Distribution Of Recurrence Score Research Articles

Clinical-pathological characteristics associated with multigene assay risk scores, and prognostic impact of multigene risk scores in patients with invasive lobular carcinoma.

546 Background: Invasive Lobular Carcinoma (ILC), a unique breast cancer subtype, exhibits distinct clinical and pathological features. Multigene assays, notably the Oncotype DX (ODX) test, provide personalized prognostic insights in breast cancer. However, a research gap exists for clinical-pathological characteristics affecting multigene assay risk scores in ILC. This study aims to address this gap, investigating factors specific to ILC, distinct from those in invasive ductal carcinoma (IDC), contributing to refined risk stratification and personalized treatment decisions for ILC patients. Methods: Retrospective analysis was conducted on 238 ILC type breast cancer patients who underwent surgery at AMC between 2012 and 2022 and had undergone the ODX test. The ODX test assessed the Recurrence Score (RS) with defined categories: low (0-15), intermediate (16-25), and high (26 or above). Additionally, binary analysis categorized patients into low and high-risk groups using a cutoff of 25. The cutoffs were determined based on existing research findings. Results: Among patients undergoing ODX testing, the distribution of RS differed significantly between ILC and invasive ductal carcinoma (IDC) patients. Notably, the percentage of high-risk cases was higher in ILC (4.2%) compared to IDC (16.9%). Examination of patient characteristics revealed a prevalence of younger individuals, premenopausal status, and those undergoing breast-conserving surgery (BCS) among the low-risk binary group. In multivariate logistic regression analysis, PR negativity emerged as a significant factor influencing ODX high risk across the entire cohort (OR 23.224, 95% CI 3.732-144.527, p=0.001). Subgroup analysis by age identified specific risk factors, including PR negativity in younger patients (OR 11.896, 95% CI 1.247-113.523, p=0.031), larger tumor size (more than 2cm) (OR 4.180, 95% CI 1.229-14.214, p=0.022), and PR negativity in older patients (OR 25.030, 95% CI 3.505-178.756, p=0.001). Conclusions: In ILC, factors predicting ODX differ from IDC, emphasizing the need for tailored risk prediction models. PR negativity emerged as a consistent predictor of ODX high risk, warranting attention in risk stratification models. Recognizing this distinction is crucial for enhancing precision in prognostic assessments and optimizing patient management in ILC.

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

BRCA1/2 mutation carriers vs the general breast cancer population (N = 799,986): 21-gene assay-based molecular characterization

PurposeWe compared 21-gene recurrence score (RS) distribution and expression of the single-gene/gene groups within this assay between BC patients with pathogenic variants (PV) in BRCA1/2 vs the general 21-gene-tested BC population.MethodsThis retrospective study included consecutive 21-gene-tested female ER + HER2-negative BC patients with germline PVs in BRCA1/2. RS/gene expression data were compared to a previously described commercial use database (CDB, N = 799,986). Chi-square and 1-sample t test were used to compare RS distribution and single-gene/gene group scores between the study group and the CDB.ResultsStudy group patients (N = 81) were younger and their RS results were higher compared to the CDB (age: median [IQR], 56 [47–61.5] vs 60 [51–67] years; p < 0.001; proportion of patients with RS ≥ 26: 49.4% vs 16.4%, p < 0.001). Expression of 12/16 cancer genes in the assay and the ER, proliferation, and invasion gene group scores differed significantly between the study group and the CDB, all in a direction contributing to higher RS. The differences between the study group and the CDB were mostly retained, upon stratifying the patients by menopausal status.ConclusionBC patients with PVs in BRCA1/2 have higher RS results that stem from distinct gene expression profiles in the majority of genes in the 21-gene assay.

Oncotype Dx Score, HER2 Low Expression, and Clinical Outcomes in Early-Stage Breast Cancer: A National Cancer Database Analysis.

The interaction between HER2-low expression, oncotype recurrence score (RS), and their influence on the prognosis of HR+/HER2- breast cancer (BC) is not very well studied. We conducted a retrospective cohort study of patients diagnosed with resectable HER2-low and HER2-zero BC from the National Cancer Database. The primary outcome was overall survival (OS), and the association of RS with the clinical outcomes in HR+/HER2- BC was analyzed as an exploratory endpoint. The distribution of RS was comparable between HER2-low and HER2-zero groups; however, the RSs of HER2-low tumors were more likely to be 16-25. Women with HER2-low tumors had longer 5-year OS than women with HER2-zero tumors in the HR-negative (84.3% vs. 83.9%; p < 0.001, HR: 0.87 (0.84-0.90), p < 0.001) but not in the HR-positive group (94.0% vs. 94.0%; p = 0.38, HR: 0.97 (0.95-0.99), p = 0.01). The survival advantage was observed in patients who received adjuvant/neoadjuvant chemotherapy (p-interaction (chemo vs. no chemo) < 0.001). Among those who received adjuvant chemotherapy in the group with higher RSs (26-100), those with HER2-low BC had higher 5-year OS than HER2-zero BC. Resectable HER2-low BC had a better prognosis than HER2-zero BC. Among those who received adjuvant chemotherapy in the higher oncotype RS group, those with HER2-low tumors had better survival.

Abstract P6-01-41: Influence of HER2 expression status in the distribution of recurrence score from the OncotypeDx assay among women with early-stage estrogen-receptor-positive/HER2-negative breast cancer

Abstract BACKGROUND: The OncotypeDX assay analyzes the expression of 21 genes, including HER2 and Grb7, to assess the predictive effect of chemotherapy in breast cancer recurrence among women with early-stage estrogen-receptor (ER) positive/HER2-negative breast cancer. In this study, we evaluate the distribution of recurrence score from the OncotypeDX assay based on the HER2 expression status by immunohistochemistry (IHC). METHODOLOGY: Utilizing the National Cancer Database, we identified adult women with a diagnosis of stage I – III ER+/HER2- invasive ductal carcinoma of the breast between the years 2010 and 2018. Recurrence scores were classified into low (&amp;lt; 11), intermediate (11-26), and high risk (&amp;gt;26); and the distribution of these recurrence scores cross-tabulated with different IHC scores of HER2 expression (0, 1+, and 2+) by IHC. Women with an IHC score of 2+ had to be negative for HER2 gene amplification by FISH. Multivariate logistic regression model adjusting for age, race, origin, progesterone receptor status, grade, and cancer stage was used to assess the odds of receiving a high OncotypeDx Score (≥26). RESULT: Among 198,931 women with ER+/HER2 negative breast cancer, 59,632 (30.0%) had HER2 IHC score of 0, 102,170 (51.4%) had IHC score of 1+, and 37,129 (18.6%) women were with IHC score of 2+. The median age at diagnosis of breast cancer among all three categories of HER2 expression was 59 years. The median recurrence score for women with IHC scores of 0,1+, and 2+ was 15, 15, and 16 respectively (p &amp;lt; 0.001). A higher proportion of women with HER2 IHC score of 2+ had a high recurrence score compared to women with an IHC score of 0 (15.2% vs. 13%, p &amp;lt; 0.001). In multivariate analysis, compared to women with HER2 IHC score of 0, women with HER2 IHC score of 2+/FISH negative were observed to have higher Odds (OR: 1.16; 95% CI: 1.11 – 1.20, p &amp;lt; 0.001) of receiving high recurrence score. There was no significant difference in the odds of receiving a high recurrence score between women with IHC 0+ and 1+(OR: 0.99; 95% CI: 0.96 – 1.03, p 0.82). CONCLUSION: Women with a HER2 IHC score of 2+ were observed to have a higher odds of receiving high-risk recurrence scores as compared to women with IHC score of 0. This needs to be further correlated with the response to chemotherapy and the risk of recurrence. Citation Format: Anish Shah, Pravash Budhathoki, Suman Gaire, Utsav Joshi, Siddhartha Yadav. Influence of HER2 expression status in the distribution of recurrence score from the OncotypeDx assay among women with early-stage estrogen-receptor-positive/HER2-negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-41.

