Key Clinical Evidence
Purpose
Validation
Evaluate DCISionRT with Residual Risk Subtype (RRt) to help identify patients with elevated IBR risk after BCS+RT.
Study
926 women with DCIS treated with BCS +/- RT were classified into three biosignature groups by DCISionRT with RRt. Total and invasive IBR rates were assessed by risk group and treatment.
Summary
DCISionRT with RRt identified 3 distinct patient risk profiles and corresponding 10-yr IBR rates:
- Low Risk – low recurrence risk after BCS +/- RT
- Total 5.1%; Invasive 2.7%
- Elevated Risk – low recurrence risk decreased after BCS + RT
- Total 20.6% vs. 4.9%; Invasive 10.9% vs. 3.1%
- Residual Risk – elevated recurrence risk even with BCS + RT
- Total 42.1% vs. 14.7%; Invasive 18.3% vs. 6.5%
Residual Risk patients may warrant intensified or alternative treatment approaches.
Purpose
To validate DCISionRT® in a large, randomized cohort (SweDCIS) with long term follow-up.
Study
A prospective-retrospective randomized clinical trial conducted on 504 women with randomized treatment of BCS or BCS+RT
Summary
- Level 1b evidence
- Predictive for radiation therapy
- Prognostic for 10-year risk
- Elevated Risk group experienced significant RT benefit
- Absolute decreases in TotBE and InvBE rates of 16% and 9%
- Low Risk group experienced minimal RT benefit
- Absolute differences in TotBe and InvBE rates of 6% and 1%
- 40% of patients meeting RTOG-9804 ‘good risk’ criteria were classified as DS Elevated risk
Purpose
Validation
Independent clinical validation of DCISionRT after breast conserving surgery in a Kaiser Permanente NW population
Study
455 health plan members of Kaiser Permanente Northwest diagnosed with DCIS and treated with BCS or BCS+RT from 1990-2007
Summary
- The continuous and categorical DS was prognostic for both TotBE and InvBE risk after adjusting for RT
- Further reinforces DCISionRT’s ability to correctly reclassify patients into Low (42%) and Elevated risk (58%) groups
- Low Risk Group had a minimal (2%) benefit from RT (10-yr invasive risk BCS: 5%, BCS+RT: 3%)
- DCISionRT reclassifies 49% of RTOG 9804 “good risk” patients as Elevated Risk patients
- >70% risk reduction from RT in Elevated Group for invasive breast events
Purpose
Validation
A biological signature that calculates an individualized Decision Score (DS) was developed and cross-validated in 526 DCIS patients treated with BCS ± RT. The relationship was assessed between DS and 10-year risk of invasive breast cancer (IBC) or any ipsilateral breast event (IBE), including IBC or DCIS. RT benefit was evaluated by risk group and as a function of DS.
Study
The study was conducted on archived tissue samples in collaboration with Uppsala University Hospital and Västmanland County Hospital, Sweden (UUH), the University of Massachusetts, Worcester (UMass). Patients were included consecutively between 1986 and 2004 at UUH and between 1999 and 2008 at UMass. Treatment decisions were neither randomized nor strictly rules-based.
Summary
- The DS was significantly associated with IBC and IBE risk, HR (per 5 units) of 4.2 and 3.1, respectively.
- For patients treated without RT, DS identified a Low Group with 10-year IBC risk of 4% (7% IBE) and an Elevated Risk Group with IBC risk of 15% (23% IBE).
- In analysis of DS and RT by group, the Elevated Risk Group received significant RT benefit, HR of 0.3 for IBC and IBE.
- In a clinicopathologically low-risk subset, DS reclassified 42% of patients into the Elevated Risk Group.
- In an interaction analysis of DS and RT, patients with elevated DS had significant RT benefit over baseline.
Purpose
Validation
Present results from analytical validity, performance assessment, and clinical performance validation and clinical utility for DCISionRT.
Study
Performed analytical validation of DCISionRT assay based on the CLSI guidelines and CAP/ASCO recommendations.
Summary
- Analytical Validation (AV) and prior Clinical Validation (CV) studies further supports adoption of DCISionRT
- AV:
- ≥95% sensitivity, specificity and accuracy/reproducibility
- CV:
- 99% NPV for RT benefit
- NNT: Treat 100 patients to prevent one invasive breast cancer recurrence.
- AV:
Purpose
Validation
Decision Impact Study: Evaluate impact of DCISionRT on clinicians’ recommendations for adjuvant radiation therapy (RT).
Study
Within cohort of 539 women diagnosed with DCIS, physicians’ treatment recommendations were captured pre- and post- DCISionRT testing.
Summary
- Post-testing, a change in radiation therapy recommendations were made in 42% of the patients
- When compared with traditional clinicopathologic features used to determine RT recommendations, the DCISionRT result was the factor most strongly associated with radiation therapy recommendations.
Purpose
Validation
External analysis of the cost-effectiveness of the DCISionRT test to guide treatment of DCIS
Study
Used a Markov model simulating 10-year outcomes for 60-year old women with DCIS based on non-randomized data.
Summary
When compared to giving RT to all women with DCIS, the use of DCISionRT to guide the decision for RT was cost-effective and minimized the number of women undergoing RT per future ipsilateral breast event.
All Clinical Evidence
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PURPOSE
Development
Evaluated the role of immune and metabolic signaling axes in predicting RT response in hormone receptor positive, HER2 negative, early-stage BC patients.
