Multivariable Cox proportional hazard regression analysis of alternative invasive score in relati... more Multivariable Cox proportional hazard regression analysis of alternative invasive score in relation to invasive breast event outcome, overall and by receipt of radiation therapy
Figure S4. Multivariate Analysis of Clinicopathologic and Molecular Factors Excluding Patients wi... more Figure S4. Multivariate Analysis of Clinicopathologic and Molecular Factors Excluding Patients with Positive Margins for 10 Year IBE Risk
Clinical and pathologic characteristics of evaluable KPNW study subjects compared to non-evaluabl... more Clinical and pathologic characteristics of evaluable KPNW study subjects compared to non-evaluable KPNW subjects among eligible study cases
A biologic signature for breast ductal carcinoma in situ
 to predict radiation therapy (RT) ben... more A biologic signature for breast ductal carcinoma in situ
 to predict radiation therapy (RT) benefit and assess recurrence risk
Purpose:A major challenge in ductal carcinoma in situ (DCIS) treatment is selection of the most a... more Purpose:A major challenge in ductal carcinoma in situ (DCIS) treatment is selection of the most appropriate therapeutic approach for individual patients. We conducted an external prospective–retrospective clinical validation of a DCIS biologic risk signature, DCISionRT, in a population-based observational cohort of women diagnosed with DCIS and treated with breast-conserving surgery (BCS).Experimental Design:Participants were 455 health plan members of Kaiser Permanente Northwest diagnosed with DCIS and treated with BCS with or without radiotherapy from 1990 to 2007. The biologic signature combined seven protein tumor markers assessed in formalin-fixed, paraffin-embedded tumor tissue with four clinicopathologic factors to provide a DCISionRT test result, termed decision score (DS). Cox regression and Kaplan–Meier analysis were used to measure the association of the DS, continuous (linear) or categorical (DS ≤ 3 vs. DS > 3), and subsequent total ipsilateral breast events and invas...
Background: For women with ductal carcinoma in situ (DCIS) treated with breast conserving surgery... more Background: For women with ductal carcinoma in situ (DCIS) treated with breast conserving surgery (BCS), the benefit of adjuvant radiation therapy (RT) remains controversial. Since there is level 1 evidence supporting the role of RT in reducing the risk of local recurrence, current guidelines generally recommend RT for all women having BCS even though the absolute benefit is variable. In response to the need for prognostic and predictive tools to better assess risk and RT benefit, a 7-gene predictive biosignature (DCISionRT, PreludeDx, Laguna Hills, CA) was developed. The test provides a validated score (DS) for assessing 10-year risk of recurrence and RT benefit using individual tumor biology, as assessed by clinical and pathologic biomarkers. The primary objective of the PREDICT registries is to understand the decision impact such a tool has on treatment decisions. Prospective Clinical Trial Design: This is a multicenter, prospective, observational registry for women diagnosed wit...
Background: NCCN treatment guidelines support de-escalation of radiotherapy (RT) for “low risk” p... more Background: NCCN treatment guidelines support de-escalation of radiotherapy (RT) for “low risk” patients with ductal carcinoma in situ (DCIS) treated with breast conserving surgery (BCS) for which improved specificity in identifying patients with low in-breast recurrence (IBR) rates who are unlikely to benefit from RT is needed. “low risk” has been defined as the absence of “high risk” clinicopathological (CP) factors, which include younger age (<50 yrs) or tumors that are 2 cm or larger, palpable, or high nuclear grade. However, these CP factors have failed to identify a patient group with lower recurrence risk that do not clinically benefit from RT after BCS. Thus, the clinical utility of a Low Risk group identified by the predictive 7-gene biosignature was characterized overall and for patient subsets meeting “low risk” or “high risk” CP criteria. Methods: DCIS patients (n=926) from four international cohorts treated with BCS (negative margins) with (n=641) and without RT (n=3...