Abstract P5-14-13: Benefits of Oncotype DX genomic screening in a geriatric vs. non-geriatric cohort. Analyzing key factors in therapy decision making process

Abstract Introduction In early luminal HER2 negative breast cancer Oncotype DX® Recurrence-Score (RS) has been broadly validated in pre- and postmenopausal patients and can predict prognosis and benefit of chemotherapy. Its value in elderly breast cancer populations has not been deeply addressed. This study analyses clinical and pathologic factors, RS distribution and outcomes in an elderly vs. non-elderly breast cancer population with the purpose of establishing RS added value to the therapy decision-making process in a geriatric cohort. Methods This is a retrospective analysis of available data from patients with early luminal HER2 negative breast cancer treated at the University Hospital Basel and the Cantonal Hospital Baselland between 2010 and 2022. Cohort A (A) consists of patients &amp;lt; 70 years old and cohort B (B) of patients aged ≥70 years. At moment of decision for adjuvant treatment all patients had known RS result. Results A and B included 266 (81%) and 60 (19%) patients, respectively. The median age in A was 55.2 and in B, 74 years. The following clinical and pathologic factors were different in B vs. A: co-morbidities (55 % vs. 35%, p=0.005), BMI (BMI≥25 (overweight vs. normal, p=0.023), tumor size (31.3 mm vs 23.6 mm p=0.021). Geriatric patients also tended to have a clinically higher risk status (83% vs. 70%; p=0.05). There was a trend for a higher mastectomy rate in B vs. A (41.7% vs. 29%, p=0.065), significantly less radiotherapy use (65% vs. 81%, p=0.009) and more osteo-oncologic treatment (61% vs 43%, p=0.013). RS distribution was not significantly different between cohorts (A vs. B was: RS 1-15: 44.3% vs 41.7%, RS 16-25 41.2% vs 35% and RS≥26 14.5% vs 23.3%; p=0.234). Adjuvant chemotherapy was performed in 11.5% of B and 22.9% of A (p=0.116) and adjuvant endocrine therapy in 98.3% of B vs. 93.5% of A (p=p=0.214). Tumor board suggested systemic treatment was not implemented in 22% vs 15 %, (B vs. A; p =0.087). With a median follow-up of 36.6 months, recurrence rate was higher, but not statistically significant in B vs. A (10% vs 6%, p=0.259). Relapse rate was higher with RS≥26 vs. RS 0-25 (13.5% in B vs. 5.7% in A; p=0.043). Conclusions Older breast cancer patients tend to have higher clinical risk status, more co-morbidities and higher BMI. RS distribution was not significantly different between the two cohorts, however higher RS did pose a higher relapse rate for older patients in our cohort. Although RS based guidelines, still apply in therapy decision making in the case of geriatric breast cancer patients, clinical practice points to a rather individualized treatment in which all clinical and pathological factors are weighted. Citation Format: Elena D Chiru, Cvetka Grasic Kuhar, Anton Oseledchyk, Christian Kurzeder, Marcus Vetter. Benefits of Oncotype DX genomic screening in a geriatric vs. non-geriatric cohort. Analyzing key factors in therapy decision making process [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-14-13.

Abstract PD1-09: Associations between the 21-gene Oncotype DX Recurrence Score (RS), Ki67, and Race in Early Breast Cancer (EBC) Using the National Cancer Database (NCDB)

Abstract Background: The 21-gene RS (Oncotype DX) is a validated genomic signature that provides prognostic information for distant recurrence risk and is predictive of adjuvant chemotherapy benefit in patients with hormone receptor (HR)-positive, HER2-negative early breast cancer (EBC). Ki67 protein expression is a proliferation marker that is determined by immunohistochemistry (IHC) and is a prognostic biomarker in HR-positive EBC. Black race is associated with poorer prognosis in patients with EBC. RS, Ki67 and race have not been evaluated together and the impact of race on the association between Ki67 and RS is unknown. The goal of this study was to evaluate the association between the 21-gene RS and Ki67 based on race in patients with HR-positive EBC using the NCDB. Methods: Women with HR-positive EBC with 0-3 involved lymph nodes, diagnosed between 2018 and 2019, who had available information on RS, IHC-measured Ki67, and race in the NCDB dataset were identified. Patients were stratified by RS of low (0-10), intermediate (11-25) and high (26-100) and categorized into Ki67 low (/=30%) based on the International Ki67 Working Group prognostic classification (PMID: 33369635). Wilcoxon rank test was used to test for continuous variables and chi-square test was used for categorical variables. Agreement between Ki67 and RS was estimated using Fleiss Kappa statistic and corresponding p-value was reported. Results: 43,898 eligible women were included. 17.43% were lymph node positive. 78% were Non-Hispanic White, 7.98% Non-Hispanic Black, 6.42% Hispanic, and 4.26% Asian American/Pacific Islander (AAPI). The table below describes the distribution of Ki67 and RS in the overall population and racial subgroups. The distribution of Ki67 scores was significantly different between races with a higher proportion of Black patients having high Ki67 scores, p&amp;lt; 0.0001. RS distribution varied as well with a greater percentage of high RS in the Black group, p&amp;lt; 0.0001. There was only slight agreement (Kappa 0.01-0.20) between Ki67 and RS in the overall population (Kappa=0.1929, p&amp;lt; 0.0001), low Ki67 subgroup (Kappa=0.069, p&amp;lt; 0.0001) and intermediate group (Kappa=0.066, p&amp;lt; 0.0001). However, there was fair agreement (Kappa 0.21-0.40) between high Ki67 and RS (Kappa=0.351, p&amp;lt; 0.0001). Based on race as a covariate, in the overall population, agreement between Ki67 and RS remained slight for White, Hispanic, and AAPI groups but was fair for Black patients (Kappa=0.2345, p&amp;lt; 0.0001). In the low Ki67 and intermediate Ki67 groups, agreement remained slight across all races, p&amp;lt; 0.0001. While there was fair agreement between high Ki67 and RS in all racial subgroups, agreement between high Ki67 and RS was highest in the Black subgroup (Kappa=0.392, p&amp;lt; 0.0001) followed by the AAPI (Kappa=0.363, p&amp;lt; 0.0001), White (Kappa=0.342, p&amp;lt; 0.0001) and Hispanic (Kappa=0.339, p&amp;lt; 0.0001) groups. Conclusions: In this large patient population from the NCDB, there was only slight agreement between Ki67 and RS in the overall, low Ki67, and intermediate Ki67 groups but fair agreement in the high Ki67 group. Agreement between high Ki67 and RS was greatest in the Black subgroup compared to other races. This may be attributed to the higher proportion of patients with high Ki67 and RS in the Black subgroup. Future analyses on overall survival will determine the impact of race on the prognostic value of Ki67 and RS. Table 1. Distribution of Ki67 and RS by Racial/Ethnic Subgroup AAPI: Asian American/Pacific Islander AIAN: American Indian and Alaska Native Citation Format: Rima Patel, Deukwoo Kwon, Grace Van Hyfte, Joseph Sparano, Amy Tiersten. Associations between the 21-gene Oncotype DX Recurrence Score (RS), Ki67, and Race in Early Breast Cancer (EBC) Using the National Cancer Database (NCDB) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD1-09.

