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Breast cancer is the most common malignant tumor in women. With the development of genomics technology and medical frontier technology, the systemic treatment of breast cancer has gradually entered the era of personalized medicine. However, the decision-making of adjuvant radiotherapy for breast cancer still mainly relies on traditional clinicopathological factors, and there is a lack of scientific and reliable tools to guide precise radiotherapy in different populations. Hormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2) negative breast cancer is the most common molecular subtype of breast cancer. The 21-Gene recurrence score (RS) test (Oncotype Dx™, Genomic Health, Redwood City, CA) is a commercially available genomic test for breast cancer. In this article, we reviewed the current research evidence on the use of 21-Gene RS test for radiotherapy decision-making in HR-positive HER2-negative early breast cancer. Current clinical studies support the predictive value of 21-Gene RS test for adjuvant radiotherapy, and several large-scale prospective clinical studies in this area are underway.

Purpose: Oncotype DX® is a frequently used multigene assay for hormone receptor-positive breast cancers. However, limited evidence is available regarding its application in Japan owing to the lack of insurance coverage. Therefore, we conducted this large-scale, retrospective study by collecting data from nine Japanese institutes and assessed postoperative treatment choice and prognosis by using Oncotype DX®. Methods: Six hundred thirty-two patients who underwent breast surgery and whose recurrence score (RS) data were available were included. They were divided into RS 0–25 and RS ≥ 26 groups. The groups were compared in terms of clinicopathological factors, treatment options, and prognosis. Results: After the median follow-up period of 10.1 years, the disease-free survival (DFS) rates were significantly better in the RS 0–25 group (p = 0.02). Per the recurrent event type, there was no significant intergroup difference in locoregional recurrence (p = 0.139). However, a trend toward better distant DFS was observed in the RS 0–25 group (p = 0.08). Overall survival was also significantly better in this group (p = 0.027). Considering chemotherapy use, DFS worsened among chemotherapy-treated patients with an RS of 0–25 and those with an RS ≥ 26 who did not receive chemotherapy (p < 0.001). Seven (1.35%) chemotherapy-treated patients with an RS of 0–25 showed disease recurrence. Conclusions: This study presents the largest database-derived prognostic data in Japanese patients, utilizing the Oncotype DX® treatment selection. Further studies are needed to determine the impact on treatment choice, considering the clinical risk, and the need for additional postoperative treatment. [ABSTRACT FROM AUTHOR]

Purpose: Pure mucinous breast cancer (PMC) is a rare histological type with a favourable prognosis. However, cases with recurrence have been reported and diagnosed in clinical practice. The mechanisms underlying PMC recurrence remain unknown. In this study, we aimed to identify the prognostic factors associated with PMC. Materials and methods: A total of 166 patients diagnosed with PMC were included. We compared the clinicopathological characteristics between patients with and without recurrence. The 21-gene assay was performed in 10 patients with recurrence and 20 TNM stage-matched patients without recurrence. Whole-exon sequencing was performed in 12 PMC primary tumours and four positive lymph nodes (LNs). Results: Tumour size, lymph node status and TNM staging differed significantly between recurrent group and non-recurrent group. And the 21-gene recurrence scores did not differ significantly between recurrent group and its TNM stage-matched non-recurrent group. The most frequently mutated genes in the primary tumours of regional LN-positive PMCs were ADCY10 (3/6) and SHANK3 (3/6), and they more recurrently harboured gains of 15q23, 17q23.2 and 20p11.21, and loss of 21p11.2. And these alterations were not detected in primary tumours of regional LN-negative PMCs. Conclusion: TNM stage is an important prognostic factor in PMC. Although we revealed that regional LN-positive PMCs show increased occurrence of duplication variants at 15q23, 17q23.2 and 20p11.21, and deletion variants at 21p11.2. Further investigation, including multi-omics studies, are needed and may provide additional insights into the nature of PMC.

In the past decade, with the introduction of precision medicine, the treatment of breast cancer has entered a new era. It now tends towards the de-escalation and individualization of treatment plans, aiming to minimize iatrogenic toxicity while maximizing benefits for patients without compromising survival outcomes. The 21-gene assay evaluates the expression levels of 21 genes associated with breast cancer recurrence and provides a 21-gene recurrence score (RS) to assess the risk of recurrence and potential benefit from chemotherapy in breast cancer patients. Currently, RS is recommended by multiple guidelines such as the American Society of Clinical Oncology (ASCO), National Comprehensive Cancer Network (NCCN), and Chinese Anti-Cancer Association(CACA) for guiding adjuvant therapy in hormone receptor-positive (HR+) and human epidermal growth factor receptor 2 negative (HER2-) early-stage breast cancer patients. However, there are still controversies surrounding its clinical application. Current research mainly focuses on optimizing RS to accurately identify patients who would benefit from adjuvant therapy, thus enabling more personalized treatment plans for breast cancer patients. This review provides an overview of the 21-gene assay, its application in HR+ breast cancer patients' adjuvant therapy, its impact on clinical decision-making, existing controversies regarding RS, and prospects for integrating RS with clinical pathological information. The aim is to guide further expansion of RS's application in clinical practice and achieve more precise adjuvant therapy for breast cancer patients.

Abstract Introduction Tumor immune microenvironment (TIME) plays a vital role in breast cancer development, treatment resistance, and prognosis. This study evaluates the association of TIME profiling and 21-gene recurrence score (RS) in early Luminal breast cancer patients. Methods ER+ /HER2-, pN0 breast cancer patients with available RS results who received surgery between January 2009 and December 2013 were enrolled. TIME markers, including stromal tumor infiltrating lymphocytes (TILs), CD3, CD4, CD8, and tumor PD-L1 expression, were comprehensively analyzed. Association of TIME markers with RS, as well as their correlation with breast cancer-specific survival (BCSS) were tested. Results Overall, 385 patients were included, of whom 341 (88.6%) had TILs ≤10%. TIME markers were positively but moderately correlated with each other (Spearman r 0.28–0.53, all P

