High-risk Recurrence Score Research Articles

Abstract PD4-08: Does genomic recurrence score predict for ipsilateral breast tumor recurrence after breast conservation therapy?

Abstract Purpose/ObjectivesGene profiling Recurrence Score (RS) assays are commonly used to identify patients with hormone receptor (HR) positive, HER-2 negative invasive breast cancer (IBC) who might benefit from systemic chemotherapy. More recently, the 21-gene recurrence score assay has been found to correlate with locoregional recurrence (LRR) after mastectomy (SWOG) or lumpectomy (NSABP). In the NSABP analysis, risk of ipsilateral breast tumor recurrence (IBTR) was not correlated with RS and was high in patients younger than 50 years of age irrespective of genomic score. However, tumor bed radiotherapy (RT) boost was not utilized in these protocols. The purpose of this study is to determine if RS predicts for IBTR or LRR in women treated with modern breast conserving therapy (BCT) using RT boost and optimal systemic treatment. Materials/MethodsWe performed a retrospective review of patients with HR positive, HER-2 negative IBC who underwent gene profile testing and were treated at our institution with BCT and sentinel lymph node biopsy (SLNB) from 2013 to 2017. Both node negative and node positive patients were included. The Oncotype® 21-gene recurrence score assay was used in 84%, Mammaprint® in 12%, and Prosigna® in 4%. 97% received hormonal therapy (HT), 18% chemotherapy (CHT), 58% hypofractionated RT, and 96% a surgical bed RT boost. IBTR and LRR were measured from the end of local treatment to IBTR or LRR, with death or last follow up date as censoring events. The Kaplan-Meier method was used to estimate event-time probabilities for the above endpoints. Predictors of IBTR/LRR were analyzed using log rank tests between groups and with Cox regression for continuous variables. P-values <0.05 were considered significant. Results 686 evaluable patients were identified with median follow-up of 50 months (Interquartile range [IQR] 36-64 months). Median age was 61 years (IQR 53-68 years). 76% had invasive ductal carcinoma, 64% grade 2 disease, and 18% positive SLNB. RS of any type was low in 60% of patients and intermediate or high in 40%. Four-year IBTR was 0.2% (95% Confidence Interval [CI] 0.0-0.6%) for any low risk RS and 1.6% (95% CI 0.0 - 3.2%) for intermediate or high-risk RS (p = 0.01). Tumor grade was also predictive for IBTR (p < 0.01), but age < 50 was not (p = 0.4). For patients younger than 50, four-year IBTR was 0.9% (95% CI 0.0 - 2.6%) and not affected by RS (p = 0.231). On multivariate analysis, grade remained a significant predictor for IBTR (p = 0.04), but RS did not (p = 0.08). Four-year LRR was 0.5% (95% CI 0.0-1.3%) in patients with a low risk RS and 3.8% (95% CI 1.3-6.3%) in those with intermediate or high risk (p < 0.01). Grade (p < 0.01) and pathologic tumor size (p < 0.01) were also correlated with LRR, although only RS (HR 5.14, 95% CI 1.02-25.9, p = 0.047) and pathologic tumor size on (HR 1.05, 95% CI 1.01- 1.09, p = 0.02) remained significant on multivariate analysis. Of the 125 patients with positive SLNB, 47% were treated with high tangents and 42% with comprehensive regional nodal irradiation. For node positive patients, LRR was not correlated with low versus intermediate or high RS (p = 0.07). However, if intermediate risk Oncotype scores were grouped with low risk Oncotype and Mammaprint scores, then LRR was 0.0% for low and intermediate risk and 9.1% for high risk (p < 0.01). ConclusionsIn this large single institution study, RS did not predict for IBTR in patients with HR positive, HER-2 negative invasive breast cancer in any age group treated with BCT utilizing a surgical bed RT boost and optimal systemic treatment. High RS did predict for high LRR because of higher regional recurrences and can be used as a guide to add comprehensive RT for node positive patients after BCT. Citation Format: Adam H Richman, Ankur K Patel, Atilla Soran, Emilia J Diego, Priscilla F McAuliffe, Ronald R Johnson, Adam Brufsky, Vikram Gorantla, Jennifer Steiman, Joanna S Lee, Sushil Beriwal. Does genomic recurrence score predict for ipsilateral breast tumor recurrence after breast conservation therapy? [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD4-08.

Abstract PS6-09: An AI-digital breast cancer risk discrimination platform (PreciseDx) using a representative H&E image and selected clinical variables accurately categorized patients with oncotype Dx low risk recurrence scores (RS)

