/HER2- breast cancer diagnosed from 2010-2020 in the National Cancer Database (NCDB). Quantitative ER, PR, and Ki-67 data became available in 2018. We included pts who received either NACT or NET, with surgical plan categorized as mastectomy or BCS. Pts who received NACT for 12–30 weeks or NET for 4–36 months prior to surgery were eligible. Predicted rates of BCS by quantitative biomarkers (ER, PR, Ki-67 percentage, and RS) were estimated using restricted cubic spline logistic regression. Multivariable logistic regression models were fit to examine the associations between surgical plan and quantitative biomarkers for the two neoadjuvant cohorts. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were calculated per 10% increase in percentages of ER, PR, and Ki-67 expression. Results: Of 44,589 pts treated with NACT, the mean age was 53 years, the median amount of time they were on NACT before surgery was 21 weeks, and 65% had cT1-2 disease. Of 10,466 pts treated with NET, the mean age was 68 years, the median amount of time they were on NET before surgery was 6 months, and 76% had cT1-2 disease. Overall, 42% of pts underwent BCS after NACT; while 64% did after NET. In the NACT cohort, 13,752 of the pts with available quantitative biomarker data were included in regression analyses; in the NET cohort, 4,003 were included. After adjusting for demographic and clinicopathologic factors, increasing ER% (aOR=0.96, 95% CI: 0.94–0.97) and PR% (aOR=0.98, 95% CI: 0.96–0.99) were associated with lower odds of BCS after NACT. Increasing Ki-67% was associated with greater odds of BCS after NACT (aOR=1.07, 95% CI: 1.04–1.10). Pts with a low (aOR=0.50, 95% CI: 0.29–0.88) or intermediate (aOR=0.58, 95% CI: 0.41–0.81) RS were significantly less likely than pts with a high RS to undergo BCS after NACT. Asian pts were less likely than White pts to have BCS (aOR=0.75, 95% CI: 0.56–0.99), while rates of BCS after NACT were similar to pts from other racial and ethnic groups. In the NET cohort, increasing ER% was associated with greater odds of BCS (aOR=1.09, 95% CI: 1.01–1.17). There was no significant association between baseline PR% or Ki-67% and BCS after NET. Pts with a low (aOR=0.92, 95% CI: 0.60–1.43) or intermediate (aOR=0.96, 95% CI: 0.65–1.41) RS were numerically less likely than pts with a high RS to have BCS after NET, though not statistically significant. Compared with White pts, Asian pts were less likely to have BCS after NET (aOR=0.60, 95% CI: 0.40–0.91). Conclusions: In this analysis of pts from the NCDB who received neoadjuvant therapy for early-stage, HR+/HER2- breast cancer, we found that BCS after NACT was higher for patients with a high RS or high Ki-67, suggesting that NACT is unlikely to downstage tumors with a low/intermediate RS or low Ki-67. Most pts receiving NET underwent BCS (likely due to a smaller clinical tumor size); BCT after NET was most dependent on ER expression. Asian pts were less likely to undergo BCS after either NACT or NET, which is consistent with previous reports. These data could facilitate appropriate neoadjuvant treatment selection based on tumor biology and improve patient counseling on the likelihood of successful BCS. Citation Format: Jincong Freeman, Sarah Shubeck, Nan Chen, Rita Nanda, Dezheng Huo, Frederick Howard. Quantitative Biomarkers and 21-Gene Assay Results Predict Breast-Conserving Surgery Following Neoadjuvant Therapy in Early-Stage, Hormone Receptor-Positive, HER2-Negative 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 PO1-14-12.

Abstract PO3-15-04: Oncotype DX Recurrence Score as an Informative Tool to Optimize Neoadjuvant Therapy in HR-positive, HER2-negative Breast Cancers