Introduction: Tumor immune microenvironment (TIME) plays a vital role in breast cancer development, treatment resistance, and prognosis. This study evaluates the association of TIME profiling and 21-gene recurrence score (RS) in early Luminal breast cancer patients. Methods: ER+ /HER2-, pN0 breast cancer patients with available RS results who received surgery between January 2009 and December 2013 were enrolled. TIME markers, including stromal tumor infiltrating lymphocytes (TILs), CD3, CD4, CD8, and tumor PD-L1 expression, were comprehensively analyzed. Association of TIME markers with RS, as well as their correlation with breast cancer-specific survival (BCSS) were tested. Results: Overall, 385 patients were included, of whom 341 (88.6%) had TILs ≤10%. TIME markers were positively but moderately correlated with each other (Spearman r 0.28–0.53, all P < 0.05). Continuous RS showed a weak correlation with continuous TILs, CD3, CD8, and PD-L1. Regarding single gene mRNA level in the 21-gene RS panel, higher expression of TIME markers was related to lower ER group genes expression, but higher proliferation and invasion group genes level. After a median follow-up of 91.67 (range 5.03–134.03) months, TILs (P = 0.049) and PD-L1 (P = 0.034) were inversely associated with BCSS. Conclusions: Breast cancer TIME markers, including TILs, CD3, CD4, CD8, and PD-L1, were correlated with 21-gene RS score. Lower expression of ER group genes, as well as higher expression of proliferation and invasion group genes were associated with a higher level of these TIME markers, warranting further exploration. [ABSTRACT FROM AUTHOR]

• In modern practice, patients age ≥70 with T1N0 ER/PR + HER2- breast cancer who are treated with breast conserving surgery and endocrine therapy have been considered candidates for omission of radiotherapy. • Recurrence score (RS) is predictive for prognostic benefit of radiotherapy in patients age ≥70 years. • There is an overall survival benefit with the use of radiotherapy in patients with RS ≥11 but not in patients with RS < 11. • Assessment of RS in patients age ≥70 years is recommended with consideration of RT when RS is ≥11. Based on the results of the Cancer and Leukemia Group B (CALGB) 9343 trial, patients age ≥70 with T1N0 hormone receptor positive (ER/PR+), human epidermal growth factor receptor-2 negative (HER2-) breast cancer who are treated with breast conserving surgery (BCS) and endocrine therapy (ET) are candidates for omission of radiotherapy (RT). Because the CALGB 9343 trial did not stratify based on recurrence score (RS) test (Oncotype Dx), we conducted the present retrospective study to determine whether RS is predictive of who may benefit from RT following BCS in this cohort. The National Cancer Database (NCDB) was queried (2004–2017) for patients age ≥ 70 with pT1N0 ER+/PR + HER2- breast cancer treated with BCS and ET. Patients were stratified based on their RS (low risk [LR] = 1–10, intermediate risk [IR] = 11–25, high risk [HR] = 26–99). Propensity score matching (PSM) created 1:1 matched cohorts of patients who received radiotherapy and those who did not. Kaplan-Meier analysis evaluated overall survival (OS). Univariable (UVA) and multivariable (MVA) Cox proportional hazard analyses identified clinical and treatment factors prognostic for OS. A total of 11,891 patients met the selection criteria: 3364 in the LR cohort, 7305 in the IR cohort, and 1222 in the HR cohort. A total of 79 % received RT: 77 % in the LR cohort, 79 % in the IR cohort, and 85 % in the HR cohort. Because PSM could not be efficiently performed in the HR cohort alone, the IR and HR cohort were merged (IRHR) for matching. After PSM, the 5-year OS in the LR cohort was 91 % for those who received RT and 89 % for those who did not (p = 0.605). In the IRHR cohort, the 5-year OS was 91 % for those who received RT and 87 % for those who did not (p = 0.003). On MVA in the LR cohort, RT (p = 0.727) was not predictive of improved OS. On MVA in the IRHR cohort, RT (p = 0.010) was a positive prognostic factor for OS. In this older cohort of patients, there is an OS benefit with the use of RT in patients with IRHR RS but not in patients with LR RS. Pending prospective evaluation, assessment of RS in this older subset of patients is recommended with consideration of RT when RS is ≥11. [ABSTRACT FROM AUTHOR]

Introduction: Breast Cancer Index (BCI) is a genomic assay that evaluates the benefit of extending endocrine therapy (ET) from 5 to 10 years and predicts recurrence risk (RR). We evaluated the association between BCI and Oncotype DX (ODX)., Patients: Women with hormone receptor (HR)-positive early-stage breast cancer (EBC) who had BCI and ODX performed were included., Methods: We performed a retrospective review of women with HR-positive EBC. BCI was categorized as predictive of extended ET versus not and ODX recurrence score (RS) as low (0-10), intermediate (11-25), and high (26-100). Univariate and multivariable logistic and linear regression models assessed the relationship between BCI and ODX, factors associated with each, and discordance between scores., Results: We identified 153 women, 22% were premenopausal and 18% were lymph node positive. The univariate logistic and linear models revealed an association between BCI predictive score and ODX RS (OR 7.84, CI, 2.63-23.36, P < .001) and log of BCI RR (Beta 0.04, CI, 0.02-0.06, P < .001). Seventy-four percent of BCI predictive scores were concordant with ODX RS and 83% of BCI RR was concordant with ODX RR. In a univariate logistic regression model, BCI predictive of ET benefit was associated with discordance (OR 28.00, CI, 10.58-74.02, P < .001). Higher ODX RR was associated with discordance (OR 1.92, CI, 1.42-2.59, P < .001)., Conclusion: We found a significant association between ODX and BCI predictive and prognostic scores. BCI predictive of extended ET benefit was associated with discordance with ODX RS. Higher predicted RR on ODX was associated with discordance with BCI predicted RR., Competing Interests: Disclosure Nicole Casasanta, Rima Patel, Melanie Kier, Sophie Sohval, Malin Hovstadius, Catherine Wu, Brittney Zimmerman, and Krystal Cascetta have no conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Abstract Background The 21-gene recurrence score (RS) can predict chemotherapy benefit in estrogen receptor-positive, human epidermal growth factor receptor-2-negative (ER+/HER2-) early breast cancer patients. Age would influence the interaction between RS and chemotherapy effect. The current study aimed to determine RS thresholds which were predictive of chemotherapy benefit in young and old women, respectively. Methods Patients diagnosed with pN0–1, ER+/HER2- breast cancer between 2009 and 2016 were retrospectively reviewed. Propensity score matching was performed according to chemotherapy usage. After stratifying patients with different cutoffs of age, the RS threshold indicating chemotherapy benefit in each age strata were determined by cox proportional hazard models. Results A total of 1227 patients were included. The median age was 58 years and the median RS was 24. After matching, the RS thresholds suggesting chemotherapy benefit varied with age. For patients ≤55 years, chemotherapy benefit was observed in those having RS > 25 (P = 0.03), with 4-year invasive disease-free survival (IDFS) of 97.0 and 89.3% in patients receiving chemotherapy or not. While patients derived no benefit from chemotherapy if they had RS ≤25 (P = 0.66, 4-year IDFS: 95.3% vs. 94.6%). For patients > 55 years, adjuvant chemotherapy was associated with better prognosis in those with RS > 36 (P = 0.014, 4-year IDFS: 94.7% vs. 76.2%), but not in those having RS ≤36 (P = 0.13, 4-year IDFS: 92.3% vs. 95.8%). Conclusions Old patients need higher RS thresholds to demonstrate the chemotherapy benefit. Further efforts are warranted to investigate the association between age and predictive RS thresholds.

