Abstract P1-10-02: Recurrence score testing does not appear to benefit patients with grade I PR positive breast cancers: An opportunity to eliminate over-treatment and decrease testing costs

Author(s):  
Rubie Sue Jackson ◽  
Thomas Sanders ◽  
Martin Rosman ◽  
Charles Mylander ◽  
Lorraine Tafra
2019 ◽  
Vol 10 ◽  
Author(s):  
Pascale A. Cohen ◽  
Olivier Loudig ◽  
Christina Liu ◽  
Joseph Albanese ◽  
Susan Fineberg

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 526-526 ◽  
Author(s):  
L. J. Goldstein ◽  
R. Gray ◽  
B. H. Childs ◽  
D. Watson ◽  
S. G. Rowley ◽  
...  

526 Background: Evidence suggests modern chemotherapy (CT) regimens are only marginally more effective in HR-pos breast cancer (Berry et al. JAMA 2006: 295: 1658). Genomic classifiers may be useful for selection of high-risk subjects for more aggressive CHT. Methods: A case-cohort sample of 776 patients enrolled on E2197 who did (N=179) or did not have a recurrence after CT (if HR-neg) or CHT (if HR-pos) and had available tissue were evaluated for Oncotype DX™ Recurrence Score (RS). E2197 included 2885 evaluable patients with 0–3 positive nodes treated with four 3-week cycles of doxorubicin (60 mg/m2) plus cyclophosphamide 600 mg/m2 (AC) or docetaxel 60 mg/m2 (AT) and hormonal therapy (if HR-pos). Median follow-up was 76 months. Results: There was no difference in DFS between treatment arms. In multivariate analysis, RS was a significant predictor of recurrence in HR-pos disease (p=0.0007, recurrence risk 21% lower for each 10 point drop in RS, 95% confidence intervals 9% to 31%). Recurrence risk was significantly elevated for an intermediate RS 18–30 (n=138, hazard ratio [HR] 2.96 [p=0.0002]) or a high RS ≥ 31 (n=108, HR 4.00, p=0.0001) compared with low RS < 18(n=196), but not for high compared with intermediate RS (HR 1.34, [p=0.32]); results were similar if only HER2-neg disease was included. The 5-year relapse free interval(RFI), breast cancer free survival (BCFS), disease-free survival (DFS), and overall survival (OS) for patients with HR-pos, HER2-neg disease are shown below (%); patients with both node-neg or node-pos breast cancers whose RS was < 18 had excellent outcomes. Conclusions: Oncotype DX™ RS identifies individuals with HR-pos, HER2-neg breast cancer with 0–3 positive axillary lymph nodes at 3–4-fold increased risk of relapse despite standard CHT, and may serve as a means to distinguish between those who do well with standard CHT (RS <18) from those who may be suitable candidates for clinical trials evaluating alternative CT regimens or other strategies (RS ≥ 18). [Table: see text] [Table: see text]


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 549-549 ◽  
Author(s):  
S. Shak ◽  
G. Palmer ◽  
F. L. Baehner ◽  
C. Millward ◽  
D. Watson ◽  
...  