Abstract Oncotype DX Recurrence Score as an Informative Tool to Optimize Neoadjuvant Therapy in HR-positive, HER2-negative Breast Cancers Background: Neoadjuvant therapy (NAT) in HR+/HER2- breast cancers rarely leads to pathological complete response (pCR) and often doesn’t achieve substantial tumor shrinkage. Therefore, neoadjuvant therapy in HR+/HER2- breast cancers has the most value in the assessment of in vivo treatment response. For this purpose, biomarkers that can predict clinical and pathological response to systemic therapy could help inform treatment. The role of Oncotype DX testing in the management of early-stage HR+/HER2- breast cancer has been widely recognized in the adjuvant setting. However, no large prospective studies evaluating the Oncotype DX test in the neoadjuvant setting have clearly shown its predictive or prognostic utility to date. In this study, we evaluated the effect of the recurrence score (RS) on systemic treatment recommendations and its correlation to NAT response. Methods: Patients with clinically selected T2-T4 and/or clinically node positive HR+/HER2- breast cancer who were referred to BC Cancer Vancouver for consideration of NAT between September 2021 – April 2023 were screened for study eligibility. Suitable candidates who agreed to participate in the study had Oncotype DX testing on core biopsy specimens and Ki-67 testing on the core biopsy and final resection specimen. Clinico-pathological information, treatment regimens, operative details, and clinical, radiologic, and pathological responses were recorded. Results: Of the 66 patients who met eligibility criteria, 40 enrolled in the study comprising the accrual rate of 60.6 %. There were multiple factors that influenced patients and/or Oncologists participation in the study highlighting the low uptake of NAT in HR+/HER2- tumors. Technical feasibility of obtaining Oncotype DX from core biopsy samples was 95% which correlates with our previously reported data on a smaller cohort. The mean turnaround time from patient consent to RS report was 18.5 calendar days. The mean time from the initial consult to the start of NAT was 18.8 calendar days. Amongst all tumors tested, 28 % had RS equal or greater than 26 while only 2 % of participants had a score less than 10. Overall, 32 % of treatment recommendations were changed based on RS. Approximately 31% of patients who were initially recommended to receive neoadjuvant chemotherapy were spared from this treatment based on low RS. Conversely, 23.8% of patients who were recommended to pursue upfront surgery were escalated to chemotherapy due to a high RS. Approximately 88 % of the participants who were treated with neoadjuvant chemotherapy had a favourable clinical response and 38.5% had a complete clinical response. There were no pCR observed amongst patients who completed surgery after neoadjuvant chemotherapy, but half of them were rendered eligible for less surgery (either spared a mastectomy and/or an axillary dissection). Conclusions: Oncotype DX testing changed systemic treatment recommendations in one third of neoadjuvant patients and presents a unique opportunity for personalized medicine. Pre-operative testing thus influenced clinical decision-making, allowing treatment de-escalation and omission of chemotherapy in those with a low RS and conversely an earlier escalation of systemic therapy for those with a high RS. Turnaround time of the Oncotype DX assay on a core biopsy sample was acceptable and did not significantly delay treatment initiation. The benefit of the Oncotype DX assay prior to NAT was valuable for predicting in vivo response although pCR was not observed in any of the patients enrolled. Analyses are ongoing to further correlate RS to neoadjuvant response and to dynamic Ki-67 and MRI changes. Citation Format: Lidiya Luzhna, Stephen Chia, Mehrnoosh Pauls, Nathalie Levasseur. Oncotype DX Recurrence Score as an Informative Tool to Optimize Neoadjuvant Therapy in HR-positive, HER2-negative Breast Cancers [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 PO3-15-04.

Abstract PO5-02-11: Is There A Survival Benefit With Adjuvant Chemotherapy Use In Elderly Breast Cancer Patients? A Retrospective Study Using The National Cancer Database