Pure mucinous breast cancer (PMC) is a rare histological type with a favourable prognosis. However, cases with recurrence have been reported and diagnosed in clinical practice. The mechanisms underlying PMC recurrence remain unknown. In this study, we aimed to identify the prognostic factors associated with PMC. A total of 166 patients diagnosed with PMC were included. We compared the clinicopathological characteristics between patients with and without recurrence. The 21-gene assay was performed in 10 patients with recurrence and 20 TNM stage-matched patients without recurrence. Whole-exon sequencing was performed in 12 PMC primary tumours and four positive lymph nodes (LNs). Tumour size, lymph node status and TNM staging differed significantly between recurrent group and non-recurrent group. And the 21-gene recurrence scores did not differ significantly between recurrent group and its TNM stage-matched non-recurrent group. The most frequently mutated genes in the primary tumours of regional LN-positive PMCs were ADCY10 (3/6) and SHANK3 (3/6), and they more recurrently harboured gains of 15q23, 17q23.2 and 20p11.21, and loss of 21p11.2. And these alterations were not detected in primary tumours of regional LN-negative PMCs. TNM stage is an important prognostic factor in PMC. Although we revealed that regional LN-positive PMCs show increased occurrence of duplication variants at 15q23, 17q23.2 and 20p11.21, and deletion variants at 21p11.2. Further investigation, including multi-omics studies, are needed and may provide additional insights into the nature of PMC. • This study revealed the clinicopathological characteristics as well as the genomic features of PMC. • TNM stage was a predominant prognostic factor in patients with PMC. • The most frequently mutated genes in regional LN-positive PMCs were ADCY10 and SHANK3. • There were gains of 15q23, 17q23.2 and 20p11.21, and loss of 21p11.2 in PMCs with positive regional LNs. [ABSTRACT FROM AUTHOR]

Background: Invasive lobular carcinoma (ILC) is traditionally considered less responsive to chemotherapy. Although the Oncotype recurrence score (RS) has been validated to identify high‐risk patients who benefit from chemotherapy, some studies have questioned its relevance in patients with ILC. The objective of this study was to better characterize potential use of the RS in these patients. Methods: The National Cancer Database was used to identify women with stage I through III, T1 through T3, N0 or N1, hormone receptor‐positive, HER2‐negative ILC or invasive ductal carcinoma (IDC) who had an available RS between 2010 and 2016. Multivariable Cox regression was used to model the effect of variables on 5‐year overall survival (OS). The Kaplan‐Meier method was used to estimate OS according to the RS, nodal status, and chemotherapy. Results: In total, 15,763 patients with ILC and 100,070 with IDC were identified. The mean age of patients with ILC and IDC was 59.2 ± 9.1 and 57.2 ± 9.8, respectively. A lower percentage of patients with ILC versus those with IDC had a high RS, defined as >25 (6.6% vs 16.0%; P <.0001). ILC patients with a high RS who had N0 or N1 disease received approximately 10% less chemotherapy compared with similar patients who had IDC. The results indicated that the RS had statistically significant prognostic value for patients with ILC. In addition, an absolute OS advantage was correlated with the receipt of chemotherapy by patients with ILC who had a high RS with N0 or N1 disease. Conclusions: Patients with ILC who have a high RS are treated less often with chemotherapy compared with similar patients who have IDC. Nevertheless, the RS has a prognostic as well as a predictive value in ILC, with an association between OS benefit and chemotherapy receipt in patients who have ILC with a high RS, especially if they have N1 disease. Lay Summary: Invasive lobular carcinoma (ILC) is a subtype of breast cancer comprising about 15% of cases.The Oncotype recurrence score (RS) is a genetic test of breast tumors that helps predict which patients might benefit from chemotherapy.Some have doubted the relevance of the RS for patients with ILC.In this study, the authors show that the RS is relevant for patients who have ILC.The RS has the potential of predicting the risk of recurrence and identifying patients with ILC who might benefit from chemotherapy. This retrospective analysis of data from the National Cancer Database demonstrates the prognostic as well as the predictive value of the Oncotype recurrence score in patients with invasive lobular carcinoma. Those who have invasive lobular carcinoma with a high recurrence score have an overall survival advantage when treated with chemotherapy, much like patients who have invasive ductal carcinoma. [ABSTRACT FROM AUTHOR]

Introduction: The aim of the present study was to analyze the performance of Oncotype DX® multigene assay (ODX®) in patients with 0–3 lymph nodes in a high-volume community hospital. Methods: Patients with non-metastatic HR+/HER2– EBC and 0–3 positive lymph nodes, who underwent primary surgery at the Red Cross Hospital Munich, Germany and consecutively had ODX® testing were included in this retrospective study. The distribution of clinicopathologic characteristics, recurrence score (RS) risk, and use of systemic therapy were compared among patients without positive lymph nodes (N0) and patients with micrometastases or 1 to 3 positive lymph nodes (N1). Disease-free survival (DFS) and overall survival (OS) were estimated. Results: From 2012 to 2017 ODX® was consecutively performed in 575 (16.4%) of 3,492 women with HR+/HER– EBC, of which 553 were eligible for this analysis (N0: 60.8%; N1: 39.2%). Among the patients included, 441 (79.7%) had an RS of 0 to 25 and 112 (20.3%) had an RS of 26 or higher. In patients with RS 0 to 25 the rate of chemotherapy use was low, independent from nodal status (N0: 17.1% and N1: 19.1%) and 5-year DFS was 90.5% and 91.7% for N0 and N1 patients, respectively. There was no significant difference in DFS (90.5% vs. 93.3%; p = 0.101) or OS (97.2% vs. 96.0%; p = 0.737) for patients with an RS of 0 to 25 when treated with chemo-endocrine therapy or endocrine therapy alone, independent from nodal status. Conclusions: The results of the study confirm the observations from randomized studies on the use of the ODX® in a real-world population in terms of risk distribution and patient outcome. Adjuvant chemotherapy could be safely omitted in patients with HR+/HER2– breast cancer with 0–3 positive lymph nodes and RS <25. [ABSTRACT FROM AUTHOR]

