Clinical trial NCT01805076: MRI and Mammography Before Surgery in Patients With Stage I-II Breast Cancer
Official title: Effect of Preoperative Breast MRI on Surgical Outcomes, Costs and Quality of Life of Women With Breast Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Estrogen Receptor-negative Breast Cancer
Progesterone Receptor-negative Breast Cancer
Stage IA Breast Cancer
Stage IB Breast Cancer
Stage II Breast Cancer
Triple-negative Breast Cancer
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: American College of Radiology Imaging Network
First posted: 2013-03-06
Enrollment: 317
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: The purpose of this study is to test whether patients undergoing a breast MRI (magnetic resonance imaging) before breast surgery will have better results after the surgery. Breast tumors are routinely evaluated using mammograms and ultrasound before surgery. This study would like to find out if using MRI in addition to mammography before surgery improves our ability to evaluate tumors and decide what kind of surgery is best for the patient.

Detailed description: This is a randomized trial of preoperative breast MRI in patients deemed eligible for breast conserving surgery by conventional clinical criteria will provide important information about the clinical and biologic relevance of occult disease identified by MRI alone. Patients will be assigned to standard pre-operative breast cancer disease assessment without the addition of MRI prior to breast conserving surgery or standard pre-operative breast cancer disease assessment with the use of MRI prior to breast conserving surgery.

The primary objective is to compare the rates of local-regional recurrence (LRR) following attempted breast conserving therapy in a cohort of women with triple negative or HER-2 amplified breast cancer randomized to preoperative staging with mammography (control arm) or mammography plus breast MRI (MRI arm).

Secondary objectives are:

* To compare the re-operation rates following attempted breast conserving therapy between women assessed preoperatively with breast MRI to those assessed without the use of breast MRI
* To compare local recurrence rates between women who undergo BCT on the control arm to women who undergo BCT on the MRI arm
* To compare the conversion rate to mastectomy secondary to persistent positive margins or poor cosmesis within the first 6 months of attempting BCT (prior to the administration of RT) between women assessed preoperatively with breast MRI to those assessed without the use of breast MRI
* To compare the contralateral breast cancer rates in women randomized to preoperative breast MRI to those not receiving pre-operative breast MRI
* To compare the disease-free survival rates between women assessed preoperatively with breast MRI to those assessed without the use of breast MRI
* To compare breast cancer specific and overall survival outcomes of women assessed preoperatively with breast MRI to those assessed without the use of breast MRI
* To estimate the rate of MRI-guided localization assisted surgery
* To estimate the rate of multi-centric disease in the index breast for women in the MRI arm
* To evaluate the accuracy of index lesion characteristics and other factors in predicting multi-centricity in the cohort randomized to breast MRI
* To assess the positive predictive values (PPV) of MRI in detecting ipsilateral multi-centric disease and contralateral disease in women with breast cancer undergoing preoperative breast MRI
* To estimate the false positive rate for detection of multiple foci of breast cancer by MRI

All registered patients will be monitored for relapse and survival for 5 years from the date of surgery. Patients will be followed a minimum of every 4 months for the first 2 years from diagnosis and a minimum of every 6 months during years 3-5. Patients will be monitored for local, regional, distant relapse and vital status.

Eligibility criteria: * Female. Men are excluded from this study because the number of men with breast cancer is insufficient to provide a statistical basis for assessment of effects in this subpopulation of people with breast cancer.
* Pathologically confirmed diagnosis of breast cancer, clinical stage I-II (T1-3 N0 M0, T0-2 N1 M0). Diagnosis must be by needle biopsy; patients diagnosed by surgical excision are excluded.
* Patients must have either:

  * Estrogen receptor (ER) negative/progesterone receptor (PR) negative (\< 10% by immunohistochemistry IHC staining) and HER-2 negative breast cancer OR
  * ER negative/PR negative (\< 10% by IHC staining) and HER-2 positive tumors
  * HER-2 status will be determined as per the 2013 ASCO CAP guidelines:

