AzTrials
AzTrials

HER2-positive Breast CancerPhase 3HERONCT05705401

Testing Radiation and HER2-targeted Therapy Versus HER2-targeted Therapy Alone for Low-risk HER2-positive Breast Cancer

A Phase 3 study of HER2-positive Breast Cancer, run by NRG Oncology at 418 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This Phase III trial compares the recurrence-free interval (RFI) among patients with early-stage, low risk HER2+ breast cancer who undergo breast conserving surgery and receive HER2-directed therapy, and are randomized to not receive adjuvant breast radiotherapy versus those who are randomized to receive adjuvant… Read more about this study

Who is it for?
Ages 40 years and older
Conditions the study is for
HER2-positive Breast Cancer
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,300 participants
Where
418 sitesin 2 countries
Study dates
19 May 2023to 1 Feb 2037
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the U.S., authorization permitting release of personal health information.
  • female and male patients who have undergone breast conserving surgery and completed a minimum of 4 cycles (12 weeks) of neoadjuvant or adjuvant chemotherapy in combination with HER2-targeted therapy.
  • -≥ 40 years of age
  • ECOG performance status of 0 ,1, or 2/Karnofsky performance status above 60
  • Histologically or cytologically confirmed invasive breast carcinoma.
  • tumor must have been determined to be HER2-positive by current ASCO/CAP guidelines based on local testing results.
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  • Patient must have undergone axillary staging, either sentinel node biopsy (SNB) or axillary lymph nodal dissection (ALND). In neoadjuvant patients, SNB following neoadjuvant therapy is strongly recommended. SNB prior to neoadjuvant therapy is discouraged, but patients are permitted if node negative (pN0).
  • The following staging criteria must be met according to AJCC 8th edition criteria:
  • Adjuvant cohort : By pathologic evaluation, the patient's primary tumor must be </= 2 cm and ipsilateral nodes must be pN0. Surgical lumpectomy margins must be negative for invasive cancer and ductal carcinoma in situ (no ink on tumor).
  • Neoadjuvant cohort: Prior to neoadjuvant therapy, the patient's primary tumor must be < 3 cm by imaging studies, with negative axillary nodes (cN0) based on axillary U/S, CT, PET or MRI. Physical examination is not sufficient documentation of cN0 status; • Must be ypT0N0 at surgery (lumpectomy); patients with residual non-invasive disease (DCIS) in the surgical specimen (ypTis), are NOT eligible.
  • For the Adjuvant cohort, adjuvant therapy must have consisted of a minimum of 4 cycles (12 weeks) of chemotherapy in combination with HER2-targeted therapy.
  • For the Neoadjuvant cohort, neoadjuvant therapy must have consisted of a minimum of 4 cycles (12 weeks) of chemotherapy in combination with HER2-targeted therapy.- ; Patients who did not receive chemotherapy in the neoadjuvant setting are not eligible, even if they achieved pCR with their preoperative treatment; nor would these patients become eligible by receiving chemotherapy after surgery.
  • In patients assigned to radiation therapy, treatment should start ≤ 12 weeks from surgery on the Neoadjuvant cohort and ≤ 8 weeks from the completion of chemotherapy on the Adjuvant cohort. Patients should continue HER2-targeted therapy during assigned study treatment (radiation or observation).
  • Bilateral mammogram or MRI within 52 weeks prior to randomization.
  • HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial.

Who cannot join

  • Definitive clinical or radiologic evidence of metastatic disease.
  • On the Adjuvant cohort, patients with a primary tumor >2 cm on pathologic examination of the surgical specimen. On the Neoadjuvant cohort, patients with a primary tumor > 3 cm or with abnormal or suspicious ipsilateral axillary nodes by pretreatment imaging, unless demonstrated to be negative by cytologic or histologic examination.
  • Pathologically positive axillary nodes at any time including of pN0(i+) or pN0(mol+) ypN0(i+) or ypN0(mol+) disease.
  • Patient planning for or status-post mastectomy.
  • Radiographically suspicious ipsilateral or contralateral axillary, supraclavicular, infraclavicular, or internal mammary lymph nodes, unless there is histological confirmation that these nodes are negative for metastatic disease.
  • Suspicious microcalcifications, densities, or palpable abnormalities (in the ipsilateral or contralateral breast), or mass or non-mass enhancement on MRI (if performed) aside from the known cancer, unless biopsied and found to be benign.
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  • Non-epithelial breast malignancies such as sarcoma or lymphoma.
  • Multicentric carcinoma (invasive cancer or DCIS) in more than one quadrant or separated by > 4 centimeters. If multifocal, all foci should be confined to a maximum tumor bed of 3 cm determined by pathological assessment.
  • Paget's disease of the nipple.
  • Synchronous (unilateral or bilateral) invasive breast cancer or DCIS. (Patients with synchronous and/or previous contralateral LCIS are eligible.)
  • On the Adjuvant cohort, surgical margins that cannot be microscopically assessed or are positive at pathologic evaluation. (If surgical margins are rendered free of disease by re-excision, the patient is eligible).
  • Treatment plan that includes regional nodal irradiation.
  • Patients treated for a prior invasive breast malignancy are excluded. Contralateral DCIS ≥ 10 years prior to enrollment is permissible.
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
  • Patients on oral, transdermal, or subdermal estrogen replacement (including all estrogen only and estrogen-progesterone formulas) are not eligible unless discontinued prior to randomization.
  • Prior ipsilateral breast or thoracic RT for any condition (contralateral RT for DCIS ≥ 10 years prior to randomization is permitted).
  • Active collagen vascular disease, specifically dermatomyositis with a CPK level above normal or with an active systemic lupus erythematosus, or scleroderma.
  • Clinicians should consider whether any conditions would make this protocol unreasonably hazardous for the patient.
  • Pregnancy or lactation at the time of randomization or intention to become pregnant during treatment. (Note: Pregnancy testing according to institutional standards for patients of childbearing potential must be performed within 14 days prior to randomization.)
  • Use of any investigational product within 30 days prior to randomization.