549 Background: Because male breast cancer (BC) is rare, there is little known about the disease and treatment is extrapolated from female BC. Newer molecular technologies have not been used to profile male BC. We report here a study of quantitative gene expression by gender status in tumor specimens submitted for Recurrence Score testing. Methods: All estrogen receptor positive tumor specimens successfully examined in the Genomic Health laboratory from June 2004 through December 2008 were included. Quantitative expression for each gene was measured by the 21 gene oncotype DX assay on a scale from 0 to 15 (relative to reference genes), where a one unit increment is associated with a 2-fold change in expression. Results: There were 347 male and 82,434 female BCs. The males were older (mean age 63.8 vs 57.4 yrs). Standard histopathology was similar, although slightly more male BCs were ductal (83% vs 78%). Like female BC, there was a wide variation in gene expression in male BC. The distribution of RS in males and females was similar - RS mean (±SD) 18.1 (±11.2) in males and 19.1 (±10.2) in females (p = NS). The proportion of tumors with RS <18, 18 - 30, and ≥ 31 was 53.6%, 35.2%, and 11.2% in males and 53.4%, 36.3%, and 10.3% in females. Although the patterns of expression of the Oncotype DX genes were more similar than different in males and females some differences were notable. Mean expression of ER, PR, and SCUBE2 were 0.5 units higher in males. Mean expression of the proliferation genes, Ki-67, MYBL2, Survivin, Cyclin B1, and STK15, were 0.5 units higher in males. Mean expression of STMY3 was 0.9 units higher in males. Of note, whereas the level of quantitative ER significantly increased with increasing patient age in females (0.4 units per decade), little increase was observed in males (<0.1 units per decade). Conclusions: This large genomic study of male BC reveals a heterogeneous biology as measured by the standardized quantitative oncotype DX breast cancer assay, similar to that observed in female BC. Some differences, which may reflect the differences in hormone biology between males and females, were noted and deserve further study. [Table: see text]


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22016-e22016
Author(s):  
F. L. Baehner ◽  
J. Anderson ◽  
C. Millward ◽  
C. Sangli ◽  
C. Quale ◽  
...  

e22016 Background: Tumor gene expression analysis using the Recurrence Score (RS) assay is frequently used in ER+ breast cancer. Manual microdissection is performed in cases where biopsy cavities (BxC) are present in the submitted specimen. The objective of this was to characterize by quantitative RT-PCR the impact of BxC on 21 gene expression profiles and the RS. Methods: 48 (15 well, 18 moderate, and 15 poorly differentiated) breast cancers were evaluated for gene expression differences between whole sections (WS; containing BxC) and enriched tumor (ET; BxC excluded). Standardized quantitative RT-PCR analysis for the 21 Oncotype DX genes was performed; reference normalized gene expression measurements ranged from 0 to 15, where each 1-unit reflects an approximate 2-fold change in RNA. Analyses of individual genes and the RS were performed on the entire sample set and stratified by tumor grade. Correlation analyses used Pearson's R, concordance analysis used Lin's sample concordance and paired t- tests to characterize differences. Results: There were statistically significant differences in reference normalized gene expression between ET and WS in 6 genes: BAG1 (ET-WS: 0.13 units, p=0.0025), CD68 (ET-WS: -0.64 units, p<0.0001), ER (ET-WS: 0.29 units, p=0.0012), GSTM1 (ET-WS: 0.18 units p=0.0025), STK15 (ET-WS: -0.18 units, p=0.0041) and STMY3 (ET-WS: 0.62 units, p<0.0001). Expression of the macrophage marker CD68 was higher and expression of ER was lower in WS containing BxC. The correlation (0.95) and concordance (0.92) were generally high between WS and ET for RS overall however among moderately differentially tumors, there was a statistically significant mean increase in RS for WS of 3.3 units (p = 0.0012) while among poorly differentiated tumors there was a trend toward a statistically significant decrease in RS for WS of 2.2 units (p=0.0569). Conclusions: Histologic identification of invasive carcinoma and exclusion of BxC is essential for precise RS assessment. Inclusion of BxC in breast cancer specimens is associated with significant changes in the expression of individual genes and impacts the RS. Removal of BxC from breast cancer specimens assessed for gene expression levels is warranted. [Table: see text]


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 526-526
Author(s):  
Jinani Jayasekera ◽  
Clyde B. Schechter ◽  
Joseph A. Sparano ◽  
Claudine Isaacs ◽  
Robert James Gray ◽  
...  