Abstract Background: Clinical practice guidelines emphasize the critical importance of grading and stage in breast cancer treatment. Although histologic grade is subjective, non-quantitative, skill-dependent, and oftentimes inaccurate it remains an independent prognostic feature and therefore plays a direct role in patient management including neoadjuvant therapy vs surgery, and interpretation of genomic studies. We developed an AI-based platform which combines digital H&E features with select clinical variables to assess risk of breast cancer recurrence and evaluated ability to predict Oncotype low risk RS categorization. Methods: Retrospective study to identify a subset of Mt. Sinai, NY invasive ductal breast cancer (IDC) patients from 2010-2016 with H&E stained slides, clinical features and OncotypeDx recurrence scores (RS). Recurrence endpoint(s): local- regional, distant-recurrence free and overall survival. Digital images generated with Philips scanning system; reviewed by two pathologist for tumor content and quality prior to image analysis and feature extraction. Support vector machine learning models were used for initial feature performance and final models generated. Positive predictive value (PPV), sensitivity (S) and likelihood ratios (LR) were used for performance. Results: 391 patients: mean age 57 years, 100% Stage I/II, 59% Grade 2, and 6% LN+ve 0-3; 97% IDC, 100% ER+ve, 94% PR+ve, 0% Her2 amplified; median follow-up 61 months; 323 (83%) low risk (</=25) RS and 68 (17%) high risk RS (>25). There were 23 events (6%) and 13 (56%) were locoregional recurrence. PreciseDx model with age, and PR levels combined with imaging features reflective of mitotic activity and nuclear characteristics (clinical grade not selected) correctly identified LR RS categorization: PPV of 91%, [95CI 0.87-0.94], Se 92% [0.86-0.95] and positive / negative likelihood ratio : 6.8, and 0.5, respectively. Conclusions: Application of an AI-digital breast cancer risk assessment platform using only the H&E image and limited clinical data successfully classified low risk RS patients with high accuracy. Future models will extend outcome to 10 years and evaluate treatment selection and duration Citation Format: Michael Joseph Donovan, Nina Shpalensky, Marcel Prastawa, SM Abishek, Richard Scott, Mary Sawyer, Jack Zeineh, Gerardo Fernandez. An AI-digital breast cancer risk discrimination platform (PreciseDx) using a representative H&E image and selected clinical variables accurately categorized patients with oncotype Dx low risk recurrence scores (RS) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-09.

Association of Race/Ethnicity and the 21-Gene Recurrence Score With Breast Cancer–Specific Mortality Among US Women

Given the widespread use of the 21-gene recurrence score for identifying candidates for adjuvant chemotherapy, it is important to examine the performance of the Oncotype DX Breast Recurrence Score test in diverse patient populations to validate this approach for tailoring treatment in women in racial/ethnic minority groups. To examine whether breast cancer-specific mortality for women with hormone-dependent breast cancer differs by race/ethnicity across risk categories defined by the Oncotype DX Breast Recurrence Score test and whether the prognostic accuracy of the 21-gene recurrence score differs by race/ethnicity. This retrospective, population-based cohort study used the Surveillance, Epidemiology, and End Results Oncotype DX 2004-2015 database to obtain breast cancer-specific survival data on US women 18 years and older who were diagnosed with first primary stage I to III, estrogen receptor-positive breast cancer between January 1, 2004, and December 31, 2015, and had tumor testing through the Genomic Health Clinical Laboratory. Data were analyzed from April 20 to September 27, 2020. The primary outcome was breast cancer-specific mortality among women from different racial/ethnic groups stratified by the 21-gene recurrence score risk categories. Secondary analyses compared the prognostic accuracy of the recurrence score among the different racial/ethnic groups. A total of 86 033 patients with breast cancer (mean [SD] age, 57.6 [10.6] years) with Oncotype DX Breast Recurrence Score test information were available for the analysis, including 64 069 non-Hispanic White women (74.4%), 6719 non-Hispanic Black women (7.8%), 7944 Hispanic women (9.2%), 6950 Asian/Pacific Islander women (8.0%), and 351 American Indian/Alaska Native women (0.4%). Black women were significantly more likely than non-Hispanic White women to have a recurrence score greater than 25 (17.7% vs 13.7%; P < .001). Among women with axillary node-negative tumors, competing risk models adjusted for age, tumor characteristics, and treatment found higher breast cancer-specific mortality for Black compared with non-Hispanic White women within each recurrence score risk stratum, with subdistribution hazard ratios of 2.54 (95% CI, 1.44-4.50) for Black women with recurrence scores of 0 to 10, 1.64 (95% CI, 1.23-2.18) for Black women with recurrence scores of 11 to 25, and 1.48 (95% CI, 1.10-1.98) for Black women with scores greater than 25. The prognostic accuracy of the recurrence score was significantly lower for Black women, with a C index of 0.656 (95% CI, 0.592-0.720) compared with 0.700 (95% CI, 0.677-0.722) (P = .002) for non-Hispanic Whites. In this cohort study, Black women in the US were more likely to have a high-risk recurrence score and to die of axillary node-negative breast cancer compared with non-Hispanic White women with comparable recurrence scores. The Oncotype DX Breast Recurrence Score test has lower prognostic accuracy in Black women, suggesting that genomic assays used to identify candidates for adjuvant chemotherapy may require model calibration in populations with greater racial/ethnic diversity.

Oncotype DX Breast Recurrence Score Distribution and Chemotherapy Benefit Among Women of Different Age Groups With HR-Positive, HER2-Negative, Node-Negative Breast Cancer in the SEER Database.