Trial locations and contacts

418 sites in 2 countries.

305 sites in 2 countries

United States300 sites

  • Hawaii Cancer Care - Westridge

    ‘Aiea, Hawaii, 96701

  • Pali Momi Medical Center

    ‘Aiea, Hawaii, 96701

  • Queen's Cancer Center - Pearlridge

    ‘Aiea, Hawaii, 96701

  • The Cancer Center of Hawaii-Pali Momi

    ‘Aiea, Hawaii, 96701

  • The Queen's Medical Center - West Oahu

    ‘Ewa Beach, Hawaii, 96706

  • Mary Greeley Medical Center

    Ames, Iowa, 50010

  • McFarland Clinic - Ames

    Ames, Iowa, 50010

  • UI Health Care Mission Cancer and Blood - Ankeny Clinic

    Ankeny, Iowa, 50023

  • Langlade Hospital and Cancer Center

    Antigo, Wisconsin, 54409

  • Kaiser Permanente-Deer Valley Medical Center

    Antioch, California, 94531

  • Mission Hope Medical Oncology - Arroyo Grande

    Arroyo Grande, California, 93420

  • PCR Oncology

    Arroyo Grande, California, 93420

  • Duluth Clinic Ashland

    Ashland, Wisconsin, 54806

  • Northwest Wisconsin Cancer Center

    Ashland, Wisconsin, 54806

  • Grady Health System

    Atlanta, Georgia, 30303

  • Emory Proton Therapy Center

    Atlanta, Georgia, 30308

  • Emory University Hospital Midtown

    Atlanta, Georgia, 30308

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Emory Saint Joseph's Hospital

    Atlanta, Georgia, 30342

  • John Fitzgerald Kennedy Medical Center

    Atlantis, Florida, 33462

  • Sutter Auburn Faith Hospital

    Auburn, California, 95602

  • Sutter Cancer Centers Radiation Oncology Services-Auburn

    Auburn, California, 95603

  • UCHealth University of Colorado Hospital

    Aurora, Colorado, 80045

  • Rush-Copley Medical Center

    Aurora, Illinois, 60504

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • Greater Baltimore Medical Center

    Baltimore, Maryland, 21204

  • Memorial Sloan Kettering Basking Ridge

    Basking Ridge, New Jersey, 07920

  • Bronson Battle Creek

    Battle Creek, Michigan, 49017

  • Northwell Health Imbert Cancer Center

    Bay Shore, New York, 11706

  • Indu and Raj Soin Medical Center

    Beavercreek, Ohio, 45431

  • UM Upper Chesapeake Medical Center

    Bel Air, Maryland, 21014

  • Nebraska Medicine-Bellevue

    Bellevue, Nebraska, 68123

  • Sanford Joe Lueken Cancer Center

    Bemidji, Minnesota, 56601

  • Saint Charles Health System

    Bend, Oregon, 97701

  • Tower Cancer Research Foundation

    Beverly Hills, California, 90211

  • Billings Clinic Cancer Center

    Billings, Montana, 59101

  • Sanford Bismarck Medical Center

    Bismarck, North Dakota, 58501

  • Saint Luke's Cancer Institute - Boise

    Boise, Idaho, 83712

  • Bozeman Health Deaconess Hospital

    Bozeman, Montana, 59715

  • Essentia Health Saint Joseph's Medical Center

    Brainerd, Minnesota, 56401

  • Henry Ford Cancer Institute-Downriver

    Brownstown, Michigan, 48183

  • University of Vermont Medical Center

    Burlington, Vermont, 05401

  • University of Vermont and State Agricultural College

    Burlington, Vermont, 05405

  • Sutter Cancer Centers Radiation Oncology Services-Cameron Park

    Cameron Park, California, 95682

  • Sands Cancer Center

    Canandaigua, New York, 14424

  • Cleveland Clinic Mercy Hospital

    Canton, Ohio, 44708

  • Saint Francis Medical Center

    Cape Girardeau, Missouri, 63703

  • Caro Cancer Center

    Caro, Michigan, 48723

  • Physicians' Clinic of Iowa PC

    Cedar Rapids, Iowa, 52402

  • Dayton Physicians LLC-Miami Valley South

    Centerville, Ohio, 45459

  • Miami Valley Hospital South

    Centerville, Ohio, 45459

  • Centralia Oncology Clinic

    Centralia, Illinois, 62801

  • Saint Mary's Hospital

    Centralia, Illinois, 62801

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Northwestern University

    Chicago, Illinois, 60611

  • John H Stroger Jr Hospital of Cook County

    Chicago, Illinois, 60612

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Clackamas Radiation Oncology Center

