Recurrence Score Testing Research Articles

Validation of the 21-gene test as a predictor of clinical response to neoadjuvant hormonal therapy for ER+, HER2-negative breast cancer: the TransNEOS study

PurposeThe Recurrence Score test is validated to predict benefit of adjuvant chemotherapy. TransNEOS, a translational study of New Primary Endocrine-therapy Origination Study (NEOS), evaluated whether Recurrence Score results can predict clinical response to neoadjuvant letrozole.MethodsNEOS is a phase 3 clinical trial of hormonal therapy ± adjuvant chemotherapy for postmenopausal patients with ER+, HER2-negative, clinically node-negative breast cancer, after six months of neoadjuvant letrozole and breast surgery. TransNEOS patients had tumors ≥ 2 cm and archived core-biopsy samples taken before neoadjuvant letrozole and subsequently sent for Recurrence Score testing. The primary endpoint was to evaluate clinical (complete or partial) response to neoadjuvant letrozole for RS < 18 versus RS ≥ 31. Secondary endpoints included evaluation of clinical response and rate of breast-conserving surgery (BCS) by continuous Recurrence Score result, ESR1 and PGR single-gene scores, and ER gene-group score.ResultsOf 295 TransNEOS patients (median age 63 years; median tumor size 25 mm; 66% grade 1), 53.2% had RS < 18, 28.5% had RS18–30, and 18.3% had RS ≥ 31. Clinical response rates were 54% (RS < 18), 42% (RS18–30), and 22% (RS ≥ 31). A higher proportion of patients with RS < 18 had clinical responses (p < 0.001 vs. RS ≥ 31). In multivariable analyses, continuous Recurrence Score result (p < 0.001), ESR1 score (p = 0.049), PGR score (p < 0.001), and ER gene-group score (p < 0.001) were associated with clinical response. Recurrence Score group was significantly associated with rate of BCS after neoadjuvant treatment (RS < 18 vs. RS ≥ 31, p = 0.010).ConclusionThe Recurrence Score test is validated to predict clinical response to neoadjuvant letrozole in postmenopausal patients with ER+, HER2-negative, clinically node-negative breast cancer.

Oncotype testing in patients undergoing intraoperative radiation for breast cancer

Oncotype DX recurrence score (RS) predicts risk of distant disease recurrence, and can guide chemotherapy recommendations in hormone positive, human epidermal growth factor 2-negative, early stage breast cancer. The present study aimed to evaluate the pattern of oncotype testing, RS and adjuvant treatment in patients undergoing intraoperative radiotherapy (IORT). Single center prospective data registry was queried for patients receiving IORT between October 2011 and February 2017. Patient demographics, tumor characteristics, RS, systemic therapy and recurrence information were analyzed. A total of 150 women with mean age of 70.8 years were included. The majority had invasive ductal cancer (60.6%) with 1.0 cm average tumor size and no lymph node involvement (99%). Oncotype testing was performed in 36 patients (24.3%). Low risk score (<18) was confirmed in 19 women (53%); intermediate risk score (18-30) in 16 women (44%); and high risk score (>30) in one woman (3%). Patients with RS testing had significantly increased tumor sizes (1.2 vs. 1.0 cm; P<0.001) and were younger (68.5 vs. 71.3 years; P=0.02) compared with those not tested. A total of 4/150 patients (2.6%) received chemotherapy; two received chemotherapy based on RS testing. Based on the current selection criteria for IORT, oncotype testing rarely results in a high-risk score or utilization of chemotherapy for IORT patients. The present study supports selective use of RS testing in IORT patients and confirms that biologically low-risk patients are being selected for IORT based on current guidelines.

Many Women With the Most Common Form of Breast Cancer Can Skip Chemotherapy: Study finds that approximately 70% of patients with this form of the disease do not need adjuvant chemotherapy.

Many Women With the Most Common Form of Breast Cancer Can Skip Chemotherapy: Study finds that approximately 70% of patients with this form of the disease do not need adjuvant chemotherapy.

21-gene recurrence score testing in the older population with estrogen receptor-positive breast cancer

The 21-gene recurrence score (RS) (Oncotype Dx, Genomic Health, Redwood City Ca) has not been validated in an older cohort with estrogen receptor (ER)-positive breast cancer. The objective of this study was to evaluate RS validity in a group of older women with ER-positive breast cancer. Utilizing the Surveillance, Epidemiology, and End Results Program (SEER) database with available RS, we evaluated women with ER-positive breast cancer aged 18-69 and those 70 years of age and older from 2004 to 2014. We utilized multivariable logistic regression models to evaluate factors associated with RS testing as well as a high-risk categorization for those who underwent testing. Survival was analyzed using Kaplan Meier curves and Cox proportional hazard models. We identified 363,876 women aged 18-69 years and 147,107 women aged 70 years and older. A smaller proportion of patients in the older group (8%) underwent RS testing than in the younger group (18%). Of the patients who underwent testing, distribution of RS was similar between groups. High-risk categorization independently predicted a higher likelihood of death for older patients (hazard ratio 1.47, 95% confidence interval 1.15-1.90). Among patients with high-risk RS, chemotherapy was associated with a decreased risk of death in the younger group, but not in the older group. Older women are less likely to receive RS testing, but when tested, older patients have a similar distribution of RS as compared to younger patients. While high-risk categorization in the older cohort was prognostic, chemotherapy was not associated with improved survival.