Abstract Background Geriatric patients (Age &amp;gt;=65 years) with Breast Cancer (BC) face a unique challenge due to the relatively lower functional status, as well as co-existing comorbidities. Studies like the recently published meta-analysis by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) group provide irrefutable evidence for the recurrence free survival benefit of anthracycline and taxane based adjuvant chemotherapy (ACT) regimes in early-stage BC patients. However, the age range of the trials analyzed ranged between 46-55 years, with underrepresentation of the geriatric group. The question on whether ACT results in an overall survival (OS) benefit for the elderly remains at large, which we hope to answer through our study. Methods The 2019 National Cancer Database (NCDB) was used to extract patients aged &amp;gt;= 65 years with breast cancer. We included stage 1-3 patients and stratified them into those who received ACT (ACT+) and those who did not (ACT-). Patients who received ACT were identified from the columns that specified the times of events from diagnosis or from the column for systemic therapy-surgery sequence. Patients should have had definitive surgery for their BC management to be included. Odds Ratio (OR) from logistic regression was used to analyze the utility of ACT based on various factors. Kaplan Meier (KM) survival curves and Hazard Ratio (HR) estimates from multivariate cox model was used to compare OS outcomes. Results Our cohort had 866,071 (ACT+: 642721, ACT-:223350) patients. The age distribution showed that ACT+ had 86.45% in the 65-80 years group and 13.55% in the &amp;gt;80 years group. ACT- had 68.32% aged 65-80 and 31.68% &amp;gt;80 years. The distribution of various demographic, pathologic and clinical factors by ACT use are shown in Table 1. Factors associated with ACT use based on OR estimates are shown in Table 2. ACT use is more likely in younger age group (65-80), lower comorbidity score, poorly differentiated and undifferentiated tumors, ER/PR negativity, T2 and lymph node positivity, those who underwent partial mastectomy and regional lymph node surgery, and HER2 positivity. Both 5-year (86.3 vs 74.2%) and 10-year (66 vs 50.8) OS were better with ACT+ (Table 2). The HR using propensity score (PS) weighted cox model revealed a higher hazard rate on omitting ACT [1.436, 95% Confidence Interval (CI) 1.417,1.456, p&amp;lt; .0001] (Table 2). HR estimates between ACT- vs ACT+, stratified by subgroups [Age (65-80, &amp;gt;80), T stage, grade (G), HER2] favored ACT use in all groups except G1 tumors (Table 3). Discussion Our study using a large national database, supports the use of ACT in the geriatric BC population by showing a clear OS advantage of 15.2% at 10 years. This benefit was observed even in BC patients aged more than 80 years with a HR of 1.683 when compared to ACT-, as represented in Table 3. While the existing literature provides robust evidence for ACT use in situations such as a high oncotype recurrence score, our study provides real-world evidence from a population-based dataset to supports its use in the elderly, including those above 80 years. The geriatric assessment recommended by the American Society of Clinical Oncology guideline for geriatric oncology should be followed in this setting. Utilization of geriatric assessment tools among oncologists has been poor with a survey revealing that 60% of providers did not utilize these tools in making treatment decisions. Limitations of our study include the potential for missing confounding factors and the retrospective nature of the study using a large database. Table 1 Demographic, pathological, and clinical characteristics of the study population and their distribution based on ACT use. Table 2 Odds Ratio for ACT use, KM survival curves and HR estimates of ACT use Table 3 HR estimates of mortality for ACT- vs ACT+ stratified by various subgroups Citation Format: Prashanth Ashok Kumar, Metlapalli Venkata Sravanthi, Dongliang Wang, Danning Huang, Abirami Sivapiragasam. Is There A Survival Benefit With Adjuvant Chemotherapy Use In Elderly Breast Cancer Patients? A Retrospective Study Using 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 PO5-02-11.

Abstract PO1-14-02: Real world application of a 21-gene recurrence score in a Swiss single center breast cancer population. A comparative analysis of treatment administration before and after TAILORx

Abstract PO1-14-02: Real world application of a 21-gene recurrence score in a Swiss single center breast cancer population. A comparative analysis of treatment administration before and after TAILORx