    Clackamas, Oregon, 97015

  • Providence Cancer Institute Clackamas Clinic

    Clackamas, Oregon, 97015

  • Michigan Healthcare Professionals Clarkston

    Clarkston, Michigan, 48346

  • Morton Plant Hospital

    Clearwater, Florida, 33756

  • Henry Ford Macomb Hospital-Clinton Township

    Clinton Township, Michigan, 48038

  • Mercy Cancer Center-West Lakes

    Clive, Iowa, 50325

  • UI Health Care Mission Cancer and Blood - West Des Moines Clinic

    Clive, Iowa, 50325

  • Baptist Memorial Hospital and Cancer Center-Collierville

    Collierville, Tennessee, 38017

  • Penrose-Saint Francis Healthcare

    Colorado Springs, Colorado, 80907

  • Rocky Mountain Cancer Centers-Penrose

    Colorado Springs, Colorado, 80907

  • UCHealth Memorial Hospital Central

    Colorado Springs, Colorado, 80909

  • Memorial Hospital North

    Colorado Springs, Colorado, 80920

  • Saint Francis Cancer Center

    Colorado Springs, Colorado, 80923

  • Central Maryland Radiation Oncology in Howard County

    Columbia, Maryland, 21044

  • Baptist Memorial Hospital and Cancer Center-Golden Triangle

    Columbus, Mississippi, 39705

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Riverside Methodist Hospital

    Columbus, Ohio, 43214

  • Grant Medical Center

    Columbus, Ohio, 43215

  • Doctors Hospital

    Columbus, Ohio, 43228

  • Memorial Sloan Kettering Commack

    Commack, New York, 11725

  • MD Anderson in The Woodlands

    Conroe, Texas, 77384

  • Mercy Hospital

    Coon Rapids, Minnesota, 55433

  • Greater Regional Medical Center

    Creston, Iowa, 50801

  • Northwest Cancer Center - Main Campus

    Crown Point, Indiana, 46307

  • UChicago Medicine Northwest Indiana

    Crown Point, Indiana, 46307

  • Noyes Memorial Hospital/Myers Cancer Center

    Dansville, New York, 14437

  • Carle at The Riverfront

    Danville, Illinois, 61832

  • Miami Valley Hospital

    Dayton, Ohio, 45409

  • Premier Blood and Cancer Center

    Dayton, Ohio, 45409

  • Dayton Physician LLC - Englewood

    Dayton, Ohio, 45415

  • Miami Valley Hospital North

    Dayton, Ohio, 45415

  • Henry Ford Medical Center-Fairlane

    Dearborn, Michigan, 48126

  • Emory Decatur Hospital

    Decatur, Georgia, 30033

  • Cancer Care Specialists of Illinois - Decatur

    Decatur, Illinois, 62526

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • Essentia Health - Deer River Clinic