Distribution of 21-Gene Recurrence Scores in Male Breast Cancer in the United States.

The 21-gene recurrence score (RS) is a RT-PCR assay estimating risk of distant recurrence in estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2) breast cancer (BC). Studies validating RS are limited to women. Our objective was to assess RS distribution and factors associated with high-risk RS in male BC. Using the Surveillance, Epidemiology, and End Results database, we identified men and women with ER+/HER2- BC from 2010 to 2013. Patients were categorized into risk groups using the traditional and the Trial Assigning Individualized Options for Treatment (TAILORx) cutoffs. Multivariable logistic regression determined factors associated with testing and high-risk TAILORx RS. We identified 1388 men and 154,196 women with ER+/HER2- BC. Twenty-five percent of men and 30% of women had RS testing. Mean age of tested men was 63; most were white (81%), had grade I or II tumors (67%), and had stage I or II (95%) BC. Factors associated with increased RS testing were younger age, recent year of diagnosis, lymph node negativity, and lower-stage tumors (p ≤ 0.05). By TAILORx, 21% of men had high-risk RS compared with 14% of tested women. Men with grade III and PR negative tumors were more likely to have a high-risk RS (p ≤ 0.05). Chemotherapy utilization was correlated with RS. Using a large population-based dataset, we found that compared with women, men were significantly more likely to have high-risk RS. Grade III and PR-negative BC were significantly associated with high-risk RS. Higher RS in men correlated with increased chemotherapy utilization.

Combined pathologic‐genomic algorithm for early-stage breast cancer improves cost-effective use of the 21-gene recurrence score assay

BackgroundThe 21-gene recurrence score (RS) (Oncotype DX®; Genomic Health, Redwood City, CA) partitions hormone receptor positive, node negative breast cancers into three risk groups for recurrence. The Anne Arundel Medical Center (AAMC) model has previously been shown to accurately predict RS risk categories using standard pathology data. A pathologic‐genomic (P-G) algorithm then is presented using the AAMC model and reserving the RS assay only for AAMC intermediate-risk patients. Patients and methodsA survival analysis was done using a prospectively collected institutional database of newly diagnosed invasive breast cancers that underwent RS assay testing from February 2005 to May 2015. Patients were assigned to risk categories based on the AAMC model. Using Kaplan–Meier methods, 5-year distant recurrence rates (DRR) were evaluated within each risk group and compared between AAMC and RS-defined risk groups. Five-year DRR were calculated for the P-G algorithm and compared with DRR for RS risk groups and the AAMC model’s risk groups. ResultsA total of 1268 cases were included. Five-year DRR were similar between the AAMC low-risk group (2.7%, n=322) and the RS<18 low-risk group (3.4%, n=703), as well as between the AAMC high-risk group (22.8%, n=230) and the RS>30 high-risk group (23.0%, n=141). Using the P-G algorithm, more patients were categorized as either low or high risk and the distant metastasis rate was 3.3% for the low-risk group (n=739) and 24.2% for the high-risk group (n=272). Using the P-G algorithm, 44% (552/1268) of patients would have avoided RS testing. ConclusionsAAMC model is capable of predicting 5-year recurrences in high- and low-risk groups similar to RS. Further, using the P-G algorithm, reserving RS for AAMC intermediate cases, results in larger low- and high-risk groups with similar prognostic accuracy. Thus, the P-G algorithm reliably identifies a significant portion of patients unlikely to benefit from RS assay and with improved ability to categorize risk.

Utilization of the 21-Gene Recurrence Score in a Diverse Breast Cancer Patient Population: Development of a Clinicopathologic Model to Predict High-Risk Scores and Response to Neoadjuvant Chemotherapy.

The 21-gene expression profile [Oncotype DX Recurrence Score (RS)] stratifies benefit from adjuvant chemotherapy in hormone receptor (HR)-positive, HER2/neu-negative, node-negative breast cancer. It is not routinely applied to predict neoadjuvant chemotherapy (NACT) response; data in diverse patient populations also are limited. We developed a statistical model based on standard clinicopathologic features to identify high-risk cases (RS > 30) and then evaluated ability of predicted high RS to predict for NACT downstaging. Primary surgery patients with Oncotype DX RS testing 2012-2016 were identified from a prospectively-maintained database. A RS predictive model was created and applied to a dataset of comparable NACT patients. Response was defined as tumor size decrease ≥ 1cm. Of 394 primary surgery patients-60.4% white American; 31.0% African American-RS distribution was similar for both groups. No single feature reliably identified high RS patients; however, a model accounting for age, HR expression, proliferative index (MIB1/Ki67), histology, and tumor size was generated, with receiver operator area under the curve 0.909. Fifty-six NACT patients were identified (25 African American). Of 21 cases with all relevant clinicopathology, 14 responded to NACT and the model generated high-risk RS in 14 (100%); conversely, of 16 cases generating high-risk RS, only 2 did not respond. Predictive modelling can identify high RS patients; this model also can identify patients likely to experience primary tumor downstaging with NACT. Until this model is validated in other datasets, we recommend that Oncotype-eligible patients undergo primary surgery with decisions regarding chemotherapy made in the adjuvant setting.