STUDY
Biomarkers from immune and metabolic signaling axes were studied in a cohort of 939 women, and RT prediction model assessed.
SUMMARY
- Immune and metabolic axes (Model) identified patients with early-stage breast cancer who had high residual risk after BCS plus RT.
- Model was predictive for RT benefit after accounting for clinicopathological factors.
PURPOSE
Clinical Utility
To evaluate the decision impact of the 7-gene predictive biosignature on DCIS treatment recommendations in an Australian setting.
STUDY
A prospective cohort study based in Australia for patients diagnosed with DCIS. The study will evaluate the percent of cases in which treatment recommendations are changed after the DCISionRT test results become available. This is an early interim analysis based on the first ~500 enrolled patients. Final enrollment will be 1,500 women from up to 100 sites across Australia.
Create a deidentified database of patients, test results, treatment decisions, and outcomes that can determine the utility of the DCISionRT test in the diagnosis and treatment of DCIS.
SUMMARY
- DCISionRT changed RT recommendations in 41% of women overall (n=483)
- 42% of women initially recommended RT were NOT recommended RT after DCISionRT
- 40% of women initially NOT recommended RT were recommended RT after DCISionRT
PURPOSE
Development
Evaluated the role of immune and metabolic signaling axes in predicting RT response in hormone receptor positive, HER2 negative, early-stage BC patients.
STUDY
Biomarkers from immune and metabolic signaling axes were studied in a cohort of 939 women, and RT prediction model assessed.
SUMMARY
- Immune and metabolic axes (Model) identified patients with early-stage breast cancer who had high residual risk after BCS plus RT.
- Model was predictive for RT benefit after accounting for clinicopathological factors.
PURPOSE
Validation
To evaluate the decision impact of the 7-gene predictive biosignature score on DCIS treatment recommendations
STUDY
PREDICT study is a prospective, multi-institutional registry trial where physicians completed treatment recommendation forms before and after receiving test reports. Analysis was performed in 2,012 patients treated at 63 clinical sites.
SUMMARY
- DCISionRT changed RT recommendations in 38% of women overall (n=2012)
- 40% of women initially recommended RT were NOT recommended RT after DCISionRT
- 34% of women initially NOT recommended RT were recommended RT after DCISionRT
PURPOSE
Validation
Prospective trials have failed to identify a low risk CP group that did not benefit from RT with respect to local control. This study assessed re-classification of patients with low-risk CP (clinicopathologic) into Risk groups defined by DCISionRT and compared to 10-yr IBR rates.
STUDY
Women (n=926) from four international DCIS cohorts treated with BCS were identified as CP low-risk using RTOG-9804-like criteria and MSKCC-like criteria. DCISionRT further reclassified these patients to Low or High Risk Groups. 10yr IBR rates +/- RT were assessed.
SUMMARY
- DCISionRT more reliably identified patients with low 10-yr IBR rates and no significant RT benefit than the traditional CP low-risk criteria (RTOG-9804-like, MSKCC-like).
- CP low-risk patients re-classified as DCISionRT High Risk had increased 10-year IBR rates and significant RT benefit.
PURPOSE
Validation
Present results from analytical validity, performance assessment, and clinical performance validation and clinical utility for DCISionRT.
STUDY
Performed analytical validation of DCISionRT assay based on the CLSI guidelines and CAP/ASCO recommendations.
SUMMARY
Analytical Validation (AV) and prior Clinical Validation (CV) studies further supports adoption of DCISionRT
- AV:
- ≥95% sensitivity, specificity and accuracy/reproducibility
- CV:
- 99% NPV for RT benefit
- NNT: Treat 100 patients to prevent one invasive breast cancer recurrence
- AV:
PURPOSE
Validation
Evaluate the decision impact for RT recommendations incorporating DCISionRT by race (White vs Black)
STUDY
Analysis was performed in 2,308 patients (80% White/12% Black) enrolled in the PREDICT study to identify a change in RT recommendations in patient subgroups based on race/ethnicity.
SUMMARY
- No significant difference in Clinpath factors and DCISionRT scores between subgroups.
- Overall significant difference in change of RT recommendations in Black (37%) and White (39%).
- Post-DCISionRT, Black patients had a 10% higher rate of RT recommendation when compared with White patients.
PURPOSE
Validation
Compare classification of women by a Clinicopathologic (CP) model similar to the MSKCC DCIS nomogram with DCISionRT and their associated total 10-yr IBR rates +/- RT.
STUDY
926 DCIS patients treated with BCS with or without RT, were analyzed using a CP model and DCISionRT.
SUMMARY
Demonstrated the ability of DCISionRT to better risk-stratify patients with DCIS following BCS. DCISionRT re-classified 63% of patients in the CP low-risk group as Elevated Risk.
- The reclassified patients had an 80% relative benefit from RT, demonstrating potential undertreatment.
PURPOSE
Validation
Assess total 10-yr IBR rates, RT benefit, and number needed to treat (NNT) for risk groups defined by DCISionRT and Clinicopathologic criteria.
STUDY
926 women with DCIS were classified into 2 risk groups by DCISionRT and Clinicopathologic criteria. Total 10-yr IBR rates were evaluated by treatment, biosignature, and CP risk groups.