BACKGROUND: The role of radiation therapy (RT) following breast-conserving surgery (BCS) in ducta... more BACKGROUND: The role of radiation therapy (RT) following breast-conserving surgery (BCS) in ductal carcinoma in situ (DCIS) remains controversial. Trials have not identified a low-risk cohort, based on clinicopathologic features, who do not benefit from RT. A biosignature (DCISionRT METHODS: The PREDICT study is a prospective, multi-institutional, observational registry in which patients underwent DCISionRT testing. The primary endpoint was to identify the percentage of patients where testing led to a change in RT recommendations. RESULTS: Overall, 539 women were included in this study. Pre DCISionRT testing, RT was recommended to 69% of patients; however, post-testing, a change in the RT recommendation was made for 42% of patients compared with the pre-testing recommendation; the percentage of women who were recommended RT decreased by 20%. For women initially recommended not to receive an RT pre-test, 35% had their recommendation changed to add RT following testing, while post-tes...
Background: The benefit of adjuvant radiation therapy (RT) for women with ductal carcinoma in sit... more Background: The benefit of adjuvant radiation therapy (RT) for women with ductal carcinoma in situ (DCIS) treated with breast conserving surgery (BCS) remains controversial. Since there is level-I evidence supporting the role of RT in reducing the risk of local recurrence, current guidelines generally recommend adjuvant RT for all women having BCS. However, the absolute benefit of RT is variable in women with DCIS and so it is important to develop prognostic and predictive tools to better assess risk and RT benefit. The DCISionRT Test (PreludeDx, Laguna Hills, CA) is a biologic signature that provides a validated score (DS) for assessing 10-year risk of recurrence and RT benefit using individual tumor biology, as assessed by clinical and pathologic biomarkers. The primary objective of the PREDICT registries is to understand the decision impact such a tool would have on treatment decisions. Prospective Clinical Trial Design: This is a multicenter, prospective, non-interventional (observational) cohort study for women diagnosed with DCIS of the breast. After diagnosis of DCIS, sites will send the most representative tissue block or sections mounted on charged slides to PreludeDx for DCISionRT testing. Treating physicians complete a treatment recommendation survey before and after receiving DCISionRT test results. Test results, treatment recommendations, patient preferences and clinicopathologic features will be stored in a de-identified registry for participating institutions from a variety of geographic regions across Australia. Women will then be followed for up to 10 years with completion of a follow-up form. The study has been approved by the North Shore Local Health District Human Research Ethics Committee, St Leonards, NSW, Australia. Universal Trial Number (UTN): U1111-1266-0439; ANZCTR: ACTRN12621000695808; ClinicalTrials.gov: NCT04916808. Eligibility Criteria: The study includes females age 26 or older who are candidates for BCS and eligible for RT and/or systemic treatment. Subjects must not have been previously treated for DCIS or have previous or current invasive or micro-invasive breast cancer. Specific Aims: The primary endpoints are changes in treatment recommendations for surgical, radiation and hormonal therapy. Secondary endpoints are identification of key drivers for treatment recommendations, including age, size, grade, necrosis, hormone receptor status and patient preference. Statistical Methods: Changes in pre- and post-DCISionRT treatment recommendations will be analyzed using McNemar's test (alpha level = 0.05). Multivariate logistic regression will be used to determine odds ratios of clinicopathologic factors leading to pre- and post-test treatment recommendations. Pre-test covariates include patient age, tumor size, palpability, margin status, hormone receptor status, nuclear grade, tumor necrosis, family history of breast cancer, race, ethnicity and patient preference, as well as physician specialty (surgeons vs. radiation oncologists) and post-test covariates will also include the DCISionRT Decision Score (DS). Differences in recurrence-free and overall survival will be assessed by Kaplan-Meier survival analysis using the log-rank test and/or the Cox Proportional Hazards model. Statistical analyses will be carried out using R (https://www.r-project.org) or SAS. An early interim analysis based on the first 200 enrolled patients is planned. Present and Planned Accrual: We are planning to enroll up to 1,500 women from up to 100 sites across Australia. A similar registry in the US has enrolled 1,985 women from 64 sites towards a goal of 2,500. Citation Format: Yvonne Zissiadis, G Bruce Mann, Steven C Shivers, Troy Bremer. The PREDICT registry Australia: A prospective registry study to evaluate the clinical utility of the DCISionRT test on treatment decisions in patients with DCIS following breast conserving surgery [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-11-01.