526 Background: The recent Trial Assigning Individualized Options for Treatment (TAILORx) was practice changing. However, several important questions remain unanswered about therapy for women with early stage, hormone receptor positive (HR+), HER2- breast cancers, including chemotherapy effects by age and different Oncotype recurrence score (RS) cut-points, and longer follow-up. We developed a simulation model to extend the trial results to begin to fill these gaps. Methods: We developed a simulation model using an empirical Bayesian approach to simulate women eligible for the TAILORx trial. The joint distributions of patient and tumor characteristics were derived from de-identified TAILORx data. The remaining inputs used data independent of the trial, including SEER, the Oxford Overview, and other trials. TAILORx was simulated to examine the effects of chemotherapy (+ hormonal Rx) vs. hormonal Rx alone on distant recurrence-free survival (DRFS) at 9- and 20-years by age (≤50 and >50 years) and RS (11-25 and 16-25). We also evaluated the effects of chemotherapy in women with RS 26-30. Hazard ratios (HR) were determined using Cox regressions and DRFS by treatment were derived from Kaplan-Meier curves. We report the mean results from 1000 trial simulations, where each simulation randomly sampled values for each parameter from their observed joint distribution. Finally, the original trial was replicated for model validation. Results: The model closely replicated actual trial results. Sample sizes ranged from 7000-10000. The model estimated that chemotherapy improved DFRS in women aged ≤50 with RS 16-25 (Table). The 20-year event rates remained low in the 11-25 category. Among women with RS 26-30, HR for no chemo vs. chemo was 1.38 (95% CI:1.18-1.58). Conclusions: Simulation suggests that chemotherapy may reduce distant recurrence in younger women at different cut points between 11-25. Simulation modeling may be useful to translate trial results to broader population subgroups than those possible to test in RCTs. Nine-year distant recurrence-free survival by chemotherapy. [Table: see text]


2021 ◽  
Author(s):  
Zohair Selmani ◽  
Chloé Molimard ◽  
Alexis Overs ◽  
Fernando Bazan ◽  
Loic Chaigneau ◽  
...  

Abstract Background: Breast cancers expressing high levels of Ki67 are associated with poor outcomes. To provide individualized patient care, reliability of prognostic and predictive information deriving from Ki67 assessment is essential. Oncotype DX® test was designed for ER+/HER2- early-stage breast cancers to help adjuvant chemotherapy decision by providing a Recurrent Score® (RS®). RS® measures the expression of 21 specific genes from tumor tissue, including Ki67, and aim to predict the benefit of chemotherapy and the risk of distant recurrence. The primary aim of this study was to assess the agreement between Ki67RNA obtained with Oncotype DX® RS® and Ki67IHC. Other objectives were to analyze the association between the event free survival (EFS) and the expression level of Ki67RNA; and association between RS® and Ki67RNA.Methods: In a cohort of 98 patients with early ER+/HER2- breast cancers, we obtained: Recurrence score®, RNA level of Ki67 expression measured when assessing RS® and Ki67 tumor labelling by immunohistochemistry (Ki67IHC). The Ki67RNA was compared to the Ki67IHC by Kappa Cohen test. With a mean follow-up of 57 months, the association between the event free survival (EFS) and Ki67 status was measured using R package survival. Results: This population was essentially composed of no special type tumor (91%), N0 or Nmic (71%), grade 1 (62%), and tumor size pT1c (1-2 cm) (58%). The RS® values were <18 in 38% (n=37), 18-30 in 51% (n=50) and >30 in 11% (n=11) of the patients. A low agreement of 0.24 was found by Cohen’s kappa test between Ki67IHC and Ki67RNA. Moreover, Ki67RNAhigh tumors were significantly associated with the occurrence of events (p=0.02). On the other hand, we did not find any association between Ki67IHC and EFS (p=0.25).Conclusion: We observed of low agreement between expression level of Ki67RNA and Ki67 protein labelling by IHC. Unlike Ki67IHC and independently of the RS®, Ki67RNA could have a prognostic value. It would be interesting to better assess the prognosis and predictive value of Ki67RNA measured by qRT-PCR. The Ki67RNA in medical routine could be a good support in countries where Oncotype DX® is not accessible.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13025-e13025
Author(s):  
Kelly Suchman ◽  
Brittney Shulman Zimmerman ◽  
Meng Ru ◽  
Krystal Pauline Cascetta ◽  
Amy Tiersten