Molecular Characterization and Mortality From Breast Cancer in Men.

Purpose Limited data exist on the molecular biology, treatment, and outcomes of breast cancer in men, and much of our understanding in this area remains largely an extrapolation from data in women with breast cancer. Materials and Methods We studied men and women with hormone receptor-positive breast cancer and the 21-gene Breast Recurrence Score (RS) results. Differences in clinical characteristics and gene expression were determined, and distribution of RS results was correlated with 5-year breast cancer-specific survival (BCSS) and overall survival. Results There were 3,806 men and 571,115 women. Men were older than women (mean age, 64.2 v 59.1 years; P < .001). RS < 18 predominated in both genders, but RS ≥ 31 was more frequent in men (12.4% v 7.4%; P < .001), as were very low scores (RS < 11; 33.8% v 22.1%; P < .001). Mean gene expression was higher in men for the estrogen receptor (ER), proliferation, and invasion groups. ER was lowest and progesterone receptor was highest in women younger than 50 years of age, with a progressive increase in ER with age. Men younger than 50 years of age had slightly lower ER and progesterone receptor compared with older men. Survival data were available from SEER for 322 men and 55,842 women. Five-year BCSS was 99.0% (95% CI, 99.3% to 99.9%) and 95.9% (95% CI, 87.6% to 98.7%) for men with RS < 18 and RS 18-30, respectively, and for women, it was 99.5% (95% CI, 99.4% to 99.6%) and 98.6% (95% CI, 98.4% to 98.8%), respectively. RS ≥ 31 was associated with an 81.0% 5-year BCSS in men (95% CI, 53.3% to 93.2%) and 94.9% 5-year BCSS (95% CI, 93.9% to 95.7%) in women. Five-year BCSS and overall survival were lower in men than in women. Conclusion This study reveals some distinctive biologic features of breast cancer in men and an important prognostic role for RS testing in both men and women.

Association between physician characteristics and the use of 21-gene recurrence score genomic testing among Medicare beneficiaries with early-stage breast cancer, 2008-2011.

We sought to determine whether physician-level characteristics were associated with 21-gene recurrence score (RS) genomic testing to evaluate recurrence risk and benefit of adjuvant chemotherapy in patients with estrogen receptor-positive, node-negative breast cancer. Retrospective cohort study of a nationally representative sample of Medicare beneficiaries using Surveillance, Epidemiology, and End Results program-Medicare data linked with the American Medical Association physician master file. The main outcome was receipt of genomic testing within 1year of diagnosis as a function of physician-level factors. A total of 24,463 patients met the study criteria; they received care from 3172 surgeons and 2475 medical oncologists. Of 4124 tests ordered, 70% were ordered by a medical oncologist and 16% by a surgeon. In multivariable regression models, multiple variables were associated with receipt of testing, including having a medical oncologist (odds ratio [OR] 2.77; 95% CI 2.00-3.82), a surgeon specializing in surgical oncology (OR 1.20; 95% CI 1.09-1.31), and a female medical oncologist (OR 1.10; 95% CI 1.02-1.20). Having a medical oncologist with 5 or more years in practice was associated with lower odds of testing (OR 0.83; 95% CI 0.76-0.92). Surgical procedures performed at academic centers were associated with higher odds of testing (OR 1.11; 95% CI 1.02-1.20). Although most RS testing was ordered by medical oncologists, physicians in other specialties ordered roughly one-third of the tests. Physician characteristics, including gender and time in practice, were associated with receiving testing, creating opportunities for targeting interventions to help patients receive optimal care.

Clinical and economic impact of the 21-gene recurrence score assay in adjuvant therapy decision making in patients with early-stage breast cancer: pooled analysis in 4 Basque Country university hospitals.

PurposeThe 21-gene recurrence score (RS) is a genomic test developed as a prognostic and predictive tool to improve the treatment decision making in cases of estrogen receptor-positive and human epidermal growth factor receptor 2-negative early-stage breast cancer. This study examined the clinical and economic impact of its use in 4 Basque Country university hospitals.MethodsTaking into consideration the RS result, we recorded the recommended initial systemic adjuvant therapy (endocrine therapy with or without chemotherapy) according to standard clinicopathologic factors and the final decision about chemotherapy. Then, if the RS was high, chemotherapy was recommended; it was not recommended if the RS was low; for those with an intermediate RS, clinicopathologic factors were considered, and the initial recommendation based on those factors was maintained. In addition, the probability of switching treatment was calculated. Then, we developed an economic evaluation by measuring the treatment’s incremental short-term budget impact from both the societal perspective and that of the Basque Health System. Patients’ characteristics and chemotherapy use were analyzed using logistic regressions and receiver operating characteristic curves.ResultsWithout an RS, chemotherapy would have been prescribed to 56% of 401 patients, but, with RS use, that percentage decreased to 25. The overall rate of decision change was 35.4%. Test inclusion led to a reduction in chemotherapy costs of €922 per patient in the total population. Although this reduction did not entirely offset the cost of the test, the productivity loss per patient was reduced by €1,977.ConclusionThe 21-gene RS test significantly changed the indication for chemotherapy. As chemotherapy treatments with no benefit were avoided, patients’ quality of life was improved. The short-term economic impact was negative for the Basque Health Service, but savings resulted when sick-leave costs were included.