Objective: To identify subgroups of hormone receptor-positive (HR+) breast cancer patients that might not benefit from adding endocrine therapy (ET) to their local treatment. Background: De-escalation in breast cancer treatment has included surgery, radiation, and chemotherapy and has often focused on older patient populations. Systemic ET has yet to be de-escalated, though it carries serious side-effects, decreasing quality of life over 5 to 10 years. We hypothesize the 21-gene recurrence score (RS) could identify subgroups of younger patients whose long-term survival is unaffected by adjuvant ET. Methods: The National Cancer Database was used to identify women aged ≥50, with HR+, HER2-negative tumors, ≤3 cm in size, N0 status, and a RS≤25, who underwent breast-conserving surgery in 2010 to 2016. Kaplan-Meier and Cox proportional hazards models were used to identify association between treatment and overall survival (OS). Results: Of the 45,217 patients identified, 80.6% were 50 to 69 years old. 42,632 (94.3%) patients received ET and 2585 (5.7%) did not. The 5-year OS was 96.4% for patients receiving ET and 93.1% for those who did not (P < 0.001). After adjusting for all covariates, patients aged 50 to 69 with RS < 11 showed no statistically significant improvement in OS when adding ET to surgery, with or without radiation (P = 0.40). With RS 11 to 25, there was a significant improvement of OS with ET plus radiation (P < 0.001). Conclusions: Local treatment only, with de-escalation of long-term ET, for patients aged 50 to 69 with RS < 11, seems not to impact OS and should have an anticipated quality of life improvement. Prospective studies investigating this approach are warranted. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the prognostic value of the 21-gene recurrence score (RS) for regional recurrence (RR) in patients with estrogen receptor-positive breast cancer. Methods: We reviewed the medical records of 446 patients who underwent 21-gene RS assay after breast-conserving surgery or mastectomy. The high-RS group was defined as patients who were (1) older than 50 years with an RS of 26 or higher, or (2) 50 years or younger with an RS of 16 or higher. Results: The 5-year rates of local recurrence (LR), RR, and distant metastasis (DM) were 2.2%, 2.7%, and 4.7%, respectively. The 5-year overall survival (OS) rate was 99.1%. Of the patients, 269 (60.3%) had low-RS, while 177 (39.7%) had high-RS. The 5-year OS rate of the high-RS group was significantly lower than that of the low-RS. The 5-year rates of RR and DM in the high-RS group were significantly higher than those in the low-RS group, while the LR rates did not differ significantly. In multivariable analysis, the high-RS group had a significant relationship with increased RR rate (p = 0.037). Patients who had both high-RS and clinical high-risk features had a significantly higher 5-year RR rate (7.9%) compared with other groups. Conclusions: High-RS was an independent risk factor for RR. The significantly higher RR rate of patients with both high-RS and clinical high-risk features compared with other groups suggests that this patient group can be a potential candidate for regional nodal irradiation. [ABSTRACT FROM AUTHOR]

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Abstract Background The benefits of chemotherapy in node-negative, hormone receptor-positive, and human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients with the 21-gene recurrence score (RS) of 18–30, particularly those with RS 26–30, are not known. Methods Using the Surveillance, Epidemiology, and End Results (SEER) data, we retrospectively identified 29,137 breast cancer patients with the 21-gene RS of 18–30 diagnosed between 2004 and 2015. Mortality risks according to the RS and chemotherapy use were compared by the Kaplan-Meier method and Cox’s proportional hazards model. Results Among the breast cancer patients with the RS 18–30, 21% of them had RS 26–30. Compared to breast cancer patients with RS 18–25, patients with RS 26–30 had more aggressive tumor characteristics and chemotherapy use and increased risk of breast cancer-specific mortality and overall mortality. In breast cancer patients who were aged ≤ 70 years and had RS of 26–30, chemotherapy administration was associated with a 32% lower risk of breast cancer-specific mortality (hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.47–0.99) and a 42% lower risk of overall mortality (HR, 0.58; 95% CI, 0.44–0.76). Survival benefits were most pronounced in breast cancer patients who were younger or had grade III tumor. Conclusions The 21-gene RS of 18–30 showed heterogeneous outcomes, and the RS 26–30 was a significant prognostic factor for an increased risk of mortality. Adjuvant chemotherapy could improve the survival of node-negative, hormone receptor-positive, and HER2-negative breast cancer patients with the 21-gene RS 26–30 and should be considered for patients, especially younger patients or patients with high-grade tumors.

Purpose: The 21-gene recurrence score assay (RS) has not been prospectively validated to predict adjuvant chemotherapy benefit in hormone receptor-positive (HR+), HER2-negative (HER2−), node-positive breast cancer patients. Nevertheless, de-escalation based on RS has been demonstrated and partially advocated by retrospective data. The purpose of this study was to identify subgroups of node-positive patients with low to intermediate RS who still benefit from adjuvant chemotherapy. Methods: The National Cancer Database was used to identify 28,591 women with stage I–III, T1–T3, N1, HR+, HER2− breast cancer and a RS ≤ 25 between 2010 and 2016. Univariate and multivariate analyses were used to identify variables correlating with chemotherapy use and 5-year survival. Subgroup analysis was performed to discern patients in whom the use of adjuvant chemotherapy correlated with better survival. Results: A 35% decline in chemotherapy use was observed from 2010 to 2016. Patients with younger age, higher RS, larger tumors and more positive lymph nodes, and those treated by mastectomy, axillary lymph node dissection and radiation, were more likely to receive chemotherapy. Chemotherapy use was associated with an improved 5-year survival (HR = 1.63, 95% CI 1.28–2.07). Upon subgroup analysis, this association was lost in patients > 70 years and those with a RS ≤ 11, while patients ≤ 70 with a RS of 12–25 treated with chemotherapy had an absolute 5-year survival advantage of 3.0% (HR = 1.91, 95% CI 1.42–2.57). Conclusion: Clinicians should be cautious when considering omission of adjuvant chemotherapy in patients ≤ 70 years, with HR+, HER2−, N1 tumors and a RS 12–25, at least until the results of the anticipated RxPONDER trial become available. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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. Conclusions: 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. Compared with non‐Hispanic White (NHW) women, American Indian and Alaska Native (AI/AN) women with estrogen receptor—positive breast cancer appear to be less likely to undergo genomic expression assay testing. Among tested women, AI/AN patients with breast cancer are more likely to have high‐risk recurrence scores compared with NHW women. [ABSTRACT FROM AUTHOR]