    * HER-2 is considered positive if there is IHC 3+ staining or ISH positive using either single probe ISH or dual probe ISH
    * HER-2 is considered negative if there is IHC 0 or 1+ staining or ISH negative using either single probe ISH or dual probe ISH
* No patients with previous ipsilateral invasive breast cancer or ductal carcinoma in situ (DCIS)
* No patients with bilateral breast cancer
* No patients with known deleterious mutations in breast cancer (BRCA) genes
* No current history of receiving hormonal therapy, tamoxifen, and or aromatase inhibitors for therapeutic measures
* No history of chemotherapy for cancer within 6 months prior to registration
* No patients scheduled to receive neoadjuvant chemotherapy or partial breast irradiation following breast conserving surgery
* Eligible for BCT based on clinical examination, mammography and, if standard practice at a given institution, ultrasound and/or tomogram. Women who cannot be appropriately selected for BCT based on these standard imaging studies, and for whom additional imaging is recommended to clarify local disease extent, will not be eligible for this trial.
* No patients with multicentric or multifocal disease scheduled to undergo multiple lumpectomies. Multifocal disease that can be encompassed in a single operative bed can be enrolled.
* Suitable to undergo MRI and receive the contrast agent gadolinium (exclusions follow):

  * No history of untreatable claustrophobia
  * No presence of metallic objects or implanted medical devices in body (i.e., cardiac pacemaker, aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants)
  * No history of sickle cell disease
  * No contraindication to intravenous contrast administration
  * No known allergy-like reaction to gadolinium or moderate or severe allergic reactions to one or more allergens as defined by the American College of Radiology (ACR); patient may be eligible if willing to undergo pre-treatment as defined by the institution's policy and/or ACR guidance
  * No findings consistent with renal failure, as determined by glomerular filtration rate (GFR) \< 30 mL/min/1.73 m\^2 based on a creatinine level obtained within 28 days prior to registration
  * Weight lower than that allowable by the MRI table
* No prior MRI of study breast within the 12 months prior to registration
* Non-pregnant and non-lactating. Patients of child-bearing potential must have a negative pregnancy test within 7 days prior to registration. Perimenopausal patients must be amenorrheic \> 12 months to be considered not of child-bearing potential
* ≥ 18 years of age
* Signed study-specific informed consent prior to registration