Impact of the 21-gene recurrence score assay in clinical treatment and prognosis analysis for patients with hormone receptor positive early-stage breast cancer

Objective: To explore the association between the 21-gene recurrence score (RS) and clinicopathologic characteristics as well as prognosis in patients with axillary lymph node negative, hormone receptor (HR) positive breast cancer. Methods: The clinicopathologic data of 439 early breast cancer patients who underwent 21 gene RS testing was retrospectively analyzed. According to the 21 gene RS, the patients were divided into low risk (295 cases), intermediate risk (111 cases) and high-risk (33 cases) group. The relationship between the 21 gene RS and clinicopathological characteristics, treatment, recurrence and metastasis was analyzed. Univariate and multivariate statistical analyses were used to analyze the risk factors for relapse free survival (RFS). Results: Tumor grade, estrogen receptor (ER), progesterone receptor (PR) and Ki-67 index were significantly different among the 3 risk cohorts (P<0.001 for all). After a median follow-up of 32 months, the recurrence rate in low risk group (3.7%) was significantly lower than that in the intermediate-high risk group (9.0%), the locoregional recurrence (LRR) rate of low, intermediate and high risk group was 2.4%, 6.3% and 9.1%; and the distant metastasis (DM) rate in low risk group was 1.4% and 2.1% in the intermediate-high risk group. Univariate analysis showed RS, ER status and endocrine therapy were prognostic factors for RFS (P<0.05 for all). Multivariate analysis showed that RS was an independent significant predictor for RFS (P=0.04). Conclusions: The 21-gene RS is related to tumor grade, ER, PR and Ki-67 index. RS is an independent risk factor for RFS in patients with hormone receptor positive early-stage breast cancer.

Abstract PD5-03: TransNEOS: Validation of the oncotype DX recurrence score (RS) testing core needle biopsy samples from NEOS as predictor of clinical response to neoadjuvant endocrine therapy for postmenopausal estrogen receptor positive (ER+), HER2 negative (HER2-) breast cancer patients

Abstract Background: Neoadjuvant therapy for locally advanced breast cancer has the potential to improve surgical therapeutic outcomes without sacrificing the survival advantages of adjuvant therapy. However, determining whether ER+ patients (pts) will respond to neoadjuvant (NA) chemotherapy (CT) or hormone therapy (HT) can be difficult. Not all ER+ pts respond to NACT, while response to NAHT can vary across ER+ pts. Thus, the ability to select pts more likely to benefit from NAHT would represent progress in clinical management of breast cancer. NEOS is a randomized phase III study assessinglong-term prognosis of ER+ primary breast cancer with/without adjuvant CT following NAHT (UMIN 000001090, http://www.umin.ac.jp/). We used archived core biopsy tumor samples from the NEOS study to validate the RS result as a predictor of clinical response and its association with successful breast conserving surgery (BCS) in pts treated with 6 months of NAHT. Methods: NEOS enrolled 904 postmenopausal pts with ER+, HER2-, clinically node negative (cN0) breast cancer to evaluate whether adjuvant CT was necessary for pts who responded to NAHT. In this current study, we enrolled pts with tumors ≥2cm from the NEOS study. Biopsy samples of 333 pts were assessed for the Oncotype DX assay. Response to NAHT was recorded as complete/partial response (CR/PR), or stable/progressive disease (SD/PD). Primary endpoint of this study was to evaluate clinical response (CR/PR) to NA letrozole between pts with low (&amp;lt;18) and high (≥31) RS result. Secondary endpoints include evaluating the relationships between clinical response and continuous RS results, and other covariates including age, tumor size, grade, Ki67 by IHC, ER and PR single gene scores, and ER and proliferation gene group scores by RT-PCR. Results: The analysis included 294 pts with median age of 63 yrs, median tumor size of 25mm, and 66% were nuclear grade 1. 156 (53.0%), 83 (28.6%) and 54(18.4%) cases were low, intermediate, and high RS groups by Oncotype DX, respectively. Six (2%), 126 (42.8%), 149 (50.3%), 13 (4.4%) cases experienced CR, PR, SD, PD as clinical response, respectively, similar to that of all NEOS pts. Clinical response rate was 54%, 42% and 22% in low, intermediate, and high RS groups, respectively. The proportion of pts with clinical response was significantly higher in the low RS group vs the high RS group (p&amp;lt;0.001). In univariate analyses, continuous RS was significantly associated with clinical response (p&amp;lt;0.001), along with ER (p=.02), PR (p&amp;lt;0.001), and ER gene group score (p&amp;lt;0.001). Other covariates were not associated with clinical response. Conclusion: The Oncotype DX RS test in core biopsy samples is validated as a predictive assay for clinical response of NAHT in postmenopausal, ER+/HER2-, cN0, primary early breast cancer pts. Further results on the association of RS results with BCS outcomes following NAHT will be presented. These results when combined with previously published data on RS in NACT studies help guide pts with ER+, HER2- breast cancer with NAHT vs NACT treatment options to maximize clinical response. Citation Format: Yamamoto Y, Iwata H, Masuda N, Fujisawa T, Toyama T, Kashiwaba M, Ohtani S, Taira N, Sakai T, Hasegawa Y, Nakamura R, Akabane H, Shibahara Y, Sasano H, Yamaguchi T, Sakamaki K, Chao C, McCullough D, Sugiyama N, Ohashi Y. TransNEOS: Validation of the oncotype DX recurrence score (RS) testing core needle biopsy samples from NEOS as predictor of clinical response to neoadjuvant endocrine therapy for postmenopausal estrogen receptor positive (ER+), HER2 negative (HER2-) breast cancer patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD5-03.