Abstract PS16-10: SPATIAL IMMUNE CELL DISTRIBUTION CAN REFINE PROGNOSIS IN EARLY-STAGE ER+/HER2-/LN- BREAST CANCER

Abstract Lymphocytic infiltrate is a known prognostic biomarker in estrogen receptor(ER)-negative breast cancers (BCs). Comparatively ER+ disease is putatively cold, however, there exists an infiltrate-rich subset of ER+ tumours with significant spatial heterogeneity and unknown clinical impact. Using serial sections taken from early-stage, ER+/HER2- breast tumours of Irish patients enrolled in the TAILORx trial (n=450), we aimed to investigate the prognostic potential of markers encompassing tumour architecture. Immunohistochemistry for Ki67 and CD45 (leukocyte common-antigen), and staining for haematoxylin and eosin was applied to all sections [1]. Classifiers for stromal fraction (SF), stromal-infiltrate (sTIL), Ki67-LI, and their spatial relationships within the tumour were generated using QuPath [2] and R Studio. Trained marker classifiers were validated against an expert pathologist (R2 of M-Score to: CD45%: 0.968, Ki67-LI: 0.814, sTIL: 0.864) to define observed lymphocytes as tumour or stromal-infiltrating, retain only tumour Ki67+ density, and to investigate SF. Cohort mean SF was 67.69% (range 16.35 – 98.29%), with marginally significant differences in recurrence prediction for cohort high v low SF by mean (c-index = 0.58, p&amp;lt; 0.032), and luminal A disease (p=0.037) only. sTILs did not differ significantly between high/low mean SF (Mann-Whitney p=0.6201), though sTIL was prognostic in the OncotypeDx intermediate Recurrence Score (RS) category overall (p=0.0076). This trend appeared strongest in intermediate RS patients receiving chemo-endocrine therapy (HT+CT) (p &amp;lt; 0.0001) vs endocrine therapy (HT) alone (p=0.86). Investigating the effects of prescribed therapy on sTIL-derived recurrence risk also revealed significant trends in those patients receiving HT+CT only (p &amp;lt; 0.00001) vs HT alone (p=0.26). Spatial analysis of sTILs suggest that tumours become more immune excluded as Oncotype Dx RS increases - particularly from intermediate to high RS (Wilcoxon Intermediate v High: p=0.0077), with significant differences in survival for high/low tumour-immune hotspots observed in Intermediate RS, HT+CT treated patients (p=0.0052). Further spatial analysis suggests that high normalised frequency of infiltrate [method adapted from 3] (within 7um of tumour cells) have negative prognostic impact for premenopausal patients (p=0.017), and inter-sectional analysis identifies niche tumour environments where high Ki67-LI colocalize with immune infiltrates[methods adapted from 4, 5], most notable in Intermediate RS tumours.. Overall these data suggest immune-spatial subsets can be used to refine risk stratification of ER+ breast cancer.

The added value of ultrasound imaging biomarkers to clinicopathological factors for the prediction of high-risk Oncotype DX recurrence scores in patients with breast cancer.

The Oncotype DX (ODX) recurrence score (RS), a 21-gene assay, has been proven to recognize patients at high risk of recurrence (RS ≥26) who would benefit from chemotherapy. However, it has limited availability and high costs. Our study thus aimed to identify ultrasound (US) imaging biomarkers and develop a prediction model for identifying patients with a high ODX RS. In this retrospective study, consecutive patients with T1-3N0-1M0 breast cancer who were hormone receptor positive and human epidermal growth factor receptor 2 (HER2) negative who had an available ODX RS were reviewed. Patients treated from May 2012 and December 2015 were placed into a training cohort, and those treated from January 2016 to January 2017 were placed in a validation cohort. Clinicopathologic data were collected, and preoperative US scans were analyzed. Univariable and multivariable regression analyses were performed to evaluate the independent predictors for a high-risk of breast cancer in the training cohort, and a nomogram was developed and evaluated with the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). A total of 363 patients were in the training cohort and 160 in the validation cohort, with the proportion with a high RS (RS 26-100) being 14% and 13.1%, respectively. Echogenic halo, enhanced posterior echo, low level of progesterone receptor (PR), and high Ki-67 index were identified as independent risk factors for high RS (all P values <0.05). The nomogram was constructed based on the combined model, which showed a better discrimination ability than did the clinicopathological model [combined model: AUC =0.95, 95% confidence interval (CI): 0.93-0.97; clinicopathological model: AUC =0.89, 95% CI: 0.86-0.92; P=0.001] and greater clinical benefit according to DCA. Furthermore, the nomogram was found to be effective in the validation cohort (AUC =0.90, 95% CI: 0.84-0.94), especially in patients with stage T1N0M0 disease (AUC =0.91, 95% CI: 0.84-0.95). US features may serve as valuable imaging biomarkers for the prediction of high recurrence risk in patients with T1-3N0-1M0 breast cancer and hormone receptor (HR)-positive and HER2-negative status. A nomogram incorporating PR status, Ki-67 index, and US imaging biomarkers showed a good discrimination ability in the early selection of patients at high risk of recurrence, especially in those with stage T1N0M0 disease.