Abstract GS1-01: Race and clinical outcomes in the RxPONDER Trial (SWOG S1007)

Abstract Introduction: Racial disparities in breast cancer (BC) outcomes continues to be a major health care challenge. The 21-gene recurrence score (RS) is an important tool to guide treatment (tx) decisions among women with early-stage BC. We report an analysis of clinical characteristics, survival outcomes and race in association with RS in participants (pts) in the RxPONDER trial. Methods: We analyzed clinical outcomes with respect to race and ethnicity. Unreported race excluded 18.7% of the pts, with most due to privacy rules. The primary outcome was invasive disease-free survival (IDFS). Distant relapse-free survival (DRFS) was also evaluated. Analyses adjusted for assigned tx arm, RS, and grade were performed. There were too few events to include Native American/Pacific Islander (NAPI) women in the survival analyses. Results: A total of 4,048 trial women with Hormone Receptor positive, HER2 negative (HR+/HER2-) BC, 1-3 involved axillary lymph nodes (LNs), RS ≤ 25 and known race/ethnicity were included in this analysis including the following: 2,833 non-Hispanic (NH) White pts (70%), 248 NH Black pts (6.1%), 610 Hispanic pts (15.1%), 324 Asian pts (8.0%), and 33 NAPI pts (0.8%). Asian and Hispanic women were younger than NH Whites (by 7.1 and 2.4 years, respectively) but NH Blacks did not differ in age. RS distribution did not differ among all racial subgroups (p=0.49). There were also no significant differences in tumor size (p=0.10) or number of positive LNs (p=0.26) across all racial groups. However, tumor grade was found to be significantly different with grade 3 tumors higher for NH Blacks (18.0%), NH NAPI (21.1%), and Hispanics (14.5%) vs. NH Whites (10.4%) and Asians (6.5%) (p&amp;lt; 0.001). Overall five-year IDFS was lower for NH Blacks (87.0%) compared to that for Asians (93.9%), NH Whites (91.5%), and Hispanics (91.4%) (Table 1). A multivariable Cox model adjusting for RS and tx arm showed worse IDFS for NH Blacks compared to NH Whites (HR=1.38; 95% CI 1.00-1.90; p=0.048), although Asian pts had better IDFS than NH Whites (HR=0.65; 95% CI 0.44-0.97; p=0.034). In a separate analysis by menopausal status the magnitude of the IDFS hazard ratios (HRs) for NH Blacks was similar, although no longer statistically significant (premenopausal HR=1.37; 95% CI 0.69-2.72; postmenopausal HR=1.38; 95% CI 0.96-1.98). While there was no statistically significant interaction between NH Blacks vs. NH Whites and tx arm for either premenopausal (p=0.99) or postmenopausal women (p=0.44), adjusting for RS, the small number of events in the NH Black cohort, particularly in premenopausal women (n = 9 IDFS events), limit power and inference about differences in chemotherapy benefit. Among postmenopausal women, NH Blacks had worse DRFS compared to NH Whites (HR=1.69; 95% CI 1.12-2.53; p=0.01), adjusting for tx and RS. A similar trend was seen among premenopausal women (HR=1.74; 95% CI 0.79-3.82; p=0.17), although not statistically significant. Data on tx adherence over 5 years was not mature, although NH Blacks were more likely to accept tx assignment compared to NH Whites at randomization (93% vs. 86%, p=0.004). Conclusion: Black women with HR+/HER2- BC, 1-3 involved LNs and RS ≤ 25 have worse outcomes compared to White women despite similar RS results. There was no significant interaction between NH Blacks vs. NH Whites and tx arm, although this analysis was limited due to sample size. There remains an important need for novel approaches to improve clinical outcomes particularly for NH Black Women. Table 1. IDFS by Race and Ethnicity. Citation Format: Yara Abdou, William E. Barlow, Julie R. Gralow, Funda Meric-Bernstam, Kathy S. Albain, Daniel F. Hayes, Nancy U. Lin, Edith A. Perez, Lori J. Goldstein, Stephen K. Chia, Sukhbinder Dhesy-Thind, Priya Rastogi, Emilio Alba, Suzette Delaloge, Anne F. Schott, Steven Shak, Priyanka Sharma, Danika L. Lew, Jieling Miao, Joseph M. Unger, Debu Tripathy, Lajos Pusztai, Gabriel N. Hortobagyi, Kevin Kalinsky. Race and clinical outcomes in the RxPONDER Trial (SWOG S1007) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS1-01.

