The ZNF217 Biomarker Predicts Low- and High-Risk Oncotype DX® Recurrence Score in ER-Positive Invasive Breast Cancers

11067 Background: The 21 gene RT-PCR assay Oncotype DX (Genomic Health, CA) stratifies patients into low, intermediate and high risk for systemic recurrence. The objective of this study was to examine the patterns of use of Oncotype DX in a single institution. Methods: All patients who had ODX testing requested by the University of Pennsylvania were identified and recurrence scores (RS) obtained. Patient and tumor characteristics, as well as treatment administered, were obtained by chart review for analysis. Results: 100 ODX tests were ordered between 1/1/05–11/30/06. RS results classified 51% of breast cancers as low risk, 38% intermediate risk, and 11% high risk. Characteristics of the tumors of the overall population and by RS group are shown in Table . 99% of patients received hormonal therapy. Of the low risk patients, only one patient was treated with chemotherapy (2%) while 34% of the intermediate risk group and 80% of the high risk group received chemotherapy. Notably, only 4/100 patients with ODX were under age 35 and 17/100 had tumors over 2cm. Conclusions: In this series, ODX use is accelerating. The results of the ODX tests appear to be used clinically as demonstrated by the very low use of chemotherapy in the low risk group. Comparison to the overall population of ER positive, node negative patients seen at this institution is underway. [Table: see text] No significant financial relationships to disclose.

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Is the Oncotype DX Assay Necessary in Strongly Estrogen Receptor-Positive Breast Cancers?

The American Surgeon ◽

10.1177/000313481107701021 ◽

2011 ◽

Vol 77 (10) ◽

pp. 1364-1367 ◽

Cited By ~ 5

Author(s):

Jenny J. Lee ◽

Jeannie Shen

Keyword(s):

Estrogen Receptor ◽

Clinical Utility ◽

Recurrence Score ◽

Distant Recurrence ◽

Good Prognosis ◽

Oncotype Dx ◽

Breast Cancers ◽

Hospital Patients ◽

Estrogen Receptor Positive ◽

Er Positive

The 21-gene Oncotype DX recurrence score (RS) assay quantifies risk of distant recurrence and predicts benefit from chemotherapy in tamoxifen-treated estrogen receptor (ER)-positive, node-negative breast cancer. Although clinically useful, the assay costs roughly $4650. Because the assay is weighted heavily towards expression of ER, our objective was to determine its clinical utility in strongly ER-positive tumors. This was a retrospective study of Huntington Hospital patients undergoing an Oncotype DX assay between 2007 and 2010. Data collected included patient age, expression of ER, progesterone receptor (PR), HER2/neu, ki67, and p53, tumor size, node status, lymphovascular invasion, and nuclear grade. Of 133 total patients, 84 (63.2%) had strongly ER-positive tumors (≥90% expression). Only seven of 84 patients (8.3%) had a high risk RS (>30), indicating statistically significant predicted benefit from chemotherapy. All seven had intermediate to high ki67 expression (>20%) and lower PR expression (≤50%). Our study demonstrates that the clinical utility of the Oncotype DX assay in these patients is limited as most patients with strongly ER-positive tumors will have a low or intermediate RS. Future studies are needed to identify additional predictive factors in these patients with otherwise good prognosis.

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Using proliferative markers and Oncotype DX in therapeutic decision-making for breast cancer: the B.C. experience

Current Oncology ◽

10.3747/co.22.2284 ◽

2015 ◽

Vol 22 (3) ◽

pp. 192 ◽

Cited By ~ 7

Author(s):

E. Baxter ◽

L. Gondara ◽

C. Lohrisch ◽

S. Chia ◽

K. Gelmon ◽

...