Abstract P1-07-14: Real-life analysis evaluating &amp;gt;1000 N0/N1mi estrogen receptor (ER)+ breast cancer patients for whom treatment decisions incorporated the 21-gene recurrence score (RS) result: Clinical outcomes with median follow up of &amp;gt; 9 years

Abstract Background: The 21-gene Recurrence Score (RS) Assay (Oncotype DX®) is a validated prognosticator and predictive of chemotherapy (CT) benefit in patients with hormone receptor (HR)+ human epidermal growth factor receptor 2 (HER2)-negative breast cancer. In Israel, the RS assay has been reimbursed by Clalit Health Services (CHS, the largest HMO in Israel) since 2006, and the assay is widely used in eligible estrogen receptor (ER)+ patients. Notably, ER+ breast cancer patients have a protracted risk of recurrence with approximately half of all distant recurrences occurring after 5 years from diagnosis. The goal of the current ongoing analysis was to investigate early (≤5 years) and late (&amp;gt;5 years) distant recurrence in N0/N1mi ER+ HER2-negative breast cancer patients who were RS-tested through CHS. Methods: This analysis of the CHS registry included breast cancer patients with ER+ HER2-negative N0/N1mi disease who underwent RS testing from 1/2006 (CHS approval of the assay) through 1/2009. Data sources included CHS claims arms (for patient/tumor characteristics), Teva Pharmaceuticals (for tumor characteristics, RS result), and medical records (for treatment/recurrence/survival). The study was approved by the institutional review boards of the CHS Community Division and was granted a waiver for obtaining patient consent. Results: The analysis included 1026 patients with median (interquartile range) follow up of 9.3 (8.8-10.2) years. Most patients were females (99%). Median (range) age was 59 (25-84) years; 92% had N0 and 8% had N1mi disease; 14%, 52%, and 16% had grade 1, 2, and 3 tumors, respectively (grade information was not available for 18% of patients); median (range) tumor size was 1.5 (0.3-6.5) cm. The majority of patients (78%) had invasive ductal carcinoma and 12% had invasive lobular carcinoma. Overall, 489 patients (48%) had RS&amp;lt;18, 434 (42%) had RS 18-30, and 103 (10%) had RS≥31. The use of adjuvant CT was consistent with the RS result: 3%, 27%, and 90% of RS&amp;lt;18, RS 18-30, and RS≥31 patients, respectively. Overall, 25 distant recurrences were reported within 5 years of RS testing: 5 (1.0%) in RS&amp;lt;18 patients, 9 (2.1%) in RS 18-30 patients, and 11 (10.6%) in RS≥31 patients. In the first 5 years, breast cancer-specific death was reported in 8 patients including 3 (0.7%) with RS 18-30 and 5 (4.9%) with RS≥31 results. Among N0 patients with RS 11-25 who did not receive adjuvant CT (n = 540), 5 (0.9%) distant recurrences and one (0.2%) breast cancer death were reported within 5 years of RS testing. Analysis of 'late' recurrences and breast cancer-specific death (from 5 to 9.3 years of follow-up) is ongoing. Conclusions: These will be the first late recurrence data from over 1000 patients for whom the RS result was used in real-life clinical decision making. Consistent with previous analyses of the CHS registry, CT use was appropriately based on the RS result, and the recurrence/survival outcomes (for the first 5 years) demonstrated the prognostic performance of the RS. Distant recurrence and breast cancer death data beyond 5 years will be presented at the meeting. Citation Format: Stemmer SM, Rizel S, Steiner M, Geffen DB, Soussan-Gutman L, Bareket-Samish A, McCullough D, Svedman C, Nisenbaum B, Ryvo L, Peretz T, Fried G, Rosengarten O, Liebermann N, Ben Baruch N. Real-life analysis evaluating &amp;gt;1000 N0/N1mi estrogen receptor (ER)+ breast cancer patients for whom treatment decisions incorporated the 21-gene recurrence score (RS) result: Clinical outcomes with median follow up of &amp;gt; 9 years [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-07-14.