SUMMARY
DCISionRT was a better predictor of 10-yr prognosis and RT benefit than CP criteria alone. The biosignature reclassified 51% of patients defined as CP low-risk to biosignature High Risk. 31% of patients defined as CP high-risk were reclassified as biosignature Low Risk.
Low Risk Group 10-yr IBR
- Minimal RT benefit: 8% absolute 10-yr IBR rate difference
- Number needed to treat to benefit 1 patient: ~100
High Risk Group 10-yr IBR
- Significant RT benefit: 7% absolute 10-yr IBR rate reduction
- Number needed to treat to benefit 1 patient: ~6
PURPOSE
Validation
Assessed the 10-yr. IBR rate in patients with HER2(+) DCIS treated with BCS and RT who were or were not in the RRt subgroup defined using DCISionRT.
STUDY
DCISionRT was evaluated on a subset of 178 women treated with BCS and RT. The IBR rate was calculated for the overall group of HER2(+) patients and those in the RRt group.
SUMMARY
DCISionRT Residual Risk group was predictive for 10-yr IBR risk in women with HER2(+) DCIS.
- 63% of HER2(+) patients classified as Residual Risk.
- BCS+RT: 10-yr total IBR rate of 16.2%
- ~40% of HER2(+) patients with no Residual Risk
- BCS+RT: 10-yr total IBR rate of 1.6%
Findings suggest that better clarity could be gained on the results of the B43 trial and impact of trastuzumab in patients with HER2(+) DCIS.
- 63% of HER2(+) patients classified as Residual Risk.
PURPOSE
Validation
A prospective cohort study for patients diagnosed with DCIS. The study will evaluate the percent of cases in which treatment recommendations are changed after the DCISionRT test results become available.
STUDY
Create a deidentified database of patients, test results, treatment decisions, and outcomes that can determine the utility of the DCISionRT test in the diagnosis and treatment of DCIS.
SUMMARY
An early interim analysis based on the first 200 enrolled patients is currently underway. We are planning to enroll up to 1,500 women from up to 100 sites across Australia.
PURPOSE
Validation
The PREDICT Registry is a prospective cohort study for 2,308 patients diagnosed with DCIS treated at 63 clinical sites.
STUDY
Identify the proportion of patients where DCISionRT testing led to a change in RT recommendation. Additional analyses include changes in recommendations in patient subgroups based on clinicopathologic factors or clinician specialty.
SUMMARY
Demonstrated significant changes in recommendations to add or omit RT based on DCISionRT.
- RT recommendation changed for 38% of women
- RT recommendations decreased 53% in DS Low Risk patients
- RT recommendations increased 25% in DS Elevated patients
- RT recommendation changed for 38% of women
PURPOSE
Validation
Prospective validation of DCISionRT’s Residual Risk Subtype to assess 10yr ipsilateral breast recurrence rate and RT benefit compared to clinicopathology criteria alone.
STUDY
926 DCIS patients were classified into 3 risk groups by DCISionRT. RT treatment and RT effect were assessed and reported by clinicopatholgy criteria (nuclear grade, palpability, screening detection, size, & age).
SUMMARY
Within the biosignature risk groups, clinicopathology criteria was not prognostic or predictive for 10yr IBR rates or RT benefit. The incorporation of genomic information yields superior risk and RT benefit prediction as compared to clinicopathology features alone.
PURPOSE
Validation
Evaluate DCISionRT with Residual Risk Subtype (RRt) to help identify patients with elevated IBR risk after BCS+RT.
STUDY
926 women with DCIS treated with BCS +/- RT were classified into three biosignature groups by DCISionRT with RRt. Total and invasive IBR rates were assessed by risk group and treatment.
SUMMARY
DCISionRT with RRt identified 3 distinct patient risk profiles and corresponding 10-yr IBR rates:
- Low Risk – low recurrence risk after BCS +/- RT
- Total 5.1%; Invasive 2.7%
- Elevated Risk – low recurrence risk decreased after BCS + RT
- Total 20.6% vs. 4.9%; Invasive 10.9% vs. 3.1%
- Residual Risk – elevated recurrence risk even with BCS + RT
- Total 42.1% vs. 14.7%; Invasive 18.3% vs. 6.5%
Residual Risk patients may warrant intensified or alternative treatment approaches.
- Low Risk – low recurrence risk after BCS +/- RT
PURPOSE
Validation
Determine if DCISionRT with Residual Risk Subtype (RRt) can identify a clinically low-risk patient group and predict recurrence risk and RT benefit better than clinicopathological factors.
STUDY
DCISionRT with RRt was evaluated in 926 DCIS patients treated with BCS +/- RT, and clinicopathologic criteria and clinical outcomes were analyzed.
SUMMARY
- DCISionRT was a better predictor of prognosis & RT benefit than standard Clinpath criteria.
- Identified a biosignature Low Risk group with no significant adjuvant RT benefit
- In biosignature Low Risk group, 10-yr IBR rate +/- RT remained consistent independent of Clinpath criteria, supporting ID of true low risk group who may forgo RT.
PURPOSE
Validation
Evaluated association of DCISionRT to assess impact of ET on 10-yr IBR risk after BCS alone or with RT.
STUDY
DCISionRT with integrated RRt was evaluated in 926 patients from 4 cohorts who were treated with BCS alone or with RT/ET.
SUMMARY
- ET was associated with lower 10-yr IBR risk within Elevated and RRt groups without RT.
- Neither ET nor RT were asssociated with significant risk reduction in Low Risk group.