Objective: To explore the distribution of Oncotype DX Breast Recurrence Score (RS), the proportion of receiving chemotherapy, and the relationship between RS and chemotherapy benefit according to detailed age groups in women with hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-negative (HR+/HER2−/N0) breast cancer.Methods: This was an extensive, comprehensive, population-based retrospective study. Data on individuals with breast cancer were obtained from the Surveillance, Epidemiology, and End Results (SEER) Program. The cohort was divided into five groups by age (≤ 35, 36–50, 51–65, 66–80, >80 years). RS distribution and chemotherapy proportion among different age groups were analyzed, and the overall survivals between patients receiving chemotherapy and those not/unknown were compared in each age group.Results: The study cohort comprised 49,539 patients and the largest age group was 51–65 years. The percentage of patients with low-risk RS (0–10) increased with age, whereas those with intermediate-risk RS (11–25) decreased with age (except for the group of 36–50 years, which had the highest rate of intermediate-risk RS). The age group ≤35 years has the greatest rate of high-risk RS (26–100). The proportion of receiving chemotherapy decreased with age in all RS risk categories. Overall survival was benefited by chemotherapy only in the age group of 66–80 years with intermediate- and high-risk RS, and chemotherapy seemed to do more harm than good for patients older than 80 years.Conclusions: In the present study, we identified the distribution of RS, the proportion of receiving chemotherapy, and the relationship between RS and chemotherapy benefit according to a detailed age grouping for women with HR+/HER2−/N0 breast cancer, which may help in making individualized clinical decisions.

Genomic expression assay testing among American Indian and Alaska Native women with breast cancer.

Breast cancer is one of the most common causes of cancer mortality for all women, including American Indian and Alaska Native (AI/AN) women. The use of the 21-gene recurrence score (RS) appears to be predictive of the benefit of chemotherapy for women with estrogen receptor (ER)-positive breast cancer. The objective of the current study was to compare RS testing between AI/AN and non-Hispanic White (NHW) women with breast cancer. The Surveillance, Epidemiology, and End Results program was used to identify women with ER-positive breast cancer from 2004 through 2015. Multivariable logistic regression was used to evaluate factors associated with RS use, with high-risk RS, and with chemotherapy use among those with a high-risk RS. A total of 363,387 NHW patients and 1951 AI/AN patients with ER-positive breast cancer were identified. AI/AN women were found to be less likely to undergo RS testing and, when tested, were more likely to have a high-risk RS. In the multivariable logistic regression analysis, AI/AN women were found to be significantly more likely to have a high-risk RS (odds ratio,1.28; 95% confidence interval, 1.01-1.66). Among untested women, chemotherapy use was higher for AI/AN women; however, the use of chemotherapy was not found to be significantly different between the groups with a high-risk RS. Using Cox proportional hazards models, AI/AN race was found to be significantly associated with worse overall survival. AI/AN women were less likely to undergo RS testing compared with NHW women and were more likely to have a high-risk RS. Reversing the disparity in genomic expression assay testing is critical to ensure guideline-based breast cancer treatment and improve survival rates for AI/AN women with breast cancer.

Racial and ethnic disparities in 21-gene recurrence scores, chemotherapy, and survival among women with hormone receptor-positive, node-negative breast cancer.

Cutoffs of the 21-gene recurrence score (RS), a commonly used genomic assay for hormone receptor-positive breast cancer, have been updated. Little is known about racial/ethnic differences in RS results, RS-guided chemotherapy use, and outcomes on updated cutoff (RS ≥ 31 defined as high-risk) in the real-world setting. A total of 81,937 women [75.0% whites, 7.7% blacks, 8.3% Asian American/Pacific Islanders (AAPIs), and 9.0% Hispanics] diagnosed with hormone receptor-positive breast cancer between 2004 and 2015, who received the 21-gene assay, were identified from the Surveillance, Epidemiology, and End Results. Logistic regressions estimated the race-associated odds ratios (ORs) of RS and chemotherapy use. Cox regressions estimated the race-associated hazard ratios (HRs) of breast cancer-specific and all-cause mortality. Compared with white women, black women were more likely to have RS-defined high-risk tumors (adjusted OR [aOR] 1.29; 95% CI 1.16-1.42). In high RS, blacks had lower odds of chemotherapy use (aOR 0.76; 95% CI 0.62-0.94) than whites, particularly among women ≥ 65years (aOR 0.51; 95% CI 0.35-0.76), while AAPI and Hispanic women had no variation in chemotherapy use compared with whites in high RS. Black women had a higher risk of breast cancer-specific mortality (HR 1.37; 95% CI 1.12-1.67) and all-cause mortality compared with white women after adjusting for demographic and pathological factors, county-level socioeconomic deprivation, treatments and RS; AAPIs had lower mortality and Hispanics had similar mortality. Black women were more likely to have a high-risk RS tumor and less likely to receive chemotherapy in the group of high RS, especially those ≥ 65years. Further studies are needed to identify barriers to chemotherapy in black patients with high RS scores.

21-gene recurrence score testing utilization among older women from different races: A population-based study

ObjectivesThe influence of older age at diagnosis in combination with race/ethnicity on utilization and results of the 21-gene recurrence score (RS) assay for breast cancer (BC) patients is not fully understood. Our objectives were to evaluate the utilization of RS among older women with BC, the likelihood of a high-risk RS, and factors associated with breast cancer-specific mortality (BCSM) among older patients across different races. Materials and methodsWe utilized the Surveillance, Epidemiology, and Results (SEER) database with linked RS results to evaluate women with estrogen receptor-positive BC diagnosed 2004–2015. Multivariable logistic regression was used to describe the differences in utilization of RS testing and the association of high-risk RS according to patient characteristics. The Cox proportional hazards model was used to analyze factors associated with BCSM. ResultsWe found that 20.4% (109,244/536,555) of all women ≥18 and 14.3% (33,584/235,171) of women ≥65 underwent RS testing. Non-whites had lower odds of RS testing at younger ages whereas among women ≥65 there was no significant difference. After taking into account stage and grade, being ≥65 reduced the odds of high-risk RS in all races except American Indian/Alaskan Native. Age ≥ 65 was independently associated with increased hazard BCSM. Among women ≥65 with high-risk RS, chemotherapy was associated with lower hazard of BCSM in all races. ConclusionsOlder women are less likely to be tested for RS, but also less likely to have high-risk RS. Older women with high-risk RS, when given chemotherapy have reduced BCSM across all races.