    Deer River, Minnesota, 56636

  • Northwestern Medicine Cancer Center Kishwaukee

    DeKalb, Illinois, 60115

  • Delaware Health Center-Grady Cancer Center

    Delaware, Ohio, 43015

  • Grady Memorial Hospital

    Delaware, Ohio, 43015

  • Iowa Methodist Medical Center

    Des Moines, Iowa, 50309

  • UI Health Care Mission Cancer and Blood - Des Moines Clinic

    Des Moines, Iowa, 50309

  • Mercy Medical Center - Des Moines

    Des Moines, Iowa, 50314

  • UI Health Care Mission Cancer and Blood - Laurel Clinic

    Des Moines, Iowa, 50314

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • Kaiser Permanente Dublin

    Dublin, California, 94568

  • Dublin Methodist Hospital

    Dublin, Ohio, 43016

  • Essentia Health Cancer Center

    Duluth, Minnesota, 55805

  • Essentia Health Saint Mary's Medical Center

    Duluth, Minnesota, 55805

  • Miller-Dwan Hospital

    Duluth, Minnesota, 55805

  • Saint Luke's Hospital of Duluth

    Duluth, Minnesota, 55805

  • Northwest Oncology LLC

    Dyer, Indiana, 46311

  • University of Maryland Shore Medical Center at Easton

    Easton, Maryland, 21601

  • Fairview Southdale Hospital

    Edina, Minnesota, 55435

  • Swedish Cancer Institute-Edmonds

    Edmonds, Washington, 98026

  • Carle Physician Group-Effingham

    Effingham, Illinois, 62401

  • Crossroads Cancer Center

    Effingham, Illinois, 62401

  • Elmhurst Memorial Hospital

    Elmhurst, Illinois, 60126

  • OSF Saint Francis Hospital and Medical Group

    Escanaba, Michigan, 49829

  • Sanford Broadway Medical Center

    Fargo, North Dakota, 58122

  • Sanford Roger Maris Cancer Center

    Fargo, North Dakota, 58122

  • Parkland Health Center - Farmington

    Farmington, Missouri, 63640

  • Farmington Health Center

    Farmington, Utah, 84025

  • Michigan Healthcare Professionals Farmington

    Farmington Hills, Michigan, 48334

  • Genesys Hurley Cancer Institute

    Flint, Michigan, 48503

  • Hurley Medical Center

    Flint, Michigan, 48503

  • Poudre Valley Hospital

    Fort Collins, Colorado, 80524

  • Cancer Care and Hematology-Fort Collins

    Fort Collins, Colorado, 80528

  • Lee Memorial Health System

    Fort Myers, Florida, 33901

  • Regional Cancer Center-Lee Memorial Health System

    Fort Myers, Florida, 33905

  • Atrium Medical Center-Middletown Regional Hospital

    Franklin, Ohio, 45005-1066

  • Dayton Physicians LLC-Atrium

    Franklin, Ohio, 45005

  • Kaiser Permanente-Fremont

    Fremont, California, 94538

  • Palo Alto Medical Foundation-Fremont

    Fremont, California, 94538

  • Fresno Cancer Center

    Fresno, California, 93720

  • Kaiser Permanente-Fresno

    Fresno, California, 93720

  • Saint Luke's Cancer Institute - Fruitland

    Fruitland, Idaho, 83619

  • Northwestern Medicine Cancer Center Delnor

    Geneva, Illinois, 60134

  • UM Baltimore Washington Medical Center/Tate Cancer Center

    Glen Burnie, Maryland, 21061

  • Northwestern Medicine Glenview Outpatient Center

    Glenview, Illinois, 60026

  • Goshen Center for Cancer Care

    Goshen, Indiana, 46526

  • Corewell Health Grand Rapids Hospitals - Butterworth Hospital

    Grand Rapids, Michigan, 49503

  • Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital

    Grand Rapids, Michigan, 49503

  • Trinity Health Grand Rapids Hospital

    Grand Rapids, Michigan, 49503

  • Northwestern Medicine Grayslake Outpatient Center

    Grayslake, Illinois, 60030

  • UCHealth Greeley Hospital

    Greeley, Colorado, 80631

  • Saint Vincent Hospital Cancer Center Green Bay

    Green Bay, Wisconsin, 54301

  • Northwell Health Cancer Institute at Huntington

    Greenlawn, New York, 11740

  • East Carolina University

    Greenville, North Carolina, 27834

  • Miami Valley Cancer Care and Infusion

    Greenville, Ohio, 45331

  • Baptist Cancer Center-Grenada

    Grenada, Mississippi, 38901

  • Legacy Mount Hood Medical Center

    Gresham, Oregon, 97030

  • Memorial Sloan Kettering Westchester

    Harrison, New York, 10604

  • Ingalls Memorial Hospital

    Harvey, Illinois, 60426

  • Essentia Health-Hayward Clinic

    Hayward, Wisconsin, 54843

  • OptumCare Cancer Care at Seven Hills

    Henderson, Nevada, 89052

  • Penn State Milton S Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • Essentia Health Hibbing Clinic