- No added benefit of ET in Elevated and RRt groups after BCS+RT
- RRt group patients still had a high IBR risk after RT.
PURPOSE
Validation
Validate DCISionRT with a novel, integrated Residual Risk subtype (RRt) biosignature (DCISionRT+RRt) to identify patients at high risk following BCS with RT.
STUDY
DCISionRT+RRt was evaluated for 926 women with DCIS treated with definitive BCS with or without RT from a multinational cohort.
SUMMARY
- DCISionRT+RRt identifies 3 distinct groups of women
- Low Risk – low 10-year IBR risk after BCS without RT (no benefit from adjuvant RT)
- Elevated Risk – increased 10-year IBR risk without RT (low 10-year IBR risk with RT)
- Residual Risk – high 10-year IBR risk after BCS without RT and elevated 10-year IBR risk after BCS without RT
- DCISionRT+RRt identifies patients with elevated recurrence risk after RT where additional therapies may be warranted.
- DCISionRT+RRt identifies 3 distinct groups of women
PURPOSE
Validation
Determine the utility of DCISionRT with Residual Risk Subtype to identify risk recurrence in subsets of women who have HER2(+) DCIS.
STUDY
DCISionRT + RRt was evaluated on a subset of 178 women with HER2(+) DCIS who were treated with BCS and RT in a multinational cohort of 926 patients.
SUMMARY
- DCISionRT with Residual Risk Subtype identified a subtype of women with HER2(+) DCIS with suboptimal benefit to adjuvant RT who had significantly elevated 10-year IBR risk remaining after BCS and RT.
- Suggestive that there is a subpopulation of patients with HER2(+) DCIS that may benefit from further therapy.
PURPOSE
Validation
A prospective cohort study for patients diagnosed with DCIS. The study will evaluate the percent of cases in which treatment recommendations are changed after the DCISionRT test results become available.
STUDY
Create a deidentified database of patients, test results, treatment decisions, and outcomes that can determine the utility of the DCISionRT test in the diagnosis and treatment of DCIS.
SUMMARY
- The PREDICT Registry Australia has consented 194 women with 50 sites currently enrolling.
- Plans to activate up to 100 sites and consent 1,500 patients.
PURPOSE
Validation
Determine the utility of DCISionRT+RRt to assess recurrence risk and RT benefit in patients in subpopulation: Age<50 years and/or High Grade DCIS
STUDY
DCISionRT and its RRT was evaluated in 926 patients overall, and also in a subpopulation of 471 young women (age<50) and/or High Grade DCIS.
SUMMARY
- Prognostic and predictive RT response among women with grade3 disease and/or young age (<50) and reclassified them into three distinct groups:
- Low Risk with 10-year total IBR risk of only 2.2% with BCS alone with no significant RT benefit;
- Elevated Risk with a 10-year IBR risk of 27.6% without RT, reduced to 3.8% with RT; and
- Residual Risk with the highest risk without RT and elevated residual 10-year risk of 13.2% after RT.
- When using grade or age alone, 1/3 of patients were overtreated with RT.
- Prognostic and predictive RT response among women with grade3 disease and/or young age (<50) and reclassified them into three distinct groups:
PURPOSE
Validation
The PREDICT Registry is a prospective cohort study for patients diagnosed with ductal carcinoma in situ (DCIS) of the breast.
STUDY
The primary objective of the study is to create a deidentified database of patients, test results, treatment decisions and outcomes that can be queried to determine the utility of the DCISionRT test in the diagnosis and treatment of ductal carcinoma in situ of the breast.
SUMMARY
- Phase I of the PREDICT Study consented 2,528 women from 67 sites and 398 physicians.
- Phase II of the registry is planning to reopen soon and enroll up to 1,500 additional women.
- A similar DCISionRT PREDICT registry has opened in Australia and others are planning to open soon in Europe.
PURPOSE
Validation
Prospective validation analysis using DCISionRT score plus residual risk subtype (RRt) to assess
stratification of ipsilateral breast recurrence (IBR) risk and RT benefit by clinicopathology.STUDY
DCISionRT and its RRt was evaluated in 493 patients from 3 cohorts for 10-yr total (invasive and in situ) IBR Risk and classified patients into three groups, a) Low Risk (DS≤2.8), b) Elevated Risk (DS>2.8 without RRt) and c) Residual Risk (DS>2.8 with RRt).
SUMMARY
- Traditional clinicopathologic features did not identify patient groups who need RT after BCS
- DCISionRT identified a Low Risk group that had no added benefit of RT after BCS
- DCISionRT identified a Residual Risk group that had high 10-yr IBR despite RT after BCS
PURPOSE
Validation
To validate DCISionRT® in a large, randomized cohort (SweDCIS) with long term follow-up.
STUDY
A prospective-retrospective randomized clinical trial conducted on 504 women with randomized treatment of BCS or BCS+RT
SUMMARY
- Level 1b evidence
- Predictive for radiation therapy
- Prognostic for 10-year risk
- Elevated Risk group experienced significant RT benefit
- Absolute decreases in TotBE and InvBE rates of 16% and 9%
- Low Risk group experienced minimal RT benefit
- Absolute differences in TotBe and InvBE rates of 6% and 1%
- 40% of patients meeting RTOG-9804 ‘good risk’ criteria were classified as DS Elevated risk
- Level 1b evidence
PURPOSE
Validation
To identify the proportion of DCIS patients whose radiation therapy (RT) treatment recommendations were changed as a result of DCISionRT test results.
