scholarly journals Prognostic Impact of the Combination of Recurrence Score and Quantitative Estrogen Receptor Expression (ESR1) on Predicting Late Distant Recurrence Risk in Estrogen Receptor–Positive Breast Cancer After 5 Years of Tamoxifen: Results From NRG Oncology/National Surgical Adjuvant Breast and Bowel Project B-28 and B-14

2016 ◽  
Vol 34 (20) ◽  
pp. 2350-2358 ◽  
Author(s):  
Norman Wolmark ◽  
Eleftherios P. Mamounas ◽  
Frederick L. Baehner ◽  
Steven M. Butler ◽  
Gong Tang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Recurrence Score ◽  
Distant Recurrence ◽  
Positive Node ◽  
National Surgical Adjuvant Breast ◽  
Cut Point ◽  
Er Positive ◽  
Bowel Project ◽  
Esr1 Expression

Purpose We determined the utility of the 21-Gene Recurrence Score (RS) in predicting late (> 5 years) distant recurrence (LDR) in stage I and II breast cancer within high and low-ESR1–expressing groups. Patients and Methods RS was assessed in chemotherapy/tamoxifen-treated, estrogen receptor (ER) –positive, node-positive National Surgical Adjuvant Breast and Bowel Project B-28 patients and tamoxifen-treated, ER-positive, node-negative B-14 patients. The association of the RS with risk of distant recurrence (DR) 0 to 5 years and those at risk > 5 years was assessed. An ESR1 expression cut point was optimized in B-28 and tested in B-14. Results Median follow-up was 11.2 years for B-28 and 13.9 years for B-14. Of 1,065 B-28 patients, 36% had low (< 18), 34% intermediate (18 to 30), and 30% high (≥ 31) RS. Of 668 B-14 patients, 51% had low, 22% intermediate, and 27% high RS. Median ESR1 expression by reverse transcriptase polymerase chain reaction was: B-28, 9.7 normalized expression cycle threshold units (CT) and B-14, 10.7 CT. In B-28, RS was associated with DR 0 to 5 years (log-rank P < .001) and > 5 to 10 years (log-rank P = .02) regardless of ESR1 expression. An ESR1 expression cut point of 9.1 CT was identified in B-28. It was validated in B-14 patients for whom the RS was associated with DR in years 5 to 15: 6.8% (95% CI, 4.4% to 10.6%) versus 11.2% (95% CI, 6.2% to 19.9%) versus 16.4% (95% CI, 10.2% to 25.7%) for RS < 18, RS 18 to 30, and RS ≥ 31, respectively (log-rank P = .01). Conclusion For LDR, RS is strongly prognostic in patients with higher quantitative ESR1. Risk of LDR is relatively low for patients with low RS. These results suggest the value of extended tamoxifen therapy merits evaluation in patients with intermediate and high RS with higher ESR1 expression at initial diagnosis.

scholarly journals Association Between the 21-Gene Recurrence Score Assay and Risk of Locoregional Recurrence in Node-Negative, Estrogen Receptor–Positive Breast Cancer: Results From NSABP B-14 and NSABP B-20

2010 ◽  
Vol 28 (10) ◽  
pp. 1677-1683 ◽  
Author(s):  
Eleftherios P. Mamounas ◽  
Gong Tang ◽  
Bernard Fisher ◽  
Soonmyung Paik ◽  
Steven Shak ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Locoregional Recurrence ◽  
Recurrence Score ◽  
Distant Recurrence ◽  
Locoregional Therapy ◽  
Second Primary ◽  
Node Negative ◽  
Er Positive ◽  
Positive Breast Cancer

Purpose The 21-gene OncotypeDX recurrence score (RS) assay quantifies the risk of distant recurrence in tamoxifen-treated patients with node-negative, estrogen receptor (ER)–positive breast cancer. We investigated the association between RS and risk for locoregional recurrence (LRR) in patients with node-negative, ER-positive breast cancer from two National Surgical Adjuvant Breast and Bowel Project (NSABP) trials (NSABP B-14 and B-20). Patients and Methods RS was available for 895 tamoxifen-treated patients (from both trials), 355 placebo-treated patients (from B-14), and 424 chemotherapy plus tamoxifen-treated patients (from B-20). The primary end point was time to first LRR. Distant metastases, second primary cancers, and deaths before LRR were censored. Results In tamoxifen-treated patients, LRR was significantly associated with RS risk groups (P < .001). The 10-year Kaplan-Meier estimate of LRR was 4.% (95% CI, 2.3% to 6.3%) for patients with a low RS (< 18), 7.2% (95% CI, 3.4% to 11.0%) for those with intermediate RS (18-30), and 15.8% (95% CI, 10.4% to 21.2%) for those with a high RS (> 30). There were also significant associations between RS and LRR in placebo-treated patients from B-14 (P = .022) and in chemotherapy plus tamoxifen–treated patients from B-20 (P = .028). In multivariate analysis, RS was an independent significant predictor of LRR along with age and type of initial treatment. Conclusion Similar to the association between RS and risk for distant recurrence, a significant association exists between RS and risk for LRR. This information has biologic consequences and potential clinical implications relative to locoregional therapy decisions for patients with node-negative and ER-positive breast cancer.