    Hibbing, Minnesota, 55746

  • UCHealth Highlands Ranch Hospital

    Highlands Ranch, Colorado, 80129

  • Northwest Cancer Center - Hobart

    Hobart, Indiana, 46342

  • Saint Mary Medical Center

    Hobart, Indiana, 46342

  • Hawaii Cancer Care Inc - Waterfront Plaza

    Honolulu, Hawaii, 96813

  • Queen's Cancer Cenrer - POB I

    Honolulu, Hawaii, 96813

  • Queen's Medical Center

    Honolulu, Hawaii, 96813

  • Straub Clinic and Hospital

    Honolulu, Hawaii, 96813

  • University of Hawaii Cancer Center

    Honolulu, Hawaii, 96813

  • Kuakini Medical Center

    Honolulu, Hawaii, 96817

  • Queen's Cancer Center - Kuakini

    Honolulu, Hawaii, 96817

  • Kapiolani Medical Center for Women and Children

    Honolulu, Hawaii, 96826

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • MD Anderson West Houston

    Houston, Texas, 77079

  • UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

    Irvine, California, 92612

  • City of Hope at Irvine Lennar

    Irvine, California, 92618

  • Swedish Cancer Institute-Issaquah

    Issaquah, Washington, 98029

  • Allegiance Health

    Jackson, Michigan, 49201

  • Emory Johns Creek Hospital

    Johns Creek, Georgia, 30097

  • NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro

    Jonesboro, Arkansas, 72401

  • Castle Medical Center

    Kailua, Hawaii, 96734

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

  • University of Kansas Cancer Center - North

    Kansas City, Missouri, 64154

  • CHI Health Good Samaritan

    Kearney, Nebraska, 68847

  • Kadlec Clinic Hematology and Oncology

    Kennewick, Washington, 99336

  • Kettering Medical Center

    Kettering, Ohio, 45429

  • Northwestern Medicine Lake Forest Hospital

    Lake Forest, Illinois, 60045

  • Northwell Health/Center for Advanced Medicine

    Lake Success, New York, 11042

  • City of Hope Antelope Valley

    Lancaster, California, 93534

  • UM Capital Region Medical Center

    Largo, Maryland, 20774

  • OptumCare Cancer Care at Charleston

    Las Vegas, Nevada, 89102

  • Radiation Oncology Centers of Nevada Central

    Las Vegas, Nevada, 89106

  • Radiation Oncology Centers of Nevada Southeast

    Las Vegas, Nevada, 89119

  • OptumCare Cancer Care at MountainView

    Las Vegas, Nevada, 89128

  • Alliance for Childhood Diseases/Cure 4 the Kids Foundation

    Las Vegas, Nevada, 89135

  • Summerlin Hospital Medical Center

    Las Vegas, Nevada, 89144

  • Comprehensive Cancer Centers of Nevada

    Las Vegas, Nevada, 89148

  • OptumCare Cancer Care at Fort Apache

    Las Vegas, Nevada, 89148

  • MD Anderson League City

    League City, Texas, 77573

  • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

    Lebanon, New Hampshire, 03756

  • University of Kansas Cancer Center - Lee's Summit

    Lee's Summit, Missouri, 64064

  • Wilcox Memorial Hospital and Kauai Medical Clinic

    Lihue, Hawaii, 96766

  • Cancer Partners of Nebraska

    Lincoln, Nebraska, 68516

  • Los Angeles General Medical Center

    Los Angeles, California, 90033

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • Cedars Sinai Medical Center

    Los Angeles, California, 90048

  • The James Graham Brown Cancer Center at University of Louisville

    Louisville, Kentucky, 40202

  • UofL Health Medical Center Northeast

    Louisville, Kentucky, 40245

  • Medical Center of the Rockies

    Loveland, Colorado, 80538

  • Michigan Healthcare Professionals Macomb

    Macomb, Michigan, 48044

  • University of Wisconsin Carbone Cancer Center - University Hospital

    Madison, Wisconsin, 53792

  • Michigan Healthcare Professionals Madison Heights

    Madison Heights, Michigan, 48071

  • OhioHealth Mansfield Hospital

    Mansfield, Ohio, 44903

  • OhioHealth Marion General Hospital

    Marion, Ohio, 43302

  • Saint Mary's Oncology/Hematology Associates of Marlette

    Marlette, Michigan, 48453

  • Carle Physician Group-Mattoon/Charleston

    Mattoon, Illinois, 61938

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • Bon Secours Memorial Regional Medical Center

    Mechanicsville, Virginia, 23116

  • Baptist Memorial Hospital and Cancer Center-Memphis

    Memphis, Tennessee, 38120

  • Froedtert Menomonee Falls Hospital

    Menomonee Falls, Wisconsin, 53051

  • Saint Luke's Cancer Institute - Meridian

    Meridian, Idaho, 83642

  • Memorial Sloan Kettering Monmouth

    Middletown, New Jersey, 07748

  • Bon Secours Saint Francis Medical Center

    Midlothian, Virginia, 23114

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Abbott-Northwestern Hospital

    Minneapolis, Minnesota, 55407

  • Memorial Medical Center

    Modesto, California, 95355

  • Kaiser Permanente-Modesto

    Modesto, California, 95356

  • Monticello Cancer Center

    Monticello, Minnesota, 55362

  • Memorial Sloan Kettering Bergen

    Montvale, New Jersey, 07645

  • Northern Westchester Hospital

    Mount Kisco, New York, 10549

  • Skagit Regional Health Cancer Care Center

    Mount Vernon, Washington, 98274

  • Palo Alto Medical Foundation-Camino Division

    Mountain View, California, 94040

  • ProHealth D N Greenwald Center

    Mukwonago, Wisconsin, 53149

  • The Community Hospital

    Munster, Indiana, 46321

  • Women's Diagnostic Center - Munster

    Munster, Indiana, 46321

  • Sarasota Memorial Hospital-Venice

    N. Venice, Florida, 34275

  • Saint Luke's Cancer Institute - Nampa

    Nampa, Idaho, 83687

  • Edward Hospital/Cancer Center

    Naperville, Illinois, 60540

  • Baptist Memorial Hospital and Cancer Center-Union County

    New Albany, Mississippi, 38652

  • UC Comprehensive Cancer Center at Silver Cross

    New Lenox, Illinois, 60451

  • Cancer Center of Western Wisconsin

    New Richmond, Wisconsin, 54017

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Providence Newberg Medical Center