Keyword(s):

Correlation Coefficients ◽

Recurrence Score ◽

Weighted Kappa ◽

Oncotype Dx ◽

Breast Cancers ◽

Ki 67 ◽

Er Positive ◽

Pathology Reports ◽

Therapeutic Decision Making ◽

Proliferative Indices

BackgroundProliferative scoring of breast tumours can guide treatment recommendations, particularly for estrogen receptor (er)–positive, her2-negative, T1–2, N0 disease. Our objectives were toestimate the proportion of such patients for whom proliferative indices [mitotic count (mc), Ki-67 immunostain, and Oncotype dx (Genomic Health, Redwood City, CA, U.S.A.) recurrence score (rs)] were obtained.compare the indices preferred by oncologists with the indices available to them.correlate Nottingham grade (ng) and its subcomponents with Oncotype dx.assess interobserver variation.Methods All of the er-positive, her2-negative, T1–2, N0 breast cancers diagnosed from 2007 to 2011 (n = 5110) were linked to a dataset of all provincial breast cancers with a rs. A 5% random sample of the 5110 cancers was reviewed to estimate the proportion that had a mc, Ki-67 index, and rs. Correlation coefficients were calculated for the rs with ng subcomponent scores. Interobserver variation in histologic grading between outside and central review pathology reports was assessed using a weighted kappa test.Results During 2007–2011, most cancers were histologically graded and assigned a mc; few had a Ki-67 index or rs. The ng and mc were significantly positively correlated with rs. The level of agreement in histologic scoring between outside and central pathology reports was good or very good. Very few cases with a low mc had a high rs (1.8%).Conclusions Patients with low ng and mc scores are unlikely to have a high rs, and thus are less likely to benefit from chemotherapy. In the context of limited resources, that finding can guide clinicians about when a rs adds the most value.

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Ovarian cycle stage critically affects 21-gene recurrence scores in Mmtv-Pymt mouse mammary tumours

BMC Cancer ◽

10.1186/s12885-021-08496-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Sarah M. Bernhardt ◽

Pallave Dasari ◽

Danielle J. Glynn ◽

Lucy Woolford ◽

Lachlan M. Moldenhauer ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Menstrual Cycle ◽

Recurrence Score ◽

Gene Signature ◽

Ovarian Cycle ◽

Oncotype Dx ◽

Mammary Tumours ◽

Er Positive ◽

The Impact

Abstract Background The Oncotype DX 21-gene Recurrence Score is predictive of adjuvant chemotherapy benefit for women with early-stage, estrogen receptor (ER)-positive, HER2-negative breast cancer. In premenopausal women, fluctuations in estrogen and progesterone during the menstrual cycle impact gene expression in hormone-responsive cancers. However, the extent to which menstrual cycling affects the Oncotype DX 21-gene signature remains unclear. Here, we investigate the impact of ovarian cycle stage on the 21-gene signature using a naturally cycling mouse model of breast cancer. Methods ER-positive mammary tumours were dissected from naturally cycling Mmtv-Pymt mice at either the estrus or diestrus phase of the ovarian cycle. The Oncotype DX 21-gene signature was assessed through quantitative real time-PCR, and a 21-gene experimental recurrence score analogous to the Oncotype DX Recurrence Score was calculated. Results Tumours collected at diestrus exhibited significant differences in expression of 6 Oncotype DX signature genes (Ki67, Ccnb1, Esr1, Erbb2, Grb7, Bag1; p ≤ 0.05) and a significant increase in 21-gene recurrence score (21.8 ± 2.4; mean ± SEM) compared to tumours dissected at estrus (15.5 ± 1.9; p = 0.03). Clustering analysis revealed a subgroup of tumours collected at diestrus characterised by increased expression of proliferation- (p < 0.001) and invasion-group (p = 0.01) genes, and increased 21-gene recurrence score (p = 0.01). No correlation between ER, PR, HER2, and KI67 protein abundance measured by Western blot and abundance of mRNA for the corresponding gene was observed, suggesting that gene expression is more susceptible to hormone-induced fluctuation compared to protein expression. Conclusions Ovarian cycle stage at the time of tissue collection critically affects the 21-gene signature in Mmtv-Pymt murine mammary tumours. Further studies are required to determine whether Oncotype DX Recurrence Scores in women are similarly affected by menstrual cycle stage.

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Comparison of PAM50 Risk of Recurrence Score With Oncotype DX and IHC4 for Predicting Risk of Distant Recurrence After Endocrine Therapy

Journal of Clinical Oncology ◽

10.1200/jco.2012.46.1558 ◽

2013 ◽

Vol 31 (22) ◽

pp. 2783-2790 ◽

Cited By ~ 378

Author(s):

Mitch Dowsett ◽

Ivana Sestak ◽

Elena Lopez-Knowles ◽

Kalvinder Sidhu ◽

Anita K. Dunbier ◽

...