A novel approach for 21-genes testing associated with prognosis in Chinese patients with ER-positive/HER2-negative breast cancer: A real-world study.

e12528 Background: We previously reported a Chinese version of 21-genes Recurrence Score (RS) provides reduction chemotherapy prescription in patients with ER-Positive/HER2-Negative node negative breast cancer, while Oncotype Dx was hardly to be reached. However, the impact on clinical outcome was not mentioned. Herein, we explored whether this 21-genes recurrence score (RS) impacted on prognosis in patients with this molecular subtype of breast cancer. Methods: From Jan 2013 to Aug 2018, 378 patients with ER-Positive/HER2-Negative early stage breast cancer were enrolled. All patients received a Chinese version of 21-genes RS test, which is a new method using RNA extracted from formalin-fixed paraffin-embedded tissue performed by SurExam Campany, Guangzhou, China. . The RS score for each patient was calculated based on expression level of 21-genes used in a prosperctively defined algorithm and calculate a recurrence score range from 0 to 100 and divided three risk groups according to TAILORs study.Distant metastases-free survival (DMFS) were correlated with the 21-genes RS by Kaplan-Meier (log-rank method), and Cox regression. Multivariable logistic regression was performed to determine factors correlated with RS testing and receipt of a high-risk RS. Results: Median patient age was 46 years (18 to 77 years). The Chinese version of 21-gene RS was generated for 378 patients: 61 (16.1%) low risk ( &lt; 11), 241 (63.8%) intermediate risk (11 to 25), and 76 (20.1%) high risk (≥ 26). At a median follow-up of 40 months, the 4-year-rate of estimated DMFS was 100%, 98.7% and 92.9% in low risk, intermediate risk and high risk groups. Meanwhile, there was no difference in RFS among three risk groups. For all patients, 21-gene RS was associated with DMFS ( P = .021). In multivariable Cox regression models, 21-gene RS was independently prognostic factor of DMFS (hazard ratio, 5.375; 95% CI, 1.00 to 28.84; P = .05). Tumor size (&gt;2cm vs ≤2cm, OR = 2.31, P = .005), high grade ( OR = 2.15, P = .013), ki67 index ( &gt; 14% vs ≤14%, OR = 4.24, P = .002), progesterone receptor expression ( &lt; 20% vs ≥20%, OR = 5.07, P &lt; .001) were predictor of high risk of RS. Conclusions: The Chinese version of 21-genes RS is independently prognostic factor for DMFS patients with ER–positive/HER2-negative node negative breast cancer. Future study was needed to explore the impact of 21 gene RS on long-term prognosis.

Do 21-Gene Recurrence Score Influence Chemotherapy Decisions in T1bN0 Breast Cancer Patients?

Purpose: Hormone receptor (HR)-positive breast cancer patients with tumor size ≤1.0 cm and negative node have favorable outcomes. The 21-gene Recurrence Score (RS) could predict response to chemotherapy for HR+ breast cancer, but its role in T1bN0 disease is challenging.Methods: T1bN0 breast cancer patients diagnosed between January 2014 and June 2019 with RS results were included and categorized as Low- (RS < 18), Intermediate- (RS 18–30), or High-risk (RS > 30) groups. Univariate and multivariate analysis were used to assess factors associated with RS distribution and chemotherapy recommendation. Chemotherapy decisions change and patient adherence after 21-gene RS testing were also evaluated.Results: Among 237 patients with T1bN0 tumors, proportions of Low-, Intermediate-, and High-risk RS were 19.8, 63.3, and 16.9%, respectively. Multivariate analysis found that ER expression (P = 0.011), PR expression (P < 0.001), and Ki-67 index (P = 0.001) were independently associated with RS distribution. Adjuvant chemotherapy was recommended for 31.6% of patients, which was more frequently given to patients with higher tumor grade [Odds ratio (OR) = 2.99 for grade II, OR = 59.19 for grade III, P = 0.006], lymph vascular invasion (OR = 8.22, P = 0.032), Luminal-B subtype (OR = 5.68, P < 0.001), and Intermediate-to High-risk RS (OR = 10.01 for Intermediate-risk, OR = 192.42 for High-risk, P < 0.001). Chemotherapy decision change was found in 18.6% of patients, mainly in those with Intermediate- to High-risk RS tumor with the majority from no-chemotherapy to chemotherapy. The treatment compliance rate after the 21-gene RS testing with MDT was 95.4%.Conclusion: RS category was related to ER, PR, and Ki-67 expression, which was recognized as an independent factor of chemotherapy recommendation in T1bN0 breast cancer. The 21-gene RS testing would lead to a chemotherapy decision change rate of 18.6% as well as a high treatment adherence, which can be applied in T1bN0 patients.