Primary outcomes:
measure: Local-regional recurrence (LRR)
timeFrame: Up to 5 years
Secondary outcomes:
measure: Re-operation rate
timeFrame: Up to 5 years
measure: Conversion rate to mastectomy secondary to persistent positive margins or poor cosmesis
timeFrame: Within the first 6 months
measure: Time to contralateral breast cancer
timeFrame: Up to 5 years post-randomization
measure: Disease-free survival (DFS)
timeFrame: Up to 5 years post-randomization
measure: Overall survival
timeFrame: Up to 5 years post-randomization
measure: Breast cancer specific survival will be measured
timeFrame: Up to 5 years post-randomization
measure: Rate of MRI-guided localization assisted surgery (Arm B)
timeFrame: Up to 5 years
measure: False positive rate for MRI detection of multiple disease foci
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Jonesboro
country: United States
facility: Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
state: Arkansas
city: Antioch
country: United States
facility: Kaiser Permanente-Deer Valley Medical Center
state: California
city: Chico
country: United States
facility: Enloe Medical Center
state: California
city: Emeryville
country: United States
facility: Bay Area Breast Surgeons Inc
state: California
city: Emeryville
country: United States
facility: Epic Care Partners in Cancer Care
state: California
city: Fremont
country: United States
facility: Kaiser Permanente-Fremont
state: California
city: Fresno
country: United States
facility: Kaiser Permanente-Fresno
state: California
city: Los Angeles
country: United States
facility: USC / Norris Comprehensive Cancer Center
state: California
city: Martinez
country: United States
facility: Contra Costa Regional Medical Center
state: California
city: Modesto
country: United States
facility: Kaiser Permanente-Modesto
state: California
city: Oakland
country: United States
facility: Bay Area Tumor Institute
state: California
city: Oakland
country: United States
facility: Kaiser Permanente-Oakland
state: California
city: Orange
country: United States
facility: Saint Joseph Hospital - Orange
state: California
city: Orange
country: United States
facility: UC Irvine Health/Chao Family Comprehensive Cancer Center
state: California
city: Redwood City
country: United States
facility: Kaiser Permanente-Redwood City
state: California
city: Richmond
country: United States
facility: Kaiser Permanente-Richmond
state: California
city: Roseville
country: United States
facility: Kaiser Permanente-Roseville
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente-South Sacramento
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente - Sacramento
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente-San Francisco
state: California
city: San Jose
country: United States
facility: Kaiser Permanente-Santa Teresa-San Jose
state: California
city: San Leandro
country: United States
facility: Kaiser Permanente San Leandro
state: California
city: San Rafael
country: United States
facility: Kaiser Permanente-San Rafael
state: California
city: San Rafael
country: United States
facility: Kaiser San Rafael-Gallinas
state: California
city: Santa Clara
country: United States
facility: Kaiser Permanente Medical Center - Santa Clara
state: California
city: Santa Rosa
country: United States
facility: Kaiser Permanente-Santa Rosa
state: California
city: South San Francisco
country: United States
facility: Kaiser Permanente-South San Francisco
state: California
city: Stockton
country: United States
facility: Kaiser Permanente-Stockton
state: California
city: Vacaville
country: United States
facility: Kaiser Permanente Medical Center-Vacaville
state: California
city: Vallejo
country: United States
facility: Kaiser Permanente-Vallejo
state: California
city: Walnut Creek
country: United States
facility: Kaiser Permanente-Walnut Creek
state: California
city: Derby
country: United States
facility: Smilow Cancer Hospital-Derby Care Center
state: Connecticut
city: Fairfield
country: United States
facility: Smilow Cancer Hospital Care Center-Fairfield
state: Connecticut
city: Guilford
country: United States
facility: Smilow Cancer Hospital Care Center - Guiford
state: Connecticut
city: Hartford
country: United States
facility: Smilow Cancer Hospital Care Center at Saint Francis
state: Connecticut
city: New Haven
country: United States
facility: Smilow Cancer Center/Yale-New Haven Hospital
state: Connecticut
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: North Haven
country: United States
facility: Yale-New Haven Hospital North Haven Medical Center
state: Connecticut
city: Trumbull
country: United States
facility: Smilow Cancer Hospital Care Center-Trumbull
state: Connecticut
city: Waterford
country: United States
facility: Smilow Cancer Hospital Care Center - Waterford
state: Connecticut
city: Newark
country: United States
facility: Helen F Graham Cancer Center
state: Delaware
city: Newark
country: United States
facility: Christiana Care Health System-Christiana Hospital
state: Delaware
city: Jacksonville
country: United States
facility: Baptist MD Anderson Cancer Center
state: Florida
city: Decatur
country: United States
facility: Dekalb Medical Center
state: Georgia
city: Savannah
country: United States
facility: Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
state: Georgia
city: Boise
country: United States
facility: Saint Alphonsus Cancer Care Center-Boise
state: Idaho
city: Coeur d'Alene
country: United States
facility: Kootenai Health - Coeur d'Alene
state: Idaho
city: Post Falls
country: United States