Purpose: New biomarkers are emerging to predict recurrence risk in women with early-stage breast cancer. High Oncotype DX Recurrence Score® (RS) is associated with worse disease-free and overall survival. Similarly, circulating tumor cells (CTCs, blood) and disseminated tumor cells (DTCs, bone marrow) have prognostic value in breast cancer. We investigated the association between high RS and CTCs or DTCs. Methods: Using a prospective database, we evaluated patients with hormone receptor-positive/HER2-negative, node-negative invasive breast cancer from 1/2005 to 1/2017. RS was classified using TAILORx study cutoff points: low (< 11), intermediate (11–25), and high (> 25). CTCs were assessed using CellSearch® and DTCs using cytospin specimens of bone marrow aspirates. Positive result was defined as one or more CTCs or DTCs identified. Chi-square analyses were utilized to evaluate the relationship between RS and CTCs or DTCs. Results: 233 patients were identified from a prospective database, of which 96 had RS results. Of these patients, 88 had CTC results and 58 had DTC results. CTCs were detected in 17/88 (19%) patients, while DTCs were detected in 20/58 (34%). Patients with high RS were not more likely to have CTCs (18%) compared to patients with low/intermediate RS (20%; p = 0.919). Similarly, high RS was not associated with DTC detection, with DTCs present in 40% of patients with high RS versus 33% with low/intermediate RS (p = 0.687). In the subgroup of patients ≤ 50 years, no associations were found between high RS and CTCs (p = 0.383) or DTCs (p = 0.234). Conclusions: High Oncotype DX RS did not correlate with CTCs in blood or DTCs in bone marrow in our study. [ABSTRACT FROM AUTHOR]

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 Background Recent studies have shown that tumors with extensive tumor-infiltrating lymphocytes (TILs) have a higher probability of pathologic complete response, even in luminal/human epidermal growth factor 2 (HER2)-negative breast cancer. We compared TIL levels and the 21-gene recurrence score (RS) in estrogen receptor (ER)-positive/HER2-negative breast cancer. Methods We evaluated the percentage of stromal TILs in 198 ER-positive/HER2-negative patients in whom RS was obtained by examining slides of surgical specimens by standardized methodology proposed by the international TIL Working Group. TIL levels were categorized as high (≥ 60%), intermediate (11–59%), or low (≤ 10%). All tumors were treatment-naïve. Results Ninety-seven (49.0%), 88 (44.4%), and 13 patients (6.6%) had low, intermediate, and high TIL levels, respectively. There was a significant but weak correlation between continuous RS and continuous TIL levels (Pearson’s R = 0.201, p = 0.004). The mean RS was significantly highest in high TIL tumors (17.8 ± 10.7 in low TIL tumors, 19.4 ± 8.7 in intermediate TIL tumors, and 26.2 ± 8.2 in high TIL tumors; p = 0.014). However, when we compared categorized RS and TIL levels, we found that tumors with high TIL levels tended to have higher RS (≥ 26) but it was not significant (p = 0.155). Furthermore, multivariate analysis revealed that high RS was not an independent factor associated with high TIL levels. Chemo-endocrine therapy was more frequently performed among patients with high TILs and less frequently among those with low or intermediate TILs (p

Recurrence score (RS) could be used to predict clinical outcomes and chemotherapy efficacy in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative and lymph node-negative breast cancer. However, the clinical features and management of patients with an RS of 26–30 are not completely understood. In the present study, 783 patients with HR+/HER2−, lymph node-negative early breast cancer and RS ≥18 were included and categorized into RS=18−25 (47.8%), 26–30 (25.5%) or ≥31 (26.7%) groups. Clinicopathological characteristics, adjuvant chemotherapy usage and disease outcomes were compared. Alterations in the adjuvant chemotherapy recommendation after 21-gene RS testing were also analyzed. The results indicated that patients with RS=26−30 had higher progesterone receptor (PR) expression [odds ratio (OR)=2.84; P<0.001] and lower Ki-67 index (OR, 1.88; P=0.032) compared with patients with RS ≥31. Multivariate analysis demonstrated that age ≤50 years (OR, 5.75; P=0.001) and luminal-B subtype (OR, 7.75; P<0.001) were factors that were independently associated with chemotherapy usage in the RS=26−30 group. Among 104 patients who were not recommended chemotherapy before 21-gene RS testing, the treatment decision for 52 patients was changed to recommend chemotherapy once an RS of 26–30 was identified. The patient adherence rate to the treatment recommendation was 95.0% (190/200). After a median follow-up of 21.5 months, 6 patients displayed disease recurrence in the RS=26−30 group, and there was no significant difference between patients receiving chemotherapy and patients not receiving chemotherapy. In conclusion, patients with RS=26−30 had tumors with higher PR expression and lower Ki-67 index compared with those of patients with RS ≥31. Age, luminal subtype and RS testing influenced chemotherapy usage in patients with RS=26−30; however, no significant benefit from adjuvant chemotherapy was observed in a short term of 2 years. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

Introduction: To assess the role of the 21-gene recurrence score (RS) assay on decision-making of postoperative radiotherapy (RT) following breast-conserving surgery (BCS) in elderly women with early-stage breast cancer.Methods: The 21-gene RS for elderly (≥65 years) women with stage T1–2N0M0 estrogen receptor-positive breast cancer who underwent BCS from 2004 to 2015 was obtained from the Surveillance, Epidemiology, and End Results program. We estimated the association of 21-gene RS and adjuvant RT related to breast cancer-specific survival (BCSS) using propensity score matching (PSM).Results: We identified 18,456 patients, of which 15,326 (83.0%) received postoperative RT. Of identified patients, 58.9, 34.0, and 7.1% of patients had a low-, intermediate-, and high-risk RS, respectively. Receipt of postoperative RT was not related to the year of diagnosis according to the 21-gene RS groups. Multivariate analysis suggested that receipt of postoperative RT was an independent predictor of better BCSS before (hazard ratio [HR] 0.587, 95% confidence interval [CI] 0.426–0.809, P = 0.001) and after (HR 0.613, 95%CI 0.390–0.963, P = 0.034) PSM. However, subgroups analyses indicated that receipt of postoperative RT was related to better BCSS in women with intermediate-risk RS before (HR 0.467, 95%CI 0.283–0.772, P = 0.003) and after (HR 0.389, 95%CI 0.179–0.846, P = 0.017) PSM, but not in women with low- and high-risk RS groups before and after PSM.Conclusions: Although causation cannot be implied, adjuvant RT in elderly women was associated with a greater effect size in patients with an intermediate-risk RS.