Keyword(s):

Breast Cancer ◽

Growth Factor Receptor ◽

Recurrence Score ◽

Risk Groups ◽

Distant Recurrence ◽

Oncotype Dx ◽

Prognostic Information ◽

Node Negative ◽

Risk Of Recurrence ◽

Er Positive

Purpose Risk of distant recurrence (DR) among women with estrogen receptor (ER) –positive early breast cancer is the major determinant of recommendations for or against chemotherapy. It is frequently estimated using the Oncotype DX recurrence score (RS). The PAM50 risk of recurrence (ROR) score provides an alternative approach, which also identifies intrinsic subtypes. Patients and Methods mRNA from 1,017 patients with ER-positive primary breast cancer treated with anastrozole or tamoxifen in the ATAC trial was assessed for ROR using the NanoString nCounter. Likelihood ratio (LR) tests and concordance indices (c indices) were used to assess the prognostic information provided beyond that of a clinical treatment score (CTS) by RS, ROR, or IHC4, an index of DR risk derived from immunohistochemical assessment of ER, progesterone receptor, human epidermal growth factor receptor 2 (HER2), and Ki67. Results ROR added significant prognostic information beyond CTS in all patients (Δ LR-χ2 = 33.9; P < .001) and in all four subgroups: node negative, node positive, HER2 negative, and HER2 negative/node negative; more information was added by ROR than by RS. C indices in the HER2-negative/node-negative subgroup were 0.73, 0.76, and 0.78 for CTS, CTS plus RS, and CTS plus ROR, respectively. More patients were scored as high risk and fewer as intermediate risk by ROR than by RS. Relatively similar prognostic information was added by ROR and IHC4 in all patients but more by ROR in the HER2-negative/node-negative group. Conclusion ROR provides more prognostic information in endocrine-treated patients with ER-positive, node-negative disease than RS, with better differentiation of intermediate- and higher-risk groups.

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Abstract Submission

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.526 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 526-526 ◽

Cited By ~ 1

Author(s):

L. J. Goldstein ◽

R. Gray ◽

B. H. Childs ◽

D. Watson ◽

S. G. Rowley ◽

...

Keyword(s):

Breast Cancer ◽

Disease Free Survival ◽

Recurrence Score ◽

Recurrence Risk ◽

Oncotype Dx ◽

Axillary Lymph Nodes ◽

Axillary Lymph ◽

Breast Cancers ◽

Free Survival ◽

Increased Risk

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]

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Molecular characterization of male breast cancer by standardized quantitative RT-PCR analysis: First large genomic study of 347 male breast cancers compared to 82,434 female breast cancers

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.549 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 549-549 ◽

Cited By ~ 11

Author(s):

S. Shak ◽

G. Palmer ◽

F. L. Baehner ◽

C. Millward ◽

D. Watson ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Male Breast Cancer ◽

Recurrence Score ◽

Cyclin B1 ◽

Oncotype Dx ◽

Male Breast ◽

Breast Cancers ◽

Genomic Study ◽

Males And Females

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]

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Is obesity associated with increased recurrence risk in estrogen receptor (ER)-positive breast cancer?

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.27_suppl.171 ◽

2011 ◽

Vol 29 (27_suppl) ◽

pp. 171-171 ◽

Cited By ~ 1

Author(s):

K. K. L. Yap ◽

D. N. Efiom-Ekaha

Keyword(s):