    Newberg, Oregon, 97132

  • CTCA at Southeastern Regional Medical Center

    Newnan, Georgia, 30265

  • Carle Cancer Institute Normal

    Normal, Illinois, 61761

  • University of Kansas Cancer Center at North Kansas City Hospital

    North Kansas City, Missouri, 64116

  • Henry Ford Medical Center-Columbus

    Novi, Michigan, 48377

  • Cancer Care Center of O'Fallon

    O'Fallon, Illinois, 62269

  • HSHS Saint Elizabeth's Hospital

    O'Fallon, Illinois, 62269

  • Drexel Town Square Health Center

    Oak Creek, Wisconsin, 53154

  • Kaiser Permanente Oakland-Broadway

    Oakland, California, 94611

  • Kaiser Permanente-Oakland

    Oakland, California, 94611

  • Health Central

    Ocoee, Florida, 34761

  • ProHealth Oconomowoc Memorial Hospital

    Oconomowoc, Wisconsin, 53066

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Mercy Hospital Oklahoma City

    Oklahoma City, Oklahoma, 73120

  • The University of Kansas Cancer Center - Olathe

    Olathe, Kansas, 66061

  • Nebraska Medicine-Village Pointe

    Omaha, Nebraska, 68118

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • UC Irvine Health/Chao Family Comprehensive Cancer Center

    Orange, California, 92868

  • Providence Willamette Falls Medical Center

    Oregon City, Oregon, 97045

  • Northwestern Medicine Orland Park

    Orland Park, Illinois, 60462

  • University of Chicago Medicine-Orland Park

    Orland Park, Illinois, 60462

  • Orlando Health Cancer Institute

    Orlando, Florida, 32806

  • Upstate Cancer Center at Oswego

    Oswego, New York, 13126

  • Upstate Cancer Center Radiation Oncology at Oswego

    Oswego, New York, 13126

  • University of Kansas Cancer Center-Overland Park

    Overland Park, Kansas, 66210

  • University of Kansas Hospital-Indian Creek Campus

    Overland Park, Kansas, 66211

  • Baptist Memorial Hospital and Cancer Center-Oxford

    Oxford, Mississippi, 38655

  • Palo Alto Medical Foundation Health Care

    Palo Alto, California, 94301

  • Stanford Cancer Institute Palo Alto

    Palo Alto, California, 94304

  • Cancer Center at Saint Joseph's

    Phoenix, Arizona, 85004

  • UPMC-Magee Womens Hospital

    Pittsburgh, Pennsylvania, 15213

  • GenesisCare USA - Plantation

    Plantation, Florida, 33324

  • Pomona Valley Hospital Medical Center

    Pomona, California, 91767

  • Trinity Health Saint Joseph Mercy Oakland Hospital

    Pontiac, Michigan, 48341

  • Legacy Good Samaritan Hospital and Medical Center

    Portland, Oregon, 97210

  • Providence Portland Medical Center

    Portland, Oregon, 97213

  • Providence Saint Vincent Medical Center

    Portland, Oregon, 97225

  • Women and Infants Hospital

    Providence, Rhode Island, 02905

  • Kaiser Permanente-Rancho Cordova Cancer Center

    Rancho Cordova, California, 95670

  • Kaiser Permanente- Marshall Medical Offices

    Redwood City, California, 94063

  • Aspirus Cancer Care - James Beck Cancer Center

    Rhinelander, Wisconsin, 54501

  • Kaiser Permanente-Richmond

    Richmond, California, 94801

  • Reid Health

    Richmond, Indiana, 47374

  • Bon Secours Saint Mary's Hospital

    Richmond, Virginia, 23226

  • Bon Secours Cancer Institute at Reynolds Crossing

    Richmond, Virginia, 23230

  • Wilmot Cancer Institute Radiation Oncology at Greece

    Rochester, New York, 14606

  • Highland Hospital

    Rochester, New York, 14620

  • Pluta Cancer Center

    Rochester, New York, 14623

  • University of Rochester

    Rochester, New York, 14642

  • Rohnert Park Cancer Center

    Rohnert Park, California, 94928

  • Kaiser Permanente-Roseville

    Roseville, California, 95661

  • Sutter Cancer Centers Radiation Oncology Services-Roseville

    Roseville, California, 95661

  • Sutter Roseville Medical Center

    Roseville, California, 95661

  • The Permanente Medical Group-Roseville Radiation Oncology

    Roseville, California, 95678

  • Corewell Health William Beaumont University Hospital

    Royal Oak, Michigan, 48073

  • Kaiser Permanente Downtown Commons

    Sacramento, California, 95814

  • Sutter Medical Center Sacramento

    Sacramento, California, 95816

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • Kaiser Permanente-South Sacramento