Abstract P3-05-59: ER+ HER2-negative mBRCA1/2 carriers breast cancer patients (n=81): Clinical outcomes and molecular characterization via the 21-gene Breast Recurrence Score (RS) test vs the general RS-tested population (799,986 samples)

Abstract Background: The RS assay is a validated prognosticator/predictor of chemotherapy (CT) benefit in ER+ HER2-negative early-stage breast cancer (BC). It is offered to pts irrespective of BRCA1/2 status. We compared RS results, single-gene expression and gene group scores, between pts with germline BRCA1/2 mutations and the general BC pt population undergoing RS testing. Treatments/outcomes in the mBRCA1/2 cohort were also examined. Methods: This real-life retrospective cohort study included consecutive ER+ HER2-negative mBRCA1/2 female carriers BC pts who had RS testing in 2004-2015. RS and gene expression data were compared to a previously described commercial use database (DB) (J Surg Oncol. 2020;122:611). Chi-square test and 1-sample t-test were used to compare RS distribution and single gene/gene group scores, respectively, between the cohort and the DB. Independent sample t-test was used to compare gene expression/gene group scores across pt subgroups within the mBRCA1/2 cohort. Fisher’s test/logistic regression were used to identify variables associated with distant recurrence in the mBRCA1/2 cohort. Results: The analysis included 81 pts in the mBRCA1/2 cohort and 799,986 BC samples in the DB. Age at diagnosis was younger in the mBRCA1/2 pts vs the DB (median [IQR], 56 [47-61.5] vs 60 [51-67] yrs; P&amp;lt;.001). In mBRCA1 and mBRCA2 pts (32 and 48 pts, respectively; for 1 pt, the BRCA gene involved was unknown), RS distribution shifted towards the high RS category when compared to the DB (Table). Comparing single-gene expression and gene group scores in mBRCA1 pts vs the DB, revealed statistically significant differences in 12 of the 16 cancer genes in the RS assay, and in 2 gene group scores, all in a direction contributing to higher RS results. Similar analysis with mBRCA2 pts, revealed significant differences in expression of 10 genes and 3 gene group scores, all in a direction contributing to higher RS results. The only statistically significant difference in gene expression between the mBRCA1 and mBRCA2 pts was in the ESR (higher in mBRCA2 pts; P=.0407) and MYBL2 gene (higher in mBRCA1 pts; P=.0365) (Table). Of the 32 mBRCA1 pts, 18 (56%) received CT (RS 0-25, 1/14 [7%]; RS 26-100, 17/18 [94%]; treatment information was unavailable for 1 pt). Of the 48 mBRCA2 pts, 19 (40%) received CT (RS 0-25, 5/27 [19%]; RS 26-100, 14/21 [67%]). With a median (IQR) follow up of 8.2 (5.6-9.7) yrs from diagnosis, 9 pts had distant recurrence (1 mBRCA1 pt, 8 mBRCA2 pts). Their median RS result was 25 (range, 16-41), and 4 received adjuvant CT. No statistically significant differences were observed between these 9 pts and the 72 non-recurring pts in terms of pt/disease characteristics and CT treatment. A trend towards significance was observed with respect to the BRCA gene involved (recurrence rate of 3.1% in mBRCA1 pts vs 16.7% in mBRCA2 pts, P=.078). A statistically significant association was found between the proliferation and invasion gene group scores and the odds of having distant recurrence (proliferation group score: odds ratio [OR], 23.60 [95% CI, 1.4-397], P=.0281; invasion group score: OR, 5.1 [95% CI, 1.1-23], P=.0339). The ER and HER2 gene groups scores were not associated with distant recurrence. Conclusions: Both mBRCA1 and mBRCA2 carriers are characterized by higher RS results that stem from a distinct gene expression profile of most genes in the RS assay. Single Gene Expression and Gene Group Scores vs the Commercial Use DB Citation Format: Rinat Yerushalmi, Adi Pomerantz, Ron Lewin, Shani Paluch-Shimon, Lior Soussan-Gutman, Frederick Baehner, Hillary Voet, Avital Bareket-Samish, Inbal Kedar, Yael Goldberg, Tamar Peretz-Yablonski, Luna Kadouri. ER+ HER2-negative mBRCA1/2 carriers breast cancer patients (n=81): Clinical outcomes and molecular characterization via the 21-gene Breast Recurrence Score (RS) test vs the general RS-tested population (799,986 samples) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-59.

Abstract P3-05-27: The impact of co-existing ductal carcinoma in situ in invasive early hormone receptor positive breast cancer on the genomic and clinical risk of recurrence

Abstract Background: Invasive early breast cancer (IBC) often presents with a co-existing ductal carcinoma in situ (DCIS) component, while about 5% of the cases present with an extensive (&amp;gt;25%) intraductal component (EIC). The presence of a DCIS component was previously shown to be associated with favorable clinico-pathological characteristics and survival outcomes. However, the association between co-existing DCIS and genomic risk of recurrence is unclear. Methods: Patients with early hormone receptor positive (HR+) HER2neu-negative (HER2-) breast cancer and known OncotypeDX breast recurrence score (RS), who underwent breast surgery in our institute, were included. A natural language processing (NLP) algorithm was used to identify co-existence of extensive DCIS (DCIS-H) and non-extensive DCIS (DCIS-L) in surgical pathological reports. Genomic risk was determined using OncotypeDX RS, while clinical risk was calculated according to the MINDACT criteria, based on tumor size and grade. The genomic and clinical risks of DCIS-H, DCIS-L and pure IBC (No-DCIS) were compared. Results: A total of 45 (5%) DCIS-H cases, 468 (56%) DCIS-L cases and 328 (39%) No-DCIS cases were identified. DCIS-H cases presented with less aggressive clinico-pathological characteristics, such as lower proportions of histologic grade III (10% vs 26% vs 21%) and lower proportions of node-positive disease (13% vs 18% vs 21%), compared to DCIS-L and No-DCIS cases, respectively. The distribution of OncotypeDX RS significantly varied between the groups. DCIS-H tumors were less likely to have a high RS and more likely to have a low or intermediate RS compared to DCIS-L and No-DCIS tumors (High RS: 4% vs 20% vs 20%, Low + intermediate RS: 96% vs 80% vs 80%, respectively; p=0.04). Additionally, the proportions of high clinical risk cases were lower in the DCIS-H group compared to the DCIS-L and No-DCIS groups (42% vs 53% vs 50%, respectively; p=0.002). Based on genomic and clinical risk and current guidelines, we found that women presented with an extensive DCIS component (DCIS-H) had a lower probability of receiving an adjuvant chemotherapy recommendation compared to women presented with a non-extensive DCIS component (DCIS-L) or pure IBC (No-DCIS) (11% vs 29% vs 25%, respectively; p=.035). No differences in disease recurrence were detected between the groups. Conclusions: Co-existing extensive DCIS in invasive early HR+Her2- breast cancer is significantly correlated with lower genomic and clinical risk of recurrence and a smaller chance for chemotherapy recommendation. The rarity of this condition (5% of cases) limited our ability to detect differences in outcomes. These findings warrant future studies of the underlying genomic landscape of co-existing extensive DCIS. Citation Format: Yael Bar, Kfir Bar, Judith Ben- Dror, Didi Feldman, Meishar Shahoha, Ahuva Weiss-Meilik, Nachum Dershowitz, Wolf Ido, Amir Sonnenblick. The impact of co-existing ductal carcinoma in situ in invasive early hormone receptor positive breast cancer on the genomic and clinical risk of recurrence [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-27.