Abstract P2-10-07: A prospective clinical utility study of the impact of the 21-gene recurrence score (RS) assay in the treatment of estrogen receptor positive (ER+), HER2 negative (HER2-), 1-3 node positive (N+) breast cancer (BC)

Abstract Background: The 21-gene RS is routinely used in node negative ER+, HER2- BC to help guide chemotherapy treatment decision making. There is emerging use of the RS in limited N+ BC, though the results from the randomized clinical trial (RxPONDER) is pending. The objective of the study is to determine whether the results of the 21-gene RS will alter physician treatment decisions in ER+ HER2- limited N+ BC. Methods: Consenting patients (pts) with ER+, HER2-, 1-3 N+ (microscopic or macroscopic) early stage BC participated in this prospective, multi-center British Columbia Cancer Agency (BCCA) study. Treating physicians completed a questionnaire after an initial visit with the patient to document their treatment recommendation before obtaining the RS assay. At a subsequent visit, the assay result and final treatment recommendations were discussed and physicians completed a second questionnaire on the final treatment plan. The statistical assumption of the study was based upon anticipating an overall treatment decision change rate (from chemo-hormonal therapy to hormone only, or vice-versa) to be at least 30%. Results: Out of 84 pts enrolled, 82 went on to have RS testing. 57% of pts had T1 tumors, 40% T2 and 2% T3 tumors. The majority of pts (77%) had N1 macroscopic disease compared to 23% that had microscopic nodal involvement. 63% of cases were grade 2, followed by 23% grade 1 and 14% grade 3. 60% of RS were low (&amp;lt;18), 33% intermediate (18-30) and 7% were high (&amp;gt;30). In 53% of cases there was an altered treatment plan (49% switched from chemo-hormonal therapy to hormone only, and 4% switched from hormone only to chemo-hormonal therapy). Of the 49% that switched to hormone only, 68% had a low RS and 33% had an intermediate RS. All 4% that switched to chemo-hormonal therapy had an intermittent RS. Conclusions: This multi-centered Canadian study showed that in 53% of cases, treatment recommendations were changed based on the RS. This suggests that there is clinical utility for the RS in 1-3 N+, ER+, and HER2- breast cancer. Citation Format: Sun J, Fenton D, Baxter S, Chan A, Roberts S, Feng X, Lohrisch C, Gelmon K, Shenkier T, Chia S. A prospective clinical utility study of the impact of the 21-gene recurrence score (RS) assay in the treatment of estrogen receptor positive (ER+), HER2 negative (HER2-), 1-3 node positive (N+) breast cancer (BC) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-10-07.

Abstract P1-06-10: Correlative analysis of breast cancer index (BCI) restratification of 21-gene recurrence score (RS) in patients with hormone receptor-positive (HR+), node-negative breast cancer

Abstract Background: In a cross-stratification analysis performed within the TransATAC cohort, Breast Cancer Index (BCI) and 21-gene Recurrence Score (RS) had a concordance of 58.2% (Sestak et al., Clin Cancer Res, 2016). Restratification by BCI of the low and intermediate RS risk groups led to subgroups with significantly different rates (P &amp;lt; 0.001 and P = 0.003, respectively); in contrast, restratified subgroups created by RS of BCI risk groups did not differ significantly. The objective of this study was to analyze the concordance of BCI and RS test results in HR+, node-negative (LN-) patients tested in the real-world setting and to investigate molecular, clinical, and pathologic correlates within discrepant cases. Methods: This study utilized a subset of cases from the BCI Clinical Database for Correlative Studies, an IRB-approved de-identified database which contains clinicopathologic and molecular variables from clinical cases submitted for BCI testing. Clinicopathologic variables, abstracted from pathology reports, were available for a subset of cases. This analysis evaluated cases from LN- patients with available RS data. Concordance was evaluated between BCI Prognostic risk groups (Low, High) and RS risk groups (Low, Intermediate, High based on TAILOR Rx cutpoints [0-10, 11-25, and 26+]). Fisher's Exact tests were used to compare molecular (HoxB13/IL17BR [H/I] endocrine response biomarker and Molecular Grade Index [MGI] proliferation marker) and clinicopathologic (age, grade, size, HER2, Ki67) data in discrepant risk groups. Results: There were 456 LN- patients included. Median age was 58.0y (range 27.2-84.0y; 73.9% ≥50y); 33.1%/50.1%/16.8% were grade 1/2/3; and 24.0%/59.5%/15.3% were T1ab/T1c/T2. BCI classified 47.8% (n=218) of patients as Low Risk vs 52.2% (n=238) as High Risk. RS classified 17.1% (n=78), 67.1% (n=306), and 15.8% (n=72) of patients as Low, Intermediate, and High Risk, respectively. BCI restratified RS-Low patients as high risk in 17.1% of cases, restratified RS-Intermediate as Low Risk in 48.4% and High Risk in 51.6%, and restratified RS-High as Low risk in 20.8% of cases. In RS-Low patients, only H/I (P=0.0004) and MGI (P=0.047) were significantly correlated with restratification to BCI-High Risk. In RS-Intermediate patients, H/I (P&amp;lt;0.0001), MGI (P&amp;lt;0.0001), grade (P&amp;lt;0.0001), and Ki67 &amp;gt;20% (P=0.0003) were significantly correlated with restratification by BCI to High or Low Risk. In RS-High patients, H/I (P=0.0008), MGI (P&amp;lt;0.0001), grade (P=0.016) were significantly correlated with restratification to Low Risk. Conclusion: BCI restratified a substantial proportion of patients in each RS risk group. Based on previous studies demonstrating that BCI has improved prognostic ability for assessment of risk of late distant recurrence (Sgroi et al., Lancet Oncol, 2013), these results highlight the clinical utility of BCI within all RS risk groups. The estrogen signaling pathway biomarker H/I and proliferative biomarkers (MGI, grade, Ki67) were associated with restratification by BCI, while age, HER2 status, and tumor size were not. Citation Format: Yan F, Master AK, Israel MA, Liu J, Schnabel CA, Hurvitz S, Gadi VK. Correlative analysis of breast cancer index (BCI) restratification of 21-gene recurrence score (RS) in patients with hormone receptor-positive (HR+), node-negative breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-06-10.