STUDY
Physician treatment recommendations of 969 patients were analyzed before and after receiving their patient’s Decision Score (DS). 63% of women were DS Low risk (DS ≤ 3) and 37% of women were DS Elevated risk (DS > 3).
SUMMARY
The analysis demonstrated a significant change in adjuvant RT treatment recommendations based on DCISionRT results.
- Overall, physician treatment recommendations changed in 40% of patients
- In DS Low risk patients, adjuvant RT recommendations decreased by 42%
- In DS Elevated risk patients, adjuvant RT recommendations increased by 22%.
- DCISionRT was factor most strongly associated with RT recommendations
- Overall, physician treatment recommendations changed in 40% of patients
PURPOSE
Validation
To evaluate the effect of DCISionRT on treatment recommendations for patients with DCIS in Australia.
STUDY
A prospective, observational cohort study for up women with DCIS with a 10-year follow up. The cohort is planned to include up to 1,500 women from up to 100 sites in Australia.
SUMMARY
The treating physician will complete a survey regarding treatment recommendations before and after receiving the results of DCISionRT. The study plans to identify changes in treatment recommendations – including surgical treatments, radiation therapy, and hormone therapy – as well as identify the key drivers of treatment recommendations.
PURPOSE
Validation
To identify and evaluate changes in treatment recommendations as a result of the DCISionRT test results.
STUDY
A prospective cohort study for women diagnosed with DCIS with a 5-year and 10-year follow up. There are currently 1,986 patients enrolled from across 64 institutions. The study plans to enroll up to 2,500 patients from up to 100 institutions.
SUMMARY
The treating physician will complete a treatment recommendation survey before and after receiving the results of the DCISionRT test. The study plans to identify changes in treatment recommendations – including surgical treatments, radiation therapy, and hormone therapy – as well as identify the key drivers of treatment recommendations.
PURPOSE
Validation
To identify women diagnosed with DCIS who have a low recurrence risk and could omit radiotherapy (RT) after breast conserving surgery (BCS), or an elevated recurrence risk after treatment with BCS plus RT
STUDY
Conducted on a subset of women treated for DCIS with BCS +/- RT with large tumor sizes (>2.5 cm) and/or nuclear grade III (n=250). DCISionRT and its response subtype biosignature classified women into three risk groups: Low risk, Elevated risk with a poor response subtype (Rst), and Elevated risk with a good Rst to RT after BCS.
SUMMARY
DCISionRT combined with a novel response subtype biosignature (Rst) identified:- An Elevated risk group with two distinct subtypes of women: (1) a poor Rst that had high IBTR/IBC rates with or without RT and (2) a good Rst deriving significant benefit from adjuvant RT.
- A Low risk group that had low 10-year IBTR/IBC rates and derived no significant benefit from adjuvant RT.
PURPOSE
Validation
DCISionRT® and its response subtype (Rst) biosignature were evaluated to identify women diagnosed with DCIS who could omit RT after BCS or remain at elevated recurrence risk after treatment with BCS plus RT
STUDY
Within 485 women diagnosed with DCIS who were treated with BCS +/-RT, biosignatures (DCISionRT and Rst) were run and IBTR and IBC assessed.
SUMMARY
- A novel biologic subtype (Rst) identified patients who had unacceptably high 10-year recurrence rates after standard BCS and adjuvant RT
- Patients were identified who had low 10-yr recurrence rates and may be candidates for omitting adjuvant RT
PURPOSE
Validation
Ongoing studies update of prospective registry study to evaluate percent of cases in which treatment recommendations are changed after DCISionRT test results become available.
STUDY
- Goal is to activate up to 100 sites and consent 2,500 patients diagnosed with DCIS.
- Similar DCISionRT PREDICT registries are planning to open soon in Australia and Europe.
SUMMARY
- Consented 1,847 women. Expected to reach enrollment target October 2021.
- 65 sites enrolled and ~5 sites pending activation.
PURPOSE
Validation
Decision Impact Study: Evaluate impact of DCISionRT on clinicians’ recommendations for adjuvant radiation therapy (RT).
STUDY
Within cohort of 539 women diagnosed with DCIS, physicians’ treatment recommendations were captured pre- and post- DCISionRT testing.
SUMMARY
- Post-testing, a change in radiation therapy recommendations were made in 42% of the patients
- When compared with traditional clinicopathologic features used to determine RT recommendations, the DCISionRT result was the factor most strongly associated with radiation therapy recommendations.
PURPOSE
Validation
Determine the utility of DCISionRT Decision Scores to predict ipsilateral breast event risk after breast conserving surgery and the benefit of radiation therapy.
STUDY
183 women had Decision Scores (DS) and outcomes available with a median follow-up of 73 months. 72 of these women received RT (39%) and 66 received endocrine therapy (ET, 36%).
SUMMARY
- After breast conserving surgery, those with a Low DS had a non-significant 2% difference in outcome with and without RT, while those with Elevated DS had a significant 27% benefit from RT.
- Consistent with prior validation studies, DCISionRT upstaged 43% of patients to elevated risk who were previously identified as “low risk” by individual clinical pathology factors (Grade 1/2, size ≤25mm)
PURPOSE
Validation
Investigated the association of DCISionRT® test results with breast cancer mortality (BCM)
STUDY
Case control study identified 96 women who died of breast cancer and 318 controls from a population of 6,964 in Sweden diagnosed with DCIS without microinvasion
SUMMARY
- The DCISionRT score, DS, was significantly associated with breast cancer mortality, while clinicopathologic factors were not.
- High Decision Scores (DS>6) were strongly associated with increased risk for breast cancer mortality (BCM).
- DCISionRT may help to identify women with more aggressive disease that warrants more aggressive upfront treatment
PURPOSE
Validation
Determine the utility of DCISionRT in reclassifying patients who met RTOG 9804 or ECOG-ACRIN E5194 ‘low-risk’ clinicopathologic criteria but remained at elevated invasive risk after BCS and benefited from RT.
STUDY
Complete biomarker and clinical data for 535 women meeting ‘good risk’ clinicopathologic criteria (negative margins vs wide margins) and 660 women meeting ECOG E5194 grade 1 or 2 criteria
SUMMARY
Outcomes in clinicopathological low-risk DCIS women after breast cancer surgery (BCS):
- DCISionRT Elevated Risk patients had substantial risk of 10-year invasive occurrence
- DS Elevated Risk patients (>3) had significant RT benefit (8-15% absolute difference)
- DS Low RIsk patients (≤3) had minimal RT benefit (1-2% absolute difference)
PURPOSE
Validation
Investigate the change in adjuvant RT recommendation by physicians based on DCISionRT.
STUDY
513 patients from 32 sites in U.S. with DCISionRT testing completed after treatment with breast conserving surgery, but prior to radiation therapy decision.
SUMMARY
- DCISionRT demonstrates high clinical utility by impacting radiation therapy recommendations in 45% of women overall
- Recommendations for RT increased 37% in patients initially recommended to omit RT in clinicopathologic low risk groups
- DCISionRT may help precent over- and under- treatment of DCIS
PURPOSE
Validation
Investigate the change in adjuvant RT recommendation by physicians based on DCISionRT.
STUDY
513 patients from 32 sites in U.S. with DCISionRT testing completed after treatment with breast conserving surgery, but prior to radiation therapy decision.
SUMMARY
- DCISionRT demonstrates high clinical utility by impacting radiation therapy recommendations in 45% of women overall
- Recommendations for RT increased 37% in patients initially recommended to omit RT in clinicopathologic low risk groups
- DCISionRT may help precent over- and under- treatment of DCIS
PURPOSE
Validation
Determine the utility of DCISionRT in reclassifying patients who met RTOG 9804 or ECOG-ACRIN E5194 ‘low-risk’ clinicopathologic criteria but remained at elevated invasive risk after BCS and benefited from RT.
STUDY
Complete biomarker and clinical data for 535 women meeting ‘good risk’ clinicopathologic criteria (negative margins vs wide margins) and 660 women meeting ECOG E5194 grade 1 or 2 criteria
SUMMARY
Outcomes in clinicopathological low-risk DCIS women after breast cancer surgery (BCS):
- DCISionRT Elevated Risk patients had substantial risk of 10-year invasive occurrence
- DS Elevated Risk patients (>3) had significant RT benefit (8-15% absolute difference)
- DS Low RIsk patients (≤3) had minimal RT benefit (1-2% absolute difference)
PURPOSE
Development
Assessment of a poor response-type (RSt) signature with breast conserving surgery to potentially identify women at elevated risk after surgery and radiation.
STUDY
284 eligible patients with biomarker data and 102 received hormone therapy and 233 received radiation therapy. The RSt biosignature was calculated using specific biomarkers scored by board certified pathologists in a CLIA certified laboratory.
SUMMARY
- A new biosignature identified a Poor Response Type in women with early stage invasive breast cancer
- Women with a Poor Response Type had high risk for ispilateral breast events after BCS + RT
- Women with a Good Response Type had an excellent outcome after BCS + RT
PURPOSE
Validation
Assessed discordance of Decision Score (DS) with a variety of clinical factors used to make treatment decisions
STUDY
De-identified datasets totaling 1,797 women grouped by age, tumor size, nuclear grade and RTOG 9804-like criteria
SUMMARY
- Clinicopathologic factors have limited utility to true low risk group
- 48% of women under the age of 50 are Low Risk by DCISionRT
- 48% of women with low to intermediate grade are Elevated Risk by DCISionRT
PURPOSE
Validation
Independent clinical validation of DCISionRT after breast conserving surgery in a Kaiser Permanente NW population
STUDY
455 health plan members of Kaiser Permanente Northwest diagnosed with DCIS and treated with BCS or BCS+RT from 1990-2007
SUMMARY
- The continuous and categorical DS was prognostic for both TotBE and InvBE risk after adjusting for RT
- Further reinforces DCISionRT’s ability to correctly reclassify patients into Low (42%) and Elevated risk (58%) groups
- Low Risk Group had a minimal (2%) benefit from RT (10-yr invasive risk BCS: 5%, BCS+RT: 3%)
- DCISionRT reclassifies 49% of RTOG 9804 “good risk” patients as Elevated Risk patients
- >70% risk reduction from RT in Elevated Group for invasive breast events
PURPOSE
Validation
External analysis of the cost-effectiveness of the DCISionRT test to guide treatment of DCIS
STUDY
Used a Markov model simulating 10-year outcomes for 60-year old women with DCIS based on non-randomized data.