Abstract P1-04-09: Correlating Predicted Adjuvant Therapy Benefit and Risk of Recurrence between Breast Cancer Index (BCI) and 21-gene Oncotype DX Recurrence Score (RS)

Abstract Background: The 21-gene Recurrence Score (Oncotype DX) is a genomic assay that provides prognostic information for distant recurrence risk and is predictive of adjuvant chemotherapy benefit in hormone receptor (HR)-positive, HER-2 negative early-stage breast cancer (EBC). The Breast Cancer Index (BCI) is another molecular gene expression-based assay that evaluates the utility of extending adjuvant endocrine therapy (ET) from 5 to 10 years and predicts risk of distant recurrence. In January 2021, the National Comprehensive Cancer Network (NCCN) Guidelines added BCI to guide duration of adjuvant ET as a category 2A recommendation. The goal of this study was to evaluate the association between BCI and RS in terms of their predicted benefit for adjuvant therapy and risk of distant recurrence. We also assessed the association of various anatomic and biologic tumor features with BCI. Methods: We performed a retrospective chart review of all patients with HR-positive EBC who had a BCI and Oncotype DX performed between 2007-2021. Demographics, tumor characteristics and BCI and RS results were extracted from the electronic medical record. Patients were categorized by BCI predictive of extended ET (formerly BCI high) versus not (formerly BCI low) and RS of low (0-10), intermediate (11-25) and high (26-100). Numerical values for distant recurrence risk were recorded for both BCI and Oncotype DX tests. Multivariable regression models were used to assess the relationship between BCI and Oncotype DX as well as factors associated with each. Results: We identified 153 women with HR-positive EBC with both RS and BCI performed. The median age of the population was 57 years and 25% were premenopausal. 32% (n=49) had a BCI result predictive of benefit from extended adjuvant ET. When comparing patients with BCI predictive of extended ET versus those with BCI not predictive of extended ET, there was no association between BCI and RS based on multivariate logistic regression models, p=0.7. A similar distribution of RS was observed between patients who had a BCI result predictive of benefit from extended ET versus not predictive. Among 49 patients with a BCI predictive of extended ET, 35% had high RS, 63% intermediate RS and 2% low RS. Among 104 patients with a BCI not predictive of extended ET, 24%, 73% and 3% had high, intermediate, and low RS, respectively. Multivariate regression models revealed an association between poorly differentiated tumors and BCI result predictive of extended ET, p=0.002. No associations were observed between BCI and menopausal status, ER%, PR%, tumor size or lymph node positivity. Regarding risk of recurrence, there was an association between BCI and Oncotype DX in terms of their predicted numerical risk of recurrence, p&amp;lt; 0.001. Higher percentage of PR positivity, poorly differentiated tumors, and lymph node positivity were associated with a higher risk of recurrence on the BCI. Conclusions: In our patient population selected to have Oncotype DX and BCI performed, we found no association between the two genomic assays in terms of their predictive benefit. However, there was an association between Oncotype DX and BCI in terms of their prognostic ability. Given the increased use of BCI since its inclusion in national guidelines, it is important to understand its relationship with other genomic assays especially when used to guide clinical decisions and estimate prognosis. Citation Format: Rima Patel, Nicole Casasanta, Zhiqiang Li, Melanie Kier, Julia Blanter, Sophie Sohval, Malin Hovstadius, Catherine Wu, Marc Fink, Xiang Zhou, Brittney Zimmerman, Krystal Cascetta, Rong Chen, William Oh, Amy Tiersten. Correlating Predicted Adjuvant Therapy Benefit and Risk of Recurrence between Breast Cancer Index (BCI) and 21-gene Oncotype DX Recurrence Score (RS) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-04-09.

Abstract P6-01-30: PgR levels and Ki67 expression of Lobular Carcinomas of the Breast might indicate OncotypeDX testing to evaluate Chemotherapy benefit

Abstract AIM: The majority of invasive lobular carcinomas (ILC) of the breast are luminal A tumors of good prognosis, having a low or intermediate OncotypeDX Recurrence Score (RS). They are usually treated with hormonal therapy only and some have doubted the relevance of the RS for patients with ILC. However, in a number of ILC cases a high RS can be found, indicating chemotherapy benefit. The aim of the present analysis was to explore in our database of lobular carcinomas analyzed with OncotypeDX, the percentage of tumors with a RS &amp;gt;25 and test the hypothesis if Progesterone Receptor (PgR) and/or Ki-67 expression could be an indicator to have patients evaluated with OncotypeDX. PATIENTS AND METHODS: Among 2.946 patients analyzed with Oncotype DX, we found 397 patients with pure lobular carcinomas (13.47%). Ki-67 expression was obtained from 315 patients and 13 of them (4%) had a high Ki-67 value of &amp;gt;30%. PgR expression was negative in 56 out of 397 patients (14%). We analyzed the possible relationship of RS values with PgR levels and Ki-67 expression. RESULTS: Overall, 94% of patients with ILC had a Recurrence Score ≤25 and only 6% (24/397) had a RS ≥26. There was a wide distribution of RS among patients with different values of PgR; however, there was a negative trend of Recurrence Score values and PgR expression levels. This trend was more obvious in the 56 patients with negative PgR expression. Although there were high RS values across all levels of Ki-67 expression, there was a trend towards high RS with higher Ki-67 expression; 5 out of 13 patients (38%) with ki-67 &amp;gt;30% had a RS ≥26. CONCLUSION: Our analysis shows that the majority of lobular carcinomas of the breast have a low OncotypeDX RS, suggesting that can be treated only with hormonal therapy. However, negative or low PgR levels and high Ki-67 expression might predict a high RS and thus chemotherapy benefit and those two parameters could be used as indicators for OncotypeDX evaluation of lobular carcinomas of the breast. Citation Format: Christos Markopoulos, Mahi Sariyanni, Asimina Karamargiou, Zoi Antonopoulou, Nikolaos Tsoulos. PgR levels and Ki67 expression of Lobular Carcinomas of the Breast might indicate OncotypeDX testing to evaluate Chemotherapy benefit [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-30.