Multivariable Cox proportional hazard regression analysis of alternative invasive score in relati... more Multivariable Cox proportional hazard regression analysis of alternative invasive score in relation to invasive breast event outcome, overall and by receipt of radiation therapy
Figure S4. Multivariate Analysis of Clinicopathologic and Molecular Factors Excluding Patients wi... more Figure S4. Multivariate Analysis of Clinicopathologic and Molecular Factors Excluding Patients with Positive Margins for 10 Year IBE Risk
Clinical and pathologic characteristics of evaluable KPNW study subjects compared to non-evaluabl... more Clinical and pathologic characteristics of evaluable KPNW study subjects compared to non-evaluable KPNW subjects among eligible study cases
A biologic signature for breast ductal carcinoma in situ
 to predict radiation therapy (RT) ben... more A biologic signature for breast ductal carcinoma in situ
 to predict radiation therapy (RT) benefit and assess recurrence risk
Purpose:A major challenge in ductal carcinoma in situ (DCIS) treatment is selection of the most a... more Purpose:A major challenge in ductal carcinoma in situ (DCIS) treatment is selection of the most appropriate therapeutic approach for individual patients. We conducted an external prospective–retrospective clinical validation of a DCIS biologic risk signature, DCISionRT, in a population-based observational cohort of women diagnosed with DCIS and treated with breast-conserving surgery (BCS).Experimental Design:Participants were 455 health plan members of Kaiser Permanente Northwest diagnosed with DCIS and treated with BCS with or without radiotherapy from 1990 to 2007. The biologic signature combined seven protein tumor markers assessed in formalin-fixed, paraffin-embedded tumor tissue with four clinicopathologic factors to provide a DCISionRT test result, termed decision score (DS). Cox regression and Kaplan–Meier analysis were used to measure the association of the DS, continuous (linear) or categorical (DS ≤ 3 vs. DS > 3), and subsequent total ipsilateral breast events and invas...
Background: For women with ductal carcinoma in situ (DCIS) treated with breast conserving surgery... more Background: For women with ductal carcinoma in situ (DCIS) treated with breast conserving surgery (BCS), the benefit of adjuvant radiation therapy (RT) remains controversial. Since there is level 1 evidence supporting the role of RT in reducing the risk of local recurrence, current guidelines generally recommend RT for all women having BCS even though the absolute benefit is variable. In response to the need for prognostic and predictive tools to better assess risk and RT benefit, a 7-gene predictive biosignature (DCISionRT, PreludeDx, Laguna Hills, CA) was developed. The test provides a validated score (DS) for assessing 10-year risk of recurrence and RT benefit using individual tumor biology, as assessed by clinical and pathologic biomarkers. The primary objective of the PREDICT registries is to understand the decision impact such a tool has on treatment decisions. Prospective Clinical Trial Design: This is a multicenter, prospective, observational registry for women diagnosed wit...
Background: NCCN treatment guidelines support de-escalation of radiotherapy (RT) for “low risk” p... more Background: NCCN treatment guidelines support de-escalation of radiotherapy (RT) for “low risk” patients with ductal carcinoma in situ (DCIS) treated with breast conserving surgery (BCS) for which improved specificity in identifying patients with low in-breast recurrence (IBR) rates who are unlikely to benefit from RT is needed. “low risk” has been defined as the absence of “high risk” clinicopathological (CP) factors, which include younger age (<50 yrs) or tumors that are 2 cm or larger, palpable, or high nuclear grade. However, these CP factors have failed to identify a patient group with lower recurrence risk that do not clinically benefit from RT after BCS. Thus, the clinical utility of a Low Risk group identified by the predictive 7-gene biosignature was characterized overall and for patient subsets meeting “low risk” or “high risk” CP criteria. Methods: DCIS patients (n=926) from four international cohorts treated with BCS (negative margins) with (n=641) and without RT (n=3...