Breast cancer estrogen and progesterone receptor values: their distribution, degree of concordance, and relation to number of positive axillary nodes.

1983 ◽  
Vol 1 (6) ◽  
pp. 349-358 ◽  
Author(s):  
B Fisher ◽  
D L Wickerham ◽  
A Brown ◽  
C K Redmond
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Progesterone Receptor ◽  
The Other ◽  
Breast Cancers ◽  
Patient Age ◽  
National Surgical Adjuvant Breast ◽  
Axillary Nodes ◽  
Bowel Project ◽  
Estrogen And Progesterone Receptor

Increasing evidence indicates the importance of ascertaining the quantitative estrogen receptor (ER) and progesterone receptor (PR) content (in femtomoles per milligram cytosol protein) of primary breast cancers. Those values obtained from the tumors of 1,887 patients participating in National Surgical Adjuvant Breast and Bowel Project protocol B-09 have been analyzed to define (1) the distribution of tumor ER or PR according to patient age, (2) the distribution of tumor PR within a specific ER interval, and (3) the concordance of tumor ER and PR levels. The present findings indicate how predictive the knowledge of the amount of one receptor (e.g., ER) may be for estimating the amount of the other (PR), when the latter is unknown.

Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: results from the National Surgical Adjuvant Breast and Bowel Project B-15.

1990 ◽  
Vol 8 (9) ◽  
pp. 1483-1496 ◽  
Author(s):  
B Fisher ◽  
A M Brown ◽  
N V Dimitrov ◽  
R Poisson ◽  
C Redmond ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Positive Node ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
National Surgical Adjuvant Breast ◽  
Significant Difference ◽  
Bowel Project ◽  
Disease Free

The National Surgical Adjuvant Breast and Bowel Project (NSABP) implemented protocol B-15 to compare 2 months of Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) and cyclophosphamide (AC) with 6 months of conventional cyclophosphamide, methotrexate, and fluorouracil (CMF) in patients with breast cancer nonresponsive to tamoxifen (TAM, T). A second aim was to determine whether AC followed in 6 months by intravenous (IV) CMF was more effective than AC without reinduction therapy. Through 3 years of follow-up, findings from 2,194 patients indicate no significant difference in disease-free survival (DFS, P = .5), distant disease-free survival (DDFS, P = .5) or survival (S, P = .8) among the three groups. Since the outcome from AC and CMF was almost identical, the issue arises concerning which regimen is more appropriate for the treatment of breast cancer patients. AC seems preferable since, following total mastectomy, AC was completed on day 63 versus day 154 for conventional CMF; patients visited health professionals three times as often for conventional CMF as for AC; women on AC received therapy on each of 4 days versus on each of 84 days for conventional CMF; and nausea-control medication was given for about 84 days to conventional CMF patients versus for about 12 days to patients on AC. The difference in the amount of alopecia between the two treatment groups was less than anticipated. While alopecia was almost universally observed following AC therapy, 71% of the CMF patients also had hair loss and, in 41%, the loss was greater than 50%. This study and NSABP B-16, which evaluates the worth of AC therapy in TAM-responsive patients, indicate the merit of 2 months of AC therapy for all positive-node breast cancer patients.

scholarly journals Evaluation of the 12-Gene Molecular Score and the 21-Gene Recurrence Score as Predictors of Response to Neo-adjuvant Chemotherapy in Estrogen Receptor-Positive, HER2-Negative Breast Cancer

2020 ◽  
Vol 27 (3) ◽  
pp. 765-771 ◽  
Author(s):  
Hatem Soliman ◽  
Susanne Wagner ◽  
Darl D. Flake ◽  
Mark Robson ◽  
Lee Schwartzberg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Adjuvant Chemotherapy ◽  
Locally Advanced ◽  
Recurrence Score ◽  
Long Term Outcome ◽  
Predictors Of Response ◽  
Er Positive ◽  
Neo Adjuvant Chemotherapy ◽  
Molecular Score

Abstract Background Neo-adjuvant chemotherapy (NaCT) facilitates complete surgical resection in locally advanced breast cancer. Due to its association with improved outcome, complete pathologic response (pCR) to neo-adjuvant treatment has been accepted as a surrogate for long-term outcome in clinical trials of human epidermal growth factor receptor 2 (HER2)-positive, triple-negative, or luminal B breast cancer patients. In contrast, NaCT is effective in only ~ 7–10% of estrogen receptor (ER)-positive, HER2-negative disease. Response biomarkers would enable such patients to be selected for NaCT. Methods Two commercially available breast cancer prognostic signatures [12-gene molecular score (MS) and the 21-gene Recurrence Score (RS)] were compared in their ability to predict pCR to NaCT in ER-positive, HER2-negative breast cancer in six public RNA expression microarray data sets. Scores were approximated according to published algorithms and analyzed by logistic regression. Results Expression data were available for 764 ER-positive, HER2-negative breast cancer samples, including 59 patients with pCR. The two scores were well correlated. Either score was a significant predictor of pCR (12-gene MS p = 9.4 × 10−5; 21-gene RS p = 0.0041). However, in a model containing both scores, the 12-gene MS remained significant (p = 0.0079), while the 21-gene RS did not (p = 0.79). Conclusions In this microarray study, two commercial breast cancer prognostic scores were significant predictors of response to NaCT. In direct comparison, the 12-gene MS outperformed the 21-gene RS as a predictive marker for NaCT. Considering pCR as surrogate for improved survival, these results support the ability of both scores to predict chemotherapy sensitivity.