Abstract PD9-09: Molecular differences between younger versus older estrogen receptor positive/human epidermal growth factor receptor-2 negative breast cancers

Abstract Background: The RxPONDER and TAILORx trials demonstrated benefit from adjuvant chemotherapy in patients &amp;lt; 50 years with node-positive breast cancer and Recurrence Score (RS) 0-25, and with node-negative disease and RS 16-25, respectively. Neither trial showed benefit in older women with RS &amp;lt; 26. It is unclear what explains the interaction between age and adjuvant chemotherapy benefit. Methods: We analyzed transcriptomic and genomic data from n=4,507 ER+/HER2- breast cancers to compare differences in estrogen receptor (ER), proliferation, and immune-related gene expressions, and somatic mutation patterns and mutation burden between younger (&amp;lt; 50 years of age) and older (&amp;gt;55 years) patients. We restricted our analysis to patients in the lower 80% range of in silico RS distribution to mimic the RxPONDER and TAILORx populations. Results: Five data sets were analyzed independently to assess consistency of results (TCGA n=530; microarray cohort A n=865; Cohort B n=609, METABRIC n=867, SCAN-B n=1636). Older patients had significantly higher somatic mutation burden and more frequent copy number gain in ESR1, LATS1, ARID1B, SGK1, and MYB genes (odds ratio [OR] &amp;gt; 8.5, FDR&amp;lt; 0.05), but lower frequency of GATA3 mutations (12% versus 26%, P&amp;lt; 0.0001). Younger patients had higher rate of ESR1 copy number loss (OR: 0.45, FDR: 0.03). There was no difference in proliferation-related gene expression. ESR1 mRNA expression was significantly lower in younger women in all cohorts (P &amp;lt; 0.001). A regression model of ESR1 mRNA expression using age and ER IHC positivity indicated that lower ER expression in younger patients is primarily driven by lower ESR1 mRNA per cancer cell and not by fewer ER positive cells. We also assessed four gene signatures associated with endocrine therapy sensitivity including a 4-gene ERS, a 7-gene ERS-Lum, a 106-gene ERS-Pos signature, and a 59-gene ERS-Neg signature associated with endocrine resistance. In the TCGA and METABRIC cohorts, the ERS, ERS-Lum, and ERS-Pos signatures were all lower (FDR&amp;lt; 0.03) while the ERS-Neg signature was higher (FDR&amp;lt; 0.001) in younger patients. Similarly, in both microarray cohorts, and in the SCAN-B-cohort, the ERS-Pos signature was lower and the ERS-Neg signature was higher in younger patients (FDR&amp;lt; 0.002). Next, we assessed 4 different immune cell signatures that have been associated with response to chemotherapy. In the TCGA, B-cell, T-cell, Mast-cell, and TIS signatures were significantly higher (FDR&amp;lt;.05). In the microarray Cohort-A, B cells and mast cells were significantly higher, and the T cell and TIS signatures showed a trend for higher expression. In Cohort-B, T cells, B cells, TIS, and dendritic cells signatures were significantly higher in younger patients. Significantly higher expression of immune gene signatures in younger patients were also seen in the METABRIC and SCAN-B data sets. The ER-related and immune-related gene signatures showed negative correlation and joint analysis defined three subpopulations in younger women: (i) immune-high/ER-low, (ii) immune-intermediate/ER-intermediate and (iii) immune-low/ER-intermediate, whereas in older women the dominant pattern was immune-low/ER-high. Conclusion: ESR1 mRNA and ER-associated gene expression is lower in ER positive cancers of younger compared to older patients, while immune infiltration is higher. The cytotoxic and endocrine effects of adjuvant chemotherapy could both contribute to the survival benefit seen in younger patients, but the relative contributions of these effects may vary by ER and immune phenotype. We hypothesize that in immune-high/ER-low cancers, the cytotoxic effect of chemotherapy may drive the benefit, whereas in immune-low/ER-intermediate cancers chemotherapy induced ovarian suppression may play a more important role. Citation Format: Tao Qing, Thomas Karn, Mariya Rozenblit, Julia Foldi, Michal Marczyk, Naing Lin Shan, Kim Blenman, uwe Holtrich, Kevin Kalinsky, Funda Meric-Bernstam, Lajos Pusztai. Molecular differences between younger versus older estrogen receptor positive/human epidermal growth factor receptor-2 negative breast cancers [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD9-09.

152P Molecular characterization by the 21-gene breast cancer (BC) Recurrence Score (RS) test of BRCA1/2 mutation carriers (mBRCA1/2) versus the general BC patient (pt) population

The RS assay is a validated test used to guide treatment decisions in ER+ HER2-negative early-stage BC. We compared RS distribution and expression of the single genes/gene groups within this assay between mBRCA1/2 carriers ER+ HER2-negative BC pts vs the general BC pt population undergoing RS testing.

Correlation of the Ki67 Working Group prognostic risk categories with the Oncotype DX Recurrence Score in early breast cancer.

The relationship between Ki67 assessed by immunohistochemistry (IHC) and the Oncotype DX Recurrence Score (RS) is unclear. The objective of this study was to determine the correlation between the 21-gene RS and IHC-measured Ki67 with the prognostic classification groups recommended by the International Ki67 Working Group (IKWG). The authors performed a retrospective chart review of women who had hormone receptor (HR)-positive, human epidermal growth factor receptor 2-negative early breast cancer with zero to three positive lymph nodes and both Ki67 and the 21-gene RS performed at their institution from 2013 to 2021. Patients were categorized into low (≤5%), intermediate (6%-29%), and high Ki67 groups (≥30%) according to IKWG recommendations. Overall agreement and risk-stratified agreement between Ki67 and RS were assessed with the proportion of agreement and the κ statistic. The study included 525 patients with HR-positive breast cancer. Among the 49% of patients with intermediate Ki67 values of 6%-29%, the distribution of low (0-10), intermediate (11-25), and high RS (26-100) was 19%, 66%, and 15%, respectively. There was slight agreement (κ=0.01-0.20) between Ki67 and RS (κ=0.027) in the overall population, although this was not significant (p=.1985). There was fair agreement (κ=0.21-0.40) between high Ki67 and RS values (κ=0.280; p < .0001). A higher progesterone receptor percentage was associated with lower RS values (p > .0001) but not lower Ki67 values. A positive nodal status and a larger tumor size were associated with higher Ki67 values (p=.0059 and p < .0001) but not with RS. In this group of patients selected to have a 21-gene RS, there was no significant correlation between Ki67 and RS in the overall population, and there was fair agreement between high Ki67 and high RS values. In patients with early-stage, hormone receptor-positive breast cancer, decisions on adjuvant chemotherapy are based on certain biological features of the cancer and genomic assays such as the Oncotype DX Recurrence Score (RS). The goal of this study was to determine the correlation between Ki67, a marker of proliferation, and the Oncotype DX RS, a 21-gene assay demonstrated to be predictive of an adjuvant chemotherapy benefit in patients with early-stage breast cancer. In 525 patients, the authors did not find a significant correlation between Ki67 and RS.

Correlation of Ki67 working group prognostic risk categories with oncotype DX recurrence score (RS) in early breast cancer (EBC).