SUMMARY
- When compared to giving RT to all women with DCIS, the use of DCISionRT to guide the decision for RT was cost-effective and minimized the number of women undergoing RT per future ipsilateral breast event.
PURPOSE
Development
A radiation-response type (RRT) biosignature for elevated risk lesions was developed with a first cohort and validated in a second cohort for differential response to RT.
STUDY
Two observational cohorts of patients treated with and without whole breast RT after Breast Conserving Surgery (BCS) were consecutively collected in Sweden (1986-2004) and the USA (1999-2008).
SUMMARY
- A new biosignature identified a subset of women with DCIS at high risk for ipsilateral breast events after BCS + RT.
- A subset of women with grade 3 tumors and HER2+ had a poor response type.
- Women with a good response type had a substantial apparent benefit from RT.
PURPOSE
Validation
A post-market decision impact registry study is being conducted to assess the impact of DCISionRT score (DS) in changing treatment recommendations for women diagnosed with pure DCIS.
STUDY
This is a planned interim analysis of the study with the first 532 patients with complete data from 32 sites.
SUMMARY
- This second PREDICT interim analysis demonstrates a significant net change in RT recommendation based on DCISionRT.
- Treatment recommendations were changed post-assay in 45% of women for RT and 15% of women for HT.
- The integration of DCISionRT into clinical-decision processes will enable clinicians and patients to identify optimal treatments while preventing over- or under-treatment.
PURPOSE
Validation
The PREDICT Registry is a prospective cohort study for patients diagnosed with ductal carcinoma in situ (DCIS) of the breast.
STUDY
The primary objective of the study is to create a deidentified database of patients, test results, treatment decisions and outcomes that can be queried to determine the utility of the DCISionRT test in the diagnosis and treatment of ductal carcinoma in situ of the breast.
SUMMARY
- The PREDICT Study has consented 747 women with 458 consented in 2019. There are 42 sites enrolled and an additional 25 sites pending activation.
- The aim of PREDICT is to activate up to 100 sites and consent 2,500 patients diagnosed with DCIS.
PURPOSE
Validation
The PREDICT Registry is a prospective cohort study for patients diagnosed with ductal carcinoma in situ (DCIS) of the breast.
STUDY
The primary objective of the study is to create a deidentified database of patients, test results, treatment decisions and outcomes that can be queried to determine the utility of the DCISionRT test in the diagnosis and treatment of ductal carcinoma in situ of the breast.
SUMMARY
- The PREDICT Study has consented 747 women with 458 consented in 2019. There are 42 sites enrolled and an additional 25 sites pending activation.
- The aim of PREDICT is to activate up to 100 sites and consent 2,500 patients diagnosed with DCIS.
PURPOSE
Development
To develop a biologic signature for 10-year ipsilateral invasive breast events in luminal stage 1 breast cancer patients treated with BCS with or without adjuvant RT.
STUDY
Studied a cohort of 423 patients from Sweden diagnosed with Stage 1 breast cancer between 1987 and 2004. Treatment was neither randomized nor strictly rules based.
SUMMARY
- The biologic risk signature identified subgroups of patients with early-stage breast cancer who will benefit from RT.
- For patients with luminal breast cancer, the biologic signature provided both prognostic and predictive value for benefit from adjuvant RT.
PURPOSE
Development
To develop a biologic signature for 10-year ipsilateral invasive breast events in luminal stage 1 breast cancer patients treated with BCS with or without adjuvant RT.
STUDY
Studied a cohort of 423 patients from Sweden diagnosed with Stage 1 breast cancer between 1987 and 2004. Treatment was neither randomized nor strictly rules based.
SUMMARY
- The biologic risk signature identified subgroups of patients with early-stage breast cancer who will benefit from RT.
- For patients with luminal breast cancer, the biologic signature provided both prognostic and predictive value for benefit from adjuvant RT.
PURPOSE
Validation
A planned early interim analysis of the DCISionRT PREDICT Study, a registry designed to assess the impact of the DCISionRT score (DS) in changing treatment recommendations for women diagnosed with pure DCIS.
STUDY
Analyzed the first 197 patients with complete data from 18 sites across the US.
SUMMARY
- Demonstrated a significant absolute overall change in RT recommendation based on DCISionRT.
- Treatment recommendations were changed post-assay for 51% of women for RT and 13% of women for HT.
- Integration of DCISionRT impacts the clinical decision process as clinicians and patients consider strategies aimed at reducing overtreatment and minimizing undertreatment.
PURPOSE
Validation
A planned early interim analysis of the DCISionRT PREDICT Study, a registry designed to assess the impact of the DCISionRT score (DS) in changing treatment recommendations for women diagnosed with pure DCIS.
STUDY
Analyzed the first 197 patients with complete data from 18 sites across the US.
SUMMARY
- Demonstrated a significant absolute overall change in RT recommendation based on DCISionRT.
- Treatment recommendations were changed post-assay for 51% of women for RT and 13% of women for HT.
- Integration of DCISionRT impacts the clinical decision process as clinicians and patients consider strategies aimed at reducing overtreatment and minimizing undertreatment.
PURPOSE
Validation
A biological signature that calculates an individualized Decision Score (DS) was developed and cross-validated in 526 DCIS patients treated with BCS ± RT. The relationship was assessed between DS and 10-year risk of invasive breast cancer (IBC) or any ipsilateral breast event (IBE), including IBC or DCIS. RT benefit was evaluated by risk group and as a function of DS.