Abstract P2-08-15: 21-gene recurrence score testing utilization among older women from different races: A surveillance, epidemiology and end results (SEER) study

Abstract Background: About 50% of breast cancers (BrCa) occur in women over the age of 65. Although chemotherapy improves survival in patients with estrogen receptor (ER) positive BrCa, benefits of chemotherapy in older woman must be weighed against the risks of morbidity associated with chemotherapy and non-BrCa associated mortality at older ages. OncotyeDX, 21-gene Recurrence Score (RS) identifies patients who may benefit from chemotherapy. In this study we looked at utilization of RS testing and likelihood of high-risk RS score in the older population across different races. Materials and Methods: We used Surveillance Epidemiology and End Result (SEER) data, linked to RS scores by the SEER program, to identify women older than 18 diagnosed with ER positive BrCa between the years 2004 and 2015. Patients with Stage 4 disease and T4 tumors were excluded. Patients were stratified into low (RS &amp;lt;11), intermediate (RS 11-25), and high-risk (RS&amp;gt;25) groups following TAILORx trial cut offs. Multivariable logistic regression model was used to identify factors associated with utilization of RS testing and association with high-risk RS. Results: Of 539,693 patients older than 18 years of age with ER positive, stage I-III BrCa identified between 2004 and 2015 in SEER registries, 109,835 (20.35%) had RS testing performed. The odds of having RS testing done was lower among women ≥65 compared to younger women in all races. The characteristics that increased odds of testing included progesterone receptor positive tumors, later years of diagnosis (2010-2015 compared to 2004-2009), negative nodes, T1 tumors, and Grade 1-2 (compared to Grade 3) tumors, were largely consistent across race groups. Blacks and American Indian/Alaskan Natives had higher odds of high-risk RS compared to non-Hispanic whites, after adjusting for stage, grade, and age. Being age 65 and older reduced the odds of having high-risk RS by odds ratio (OR) 0.58 in non-Hispanic whites, adjusted for progesterone receptor status, tumor size, positive nodes, and grade. The reduced odds of high-risk RS associated with being age 65 and older was more pronounced among black women, adjusted OR 0.44 (0.37 - 0.51) and among Asian or Pacific Islander women OR 0.44 (0.37 - 0.51). Conclusion: Older women of all races are less likely to be tested for 21-gene RS. Among women who were tested, those age 65 and older were less likely to have high-risk RS result. Blacks and American Indian/Alaskan Natives have higher risk of having high-risk RS after controlling for stage, age and other clinical and pathologic predictors. Citation Format: Evin Gulbahce, Sandra White, Gregory J Stoddard, Kim Herget, Carol Sweeney. 21-gene recurrence score testing utilization among older women from different races: A surveillance, epidemiology and end results (SEER) study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-08-15.

Abstract P3-14-05: Oncotype DX assay’s real world data in early stage breast cancer patients. Outcomes of a cohort treated in the Basurto University Hospital, Spain

Abstract Introduction: Oncotype DX (ODX) Recurrence Score (RS) is a gene-expression assay that provides prognostic and predictive information in hormonal-receptor positive (HR +), human epidermal growth factor receptor 2 negative (HER2-), axilary lymph node negative (LN-) disease. It estimates the 10 year-risk of distant recurrence and it is recommended to asses this issue and the potential benefit of adjuvant systemic therapy in early stage breast cancer (ESBC). (JCO 2016, NCCN 2019). Objective: To evaluate the impact of RS on our adjuvant treatment decision making and follow-up (FU). Materials and methods: Observational, prospective single institution study. Eligible patients (pts) were diagnosed between September 2012 and December 2018 with HR+, HER2 -, N0 and N+ (N1mic) ESBC for who underwent ODX assay. Criteria for ordered ODX assay were established by the group of experts from the Basque Country Health System. Treatment recommendations were documented before and after the conventional RS results. We reviewed clinical and pathology reports for FU and events. Descriptive statistics were used to summarize patient and tumor characteristics and changes in oncologists’ treatment recommendations. Mc Nemar’s test was used to identify how these tests impact in decisión. Results: N=337 pts. Median age was 57 years (SD 9,11); women 328 pts (97%); premenopausical 114 (34%); conservative surgery 271 pts (80%); sentinel node 318 pts (94 %); pN0: 248 pts (74%), pN1mic: 89 (26%); tumor size: pT1a-b: 41 pts (12 %), pT1c: 234 pts (69%) and pT2: 62 pts (18%); histologic type: ductal 280 pts (83%); histological grade: G1 49 pts (16%), G2 250 pts (74 %), G3 34 pts (10%); Ki 67 index &amp;gt;=13: 221 pts (66 %); progesterone receptors: positives: 304 pts (90%); presence of lymphovascular invasión:36 pts (11%). Treatment decision before assay was hormonal therapy (HT) in 242 pts (72 %) and chemotherapy (CT) in 95 pts (28 %). Conventional RS were: low risk RS&amp;lt;18 (LR): 180 pts (53%), intermediate risk RS 18-30 (IR): 135 pts (40%) and high risk RS &amp;gt;30 (HR): 22 pts (7%). TAILORx RS cutpoints were: LR RS &amp;lt;11: 78 pts (23%), IR RS 11-25: 207 pts (61%), HR RS &amp;gt;25: 52 pts (15%). Post-assay treatment: 278 pts (82.5%) received HT and 59 pts (17.5 %) CT. Treatment recomendation pre and post ODX assay changed in 17,5% of pts: in 10,5% from CT to HT and 7% from HT to CT. The McNemar's test was significant value (0.000). With a median FU of 35 months (range 1-77) there were 5 events: (1.5%): 1 local (0.3%) and 4 distant (1.2%). Conclusions: In our cohort, the 82.5% of pts received HT. The treatment decisión changed 17.5% of pts. The ODX avoided CT in 10.5% of 38 pts (28% pre and 17.5% post). At this time, insufficient median FU and number of events are available to examine long-term prognosis and CT benefit. Citation Format: Maria Purificacion Martínez del Prado, Borja López de San Vicente, Juan Fernando Arango Arteaga, Jairo Legaspi Folgueira, Ane Zumárraga Cuesta, Fernando Pikabea Diaz, Patricia Novas Vidal, María López Santillán, Laura Sande Sardina, Maitane Nuño Escolástico, María Teresa Abad Villar, Maria Ángeles Sala Gonzalez, Covadonga Figaredo Berjano, María Teresa Pérez Hoyos, Elena Galve Calvo. Oncotype DX assay’s real world data in early stage breast cancer patients. Outcomes of a cohort treated in the Basurto University Hospital, Spain [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-14-05.