    Sacramento, California, 95823

  • South Sacramento Cancer Center

    Sacramento, California, 95823

  • MyMichigan Medical Center Saginaw

    Saginaw, Michigan, 48601

  • Oncology Hematology Associates of Saginaw Valley PC

    Saginaw, Michigan, 48604

  • Coborn Cancer Center at Saint Cloud Hospital

    Saint Cloud, Minnesota, 56303

Other trials in United States

Puerto Rico5 sites

  • Cancer Center-Metro Medical Center Bayamon

    Bayamón, 00959-5060

  • Doctors Cancer Center

    Manati, 00674

  • San Juan Community Oncology Group

    San Juan, 00917

  • Centro Comprensivo de Cancer de UPR

    San Juan, 00927

  • San Juan City Hospital

    San Juan, 00936

Other trials in Puerto Rico

About this study

Official title: A Phase III Randomized Trial of Radiotherapy Optimization for Low-Risk HER2-Positive Breast Cancer (HERO)

This Phase III trial compares the recurrence-free interval (RFI) among patients with early-stage, low risk HER2+ breast cancer who undergo breast conserving surgery and receive HER2-directed therapy, and are randomized to not receive adjuvant breast radiotherapy versus those who are randomized to receive adjuvant radiotherapy per the standard of care.

Read the detailed description

The landmark trials that established breast conservation therapy (BCT) (breast-conserving surgery followed by adjuvant breast irradiation) as a suitable alternative to mastectomy were conducted in an era that predated biological subtyping of breast cancer and the use of HER2-directed therapies in patients with HER2+ cancers. These trials established adjuvant radiotherapy following breast-conserving surgery as necessary to maximize local control, yet, in the intervening years, overall outcomes have improved significantly owing to widespread adoption of screening mammography, resulting in a substantial reduction in average tumor size at diagnosis, as well as improvements in surgical techniques and, crucial for this proposal, the development of highly active systemic therapies.

Before the development of HER2-targeted therapies, patients with HER2-driven localized breast cancer had among the highest rates of local recurrence. However, with improved identification of these patients and the advent of HER2-directed therapies, outcomes have improved significantly, and trials have sought to optimize treatment to reduce the morbidity of both local and systemic treatment. Among the most salient of these examples is the APT trial, a single-arm adjuvant study that enrolled 410 breast cancer patients with HER2+ tumors ≤ 3cm in size and negative axillary nodes, who received adjuvant systemic therapy with weekly paclitaxel and trastuzumab for 12 weeks (TH) followed by 9 months of trastuzumab monotherapy. In addition to demonstrating a very low incidence of distant recurrence, among those on the trial who underwent BCT (lumpectomy and radiation, n = 244), only 2 local recurrence (LR) events have been reported after 7 years of follow-up (7-year LR = 1.2%), representing among the most favorable local outcomes of any breast cancer cohort studied to date. Confirmatory results are forthcoming from the ATEMPT trial, which evaluated the antibody-drug conjugate T-DM1 (ado-trastuzumab emtansine) (n=383) vs the TH regimen from the APT trial (n = 114), thus far showing only 3 LRs in each arm with a median 3-years of follow-up. Importantly, per the current standard of care for HER2+ patients undergoing BCT, all patients presumably received adjuvant breast radiotherapy.

The balance of the BCT literature, including a landmark meta-analysis by the Early Breast Cancer Trialists' Collaborative Group, suggests that adjuvant radiotherapy approximately halves the risk of local recurrence following lumpectomy across all analyzable subgroups. While the relative benefit appears constant across subgroups, the absolute benefit of adjuvant radiotherapy varies with the underlying risk. Taking the favorable results of the APT trial (1.2% 7-year LR), if one presumes that omission of radiotherapy yields a doubling or tripling of local recurrence (based on the observed RR of 0.5 - 0.66 for those receiving radiotherapy across the preponderance of historical trials), this population might have manifested a LR rate of 2.4 - 3.6% with the omission of radiotherapy. That is to say, the hypothesis is that administration of RT to APT patients undergoing BCT may have reduced the 7-year absolute risk of LR by only 1.2-2.4%. Through the identification of patients who are at low risk of LR, it may be acceptable for such patients to forego radiation. This hypothesis will be studied by evaluating omission of radiotherapy among patients with pT1N0 disease at breast-conserving surgery who receive adjuvant HER2-directed therapy (trastuzumab/paclitaxel preferred, other options per protocol), or with clinical tumors ≤ 3 cm and clinically negative axillary nodes (cN0) who achieve a pathologic complete response (pCR; ypT0N0) following preoperative (neoadjuvant) administration of HER2-directed therapy (trastuzumab/paclitaxel preferred, other options per protocol). It is expcted that the 5-year LR rate for this population omitting radiotherapy will be 2% or less, and that omission of radiation will not have a measurable impact on regional and distant recurrences or overall survival.