Age distribution of tumor gene expression in patients with stage II/III colon cancer.

552 Background: Colorectal cancer (CRC) incidence and mortality have been rising in the US among adults &lt;55 y. Younger patients with CRC are more likely than older patients to receive postoperative systemic chemotherapy, despite lack of consensus on the prognostic value of age in this disease. CRC diagnosed in younger patients may be biologically different from that in older patients, but characteristics are unknown. Thus, we examined whether age-specific differences were measurable by tumor gene expression using the 12-gene Oncotype DX Colon Recurrence Score (RS) test (Genomic Health, Inc. [GHI]; Redwood City, CA). The Colon RS test is validated to predict risk of recurrence in patients with stage II/III colon cancer. Methods: We analyzed Colon RS test results and single-gene results for the 12 genes by age group (age &lt;40, 40-54, 55-64, and ≥65) using data from the GHI clinical laboratory dated 1/2010 to 7/2017. Results: As of 7/2017, 21,925 Colon RS reports have been delivered. Median age was 63 y; 50% were male. About 23% of patients were &lt;55 y (Table). Mean (SD) RS result was 25 (11). Colon RS result distributions were similar by age group (Table). Expression of individual tumor genes measured in the Colon RS test were also similar by age group (data to be presented). Conclusions: The etiology of the increase in both incidence and mortality from CRC in adults &lt;55 y is poorly understood. Our findings suggest that colon cancer in younger patients is not biologically different from that in older patients, as measured by the Colon RS test in a large cohort referred for testing. As shown by this test in the GHI clinical laboratory experience, most patients with stage II/III colon cancer have low-risk disease, including patients &lt;55 years. Our findings support a biology-driven approach to disease management of patients with stage II/III colon cancer regardless of age. This well-validated genomic assay may identify a group of younger patients for whom adjuvant chemotherapy might represent overtreatment. [Table: see text]

The 12-gene Oncotype DX Colon Recurrence Score (RS) test: Experience with &gt; 20,000 stage 2 patients (pts).

618 Background: Genomic assays can provide information beyond the traditional methods used to assess risk of recurrence. The 12-gene Oncotype DX Colon RS test is clinically validated to predict recurrence risk after surgical resection in pts with stage 2 colon cancer (CC). The test measures expression of 12 genes (7 cancer-related; 5 reference) to give an RS result (scale 0-100) that estimates the risk of recurrence based on individual tumor biology in MMR-proficient tumors. Here, we report the Genomic Health Clinical Laboratory experience with stage 2 CC since its commercially availability. Methods: Over 20,000 samples from stage 2 CC pts submitted from 4/2010 to 8/2017 were analyzed. Descriptive statistics for the clinical characteristics of pts and RS results were calculated. Standard low (RS &lt; 30), intermediate (RS 30-40), and high (RS ≥41) RS subgroups were used. Results: In 20,406 samples, 92.4% were adenocarcinoma and 7.6% were mucinous carcinoma. Median age was 64 y; 51% were men. Samples were received from 42 countries. The median RS result was 24 (range 0-77); 72% had low, 20% had intermediate, and 8% had high RS results. Mucinous carcinoma had a significantly higher median RS result than adenocarcinoma (34 vs. 23; p &lt; 0.001). Of adenocarcinoma pts, 74% had low, 20% intermediate, and 6% had high RS results. Of mucinous carcinoma pts, 35% had low, 35% had intermediate, and 30% had high RS results. Conclusions: More than 20,000 samples from stage 2 CC pts were submitted over a 7-year period for Colon RS testing. Compared with adenocarcinoma, mucinous carcinoma had a higher median RS result and more high RS results. Overall, there was a wide range of RS results (0-77), indicating that risk of recurrence is continuous and not simply dichotomous. Traditional methods for assessing risk do not reveal the full picture. Because the 12-gene Colon RS result provides a quantitative and more individualized risk assessment for stage 2 CC pts beyond T-stage and MMR status, the test greatly improves the ability of clinicians to personalize care and treatment decisions for these pts.

Racial Differences in 21-Gene Recurrence Scores Among Patients With Hormone Receptor-Positive, Node-Negative Breast Cancer.