Impact of 21-gene recurrence score testing on adjuvant chemotherapy decision making in older patients with breast cancer

PurposeTo evaluate the role of 21-gene recurrence score (RS) assay in adjuvant chemotherapy decision-making among older patients with early breast cancer. MethodsConsecutive hormonal receptor-positive, aged ≥60 patients with breast cancer were enrolled from Shanghai Ruijin Hospital between January 2014 and December 2017. Treatment decisions were made by multi-disciplinary team (MDT) before and after 21-gene RS testing, and the actual treatment for each patient was also analyzed. ResultsA total of 511 patients were enrolled, with 331 (64.8%) aged between 60 and 69, 140 (27.4%) between 70 and 79, and 40 (7.8%) over 80 years. There were 138 (27.0%), 287 (56.2%), and 86 (16.8%) patients classified as low, intermediate, and high risk RS, respectively. Multivariable analysis demonstrated that age, tumor stage, nodal status, PR expression, Ki-67, and 21-gene RS were independent impact factors for chemotherapy recommendations (P < .05). Patients with high risk RS and intermediate risk RS (both P < .001) were more often recommended to receive chemotherapy than patients with low risk RS. Treatment recommendations changed in 74 (14.5%) patients after 21-gene RS testing: 17 (3.3%) from chemotherapy to no chemotherapy and 57 (11.2%) from no chemotherapy to chemotherapy. Overall compliance rate to MDT recommendation after 21-gene RS testing was 95.7%. ConclusionAn intermediate and/or high risk 21-gene RS assay was independently associated with receiving adjuvant chemotherapy among older patients with breast cancer. However, it showed a limited impact on adjuvant chemotherapy decision-making. After 21-gene RS testing, compliance with MDT recommendation was relatively high in older patients with breast cancer.

Impact of the 21-gene recurrence score assay on chemotherapy decision making and outcomes for breast cancer patients with four or more positive lymph nodes.

To assess the impact of the 21-gene recurrence score (RS) on chemotherapy decision making and survival outcomes for breast cancer patients with >4 positive lymph nodes. Patients with non-metastatic estrogen receptor-positive breast cancer with >4 positive lymph nodes diagnosed between 2004 and 2013 were identified using the Surveillance, Epidemiology, and End Results database. The relationships between the 21-gene RS value and survival outcomes, chemotherapy decision-making, and chemotherapy benefit were analyzed. A total of 410 patients were identified, including 191 (46.6%), 164 (40.0%), and 55 (13.4%) in the low-, intermediate-, and high-risk RS groups, respectively. The 21-gene RS assay results were independently related to chemotherapy receipt. A total of 59.0%, 68.0%, and 78.0% of patients received chemotherapy in the low-, intermediate-, and high-risk RS groups, respectively. The 21-gene RS was an independent indicator of breast cancer specific survival (BCSS) and overall survival (OS). Intermediate-risk [BCSS: hazards ratio (HR), 2.832, 95% confidence interval (CI): 1.160-6.910, P=0.022; OS: HR, 3.704, 95% CI: 1.750-7.836, P=0.001] and high-risk RS (BCSS: HR, 6.440, 95% CI: 2.597-15.974, P<0.001; OS: HR, 5.053, 95% CI: 2.199-11.608, P<0.001) cohorts had significantly lower survival outcomes compared to low-risk RS cohort. The 5-year BCSS were 92.7%, 88.3%, and 70.7% in patients in the low-, intermediate-, and high-risk RS cohorts, respectively (P<0.001), and the 5-year OS were 92.1%, 80.6%, and 66.6%, respectively (P<0.001). The 21-gene RS is an independent predictor of chemotherapy receipt and survival outcomes for breast cancer patients with > 4 positive lymph nodes.

Progesterone Receptor Status and Tumor Grade Predict the 21-Gene Recurrence Score of Invasive Lobular Breast Cancer

Aim: To assess the association between established clinicopathological variables and the 21-gene recurrence score (RS) stratification of invasive lobular carcinoma (ILC) of the breast. Materials & methods: We identified 9030 ILC patients from the Surveillance, Epidemiology and End Results database. Results: Older age, higher grade tumor and progesterone receptor (PR)-negative disease were independent predictors of high-risk RS stratification. Among patients with PR-positive tumors, 3, 6 and 15% with well-differentiated (G1), moderately-differentiated (G2) and poorly and/or undifferentiated (G3) disease were in the high-risk cohort, respectively. In patients with PR-negative tumors: 16, 24 and 41% of patients with G1, G2 and G3 disease were in the high-risk cohort, respectively. Conclusion: The 21-gene RS testing may not be necessary for patients with PR+/G1-2 ILC.