553 Background: The 21-gene RS (Oncotype DX) provides prognostic information for distant recurrence risk and is predictive of adjuvant chemotherapy benefit in hormone receptor (HR)-positive, HER-2 negative EBC. Ki67 protein expression is a proliferation marker that is determined by immunohistochemistry (IHC). The International Ki67 Working Group (IKWG) has provided guidelines for clinical use of Ki67 for prognostic classification (PMID: 33369635). The objectives of this study were to determine the correlation between IHC-measured Ki67 with the 21-gene RS, and evaluate their association with other anatomic and biologic tumor features. Methods: We performed a retrospective chart review of women with HR-positive, HER-2 negative EBC with 0-3 positive lymph nodes who had both Ki67 (via IHC using MIB-1 antibody on surgical specimen at our institutional pathology CLIA laboratory) and 21-gene RS between 2013 to 2021. Patients were categorized into Ki67 low (≤ 5%), intermediate (6-29%), and high (≥30%) based on IKWG recommendations. Overall and risk stratified agreement between Ki67 and RS were assessed using the proportion of agreement and Kappa statistic. Linear regression was used to test for associations between tumor features of ER%, PR%, and tumor size and log transformed Ki67 and RS. A t-test was used to compare average log transformed Ki67 and RS by tumor differentiation and nodal status. Results: We identified 461 patients with HR-positive BC of whom 26.7% were ≤ 50 years at diagnosis, 30% pre-menopausal and 10% node-positive. Overall, 29% (n = 137) of patients had low Ki67, 49% (n = 227) intermediate, and 21% (n = 97) high Ki67. 18% (n = 85) had RS 0-10, 67% (n = 311) had RS 11-25 and 14% (n = 65) had RS ≥ 26. There was no significant agreement (kappa &lt; 0) between Ki67 and RS (Kappa = -0.0035, p = 0.5406) in the overall population and fair agreement (kappa 0.21-0.40) between high Ki67 and RS (Kappa = 0.2510, p &lt; 0.0001). Higher ER% was significantly associated with lower RS (p &lt; 0.0001) and lower Ki67 (p = 0.0042). High tumor grade was associated with higher RS and higher Ki67 (p &lt; 0.0001). Higher PR% was associated with lower RS (p &gt; 0.0001) but not lower Ki67. Positive nodal status and larger tumor size were associated with higher Ki67 (p = 0.0081, p &lt; 0.0001) but not RS. Among the 49% of patients with intermediate Ki67 of 6-29%, the distribution of low, intermediate, and high RS was 24%, 65%, and 11%, respectively. Conclusions: In this group of patients selected to have a 21-gene RS, there was no correlation between Ki67 and RS in the overall population, and fair agreement between high Ki67 and high RS. Among the approximately one-half with an intermediate Ki67 of 6-29%, 89% would be spared chemotherapy based on a low-intermediate RS. In patients with high Ki67, 68% might be spared chemotherapy based on the RS. In the low Ki67 group, 6% had a high RS. Ki67 has limited utility in identifying patients with high or low RS.

Abstract P1-08-14: Differences in Recurrence Score (RS) results between primary and second primary breast cancer (BC): Exploratory analysis of the Clalit Health Services (CHS) registry

Abstract Background: The first invasive disease-free survival event in patients (pts) with estrogen receptor (ER)+ early-stage breast cancer (BC) is often contralateral BC, as reflected in the TAILORx data. We analyzed the CHS registry to study differences in RS results and clinicopathological characteristics between the primary and second primary BC. Methods: This exploratory analysis included all ER+ HER2-negative BC pts who underwent RS testing through CHS between 1/2006 and 12/2020 and for whom ≥2 RS results were identified which were &amp;gt;1 year apart. Results: In this timeframe, 11,040 RS assays were ordered through CHS for 10,659 unique patients. The current analysis included 62 pts for whom multiple RS assays were performed &amp;gt;1 year apart. All 62 pts were females; their median (interquartile [IQR]) age at diagnosis was 56 (44-63) yrs, and 77% were initially diagnosed with node-negative disease. The median (IQR) time between the first and the latest RS assay was 5.3 (3.1-7.6) yrs. Tumor characteristics for the first and subsequent (second/third) primary BC tumors are presented (Table). Clinicopathologic characteristics were overall similar between the first and second/third primary BC tumors. The RS results, however, were statistically significantly higher in the second/third primary BC (P=0.0002), and the RS distribution was also significantly different with more tumors in the RS 26-100 category in the second/third primary BC (P=0.0036) (Table). The median (IQR) difference in the RS results between the first and latest RS assay for all 62 pts was 6 (-0.25-11.25). In 46 pts, (74%), the latest BC tumor had higher RS (a median [IQR] difference of 9 [5-13]) compared to the first BC tumor, and in 15 pts (24%) it had lower RS (a median [IQR] difference of -6 [-10 to -3]). One pt (2%) had the same RS result in both tumors. In 42 pts (68%), the latest primary BC was ipsilateral and in 20 pts (32%), it was contralateral. A higher RS result was observed in 33/42 (79%) of pts with ipsilateral second primary BC, and in 13/20 (65%) of pts with contralateral second primary BC (P=NS, Chi-square test). Conclusions: In ER+ HER2-negative BC pts, the characteristics of the first and second/third primary BC tumors were overall similar except for the RS result which was generally higher in the second/third primary BC. First BC; 62 tumorsSecond/third BC; 65 tumorsMedian (IQR) tumor size in the greatest dimension, cm1.55 (1.0-2.2)1.5 (1.0-1.95)Tumor size category, n (%)≤1 cm16 (25.8%)18 (27.7%)&amp;gt;1 - 2 cm28 (45.2%)33 (50.8%)&amp;gt;218 (29.0%)10 (15.4%)Unknown0 (0%)4 (6.2%)Tumor grade category, n (%)Grade 19 (14.5%)6 (9.2%)Grade 232 (51.6%)39 (60.0%)Grade 311 (17.7%)10 (15.4%)Not applicable/Unknown10 (16.1%)10 (15.4%)Histology, n (%)Invasive ductal carcinoma49 (79.0%)51 (78.5%)Invasive lobular carcinoma8 (12.9%)11 (16.9%)Mucinous/colloid/papillary2 (3.2%)2 (3.1%)Other/unknown3 (4.8%)1 (1.5%)Recurrence Score Mean (SD)a 18 (10)24 (12)Median (IQR)17 (13-22)23 (17-30)RS categoryb, n (%)0-1525 (40.3%)13 (20.0%)16-2528 (45.2%)27 (41.5%)26-1009 (14.5%)25 (38.5%)aP = 0.0002 (Mann–Whitney test); bP = 0.0036 (Chi-square test) Citation Format: Shlomit Strulov Shachar, Michelle Leviov, Rinat Yerushalmi, Karen Drumea, Margarita Tokar, Lior Soussan-Gutman, Avital Bareket-Samish, Amir Sonnenblick, Noa Efrat Ben-Baruch, Shani Paluch-Shimon, Gil Bar Sela, Salomon M Stemmer. Differences in Recurrence Score (RS) results between primary and second primary breast cancer (BC): Exploratory analysis of the Clalit Health Services (CHS) registry [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-08-14.