facility: Kootenai Clinic Cancer Services - Post Falls
state: Idaho
city: Arlington Heights
country: United States
facility: Northwest Community Hospital
state: Illinois
city: Carbondale
country: United States
facility: Memorial Hospital of Carbondale
state: Illinois
city: Chicago
country: United States
facility: University of Illinois
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Chicago
country: United States
facility: Advocate Illinois Masonic Medical Center
state: Illinois
city: Evanston
country: United States
facility: NorthShore University HealthSystem-Evanston Hospital
state: Illinois
city: Glenview
country: United States
facility: NorthShore University HealthSystem-Glenbrook Hospital
state: Illinois
city: Harvey
country: United States
facility: Ingalls Memorial Hospital
state: Illinois
city: Highland Park
country: United States
facility: NorthShore University HealthSystem-Highland Park Hospital
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Naperville
country: United States
facility: Edward Hospital/Cancer Center
state: Illinois
city: Park Ridge
country: United States
facility: Advocate Lutheran General Hospital
state: Illinois
city: Plainfield
country: United States
facility: Edward Hospital/Cancer Center?Plainfield
state: Illinois
city: Springfield
country: United States
facility: Memorial Medical Center
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center
state: Illinois
city: Avon
country: United States
facility: IU Health West Hospital
state: Indiana
city: Carmel
country: United States
facility: IU Health North Hospital
state: Indiana
city: Elkhart
country: United States
facility: Elkhart Clinic
state: Indiana
city: Elkhart
country: United States
facility: Michiana Hematology Oncology PC-Elkhart
state: Indiana
city: Fort Wayne
country: United States
facility: Parkview Hospital Randallia
state: Indiana
city: Fort Wayne
country: United States
facility: Parkview Regional Medical Center
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University/Melvin and Bren Simon Cancer Center
state: Indiana
city: Mishawaka
country: United States
facility: Michiana Hematology Oncology PC-Mishawaka
state: Indiana
city: Munster
country: United States
facility: The Community Hospital
state: Indiana
city: Plymouth
country: United States
facility: Michiana Hematology Oncology PC-Plymouth
state: Indiana
city: South Bend
country: United States
facility: Memorial Hospital of South Bend
state: Indiana
city: South Bend
country: United States
facility: Michiana Hematology Oncology PC-South Bend
state: Indiana
city: Ames
country: United States
facility: McFarland Clinic PC - Ames
state: Iowa
city: Cedar Rapids
country: United States
facility: Physicians' Clinic of Iowa PC
state: Iowa
city: Cedar Rapids
country: United States
facility: Oncology Associates at Mercy Medical Center
state: Iowa
city: Westwood
country: United States
facility: University of Kansas Hospital-Westwood Cancer Center
state: Kansas
city: Lexington
country: United States
facility: Baptist Health Lexington
state: Kentucky
city: Lexington
country: United States
facility: University of Kentucky/Markey Cancer Center
state: Kentucky
city: Louisville
country: United States
facility: The James Graham Brown Cancer Center at University of Louisville
state: Kentucky
city: Owensboro
country: United States
facility: Owensboro Health Mitchell Memorial Cancer Center
state: Kentucky
city: Baltimore
country: United States
facility: Saint Agnes Hospital
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University/Sidney Kimmel Cancer Center
state: Maryland
city: Bethesda
country: United States
facility: Walter Reed National Military Medical Center
state: Maryland
city: Gaithersburg
country: United States
facility: Kaiser Permanente-Gaithersburg Medical Center
state: Maryland
city: Worcester
country: United States
facility: UMass Memorial Medical Center - University Campus
state: Massachusetts
city: Ann Arbor
country: United States
facility: Saint Joseph Mercy Hospital
state: Michigan
city: Detroit
country: United States
facility: Wayne State University/Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Detroit
country: United States
facility: Ascension Saint John Hospital
state: Michigan
city: Flint
country: United States
facility: Genesys Hurley Cancer Institute
state: Michigan
city: Grand Rapids
country: United States
facility: Mercy Health Saint Mary's
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health at Butterworth Campus
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Novi
country: United States
facility: Ascension Providence Hospitals - Novi
state: Michigan
city: Pontiac
country: United States
facility: Saint Joseph Mercy Oakland
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital-Royal Oak
state: Michigan
city: Troy
country: United States
facility: William Beaumont Hospital - Troy
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Missouri Baptist Medical Center
state: Missouri
city: Springfield
country: United States
facility: Mercy Hospital Springfield
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Paterson
country: United States
facility: Saint Joseph's Regional Medical Center
state: New Jersey
city: Pennington
country: United States
facility: Capital Health Medical Center-Hopewell
state: New Jersey
city: Somerville
country: United States
facility: Robert Wood Johnson University Hospital Somerset
state: New Jersey
city: Toms River
country: United States
facility: Community Medical Center
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center-Einstein Campus