e13025 Background: Invasive lobular carcinomas (ILC) account for approximately 10-15% of all invasive breast cancers, with the majority of cases presenting as ER/PR positive and HER2 negative. As a result, they often exhibit more robust responses to hormone therapy than adjuvant chemotherapy. Oncotype Recurrence Score (RS) RS is a 21-gene assay used to predict the rate of distant recurrence and response to chemotherapy in women with node-negative, hormone-positive breast cancers. Limited evidence exists regarding oncotype scores for ILC tumors, thus the aim of this study was to examine the distribution and risk stratification of Oncotype RS in ILC tumors. Methods: We analyzed patient and tumor characteristics of 492 patients- 417 (85%) IDC (intraductal carcinoma) and 75 (15%) ILC. Chi-square tests and Wilcoxon rank-sum tests were used to compare categorical and numerical outcomes, respectively. Results: No significant difference was found between IDC and ILC in terms of age and ER/PR positivity. The RS raw scores were also not significantly different between the two groups (both had median scores of 16). ILC patients were significantly more likely to be in the lower RS risk groups using the traditional (Paik) cutoff than ILC patients (61%, 39% and 0% in low, medium and high-risk groups as compared to 57%, 33% and 10% in IDC, p < 0.01). Of 417 patients with IDC, there were 16 recurrences (4%) with a median time from diagnosis to recurrence of 43 months (IQR: 28 Ð 58 months), while 1 in 75 ILC patients had recurrence at 50 months. Conclusions: Oncotype RS scores have the potential to guide treatment decisions in node-negative breast cancers. Though mean RS were similar between ILC and IDC patients, ILC were more likely to be distributed in low-risk groups. Our study was limited by a small sample size and a single ILC recurrence. Further research is needed to determine oncotype RS and recurrence rates. Future studies with longer term follow up can help better elucidate patterns of recurrence scores and recurrence rates based on histologic tumor type. [Table: see text]


2019 ◽  
Vol 17 (3.5) ◽  
pp. QIM19-139
Author(s):  
Mara A. Piltin ◽  
Kathryn Eckert ◽  
Margaret Wight ◽  
Alan J. Shienbaum ◽  
Jeanine Chiffarano ◽  
...  

Background: Implementation of genomic assays has led to treatment of early-stage breast cancers with high risk of recurrence with adjuvant systemic chemotherapy while sparing those with a low risk of recurrence from systemic therapy with minimal benefit. Genomic assays are becoming a more widely used tool, evident by the eighth edition of the American Joint Committee on Cancer (AJCC) Breast Cancer Staging System, which includes recurrence score as part of the treatment algorithm in certain subgroups of tumors. Our institution identified the time to assay result as a quality improvement opportunity. We instituted a protocol to have a reflex testing of Oncotype DX based on certain criteria to decrease time to assay results and ultimately time to treatment. Methods: Our Multidisciplinary Breast Leadership Committee instituted a policy for reflex Oncotype DX testing on patients under the age of 70 with estrogen receptor positive, HER2-neu protein–negative, and node-negative invasive breast cancers measuring between 0.5 cm to 5 cm in January 2018. We compared our data available from pre- and postimplementation using the single factor analysis of variance (ANOVA) as well as an independent t-test and a post-hoc Tukey-Kramer test. Results: We have observed 45 cases that met the criteria for reflex Oncotype Dx testing since the initiation of this quality improvement protocol. The recurrence scores ranged from 0 to 55. There was a statistically significant difference in the number of days from operation to result day from 2016 to 2018 (55 days vs 18 days; P<.001). The number of days from the test order date to result date also saw a significant improvement from 2016 to 2018 (12 vs 9 days; P<.05). Conclusions: Breast cancer treatment options continue to evolve, particularly with the use of genomic assays. Our single institution review confirms the utility of our reflex Oncotype DX protocol with a decreased time to result with reflex testing of patients in the appropriate clinical setting. Further development of similar pathways may be necessary to streamline our patients’ care in the treatment of breast cancer.


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