BACKGROUND: The role of radiation therapy (RT) following breast-conserving surgery (BCS) in ducta... more BACKGROUND: The role of radiation therapy (RT) following breast-conserving surgery (BCS) in ductal carcinoma in situ (DCIS) remains controversial. Trials have not identified a low-risk cohort, based on clinicopathologic features, who do not benefit from RT. A biosignature (DCISionRT METHODS: The PREDICT study is a prospective, multi-institutional, observational registry in which patients underwent DCISionRT testing. The primary endpoint was to identify the percentage of patients where testing led to a change in RT recommendations. RESULTS: Overall, 539 women were included in this study. Pre DCISionRT testing, RT was recommended to 69% of patients; however, post-testing, a change in the RT recommendation was made for 42% of patients compared with the pre-testing recommendation; the percentage of women who were recommended RT decreased by 20%. For women initially recommended not to receive an RT pre-test, 35% had their recommendation changed to add RT following testing, while post-tes...
Background: The benefit of adjuvant radiation therapy (RT) for women with ductal carcinoma in sit... more Background: The benefit of adjuvant radiation therapy (RT) for women with ductal carcinoma in situ (DCIS) treated with breast conserving surgery (BCS) remains controversial. Since there is level-I evidence supporting the role of RT in reducing the risk of local recurrence, current guidelines generally recommend adjuvant RT for all women having BCS. However, the absolute benefit of RT is variable in women with DCIS and so it is important to develop prognostic and predictive tools to better assess risk and RT benefit. The DCISionRT Test (PreludeDx, Laguna Hills, CA) is a biologic signature that provides a validated score (DS) for assessing 10-year risk of recurrence and RT benefit using individual tumor biology, as assessed by clinical and pathologic biomarkers. The primary objective of the PREDICT registries is to understand the decision impact such a tool would have on treatment decisions. Prospective Clinical Trial Design: This is a multicenter, prospective, non-interventional (observational) cohort study for women diagnosed with DCIS of the breast. After diagnosis of DCIS, sites will send the most representative tissue block or sections mounted on charged slides to PreludeDx for DCISionRT testing. Treating physicians complete a treatment recommendation survey before and after receiving DCISionRT test results. Test results, treatment recommendations, patient preferences and clinicopathologic features will be stored in a de-identified registry for participating institutions from a variety of geographic regions across Australia. Women will then be followed for up to 10 years with completion of a follow-up form. The study has been approved by the North Shore Local Health District Human Research Ethics Committee, St Leonards, NSW, Australia. Universal Trial Number (UTN): U1111-1266-0439; ANZCTR: ACTRN12621000695808; ClinicalTrials.gov: NCT04916808. Eligibility Criteria: The study includes females age 26 or older who are candidates for BCS and eligible for RT and/or systemic treatment. Subjects must not have been previously treated for DCIS or have previous or current invasive or micro-invasive breast cancer. Specific Aims: The primary endpoints are changes in treatment recommendations for surgical, radiation and hormonal therapy. Secondary endpoints are identification of key drivers for treatment recommendations, including age, size, grade, necrosis, hormone receptor status and patient preference. Statistical Methods: Changes in pre- and post-DCISionRT treatment recommendations will be analyzed using McNemar's test (alpha level = 0.05). Multivariate logistic regression will be used to determine odds ratios of clinicopathologic factors leading to pre- and post-test treatment recommendations. Pre-test covariates include patient age, tumor size, palpability, margin status, hormone receptor status, nuclear grade, tumor necrosis, family history of breast cancer, race, ethnicity and patient preference, as well as physician specialty (surgeons vs. radiation oncologists) and post-test covariates will also include the DCISionRT Decision Score (DS). Differences in recurrence-free and overall survival will be assessed by Kaplan-Meier survival analysis using the log-rank test and/or the Cox Proportional Hazards model. Statistical analyses will be carried out using R (https://www.r-project.org) or SAS. An early interim analysis based on the first 200 enrolled patients is planned. Present and Planned Accrual: We are planning to enroll up to 1,500 women from up to 100 sites across Australia. A similar registry in the US has enrolled 1,985 women from 64 sites towards a goal of 2,500. Citation Format: Yvonne Zissiadis, G Bruce Mann, Steven C Shivers, Troy Bremer. The PREDICT registry Australia: A prospective registry study to evaluate the clinical utility of the DCISionRT test on treatment decisions in patients with DCIS following breast conserving surgery [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-11-01.
Uploads
Papers by Troy Bremer