Breast Cancer ◽

Weight Gain ◽

Pearson Correlation ◽

Cancer Recurrence ◽

Oncotype Dx ◽

Breast Cancer Recurrence ◽

Breast Cancers ◽

Obese Women ◽

Er Positive ◽

Positive Breast Cancer

171 Background: Oncotype DX Score is a 21-gene expression analysis that has been validated clinically as a reliable predictor of breast cancer recurrence for ER-positive, node-negative breast cancers. Obesity is recognized as a risk factor for many cancers, including breast cancer. Additionally obesity has been shown to be an independent prognostic factor in breast cancer. The primary objective of this study is to determine the correlation between obesity and Oncotype DX score, hence the relationship between obesity and breast cancer recurrence in ER-positive breast cancer. The secondary objective is to investigate the association between weight gain after diagnosis and breast cancer recurrence. Methods: An IRB-exempted retrospective chart review of female patients at Wellspan Group with ER-positive breast cancer who had Oncotype DX analysis in 2008 and 2009. Data collected included Oncotype DX score and BMI (at diagnosis, 6 months and 12 months). Data were analyzed to determine the correlation between Oncotype DX score and BMI at diagnosis, at 6 months and at 12 months. The correlation between Oncotype DX score and BMI changes at 12 months also was determined. Results: A total of 125 patients were identified; 103 had BMI recorded at diagnosis, 88 had BMI recorded at 6 months and 87 had BMI recorded at 12 months. Of these, we were able to determine the BMI changes at 12 months for 82 patients. The Pearson correlation scores were 0.091 (p = 0.361), 0.074 (p = 0.492), and 0.047 (p = 0.669) for BMI at diagnosis, at 6 months and at 12 months respectively. The Pearson correlation score was 0.007 (p = 0.948) for BMI changes at 12 months. Conclusions: Obesity and weight gain are not independent predictors of recurrence in patients with ER-positive breast cancer. The reported adverse prognostic associations may be more prominent in ER-negative breast cancers. This is consistent with the reports suggesting a higher rate of ER-negative, high-grade cancers in obese women as well as a greater magnitude of benefit from dietary and weight reduction interventions seen in women with ER-negative cancers.

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Discordance between Oncotype Dx and Saint Gallen criteria, Adjuvant!, NCCN 2011 guidelines, and initial physician treatment recommendation.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e11014 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e11014-e11014

Author(s):

Allan Andresson Lima Pereira ◽

Fernando Costa Santini ◽

Andrea Kazumi Shimada ◽

Ellen Caroline Nascimento ◽

Artur Katz ◽

...

Keyword(s):

High Risk ◽

Recurrence Score ◽

Kappa Coefficient ◽

Oncotype Dx ◽

Treatment Recommendation ◽

Risk Allocation ◽

Axillary Lymph ◽

Curative Intent ◽

Nccn Guidelines ◽

The Impact

e11014 Background: The Oncotype Dx recurrence score (RS) assay quantifies the risk of distant recurrence (rDR) and its use has increased despite the lack of prospective studies. Methods: This is a cross sectional retrospective study of consecutive patients (PTS) from our institution with histologically confirmed invasive breast cancer who underwent surgery with curative intent and in whom Oncotype was performed. The main objectives were to compare (1) the predicted rDR by RS and Adjuvant! (2) Risk allocation by RS and St Gallen Criteria, (3) chemotherapy indication according to RS results and NCCN guidelines and (4) to evaluate the impact of RS results on the recommendation of adjuvant chemotherapy (aCT). Results: Between October/2006-June/2011, 74 PTS were evaluated. Forty seven (63,5%) were EC IA and all had estrogen receptor positive; axillary lymph node involvement was seen in 19 PTS (13 micro and 6 macrometastasis). The rDR by RS was low in 50 PTS (67%), intermediate in 19 (26%) and high in 5 (7%). According to Saint Gallen, 7 (9%), 51 (69%) and 14 PTS (19%) were classified as low, intermediate and high risk, respectively. There was a statistical significant discordance between risk allocation according to RS and Saint Gallen (Kappa coefficient=-0.002; p=0.971). Among the 55 node-negative PTS, there was also a statistical significant discordance between the predicted average rDR, obtained from Oncotype, and Adjuvant! with median risk of 8,5% vs 15,7%, respectively (p = 0.00001 rank sum Mann Whitney test). The NCCN 2011 would have indicated aCT to 62 PTS. Among 55 classified as low and high risk by RS, the NCCN would have indicated aCT to 46 PTS. In other words, 89% (41) of PTS who would receive aCT by NCCN were classified as low risk by RS, with a statistically significant discordance (Kappa coefficient=0.035, p=0.328). Conclusions: Oncotype changed the medical management in 28 (55%) of 51 PTS in which the initial intention of the physician was known. Of these, 93% were spared aCT. We found no statistical significant concordance among the Saint Gallen, Adjuvant! or NCCN guidelines with Oncotype Dx. The rDR may be overestimated by clinicopathological-based classifications.

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