Breast cancer-specific survival outcomes among patients based on 21-gene recurrence score.

537 Background: The 21-gene recurrence assay predicts cancer recurrence rates and benefit from adjuvant chemotherapy among patients with hormone-receptor-positive breast cancer. The National Cancer Institute and Genomic Health collaborated to provide Recurrence Score (RS) results to complement data from 17 population-based cancer registries in the Surveillance, Epidemiology, and End Results (SEER) Program. Methods: Using the SEER database with linked RS results, a cohort of female breast cancer patients, age greater than 20 years, was identified by RS (low: &lt; 18, intermediate: 18-30, high: &gt; 30) diagnosed between the years 2004 and 2007. A retrospective analysis was conducted to determine eight-year breast cancer-specific survival rates based on RS and other variables. Results: 10,318 patients were identified in the cohort. 5,194 had a low risk RS; 4,282 had an intermediate risk RS; 872 had a high risk RS. Histologic subtypes were: 7,459 infiltrating ductal carcinoma, 941 mixed infiltrating and lobular carcinoma, 933 lobular carcinoma, 327 mixed infiltrating ductal and other histology, 244 mucinous adenocarcinoma, 101 tubular adenocarcinoma, 45 mixed lobular and other histology, 268 other histologies. 644 low risk RS patients received chemotherapy (12.4%); 1,608 intermediate risk RS patients received chemotherapy (37.8%); 593 high risk patients received chemotherapy (68.0%). The eight-year breast cancer-specific survival rates (with 95% confidence intervals) among low risk RS patients without known chemotherapy administration was 98.9% (98.5, 99.2), and 98.4% (97.0, 99.1) with chemotherapy; intermediate risk RS patients without known chemotherapy was 97.0% (96.2, 97.6), and 96.9% (95.9, 97.7) with chemotherapy; high risk RS patients without known chemotherapy was 89.7% (85.4, 92.8), and 92.9% (90.4, 94.7) with chemotherapy. Conclusions: Among a large cohort of patients identified in a population-based cancer registry between 2004 and 2007, there was no statistically significant difference in eight-year breast cancer-specific survival rates among those who received chemotherapy and those who did not, regardless of RS risk group.

Hormone replacement therapy (HRT) and risk of distant recurrence in newly diagnosed ER+, node-negative (N-) breast-cancer (BC) patients: A retrospective population-based matched-cohort study.

6591 Background: Observational studies have shown an increased risk of BC with use of HRT. However, data on the prognosis of BC that develop in HRT users are inconsistent. The association between HRT use and results of the 21-gene Recurrence Score (RS) assay (Oncotype DX, Genomic Health Inc.) has not been investigated. We aimed to analyze this association, and examine the actual rate of distant recurrence or death in this population. Methods: Clalit Health Services (CHS) is the largest health maintenance organization (HMO) in Israel. We identified all CHS newly diagnosed ER+, N- breast-cancer patients, aged 45-60 that performed a RS assay between 01/2006-12/2012 and that were treated for at least three months with HRT during the eight years before BC diagnosis. A 1:4 matched-cohort analysis was performed, with matching made according to age and year of BC diagnosis. Clinical and demographic data were extracted from the CHS centralized registry for all patients. RS assay scores was grouped according to the TAILORX categorization and distribution was compared using Chi-square test. Kaplan-Meier analysis with log-rank test was performed in order to compare time to a combined outcome of distant-recurrence and mortality. Results: A cohort of 259 HRT-treated patients was identified and matched with 1001 controls, not treated with HRT. The proportions of low-risk patients (RS 0-25) and high-risk patients (RS 26-100) were 76.8% and 23.2%, respectively, within HRT-treated patients, and 80.4% and 19.6% within controls. Chi square test was not found significant (χ2= 1.634, p = 0.201). The mean follow-up time was 148.4 months for the cases and 146.9 months for controls, with log-rank test not showing a significant difference between groups. Conclusions: These data did not show significant association between HRT use and higher RS assay scores, and also did not find an association between HRT use and actual distant recurrence or death. Although the proportion of patients with high risk RS appeared to be slightly higher within HRT treated patients, this difference had not reached significance and further studies are required.

Oncotype recurrence score (RS) and discordance in patients with secondary invasive breast events (SIBE).

e12016 Background: Oncotype RS is a 21-gene assay used to predict the likelihood of distant recurrence and benefit of chemotherapy in patients with node-negative, tamoxifen treated breast cancer (BC). We developed a database to determine rates of SIBE and identify cases of discordance between Oncotype RS and tumor grade (TG). Our goal was to recognize patients with discordant tumors who had SIBE, with implications for patient management. Methods: We identified 618 patients (645 samples) with early-stage, hormone positive BC treated between 2006-2018, with tumor characteristics available for analysis. Among these patients, there were 24 SIBE (n = 24) from 23 patients (3.7%). When stratified by RS using traditional cutoffs (Paik, 2004), rates of SIBE were 2.8%, 5.0% and 4.5% in low, intermediate and high-risk groups respectively. Discordance was defined as 1 or 2-step difference between RS (low, intermediate, high risk) and TG (well (WD), moderately (MD) and poorly (PD) differentiated). Prior studies demonstrated 7-19% “2-step discordance” between TG and RS (i.e. PD tumors with low-risk RS or WD tumors with high-risk RS). N(%) or median were used to describe patients’ characteristics between groups and compared by Mann-Whitney U test at the confidence level of 5%. Results: Of the 24 SIBE, 42% had low RS ( &lt; 18), 46% had intermediate RS (18-30) 12% had high RS ( &gt; 31). Median RS was 22 and median age at secondary event was 61 (67% post-menopausal). At time of SIBE, 54% were metastatic, 25% locally recurrent and 21% contralateral. Within this dataset, 63% were 1-step and 4% were 2-step discordant. Significantly fewer patients were treated with systemic chemotherapy in the discordant group (p &lt; 0.01), though 94% displayed MD or PD TG. Discordant tumors tended to have lower RS (median 14 vs. 24) and be larger. There were no significant differences in menopausal status or Oncotype ER/PR score. Conclusions: Although the sample size of patients with SIBE is small, our data suggests that patients with discordant tumors of low-risk RS but higher TG may be receiving inadequate treatment (i.e. no chemotherapy). In addition to RS, other factors such as discordance, TG and size should perhaps be considered when determining treatment plans.