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

2013 ◽  
Vol 31 (22) ◽  
pp. 2783-2790 ◽  
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.

Chemoprevention of breast cancer and the trials of the National Surgical Adjuvant Breast and Bowel Project and others.

2003 ◽  
pp. 347-357 ◽  
Author(s):  
R E Smith ◽  
B C Good
Keyword(s):  
Breast Cancer ◽  
Cancer Recurrence ◽  
Future Research ◽  
Thromboembolic Events ◽  
National Surgical Adjuvant Breast ◽  
Results Of Treatment ◽  
Er Positive ◽  
Bowel Project ◽  
Prevention Trials

The idea of breast cancer prevention by hormonal means stemmed from the results of treatment trials, many of them carried out by the National Surgical Adjuvant Breast and Bowel Project (NSABP). Over the years, a number of NSABP treatment studies demonstrated that breast cancer recurrence was reduced in women with the disease who were given tamoxifen, a selective estrogen receptor (ER) modulator (SERM). Five subsequent tamoxifen prevention trials with this agent have shown a 48% reduction in ER-positive cancers, but no effect for ER-negative cancers, and an increase in endometrial cancer and thromboembolic events. The drug raloxifene, another SERM, originally examined as an osteoporosis agent, has also shown promise for the prevention of breast cancer, although, as with tamoxifen, the drug carries a risk for thromboembolic events. There is recent evidence in a large treatment trial that the aromastase inhibitor anastrazole, a 'pure anti-estrogen', holds promise as a breast cancer preventive agent. Longer follow-up and the testing of additional agents is required before these drugs can be used widely for prevention. In addition, future research should focus on the identification of at-risk women who can perhaps be targeted for specific prevention agents.

A comparative analysis of distant recurrence risk assessments by Oncotype DX recurrence score alone and integrated with clinicopathologic factors in early-stage breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 598-598 ◽  
Author(s):  
Ciara Marie Kelly ◽  
Rose Beamish ◽  
John McCaffrey ◽  
Martina SMITH ◽  
John Crown ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Recurrence Score ◽  
Risk Groups ◽  
Recurrence Risk ◽  
Distant Recurrence ◽  
Oncotype Dx ◽  
Node Negative ◽  
Er Positive ◽  
Clinicopathologic Factors ◽  
Oncotype Dx Recurrence Score

598 Background: Treatment planning for patients with node negative, ER-positive, HER-2 negative breast cancer often incorporates the use of prognostic and predictive tools like Oncotype DX. Prior to the availabilty of Oncotype DX, clinicopathologic factors such as age, nodal status, tumour size and grade were used to determine risk of recurrence (ROR). RSPC represents a validated formal integration of oncotype DX recurrence score (RS) and clinicopathologic factors that further refines prognostic accuracy. RSPC does not improve the prediction of likelihood of chemotherapy benefit. The objective of this study was to compare distant recurrence risk assessment by RS and RSPC. Methods: We included patients with node negative, ER-positive, HER2-negative breast cancer who had Oncotype DX testing routinely or on clinical trial. We retrospectively reviewed patient charts and extracted clinicopathological and RS data. We calculated the RSPC using the RSPC educational tool. A comparative analysis was performed looking at the statification of patients into low (LR), intermediate (IR) and high (HR) ROR groups by RS and RSPC. The cut offs for low, intermediate and high risk by the RSPC were set to less than 12%, 12-20% and more than 20% risk of distant recurrence at 10yrs, corresponding to the risks of recurrence associated with the RS categories. Results: We identified 658 patients from 5 academic hospitals in Ireland and the US. Oncotype DX RS classified the following proportions of patients into three risk groups for distant recurrence: LR, n=334 (50.5%), IR, n=259 (39.4%), HR, n=67 (10.1%). RSPC classified the following proportion of patients into the three risk groups for recurrence: LR, n= 455 (69.1%), IR, n=110 (16.7%), HR, n=93 (14.1%). RSPC reclassified 72.6% (n=188) of the IR group (59.1% (n=153) from IR to LR and 13.5% (n=35) from IR to HR). RPSC reclassified 10.5% (n=35) of the LR group (8.1% (n=27) from LR to IR, and 2.4% (n=8) from LR to HR). RSPC reclassified 25.3% (n=17) of the HR group (17.9% (n=12) from HR to IR, and 7.4% (n=5) from HR to LR). Conclusions: RSPC reclassified 240 patients (36.5%) and was most helpful reassigning the IR group.

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