STUDY
The study was conducted on archived tissue samples in collaboration with Uppsala University Hospital and Västmanland County Hospital, Sweden (UUH), the University of Massachusetts, Worcester (UMass). Patients were included consecutively between 1986 and 2004 at UUH and between 1999 and 2008 at UMass. Treatment decisions were neither randomized nor strictly rules-based.
SUMMARY
- The DS was significantly associated with IBC and IBE risk, HR (per 5 units) of 4.2 and 3.1, respectively.
- For patients treated without RT, DS identified a Low Group with 10-year IBC risk of 4% (7% IBE) and an Elevated Risk Group with IBC risk of 15% (23% IBE).
- In analysis of DS and RT by group, the Elevated Risk Group received significant RT benefit, HR of 0.3 for IBC and IBE.
- In a clinicopathologically low-risk subset, DS reclassified 42% of patients into the Elevated Risk Group.
- In an interaction analysis of DS and RT, patients with elevated DS had significant RT benefit over baseline.
PURPOSE
Validation
Validation of predictive biologic profile
STUDY
584 patients. Randomized to BCS or BCS+RT. Prospective-retrospective randomized clinical trial.
SUMMARY
- Predicted RT benefit: Absolute invasive risk reduction.
- Low group = 1% (HR 0.8, p=NS)
- Elevated group = 9% (HR 0.2, p=0.01).
PURPOSE
Validation
The utility of a novel biologic risk profile was compared with weighted clinicopathologic factors.
STUDY
The biologic risk profile was developed in two large female patient cohorts treated with or without radiation therapy (RT) after BCS and subsequently validated in an independent Kaiser Permanente Northwest (KPNW) population treated with BCS and optionally RT.
SUMMARY
- The Biological Risk Profile outperformed clinicopathologic factors for assessing total IBE risk.
- The patients with the highest DCIS Risk Profiles tended to have higher risk clinicopathologic factors.
- The Biological Risk Profile reclassified 59% of patients with multiple low risk clinico–pathologic factors to elevated total risk.
- The Biological Risk Profile reclassified 27% of patients with multiple high risk clinicopathologic factors to low total risk.
PURPOSE
Comparison
Comparison of biologic risk profile to MSKCC
STUDY
999 patients. Biologic risk profile vs. MSKCC weighted clin/path risk.
SUMMARY
- Biologic Risk Profile reclassified 59% of the clin/path low risk group and 27% of the clin/path high risk group
PURPOSE
Development
Early Validation of biologic profile
STUDY
650 patients. BCS & BCS+RT patients.
SUMMARY
- 10-yr total risk after BCS: Low group = 1%, Elevated group = 25%.
- 10-yr total risk after BCS+RT: Low group = 9%, Elevated group = 13%.
PURPOSE
Development
A multi-biomarker prognostic risk assessment was developed using cross-validation modeling within two large patient cohorts treated with and without RT after BCS.
STUDY
Patients were from Uppsala University Hospital (UUH), diagnosed 1986-2004, and University of Massachusetts (UMass), diagnosed 1999-2008, had been treated with BCS with (56%) or without (44%) adjuvant RT.
SUMMARY
- The biomarker-based risk stratification identified patients at risk for invasive ipsilateral breast events in cross-validation.
- Patients with low biomarker based risk had a 10-year invasive recurrence risk without RT that is low and similar to that with RT.
PURPOSE
Development
Biomarkers (p16/INK4A, Ki-67, COX-2, PgR, HER2, FOXA1, SIAH2) were assessed using IHC in FFPE tissue by board certified pathologists.
STUDY
Two recurrence risk signatures were developed, one for invasive and another for overall ipsilateral breast events (IBEs).
SUMMARY
- Over 2/3 of patients had a low risk invasive signature.
- Over 1/3 of patients had a low risk signature for ipsilateral breast events.
- The 10-year recurrence risk was substantially lower for patients with low risk signatures (p<.001, invasive and overall).
- Both algorithms maintained significance when adjusted for nuclear grade, tumor size, age, necrosis and margin status.
- Invasive and overall IBE risks were similar regardless of RT in low risk patients.
- Patients whose risk signatures were not low and had RT had less than half the 10-year recurrence risk of those without RT.
PURPOSE
Development
To develop and blindly validate a multi-marker risk stratification test in DCIS patients treated with BCS.
STUDY
Separate models to predict DCIS and invasive event risk were developed using statistical pattern recognition and modeling methods on UUH patients treated with BCS in the absence of adjuvant therapy (n=200). In addition, an “overall” risk model was created by combining the DCIS and invasive models.
SUMMARY
- This study indicates that the present approach to risk stratification modeling can accurately identify patients at risk for DCIS or invasive events after a primary DCIS diagnosis.
- The models presented here were the basis of a comprehensive multi-marker panel undergoing formal validation.
PURPOSE
Development
Development of biologic profiles
STUDY
329 Patients. BCS & BCS+RT
SUMMARY
- Algorithm identified a low risk group with 8% total recurrence risk at 8 years.
- Phase 1 of risk algorithm development identifies patients at increased risk of invasive breast cancer.
PURPOSE
Discovery
Discovery of biologic profile
STUDY
70 patients.
SUMMARY
- Assessment of Rb & cellular stress response pathways allow early prediction of recurrence.
- Cell line investigation of DCIS progression/recurrence mechanisms.