The 21-gene recurrence score and effects of adjuvant radiotherapy after breast conserving surgery in early-stage breast cancer.

Aim: To investigate the associations with the 21-gene recurrence score (RS) and effect of adjuvant radiotherapy (RT) for early-stage breast cancer after breast conserving surgery. Methods: We included 13,246 patients in the SEER database. Results: Patients with a higher RS were independently related to nonreceipt of RT (p < 0.001). In both the traditional and Trial Assigning Individualized Options for Treatment (TAILORx) RS cut-offs, the receipt of RT was not related to better breast cancer-specific survival in low- and high-risk RS groups, but was independently related to better breast cancer-specific survival in intermediate-risk RS group before (p =0.029) and after (p =0.001) propensity score matching. Conclusion: The 21-gene-RS may impact the decision-making of adjuvant RT in early-stage breast cancer after breast conserving surgery. The survival benefit of adjuvant RT may be limited to patients with intermediate-risk RS.

Impact of 21-Gene Recurrence Score on Chemotherapy Decision in Invasive Ductal Carcinoma of Breast with Nodal Micrometastases.

PurposeThe purpose of this study was to investigate the effect of 21-gene recurrence score (RS) on predicting prognosis and chemotherapy decision in node micrometastases (N1mi) breast invasive ductal carcinoma (IDC).MethodsPatients with stage T1-2N1mi and estrogen receptor-positive IDC diagnosed between 2004 and 2015 were included. The associations of 21-gene RS with breast cancer-specific survival (BCSS), chemotherapy decision, and benefit of chemotherapy were analyzed.ResultsWe identified 4,758 patients including 1,403 patients (29.5%) treated with adjuvant chemotherapy. In the traditional RS cutoffs, 2,831 (59.5%), 1,634 (34.3%), and 293 (6.2%) patients were in the low-, intermediate-, and high-risk RS groups, respectively. In 3,853 patients with human epidermal growth factor receptor-2 (HER2) status available, most patients were HER2-negative disease (98.3%). A higher RS was independently related to chemotherapy receipt, and 14.0%, 47.7%, and 77.8% of patients in the low-, intermediate-, and high-risk RS groups received chemotherapy, respectively. The multivariate analysis indicated that a higher RS was related to worse BCSS (p < 0.001). The 5-year BCSS rates were 99.3%, 97.4%, and 91.9% in patients with low-, intermediate-, and high-risk RS groups, respectively (p < 0.001). However, chemotherapy receipt did not correlate with better BCSS in low-, intermediate-, or high-risk RS groups. There were similar trends using Trial Assigning Individualized Options for Treatment RS cutoffs.ConclusionThe 21-gene RS does predict outcome and impact on chemotherapy decision of N1mi breast IDC. Large cohort and long-term outcomes studies are needed to identify the effects of chemotherapy in N1mi patients by different 21-gene RS groups.

Effect of 21-gene recurrence score in decision-making for surgery in early stage breast cancer.

AimWe aimed to assess the role of 21-gene recurrence score (RS) in the decision-making for surgical treatment in early stage breast cancer and compared the outcomes between breast-conserving surgery (BCS) and mastectomy (MAST) among various 21-gene RS groups.MethodsWe included patients with stage T1-2M0M0 and estrogen receptor-positive breast invasive ductal carcinoma who underwent BCS + radiotherapy or MAST between 2004 and 2012 as part of the Surveillance, Epidemiology, and End Results program. Data were analyzed using binomial logistic regression, multivariate Cox proportional hazards models, and propensity score matching (PSM).ResultsWe enrolled 34,447 patients including 22,681 (65.8%) and 11,766 (34.2%) who underwent BCS and MAST, respectively. Patients with high-risk RS were more likely to receive MAST. Multivariate analysis indicated that patients with intermediate-risk (P<0.001) and high-risk (P<0.001) RS had poor breast cancer-specific survival (BCSS), as compared to those with low-risk RS. Moreover, patients who underwent MAST also exhibited poor BCSS (P<0.001), as compared to those who underwent BCS. In low-risk (P<0.001) and intermediate-risk (P=0.020) RS groups, patients who underwent MAST had poor BCSS, as compared to those treated with BCS. However, BCSS was comparable between patients who underwent MAST and BCS (P=0.952); similar trends were also observed after PSM.ConclusionThe 21-gene RS may impact the decision-making for surgery in early stage breast cancer. Our study provides additional support for a shared decision-making process for BCS when both local management options are appropriate choices regardless of the 21-gene RS.