Enhancing clinical decision support with genomic tools in breast cancer: A Scottish perspective

IntroductionThe Oncotype DX Breast RS test has been adopted in Scotland and has been the subject of a large population-based study by a Scottish Consensus Group to assess the uptake of the recurrence score (RS), evaluate co-variates associated with the RS and to analyse the effect it may have had on clinical practice.Materials & Methods: Pan-Scotland study between August 2018–August 2021 evaluating 833 patients who had a RS test performed as part of their diagnostic pathway. Data was extracted retrospectively from electronic records and analysis conducted to describe change in chemotherapy administration (by direct comparison with conventional risk assessment tools), and univariate/multivariate analysis to assess relationship between covariates and the RS. ResultsChemotherapy treatment was strongly influenced by the RS (p < 0.001). Only 30 % of patients received chemotherapy treatment in the intermediate and high risk PREDICT groups, where chemotherapy is considered. Additionally, 55.5 % of patients with a high risk PREDICT had a low RS and did not receive chemotherapy. There were 17 % of patients with a low risk PREDICT but high RS who received chemotherapy.Multivariate regression analysis showed the progesterone receptor Allred score (PR score) to be a strong independent predictor of the RS, with a negative PR score being associated with high RS (OR 4.49, p < 0.001). Increasing grade was also associated with high RS (OR 3.81, p < 0.001). Classic lobular pathology was associated with a low RS in comparison to other tumour pathology (p < 0.01). Nodal disease was associated with a lower RS (p = 0.012) on univariate analysis, with menopausal status (p = 0.43) not influencing the RS on univariate or multivariate analysis. ConclusionsGenomic assays offer the potential for risk-stratified decision making regarding the use of chemotherapy. They can help reduce unnecessary chemotherapy treatment and identify a subgroup of patients with more adverse genomic tumour biology. A recent publication by Health Improvement Scotland (HIS) has updated guidance on use of the RS test for NHS Scotland. It suggests to limit its use to the intermediate risk PREDICT group. Our study shows the impact of the RS test in the low and high risk PREDICT groups. The implementation across Scotland has resulted in a notable shift in practice, leading to a significant reduction in chemotherapy administration in the setting of high risk PREDICT scores returning low risk RS. There has also been utility for the test in the low risk PREDICT group to detect a small subgroup with a high RS.We have found the PR score to have a strong independent association with high risk RS. This finding was not evaluated by the key RS test papers, and the potential prognostic information provided by the PR score as a surrogate biomarker is an outstanding question that requires more research to validate.

Racial/ethnic differences in 21-gene recurrence score and survival among patients with estrogen receptor-positive breast cancer

BackgroundDespite numerous studies on racial/ethnic disparities among patients with breast cancer, there is a paucity of literature evaluating racial/ethnic differences in 21-gene recurrence score (RS) and survival differences stratified by RS risk categories. We thus performed an observational cohort study to examine racial/ethnic disparities in the context of RS.MethodsThe National Cancer Database (NCDB) was queried for female patients diagnosed between 2006 and 2018 with estrogen receptor (ER)-positive, pT1-3N0-1aM0 breast cancer who received surgery followed by adjuvant endocrine therapy and had RS data available. Logistic multivariable analysis (MVA) was built to evaluate variables associated with RS ≥ 26. Cox MVA was used to evaluate OS. Subgroup analyses were performed to compare the magnitude of racial/ethnic differences stratified by RS. P values less than 0.017 were considered statistically significant based on Bonferroni correction.ResultsA total of 140,133 women were included for analysis. Of these, 115,651 (82.5%), 8,213 (5.9%), 10,814 (7.7%), and 5,455 (3.9%) were NHW, Hispanic, Black, and API women, respectively. Median (IQR) follow up was 66.2 months (48.0–89.8). Logistic MVA showed that, compared with NHW women, Black women were associated with higher RS (≥ 26 vs < 26: adjusted odds ratio [aOR] 1.19, 95% confidence interval [CI] 1.12–1.26, p < 0.001), while HW (aOR 0.93, 95% CI 0.86–1.00, p = 0.04) and API women (aOR 1.03, 95% CI 0.95–1.13, p = 0.45) were not. Cox MVA showed that, compared with NHW women, Black women had worse OS (adjusted hazards ratio [aHR] 1.10, 95% CI 1.02–1.19, p = 0.012), while HW (aHR 0.85, 95% CI 0.77–0.94, p = 0.001) and API (aHR 0.66, 95% CI 0.56–0.77, p < 0.001) women had better OS. In subgroup analysis, similar findings were noted among those with RS < 26, while only API women were associated with improved OS among others with RS ≥ 26.ConclusionTo our knowledge, this is the largest study using nationwide oncology database to suggest that Black women were associated with higher RS, while HW and API women were not. It also suggested that Black women were associated with worse OS among those with RS < 26, while API women were associated with improved OS regardless of RS when compared to NHW women.