Purpose: To develop a nomogram to predict the high-risk recurrence score (RS) and to customize the nomogram for different races in early-stage hormone receptor (HoR)-positive, human epidermal growth factor receptor-2 (HER2)-negative breast cancer., Methods: Patients diagnosed between 2010 and 2015 were included from the surveillance, epidemiology, and end results oncotype DX database. The nomogram was assessed with a receiver operating characteristic curve to measure the area under the curve (AUC) with a 95% confidence interval (95% CI). The nomogram was developed and internally validated for discrimination and calibration, and then validated in different races., Results: A total of 48,464 patients were included and randomly assigned to the training cohort (n = 36370, 75.0%) and validation cohort (n = 12,094, 25.0%). Patients in the training cohort were identified to develop the nomogram, including 32,683 (89.9%) White women, 3135 (8.6%) Black women, and 552 (1.5%) Chinese women. Five independent predictive factors for high-risk RS were included to develop the nomogram, including tumor grade, progesterone receptor status, histological subtype, race, and tumor stage. The AUC was 0.696 (95% CI, 0.682-0.710) in the training cohort and 0.700 (95% CI, 0.676-0.724) in the validation cohort. There was no significant difference between the training cohort and the validation cohort. When validating the nomogram classified by race, the AUC was 0.694 (95% CI, 0.682-0.706) for the White cohort, 0.708 (95% CI, 0.673-0.743) for the Black cohort, and 0.653 (95% CI, 0.565-0.741) for the Chinese cohort., Conclusion: The developed nomogram for predicting high-risk RS is available for different races in patients with HoR+/HER2- breast cancer, which could be used as qualified surrogates before ordering the 21-gene RS testing., Competing Interests: Disclosure The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective To investigate the postoperative adjuvant therapeutic decision-oriented role of 21-gene recurrence score (RS) in hormone receptor positive and lymph node negative early stage breast cancer. Methods Our study included 110 hormone receptor positive and lymph node negative early stage breast cancer patients who were tested for 21-gene RS and underwent surgical treatment between June 2013 and December 2016 at The First Affiliated Hospital of Xi'an Jiaotong University. According to the 21-gene RS, the included patients were divided into low-, intermediate- and high-risk groups. We compared the changes of treatment decisions before and after the 21-gene test. Results Before taking the 21-gene test, 61 patients (55%) were recommended both adjuvant chemotherapy and endocrine therapy. However, after taking the test, 32 patients (29%) were treated with only adjuvant endocrine therapy (McNemar's test, P <0.001). Among them, in the low-risk and intermediate risk groups, 24 patients (39%) and 8 patients (20%) were respectively treated with only adjuvant endocrine therapy instead of adjuvant chemotherapy combined with endocrine therapy (McNemar's test, P<0.001; P=0.008) after taking the 21-gene test. Conclusion For patients with hormone receptor positive and lymph node negative early stage breast cancer, taking the 21-gene test can significantly avoid excessive postoperative adjuvant chemotherapy in both low- and intermediate-risk groups. Moreover, it can reduce the postoperative chemotherapy rate and lessen the side effects of chemotherapy. [ABSTRACT FROM AUTHOR]

The 21-gene recurrence score (RS) predicts the prognosis of patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer and the effectiveness of adding adjuvant chemotherapy on the basis of endocrine therapy to avoid excessive chemotherapy. The present study aimed to analyze clinicopathological characteristics and chemotherapeutic efficacy-related target genes with the 21-gene RS in hormone receptor-positive early-stage breast cancer in China. The prognostic value of chemotherapeutic efficacy-related target genes was also examined. In addition, this study investigated the postoperative adjuvant therapeutic decision-oriented role of 21-gene RS in hormone receptor-positive and lymph node-negative early-stage breast cancer. In the present retrospective study, 110 ER+/HER2− early-stage breast cancer patients were tested with the 21-gene RS. The analyses of clinicopathological characteristics and chemotherapeutic efficacy-related target genes with the 21-gene RS were performed using the χ2 test, the Wilcoxon rank-sum test and binary logistic regression. Kaplan-Meier survival plots were drawn in www.kmplot.com. Furthermore, the McNemar χ2 test was used to compare the changes of treatment decisions before and after the 21-gene test. The median RS of 110 patients was 16 (range, 2–47), and patients were categorized as low (59.1%), intermediate (34.5%) or high risk (6.4%). The results revealed that higher body mass index, invasive ductal carcinoma type, higher histological grade, luminal B molecular type and higher thymidylate synthetase (TYMS) and DNA topoisomerase IIα (TOP2A) gene expression levels were more likely to have a higher RS. Kaplan-Meier plots suggested that expression of TYMS, tubulin β3 class III (TUBB3) and TOP2A genes was significantly associated with relapse-free survival for ER+ breast cancer. Additionally, prior to 21-gene RS testing, 61 patients (55%) were recommended adjuvant chemotherapy and endocrine therapy; however, following 21-gene test, 32 patients (29%) were treated with only adjuvant endocrine therapy. TYMS, TUBB3 and TOP2A gene expression may have prognostic value for ER+ breast cancer. In addition, 21-gene RS testing may aid to avoid excessive postoperative adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Introduction: To assess the role of the 21-gene recurrence score (RS) assay on decision-making of postoperative radiotherapy (RT) following breast-conserving surgery (BCS) in elderly women with early-stage breast cancer. Methods: The 21-gene RS for elderly (≥65 years) women with stage T1–2N0M0 estrogen receptor-positive breast cancer who underwent BCS from 2004 to 2015 was obtained from the Surveillance, Epidemiology, and End Results program. We estimated the association of 21-gene RS and adjuvant RT related to breast cancer-specific survival (BCSS) using propensity score matching (PSM). Results: We identified 18,456 patients, of which 15,326 (83.0%) received postoperative RT. Of identified patients, 58.9, 34.0, and 7.1% of patients had a low-, intermediate-, and high-risk RS, respectively. Receipt of postoperative RT was not related to the year of diagnosis according to the 21-gene RS groups. Multivariate analysis suggested that receipt of postoperative RT was an independent predictor of better BCSS before (hazard ratio [HR] 0.587, 95% confidence interval [CI] 0.426–0.809, P = 0.001) and after (HR 0.613, 95%CI 0.390–0.963, P = 0.034) PSM. However, subgroups analyses indicated that receipt of postoperative RT was related to better BCSS in women with intermediate-risk RS before (HR 0.467, 95%CI 0.283–0.772, P = 0.003) and after (HR 0.389, 95%CI 0.179–0.846, P = 0.017) PSM, but not in women with low- and high-risk RS groups before and after PSM. Conclusions: Although causation cannot be implied, adjuvant RT in elderly women was associated with a greater effect size in patients with an intermediate-risk RS. [ABSTRACT FROM AUTHOR]

Purpose: The 21-gene recurrence score (RS) assay is increasingly utilized to predict the risk of recurrence in early stage estrogen receptor (ER)-positive breast cancer. We hypothesize that tumor grade and progesterone receptor (PR) status predict RS categorization.Methods: We identified women between the ages of 18 and 74 years with stage I or II, ER-positive, invasive carcinoma of the breast from the Surveillance Epidemiology End-Results database from 2010 to 2013. Multivariable logistic regression was performed to determine factors associated with high-risk RS.Results: We identified 42,530 patients that met inclusion criteria. Multivariable logistic regression demonstrated that grade I tumors [OR (odds ratio) 0.33, 95% CI (confidence interval) 0.31-0.37] and PR positive (PR+) status (OR 0.16, 95% CI 0.15-0.17) were significantly less likely to be associated with high-risk RS. Of patients with grade I PR+ tumors, 1% was in the high-risk group by the traditional cutoffs and 4% was in the high-risk group by the TAILORx cutoffs. The percentage of patients with high-risk RS remained low for grade I PR+ tumors regardless of age, race, tumor size, and lymph node status.Conclusions: We found that grade I PR+ tumors are associated a < 5% probability of having high-risk RS regardless of other patient demographic or pathologic factors. This suggests that the histologic factors of grade and PR status should be taken into consideration before ordering the 21-gene recurrence score assay. [ABSTRACT FROM AUTHOR]