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center - Moses Campus
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center at NYU Langone
state: New York
city: New York
country: United States
facility: NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Poughkeepsie
country: United States
facility: Vassar Brothers Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: White Plains
country: United States
facility: Dickstein Cancer Treatment Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Wilmington
country: United States
facility: New Hanover Regional Medical Center/Zimmer Cancer Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Fargo
country: United States
facility: Sanford Broadway Medical Center
state: North Dakota
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Portsmouth
country: United States
facility: Southern Ohio Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: Providence Saint Vincent Medical Center
state: Oregon
city: Portland
country: United States
facility: Kaiser Permanente Northwest
state: Oregon
city: Bethlehem
country: United States
facility: Saint Luke's University Hospital-Bethlehem Campus
state: Pennsylvania
city: Bryn Mawr
country: United States
facility: Bryn Mawr Hospital
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Milton S Hershey Medical Center
state: Pennsylvania
city: Meadowbrook
country: United States
facility: Holy Redeemer Hospital and Medical Center
state: Pennsylvania
city: Media
country: United States
facility: Riddle Memorial Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania/Abramson Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: York
country: United States
facility: WellSpan Health-York Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Boiling Springs
country: United States
facility: Prisma Health Cancer Institute - Spartanburg
state: South Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Easley
country: United States
facility: Prisma Health Cancer Institute - Easley
state: South Carolina
city: Greenville
country: United States
facility: Prisma Health Cancer Institute - Butternut
state: South Carolina
city: Greenville
country: United States
facility: Prisma Health Cancer Institute - Faris
state: South Carolina
city: Greenville
country: United States
facility: Prisma Health Greenville Memorial Hospital
state: South Carolina
city: Greenville
country: United States
facility: Prisma Health Cancer Institute - Eastside
state: South Carolina
city: Greer
country: United States
facility: Prisma Health Cancer Institute - Greer
state: South Carolina
city: Greer
country: United States
facility: Gibbs Cancer Center-Pelham
state: South Carolina
city: Seneca
country: United States
facility: Prisma Health Cancer Institute - Seneca
state: South Carolina
city: Spartanburg
country: United States
facility: Spartanburg Medical Center
state: South Carolina
city: Sioux Falls
country: United States
facility: Sanford Cancer Center Oncology Clinic
state: South Dakota
city: Sioux Falls
country: United States
facility: Sanford USD Medical Center - Sioux Falls
state: South Dakota
city: Cookeville
country: United States
facility: Cookeville Regional Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Fort Sam Houston
country: United States
facility: Brooke Army Medical Center
state: Texas
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: Laredo
country: United States
facility: Doctor's Hospital of Laredo
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute/University of Utah
state: Utah
city: South Jordan
country: United States
facility: South Jordan Health Center
state: Utah
city: Hampton
country: United States
facility: Sentara Cancer Institute at Sentara CarePlex Hospital
state: Virginia
city: Norfolk
country: United States
facility: Sentara Leigh Hospital
state: Virginia
city: Norfolk
country: United States
facility: Sentara Norfolk General Hospital
state: Virginia
city: Vancouver
country: United States
facility: PeaceHealth Southwest Medical Center
state: Washington
city: Morgantown
country: United States
facility: West Virginia University Healthcare
state: West Virginia
city: Appleton
country: United States
facility: Fox Valley Surgical Associates Limited
state: Wisconsin
city: Appleton
country: United States
facility: ThedaCare Regional Cancer Center
state: Wisconsin
city: Appleton
country: United States
facility: ThedaCare Regional Medical Center - Appleton
state: Wisconsin
city: Grafton
country: United States
facility: Aurora Cancer Care-Grafton
state: Wisconsin
city: Green Bay
country: United States
facility: Aurora BayCare Medical Center
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
city: Milwaukee
country: United States
facility: Aurora Saint Luke's Medical Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Aurora Sinai Medical Center
state: Wisconsin
city: Neenah
country: United States
facility: Surgical Associates of Neenah SC
state: Wisconsin
city: Oshkosh
country: United States
facility: Vince Lombardi Cancer Clinic - Oshkosh
state: Wisconsin
city: Sheboygan
country: United States
facility: Vince Lombardi Cancer Clinic-Sheboygan
state: Wisconsin
city: Summit
country: United States
facility: Aurora Medical Center in Summit
state: Wisconsin
city: Two Rivers
country: United States
facility: Vince Lombardi Cancer Clinic-Two Rivers
state: Wisconsin
city: West Allis
country: United States
facility: Aurora West Allis Medical Center
state: Wisconsin
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Isabelle Bedrosian, MD
role: STUDY_CHAIR
References: