NBRST: Prospective Neo-adjuvant REGISTRY Trial (NBRST)

Prospective Neo-adjuvant REGISTRY Trial Linking MammaPrint, Subtyping and Treatment Response: Neoadjuvant Breast Registry - Symphony Trial (NBRST) (Pronounced "in Breast")

The scope of this registry study is to measure chemosensitivity as defined by pCR (primary endpoint), or endocrine sensitivity as defined by partial response (decrease in longest tumor diameter or residual cancer burden category 1 (RCB1), a primary endpoint for neo-adjuvant endocrine therapy and a secondary endpoint for neoadjuvant chemotherapy), metastasis-free survival and relapse-free survival(secondary endpoints) in molecular subgroups, determined by the established MammaPrint, BluePrint, Targetprint and Theraprint profiles in addition to possible novel expression profiles.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Other: MammaPrint 70-gene expression profile; Other: BluePrint 80 gene expression profile

Detailed Description

This will be a prospective observational, case-only study linking MammaPrint, BluePrint, TargetPrint, TheraPrint and possible additional profiles of interest to treatment response and Distant Metastases Free Survival (DMFS) and Relapse Free Survival (RFS). Only patients who receive neo-adjuvant therapy can participate.

For this project, approximately 50-70 institutions in the US will be invited to contribute clinical patient data from enrolled patients after a MammaPrint, TargetPrint, BluePrint and TheraPrint test has been successfully performed and the patient has started neo-adjuvant therapy.

Treatment is at the discretion of the physician, adhering to NCCN approved regimens or a recognized alternative.

The clinical data is to be entered online at 4 time points; amounting to four Case Report Forms (CRFs). Data will be collected on an ongoing basis, the first CRF must be completed within 6 weeks after the MammaPrint, BluePrint, TargetPrint, and TheraPrint result was provided. The second CRF should be completed 4 weeks after definitive surgery. CRF 3 and CRF4 will be completed 2-3 and 5 years after surgery.

It is expected that we will enroll around 1000 patients in 4 years.

OBJECTIVES

• Measure chemosensitivity (as defined by pCR) or endocrine sensitivity (as defined by decrease in longest tumor diameter or RCB1)in the molecular subgroups as determined by combining MammaPrint and BluePrint results.
• Correlate chemosensitivity (as defined by pCR) to TheraPrint Therapy Gene Assay results.
• Compare local IHC and FISH results (if available) with TargetPrint results. Compare the three BluePrint molecular subgroups with IHC-based subtype classification.
• Document impact of MammaPrint, TargetPrint and BluePrint result on treatment decision.
• Assess the 2-3 and 5 years DMFS and RFS for the different molecular subgroups.
• Measure chemosensitivity or endocrine sensitivity correlation with novel expression profiles.

• Study Type: Observational
• Enrollment (Actual): 1142

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Arizona Center for Cancer Care
    • Scottsdale, Arizona, United States, 85251
      • 21 Century Oncology
  • California
    • Berkeley, California, United States, 94705
      • Alta Bates Summit Comprehensive Cancer Center
    • Fresno, California, United States, 93710
      • Fresno Breast Surgery
    • Long Beach, California, United States, 90806
      • Long Beach Memorial Medical Center
    • Long Beach, California, United States, 90806
      • BreastLink
    • Monterey, California, United States, 93940
      • Community Hospital of Monterey Peninsula
    • Oakland, California, United States, 94609
      • Alta Bates
    • Palm Springs, California, United States
      • Comprehensive Cancer Center - Palm Springs
    • Roseville, California, United States, 95661
      • Sutter Roseville Medical Center
    • San Diego, California, United States
      • Sharp Memorial
    • Santa Rosa, California, United States
      • Redwood Regional
    • West Hills, California, United States, 91307
      • Wellness Oncology Hematology
    • West Hills, California, United States
      • Wellness Oncology Hematology
  • Colorado
    • Denver, Colorado, United States, 80218
      • Exempla Health St Joseph
  • Connecticut
    • Greenwich, Connecticut, United States, 06830
      • Greenwich Hospital
    • Stamford, Connecticut, United States, 06902
      • Stamford Hospital
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Florida Hospital Memorial Medical Center
    • Daytona Beach, Florida, United States, 32114
      • Halifax Health Center for Oncology
    • Fort Myers, Florida, United States, 33907
      • 21st Century Oncology
    • Jacksonville, Florida, United States, 322004
      • St. Vincent Healthcare
    • Lake Worth, Florida, United States, 33461
      • The Breast Institute at JFK Medical Center
    • Miami, Florida, United States, 33183
      • Baptist Health South Florida
    • Miami Lakes, Florida, United States, 33014
      • Lakes Research
  • Georgia
    • Decatur, Georgia, United States
      • Dekalb Medical
    • Gainesville, Georgia, United States, 30501
      • Northeast Georgia Medical Center
    • Savannah, Georgia, United States, 31404
      • Center for Breast Care
  • Illinois
    • Bloomingdale, Illinois, United States, 60108
      • Advanced Breast Care Specialists
    • Elk Grove Village, Illinois, United States, 60007
      • University Surgical Consultants
    • Park Ridge, Illinois, United States, 60068
      • Advocate Lutheran General Hospital
    • Skokie, Illinois, United States, 60076
      • Hematology/Oncology of the North Shore
  • Indiana
    • Evansville, Indiana, United States, 47710
      • Evansville Surgical Associates
    • South Bend, Indiana, United States, 46601
      • Northern Indiana Cancer Research
  • Louisiana
    • Shreveport, Louisiana, United States, 71103
      • Willis-Knighton Cancer Center
  • Maryland
    • Lanham, Maryland, United States, 20706
      • Signature Breast Care
  • Michigan
    • Burton, Michigan, United States, 48509
      • McLaren Health Care
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Great Lakes Cancer Management Specialists
    • Southfield, Michigan, United States, 48075
      • Providence Cancer Institute
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • St Lukes Cancer Center
    • Saint Louis, Missouri, United States, 63136
      • Christian Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Compehensive Cancer Care of Nevada
  • New Jersey
    • Willingboro, New Jersey, United States, 08046
      • Virtua Health
  • New York
    • Cortlandt Manor, New York, United States, 10567
      • Ashikari Breast Center
    • East Syracuse, New York, United States, 13057
      • Hematology Oncology Associates of Central New York
    • Flushing, New York, United States, 11355
      • Theresa & Eugene M. Lang Research Center
  • Ohio
    • Akron, Ohio, United States, 44302
      • Akron General Hospital
    • Toledo, Ohio, United States, 43614
      • University of Toledo
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18104
      • Breast Care Specialists
    • Kittanning, Pennsylvania, United States, 16201
      • ACMH Cancer Center
    • Langhorne, Pennsylvania, United States, 19047
      • St. Mary Medical Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Pittsburgh, Pennsylvania, United States, 15243
      • St. Clair Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • The Breast Place
    • Charleston, South Carolina, United States, 29414
      • Cancer Specialists of Charleston
    • Murrells Inlet, South Carolina, United States, 29576
      • Coastal Carolina Breast Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Nashville Breast Center
  • Texas
    • Amarillo, Texas, United States
      • Texas Tech University
    • Austin, Texas, United States, 78303
      • Austin Cancer Center
    • Dallas, Texas, United States, 75230
      • Dallas Surgical Group
    • Dallas, Texas, United States, 75230
      • Texas Health
    • Edinburg, Texas, United States
      • McAllen Oncology
    • Houston, Texas, United States, 77396
      • East Houston General Surgery
    • San Antonio, Texas, United States, 78205
      • Kathryn A. Wagner Private Practice
    • San Antonio, Texas, United States
      • Radiation Oncology of San Antonio
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Virginia Breast Care
    • Harrisonburg, Virginia, United States, 22801
      • Rockingham Memorial Hospital
    • Lynchburg, Virginia, United States, 24501
      • Lynchburg Hematology Oncology Clinic
    • Midlothian, Virginia, United States, 23114
      • Bon Secours Virginia Breast Center
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute
    • Spokane, Washington, United States, 99216
      • Rockwood Clinic
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54313
      • Bellin Hospital
    • Milwaukee, Wisconsin, United States, 53211
      • Columbia St. Marys Cancer Center
    • Waukesha, Wisconsin, United States, 53188
      • Waukesha Memorial Hospital
    • Wauwatosa, Wisconsin, United States, 53226
      • Wheaton Franciscan Healthcare

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Women with histologically proven breast cancer, who have started or are scheduled to start neo-adjuvant chemotherapy therapy or neo-adjuvant hormone therapy.

Description

Inclusion Criteria:

• Women with histologically proven breast cancer, who have started or are scheduled to start neo-adjuvant chemotherapy therapy or neo-adjuvant hormone therapy, after successful MammaPrint assay
• Age 18-90
• Written informed consent

Exclusion Criteria:

• Patients who have had excisional biopsy or axillary dissection Patients with confirmed distant metastatic disease
• Tumor sample shipped to Agendia with ≤ 30% tumor cells or that fails QA or QC criteria
• Patients who have had any prior chemotherapy, radiotherapy, or endocrine therapy for the treatment of breast cancer
• Any serious uncontrolled intercurrent infections, or other serious uncontrolled concomitant disease

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
MammaPrint, BluePrint, neo-adj CT or HT; All patients receive the MammaPrint and BluePrint gene expression profile. Treatment at the discretion of the physician while adhering to NCCN guidelines.	Other: MammaPrint 70-gene expression profile; Other: BluePrint 80 gene expression profile