Purpose The 21-gene recurrence score (RS) breast cancer assay is clinically used to quantify risk of 10-year distant recurrence by category (low, < 18; intermediate, 18 to 30; high, ≥ 31) for treatment management among women diagnosed with hormone receptor-positive, human epidermal growth factor receptor 2-negative, lymph node-negative breast cancer. Although non-Hispanic black (NHB) women have worse prognosis compared with non-Hispanic white (NHW) women, the equivalency of 21-gene RS across racial groups remains unknown. Patients and Methods Using the Metropolitan Detroit Cancer Surveillance System, we identified women who were diagnosed with hormone receptor-positive, human epidermal growth factor receptor 2-negative, lymph node-negative invasive breast cancer between 2010 and 2014. Multinomial logistic regression was used to quantify racial differences in 21-gene RS category. Results We identified 2,216 women (1,824 NHW and 392 NHB) with invasive breast cancer who met clinical guidelines for and underwent 21-gene RS testing. The mean RS was significantly higher in NHBs compared with NHWs (19.3 v 17.0, respectively; P = .0003), where NHBs were more likely to present with high-risk tumors compared with NHWs (14.8% v 8.3%, respectively; P = .0004). These differences were limited to patients younger than 65 years at diagnosis, among whom NHBs had significantly higher RS compared with NHWs (20 to 49 years: 23.6 v 17.3, respectively; P < .001 and 50 to 64 years: 19.6 v 17.4, respectively; P = .023). NHBs remained more likely to have high-risk tumors compared with NHWs after adjusting for age, clinical stage, tumor grade, and histology (odds ratio [OR], 1.75; 95% CI, 1.18 to 2.59). Conclusion NHBs who met clinical criteria for 21-gene RS testing had tumors with higher estimated risks of distant recurrence compared with NHWs. Further study is needed to elucidate whether differences in recurrence are observed for these women, which would have clinical implications for 21-gene RS calibration and treatment recommendations in NHB patients.

Distribution and Clinical Utility of the 21-gene Recurrence Score in Pure Mucinous Breast Cancer Patients: a case-control study.

The 21-gene recurrence score (RS) is increasingly being used for patients with early stage, hormone receptor-positive, Her-2-negative breast cancer. However, these results are largely from populations with infiltrating ductal carcinoma (IDC). The clinical value of RS testing in mucinous carcinoma has not been well investigated. Pure mucinous breast cancer (PMBC) and paired pure IDC patients who underwent 21-gene RS were retrospectively reviewed and matched with tumor stage and molecular subtype. Clinic-pathological factors, treatment strategies, and RS distribution were compared between the PMBC and IDC patients. A total of 35 PMBC and 70 IDC patients were included. We found that RS was lower in the PMBC as compared with the IDC group: 21.26 vs. 24.40 (P=0.037). Regarding RS categories, PMBC patients had a relatively lower percentage of high RS patients than the IDC group: 8.57% vs. 22.86% (P = 0.048). Multivariate analysis showed that histologic type was an independent factor predicting RS distribution: IDC patients were associated with a higher RS as compared with PMBC patients (OR: 1.27, 95% CI: 1.03-2.13; P=0.014). Among genes in 21-gene RS testing, HER2, STMY3, STK15, and BAG1 were significantly different between the PMBC and IDC groups (P < 0.05). Two patients (5.71%) in the PMBC group, both with high RS, were recommended to receive adjuvant chemotherapy, much lower than patients with IDC (57.14%, P < 0.001). In multivariate analysis, histologic type of IDC was an independent factor for chemotherapy recommendation (OR = 22.00, 95% CI: 4.89-98.97, P<0.001). With a medium follow-up time of 24 months, one IDC patient had ipsilateral axillary lymph nodes recurrence and one PMBC patient had contralateral breast cancer. In conclusion, PMBC patients, mostly classified with low or intermediate RS category, were associated with lower RS as compared with IDC patients. PMBC and IDC had different genes expression patterns. Patients with high RS in the PMBC group might be recommended to receive adjuvant chemotherapy, which deserves further clinical evaluation.

Clinical Impact of 21-Gene Recurrence Score Test Within the Veterans Health Administration: Utilization and Receipt of Guideline-Concordant Care

IntroductionEnsuring guideline-concordant cancer care is a Department of Veterans Affairs (VA) priority, especially as the number of breast cancer patients at VA medical centers (VAMCs) grows. We assessed the utilization and clinical impact of the 21-gene Recurrence Score test, which predicts 10-year risk of breast cancer recurrence and the likelihood of chemotherapy benefit, on veterans newly diagnosed with breast cancer. Patients and MethodsWe conducted a retrospective cohort study using 2011-2012 VA Central Cancer Registry, chart review, and laboratory test data. Independent variables assessed included patient and site-of-care characteristics. The outcome of interest was whether newly diagnosed, eligible (node negative, hormone-receptor positive, human epidermal growth factor receptor 2 [HER2] negative) veterans underwent the 21-gene test. We performed descriptive statistics on all patients and multivariate logistic regression to determine associations. We correlated treatments received with test results. ResultsAmong 328 eligible veterans, 82 (25%) had the 21-gene test; 100 eligible veterans (30%) sought care at a VAMC where no tests were ordered. Receiving care at a VAMC that had women's health services (odds ratio [OR], 1.84, 95% confidence interval [CI], 1.05-3.22) and having tumor characteristics meeting the National Comprehensive Cancer Network 2010 test criteria (OR, 3.06, 95% CI, 1.69-5.57) were positive predictors of testing; increasing age (OR, 0.93, 95% CI, 0.91-0.96 per year) and fee-based care (OR, 0.46, 95% CI, 0.26-0.82) were negative predictors. The majority of tested patients received guideline-concordant care. ConclusionSite of care and tumor characteristics were important predictors of test uptake. Facilitating delivery of guideline-concordant cancer care requires improved laboratory informatics and clinical decision support.