Background: The nationwide use of the 21-gene recurrence score (21-RS) and implications regarding chemotherapy administration in relation to clinical risk in early breast cancer patients are investigated. Methods: Breast cancer patients surgically treated between 2014 and 2016 were selected from the Netherlands Cancer Registry and categorized as having a clinical low, intermediate, or high risk of developing metastases. Deployment of the 21-RS is advocated in patients with an intermediate risk of developing metastases. The use and impact of the 21-RS test result on chemotherapy administration were assessed in relation to the clinical risk as well as patient and tumor characteristics; χ2 tests were used for analysis. Results: Of all patients, 20,488 were considered as clinical low-, 4,309 as intermediate-, and 15,266 as high-risk patients. The 21-RS was deployed in 0.1% (n = 23), 3.2% (n = 137), and 0.6% (n = 90) of these categories, respectively. In the clinical intermediate-risk group, the 21-RS assigned 73.7, 13.1, and 13.1% of patients to the genomic low-, intermediate-, and high-risk category, respectively. Adherence to the 21-RS was 95.6% in these patients. Conclusion: In the Netherlands, the 21-RS test is applied both inside and outside the guideline-directed area. In case of discordance between the genomic and clinical risk, patients were treated in line with the result of the 21-RS. [ABSTRACT FROM AUTHOR]

To determine the most suitable strategy in treating patients with invasive breast cancer from Northwest China. Lower recurrence score (RS) correlated with lower recurrence ratio. Patients having a medium-high 21-gene RS who received adjuvant therapy presented lower recurrence risk. Younger patients having RS results (⩾31) tended to accept adjuvant therapy more often, however, those having intermediate RS results were inclined to wait and did not receive chemotherapy. These results suggested that RS-based precision medicine will allow individualized diagnosis and treatment, resulting in better outcomes and preserved medical resources. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of 21-gene recurrence score on adjuvant chemotherapy decisions for patients with estrogen receptor (ER)-positive, epidermal growth factor receptor 2 (HER-2)-negative and lymph node (LN)-negative early stage-breast cancer. Methods One hundred and forty-eight patients with ER+ , HER-2- and LN- early stage breast cancer were recruited in the Ruijin hospital, Shanghai Jiao Tong University School of Medicine. The 21-gene recurrence score (RS)assay was performed and systemic therapeutic decisions were made before and after knowing the RS results under multidisciplinary discussion. The effects of RS assay and the other influential factors on adjuvant chemotherapy decision were further analyzed. Results After knowing the RS results, treatment decisions were changed in 26 out of 148 patients(17.6%). Among them, 9 out of 26 patients were not recommended for chemotherapy; 16 of 26 had treatment recommendation changed to chemotherapy, and chemotherapy regimen was changed in the last one patient. Multivariate analysis showed that RS, age and histological grade were independent factors of decision-making for adjuvant chemotherapy. Conclusion Our results suggest that 21-gene recurrence score significantly influences decision making for adjuvant chemotherapy in patients with ER+ , HER-2- and LN- early stage breast cancer. [ABSTRACT FROM AUTHOR]

Background: The 21-gene recurrence score (RS) assay predicts response to adjuvant chemotherapy in patients with early-stage, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative invasive breast cancer, but to the authors' knowledge, the role of the assay in guiding the selection of chemotherapy regimen has not been established. The current study was conducted to examine patterns of use of the RS assay for selecting chemotherapy regimens across a statewide registry from 2006 through 2013.Methods: Demographic, pathologic, and treatment data were abstracted from medical records for 16,666 women with breast cancer who were treated at 25 hospital systems across Michigan that were participating in the Michigan Breast Oncology Quality Initiative. Treatment patterns were examined based on the RS assay test result.Results: Approximately 25% of patients with lymph node-negative disease who underwent testing with the RS assay and who were treated with chemotherapy received an anthracycline-based regimen, compared with 49% of patients with lymph node-negative disease who were treated with chemotherapy and who had not undergone testing with the RS assay. Of those patients with lymph node-positive disease who underwent testing with the RS assay and who received chemotherapy, 31% received an anthracycline-based regimen. In comparison, 71% of patients with lymph node-positive, chemotherapy-treated disease who did not undergo testing received an anthracycline. From 2006 through 2013, there was a statistically significant decrease in the use of anthracycline-containing regimens in both patients with lymph node-negative and lymph node-positive disease.Conclusions: Use of anthracycline-containing chemotherapy regimens in eligible patients appears to vary with use of the RS assay, despite the lack of evidence supporting use of the assay to guide regimen selection. Results of ongoing prospective trials should help to define the role of the RS assay in this setting. Cancer 2017;123:948-56. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

High 21-gene recurrence score (RS) is associated with an impaired prognosis in patients with HR-positive/HER2-negative early breast cancer (EBC) and predictive of response to adjuvant chemotherapy. Detection of disseminated tumor cells (DTCs) in the bone marrow is a surrogate of minimal residual disease and of prognostic value. The aim of this study was to compare DTC detection with the 21-gene RS. DTCs were identified in bone marrow aspirates of HR-positive/HER2-negative EBC patients by immunocytochemistry (pancytokeratin antibody A45-B/B3) and cytomorphology at primary surgery. The 21-gene RS was assessed in paraffin-embedded tumor tissue samples using Oncotype DX (Genomic Health). A total of 114 patients were included in this study. DTCs were detected in 13 of these (11 %). Of the women with a low RS (<18), 5/75 (7 %) were DTC positive. Of the women with an intermediate/high RS (≥18), 8/39 (21 %) were DTC positive ( p = 0.03, Chi-squared test). The median RS in DTC-negative patients was significantly lower as compared to DTC-positive patients (15 vs. 20, p = 0.04, Mann-Whitney U test). In conclusion, detection of DTCs in patients with EBC is associated with high 21-gene recurrence score. These findings are meaningful for further basic research that aims to investigate the biological mechanism of tumor cell spread and cancer progression and may have prognostic and/or predictive clinical implications that should be evaluated in future clinical trials. [ABSTRACT FROM AUTHOR]