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chemosensitivity as defined by pCR	For neo-adjuvant chemotherapy patients the primary endpoint is pathological complete response (pCR) which is defined as the absence of invasive carcinoma in both the breast and axilla at microscopic examination of the resection specimen, regardless of the presence of carcinoma in situ. The response rate and corresponding confidence intervals will be presented as a proportion of all patients enrolled. Comparison of response rates between different molecular subgroups will be conducted using Pearson Chi-square test.	Up to 6 months
Endocrine sensitivity as defined by partial response (decrease in longest tumor diameter or residual cancer burden category 1 (RCB1)	The primary endpoint for patients with neo-adjuvant hormonal therapy is partial response which is defined as decrease in longest tumor diameter. The response rate and corresponding confidence intervals will be presented as a proportion of all patients enrolled. Comparison of response rates between different molecular subgroups will be conducted using Pearson Chi-square test.	Up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlate chemosensitivity (as defined by pCR) to TheraPrint Therapy Gene Assay results.	Correlation of chemosensitivity and endocrine sensitivity (as defined by pCR) to TheraPrint Therapy Gene Assay results will be determined using Pearson correlation and linear fit models.	Up to 6 months.
Assess metastasis-free survival and relapse-free survival in molecular subgroups, determined by the established MammaPrint, BluePrint, profiles.	Kaplan-Meier curves for DMFS will be calculated for the following eight subgroups; Luminal subtype; ERBB2 subtype; Basal subtype; Luminal subtype and high risk MammaPrint; Luminal subtype and low risk MammaPrint; ERBB2 subtype and high risk MammaPrint; ERBB2 subtype and low risk MammaPrint	At -2-3 years and 5 years after definitive surgery.
Compare local IHC and FISH results (if available) with TargetPrint results.	Correlation of TargetPrint ER, PR, and HER2 microarray readout with IHC/FISH assessment will be determined using Pearson correlation and linear fit models. Agreement measurements between binary microarray and IHC classifications will be based on 2-way contingency table analysis and include overall concordance, positive agreement defined as the number of samples classified positive by both IHC and TargetPrint divided by the number of positive samples using IHC, negative agreement and Cohen's Kappa coefficient score.	Baseline; before start of neo-adjuvant therapy.
Compare the three BluePrint molecular subgroups with IHC-based subtype classification.	Correlation of BluePrint molecular subgroup microarray readout with IHC-based subtype classification.	Baseline; before start of neo-adjuvant therapy.
Document impact of MammaPrint, TargetPrint and BluePrint result on treatment decision.	Review the impact of MammaPrint, TargetPrint, and BluePrint on physician treatment decisions.	Baseline; before start neo-adjuvant therapy.

Collaborators and Investigators

• Sponsor: Agendia
• Investigators: Principal Investigator: Stephanie Akbari, MD, Reinsch Pierce Family Center for Breast Health; Principal Investigator: Mark Gittleman, MD, Breast Care Specialists

Publications and helpful links

General Publications

• Whitworth PW, Beitsch PD, Murray MK, Richards PD, Mislowsky A, Dul CL, Pellicane JV, Baron PL, Rahman RL, Lee LA, Dupree BB, Kelemen PR, Ashikari AY, Budway RJ, Lopez-Penalver C, Dooley W, Wang S, Dauer P, Menicucci AR, Yoder EB, Finn C, Blumencranz LE, Audeh W. Genomic Classification of HER2-Positive Patients With 80-Gene and 70-Gene Signatures Identifies Diversity in Clinical Outcomes With HER2-Targeted Neoadjuvant Therapy. JCO Precis Oncol. 2022 Sep;6:e2200197. doi: 10.1200/PO.22.00197.
• Whitworth PW, Beitsch PD, Pellicane JV, Baron PL, Lee LA, Dul CL, Murray MK, Gittleman MA, Budway RJ, Rahman RL, Kelemen PR, Dooley WC, Rock DT, Cowan KH, Lesnikoski BA, Barone JL, Ashikari AY, Dupree BB, Wang S, Menicucci AR, Yoder EB, Finn C, Corcoran K, Blumencranz LE, Audeh W; NBRST Investigators Group. Distinct Neoadjuvant Chemotherapy Response and 5-Year Outcome in Patients With Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Tumors That Reclassify as Basal-Type by the 80-Gene Signature. JCO Precis Oncol. 2022 Apr;6(1):e2100463. doi: 10.1200/PO.21.00463.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (ACTUAL): January 1, 2015
• Study Completion (ACTUAL): January 1, 2021

Study Registration Dates

• First Submitted: November 18, 2011
• First Submitted That Met QC Criteria: November 22, 2011
• First Posted (ESTIMATE): November 24, 2011

Study Record Updates

• Last Update Posted (ACTUAL): January 19, 2021
• Last Update Submitted That Met QC Criteria: January 14, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: neo adjuvant, breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: P0339 NBRST Registry