Abstract P1-08-13: Comparison of gene expression profiling results and clinical outcomes among patients with pleomorphic ILC and classic ILC

Abstract Background Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer. Pleomorphic ILC (pILC) is a pathologically defined subtype of ILC that often presents at a higher stage compared to Classical ILC (cILC). pILC is traditionally thought to have poor outcomes compared with cILC. Utility and application of gene expression profiling, such as Oncotype Dx testing, for these patients is unknown. The purpose of this study is to compare Oncotype Dx recurrence scores, treatment patterns, and clinical outcomes for patients with cILC and pILC at our institution. Methods A retrospective analysis of a large institutional cancer database was performed to identify patients with ILC treated between 2004 and 2017. Patient and disease characteristics were collected, including subtype of ILC (classical vs pleomorphic), staging, treatment history, and presence of Oncotype Dx testing. Findings were analyzed for differences in clinical characteristics, Oncotype Dx results, progression free survival (PFS) and overall survival (OS) between patients who received endocrine therapy/chemotherapy (CET) versus endocrine therapy alone (ET) in both cILC and pILC groups. Results: 692 patients with ILC were identified with 100 (14.5%) categorized as pILC. The mean age at presentation was 62 for cILC and 60 for pILC. cILC was more frequently ER positive (98.5% vs. 94.0%, p=0.004). and less likely HER2 positive (7.0% vs 12.2%, p=0.07). pILC more commonly had more advanced tumor stage (Stages II-III 61% vs 41%, p&amp;lt;0.001) but lower nodal stage (N+ 48.5% vs 66%, p&amp;lt;0.001) 25% (25/100) of pILC patients had Oncotype Dx testing performed compared to 33% (198/592) of cILC patients. The majority of patients who had testing had T1cN0 or T2N0 disease (36% and 44% for pILC vs 34%, and 27% for cILC, respectively). A low risk recurrence score (0-10) accounted for 8% (2/25) of pILC cases and 18.2% (36/198) of cILC. Intermediate risk (11-25) accounted for 72% (18/25) of pILC and 73.2% (145/198) of cILC. High risk (26+) accounted for 20% (5/25) of pILC and 8.6% (17/198) of cILC. There was no statistically significant difference in Oncotype Dx recurrence score distribution between pILC and cILC (p=0.117). More patients with pILC received CET compared to cILC (62.0% vs 36.7%, p&amp;lt;0.001). Among pILC cases, 62% received CET and 34% received ET. There was no significant difference in RFS or OS between CET and ET among pILC cases (10-year RFS 74.7% (ET) vs. 76.6% (CET), p=0.52. 10-year OS 92.6% (ET) vs 78.0% (CET), p=0.40). Conclusions At our institution, patients with cILC more often had Oncotype Dx testing compared to those with pILC. Some of the difference may be related to more frequent HER2-positivity in pILC. When testing was done, pILC was twice as likely to have a high risk recurrence score compared to cILC, but this result was not statistically significant. Patients with pILC were more likely to receive CET than patients with cILC. There was no difference in survival between patients with pILC treated with CET versus those treated with ET alone although the sample size is small and this is worthy of further study in a larger population. These results suggest that gene expression testing may be underutilized in pILC. Citation Format: Marcus Dempster, Matthew Wright, Daniela Cocco, Ayat Elsherif, Stephanie A Valente, Hong Li, Megan L Kruse. Comparison of gene expression profiling results and clinical outcomes among patients with pleomorphic ILC and classic ILC [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-08-13.

Distribution, Chemotherapy Use, and Outcome of the 21-Gene Recurrence Score Between Chinese and White breast Cancer in the United States

To compare the distribution, chemotherapy-decision making, and prognosis of the 21-gene recurrence score (RS) between Chinese breast cancer (BC) in the United States and White American (WA) BC. We identified early-stage and estrogen receptor-positive BC patients diagnosed between 2004 and 2015. Multivariate logistic regression, Kaplan-Meier analysis, and multivariate Cox proportional hazards models were used for statistical analyses. A total of 67,486 patients were identified, including 66,215 (98.1%) WA patients and 1271 (1.9%) Chinese patients. Regarding the RS, 38,894 (57.6%) had low RS, 23,882 (35.4%) had intermediate RS, and 4710 (7.0%) had high RS. A similar distribution of RS was found between WA and Chinese BC (P=.280). The race was not the predictor associated with high RS. Similar trends of chemotherapy use were found in Chinese and WA BC. In WA BC, there were 4.1%, 31.5%, and 72.2% of patients receiving chemotherapy in low, intermediate, and high RS cohorts, respectively (P < .001). The proportion of chemotherapy use was 6.8%, 30.9%, and 74.0% in Chinese BC with low, intermediate, and high RS cohorts, respectively (P < 0.001). The multivariate prognostic analyses indicated that a higher RS was independently associated with an inferior breast cancer-specific survival. Similar trends were found among those with Chinese and WA BC. Our results demonstrate similar distribution, chemotherapy use, and outcome of the 21-gene RS between Chinese and WA BC in the United States.

Withdrawal: “Distribution, chemotherapy use, and outcome of the 21‐gene recurrence score between Chinese and White breast cancer in the United States” Guan‐Qiao Li, Jia Yao, Ping Zhou, Dan‐Xia Chen, Chen‐Lu Lian, Shi‐Ping Yang, San‐Gang Wu

To compare the distribution, chemotherapy-decision making, and prognosis of the 21-gene recurrence score (RS) between Chinese breast cancer (BC) in the United States and White American (WA) BC. We identified early-stage and estrogen receptor-positive BC patients diagnosed between 2004 and 2015. Multivariate logistic regression, Kaplan-Meier analysis, and multivariate Cox proportional hazards models were used for statistical analyses. A total of 67486 patients were identified, including 66215 (98.1%) WA patients and 1271 (1.9%) Chinese patients. Regarding the RS, 38894 (57.6%) had low RS, 23882 (35.4%) had intermediate RS, and 4710 (7.0%) had high RS. A similar distribution of RS was found between WA and Chinese BC (P=0.280). Race was not the predictor associated with high RS. Similar trends of chemotherapy use were found in Chinese and WA BC. In WA BC, there were 4.1%, 31.5%, and 72.2% of patients receiving chemotherapy in low, intermediate, and high RS cohorts, respectively (P<0.001). The proportion of chemotherapy use was 6.8%, 30.9%, and 74.0% in Chinese BC with low, intermediate, and high RS cohort, respectively (P<0.001). The multivariate prognostic analyses indicated that a higher RS was independently associated with an inferior breast cancer-specific survival. Similar trends were found among those with Chinese and WA BC. Our results demonstrate similar distribution, chemotherapy use, and outcome of the 21-gene RS between Chinese and WA BC in the United States.