Ixabepilone and the taxanes have similar activity in the first-line treatment of metastatic breast cancer, and ixabepilone is sometimes effective in taxane-refractory patients. We conducted a phase 2 trial to evaluate ixabepilone in combination with cyclophosphamide as neoadjuvant treatment for patients with locally advanced HER2-negative breast cancer. Response to neoadjuvant treatment was correlated with the baseline 21-gene Recurrence Score (Oncotype DX; Genomic Health Inc, Redwood City, CA). Eligible women with HER2-negative locally advanced breast cancer received ixabepilone 40 mg/m plus cyclophosphamide 600 mg/m on day 1 of each 21-day cycle. Following 6 cycles, patients underwent definitive surgery. Primary endpoint was rate of pathologic complete response (pCR). Breast biopsy tumor samples were obtained at pretreatment and at surgery in patients with residual disease. Tumor specimens were analyzed using the 21-gene assay. One hundred sixty-eight patients (median age 52 years; 45 % triple-negative) were enrolled; 161 (96 %) underwent definitive surgery following neoadjuvant ixabepilone/cyclophosphamide. Overall, 27 patients (17 %) achieved pCR, including 19 of 73 (26 %) triple-negative patients. The most frequently occurring grade 3/4 toxicity was neutropenia (98 patients; 58 %). Recurrence Scores were highly correlated with achievement of pCR (0/36 with low or intermediate Recurrence Scores vs. 19/72 with high Recurrence Scores; p = 0.002). There was high concordance between baseline and post-treatment Recurrence Scores in the 72 patients with paired samples. The combination of ixabepilone and cyclophosphamide yielded a pCR rate of 17 %, similar to other neoadjuvant chemotherapy regimens. Pathologic complete responses occurred only in patients with high-risk baseline Recurrence Scores. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: The primary purpose of this study was to measure the impact of the 21-gene Recurrence Score® result on systemic treatment recommendations and to perform a prospective health economic analysis in stage I–II, node-negative, oestrogen receptor positive (ER+) breast cancer. Methods: Consenting patients with ER+ node negative invasive breast cancer and their treating medial oncologists were asked to complete questionnaires about treatment preferences, level of confidence in those preferences and a decisional conflict scale (patients only) after a discussion of their diagnosis and risk without knowledge of the Recurrence Score. At a subsequent visit, the assay result and final treatment recommendations were discussed prior to both parties completing a second set of questionnaires. A Markov health state transition model was constructed, simulating the costs and outcomes experienced by a hypothetical ‘assay naïve’ population and an ‘assay informed’ population. Results: One hundred and fifty-six patients across two cancer centres were enrolled. Of the 150 for whom successful assay results were obtained, physicians changed their chemotherapy recommendations in 45 cases (30%; 95% confidence interval (CI) 22.8–38.0%); either to add (10%; 95% CI 5.7–16.0%) or omit (20%; 95% CI 13.9–27.3%) adjuvant chemotherapy. There was an overall significant improvement in physician confidence post-assay (p <0.001). Patient decisional conflict also significantly decreased following the assay (p <0.001). The simulation model found an incremental cost-effectiveness ratio of Canadian Dollars (CAD) $6630/quality-adjusted life years (QALY). Conclusion: Within the context of a publicly funded health care system, the Recurrence Score assay significantly affects adjuvant treatment recommendations and is cost effective in ER+ node negative breast cancer. [Copyright &y& Elsevier]

The present study was performed to evaluate the significance of biologic subtype and 21-gene recurrence score relative to local recurrence and local-regional recurrence after breast conservation treatment with radiation. Eastern Cooperative Oncology Group E2197 was a prospective randomized clinical trial that compared two adjuvant systemic chemotherapy regimens for patients with operable breast carcinoma with 1-3 positive lymph nodes or negative lymph nodes with tumor size >1.0 cm. The study population was a subset of 388 patients with known 21-gene recurrence score and treated with breast conservation surgery, systemic chemotherapy, and definitive radiation treatment. Median follow-up was 9.7 years (range = 3.7-11.6 years). The 10-year rates of local recurrence and local-regional recurrence were 5.4 % and 6.6 %, respectively. Neither biologic subtype nor 21-gene Recurrence Score was associated with local recurrence or local-regional recurrence on univariate or multivariate analyses (all P ≥ 0.12). The 10-year rates of local recurrence were 4.9 % for hormone receptor positive, HER2-negative tumors, 6.0 % for triple negative tumors, and 6.4 % for HER2-positive tumors ( P = 0.76), and the 10-year rates of local-regional recurrence were 6.3, 6.9, and 7.2 %, respectively ( P = 0.79). For hormone receptor-positive tumors, the 10-year rates of local recurrence were 3.2, 2.9, and 10.1 % for low, intermediate, and high 21-gene recurrence score, respectively ( P = 0.17), and the 10-year rates of local-regional recurrence were 3.8, 5.1, and 12.0 %, respectively ( P = 0.12). For hormone receptor-positive tumors, the 21-gene recurrence score evaluated as a continuous variable was significant for local-regional recurrence (hazard ratio 2.66; P = 0.03). The 10-year rates of local recurrence and local-regional recurrence were reasonably low in all subsets of patients. Neither biologic subtype nor 21-gene recurrence score should preclude breast conservation treatment with radiation. [ABSTRACT FROM AUTHOR]

Both the 70-gene signature and the 21-gene assay are novel prognostic tests used to guide adjuvant chemotherapy decisions in patients with early breast cancer. Although the results of ongoing prospective trials will only become available in some years, the tests have already been included in clinical guidelines such as St. Gallen's. In literature, the cost-effectiveness (CE) of both tests as compared to conventional prognostic tests has been described. We report on a direct comparison of CE; as different compliance rates were reported, we also taken these into account. A Markov decision model with a time horizon of 20 years was developed to assess the effects, costs and CE of three alternatives; 21-gene, 70-gene, and St. Gallen (SG) or Adjuvant Online (AO), dependent on the dataset used in patients with early, node-negative, breast cancer. Sensitivity and specificity were based on two datasets, incorporating compliances rates based on literature. For both datasets, whereas the 70-gene signature yielded more quality adjusted life years (QALYs) and was less costly; the 21-gene amounted more life years (LYs) but was more costly. The decision uncertainty surrounding the probability of CE of the Thomassen-series amounted 55% for both cost/LY and cost/QALY, for the Fan-series 80% for LY and 65% for QALYs. Taking reported compliance with discordant test results into account, in general, the effect of all strategies decreased, while the costs increased, without relatively influencing the CEA performance. This comparison indicates that the performances of the 70-gene and the 21-gene based on reported studies are close. The 21-gene has the highest probability of being cost-effective when focusing on cost/LY, while focusing on cost/QALY, the 70-gene signature was most cost-effective. The level of compliance can have serious impact on the CE. With additional data, preferably from head-to-head outcome studies and especially on compliance concerning discordant test results, calculations can be made with higher degrees of certainty. [ABSTRACT FROM AUTHOR]