The practice of breast radiation oncology has benefited immensely from practice-changing trials that have refined the application of adjuvant radiotherapy since the early surgical studies determined whole breast radiotherapy to be necessary following lumpectomy. There are now several favorable breast cancer subtypes in which patients routinely forego radiotherapy after trials demonstrating modest benefits in terms of local recurrence and no impact on distant recurrence or survival, such as among small, low grade luminal cancers in older women and "good-risk" DCIS. Therefore, this will study the omission of radiotherapy among a population of HER2+ breast cancer patients who are now appreciated to also have favorable risk, so as to similarly weigh the attendant inconveniences, cost and morbidity of radiotherapy in light of an established absolute benefit, which may prove to be modest.

Being tested
Standard of Care Adjuvant Breast Radiation, Standard of Care HER2-targeted Therapy Without Adjuvant Breast Radiation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Standard of Care Adjuvant Breast RadiationRadiation

    adjuvant breast radiotherapy per the current standard of care

  • Standard of Care HER2-targeted Therapy Without Adjuvant Breast RadiationDrug

    participants are randomized to continue their standard of care systemic HER2-targeted therapy without adjuvant breast radiotherapy

Study groups in NCT05705401
Study groupRoleWhat they receive
Standard of Care Adjuvant Breast RadiationActive comparatorPatients continue to receive their current planned adjuvant breast radiation and systemic HER2-targeted therapies
Receives: Radiation: Standard of Care Adjuvant Breast Radiation
Standard of Care HER2-targeted Therapy Without Adjuvant Breast RadiationActive comparatorPatients continue to receive their current systemic HER2-targeted therapy without breast adjuvant radiation
Receives: Drug: Standard of Care HER2-targeted Therapy Without Adjuvant Breast Radiation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. recurrence-free interval (RFI)

    Time to recurrence event or censoring

    Measured: From randomization to first recurrence event or censoring for the duration of the trial, at 10.5 years

Secondary outcomes (7)

  1. ipsilateral breast recurrence (IBR) for radiation omitting arm

    Time to IBTR event or censoring

    Measured: From randomization to first recurrence event or censoring for the duration of the trial , measured at year 7

  2. ipsilateral breast recurrence (IBR) by treatment arm

    Time to ipsilateral breast recurrence (IBR) by treatment arm.

    Measured: From randomization to first recurrence event or censoring for the duration of the trial at 10.5 years.

  3. local regional recurrence (LRR) by treatment arm

    Time to local regional recurrence (LRR) by treatment arm.

    Measured: From randomization to first recurrence event or censoring for the duration of the trial at 10.5 years.

  4. disease-free survival (DFS) by treatment arm.

    To determine disease-free survival (DFS) by treatment arm.

    Measured: From the time of randomization for the duration of the trial at 10.5 years.

  5. overall survival (OS) by treatment arm.

    To determine overall survival (OS) by treatment arm.

    Measured: From the time of randomization for the duration of the trial at 10.5 years.

  6. patient-reported breast pain by treatment arm using the Breast Cancer Treatment Outcome Scale (BCTOS)

    To evaluate whether there is a difference in patient-reported breast pain in patients who do and do not receive breast radiation in cohort A and cohort B. The BCTOS pain score has a range from 1-5 with higher scores indicating worse pain.

    Measured: At 3 years after randomization

  7. patient-reported worry about recurrence by treatment arm using a the three-item worry about recurrence score

    To evaluate whether there is a difference in patient-reported worry about recurrence in patients who do and do not receive breast radiation in cohort A and cohort B. The worry about recurrence score has a range from 1-5 with higher scores indicating more worry.

    Measured: At 3 years after randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jan 2023
  2. Study start19 May 2023
  3. Primary completion1 Feb 2034 (estimated)
  4. Study completion1 Feb 2037 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Subjects who are receiving standard of care systemic HER2-targeted therapies are randomized to standard of care adjuvant breast radiation or no breast radiation
Masking
None (open label)
Enrolment
1,300 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05705401
Sponsor's protocol ID
NRG-BR008
Other IDs
5U10CA180868, NCI-2022-09157
Acronym
HERO
Status last verified
Apr 2026
First submitted
5 Jan 2023
Last updated
27 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Braunstein LZ, Mitchell MP, Bandos H, Sikov WM, Khan AJ, Chen PY, Ganz PA, Jagsi R, White JR, Cecchini RS, Kang H, Puhalla SL, Bolton KL, Connolly EP, Stringer-Reasor EM, Gergelis KR, Julian TB, Mamounas EP, Wolmark N. NRG-BR008/HERO study: a Phase III randomized trial of radiotherapy optimization for low-risk HER2-positive breast cancer. Future Oncol. 2025 Jul;21(16):2017-2025. doi: 10.1080/14796694.2025.2511586. Epub 2025 Jun 26.

    PubMed 40574381

Questions about this trial

What is this clinical trial studying?

A Phase 3 study of HER2-positive Breast Cancer, run by NRG Oncology at 418 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 27 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 418 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

recurrence-free interval (RFI) (time frame: From randomization to first recurrence event or censoring for the duration of the trial, at 10.5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05705401, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2026.

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