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

April 22, 2026 updated by: NRG Oncology

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.

Study Overview

Status

Active, not recruiting

Conditions

HER2-positive Breast Cancer

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

1300

Phase

Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Puerto Rico
- - Bayamón, Puerto Rico, 00959-5060
    - Cancer Center-Metro Medical Center Bayamon
  - Manati, Puerto Rico, 00674
    - Doctors Cancer Center
  - San Juan, Puerto Rico, 00917
    - San Juan Community Oncology Group
  - San Juan, Puerto Rico, 00927
    - Centro Comprensivo de Cancer de UPR
  - San Juan, Puerto Rico, 00936
    - San Juan City Hospital
United States
- Arizona
  - Phoenix, Arizona, United States, 85004
    - Cancer Center at Saint Joseph's
  - Tucson, Arizona, United States, 85719
    - Banner University Medical Center - Tucson
  - Tucson, Arizona, United States, 85719
    - University of Arizona Cancer Center-North Campus
- Arkansas
  - Jonesboro, Arkansas, United States, 72401
    - NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
- California
  - Antioch, California, United States, 94531
    - Kaiser Permanente-Deer Valley Medical Center
  - Arroyo Grande, California, United States, 93420
    - PCR Oncology
  - Arroyo Grande, California, United States, 93420
    - Mission Hope Medical Oncology - Arroyo Grande
  - Auburn, California, United States, 95602
    - Sutter Auburn Faith Hospital
  - Auburn, California, United States, 95603
    - Sutter Cancer Centers Radiation Oncology Services-Auburn
  - Beverly Hills, California, United States, 90211
    - Tower Cancer Research Foundation
  - Cameron Park, California, United States, 95682
    - Sutter Cancer Centers Radiation Oncology Services-Cameron Park
  - Duarte, California, United States, 91010
    - City of Hope Comprehensive Cancer Center
  - Dublin, California, United States, 94568
    - Kaiser Permanente Dublin
  - Fremont, California, United States, 94538
    - Kaiser Permanente-Fremont
  - Fremont, California, United States, 94538
    - Palo Alto Medical Foundation-Fremont
  - Fresno, California, United States, 93720
    - Kaiser Permanente-Fresno
  - Fresno, California, United States, 93720
    - Fresno Cancer Center
  - Irvine, California, United States, 92618
    - City of Hope at Irvine Lennar
  - Irvine, California, United States, 92612
    - UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
  - Lancaster, California, United States, 93534
    - City of Hope Antelope Valley
  - Los Angeles, California, United States, 90033
    - USC / Norris Comprehensive Cancer Center
  - Los Angeles, California, United States, 90048
    - Cedars Sinai Medical Center
  - Los Angeles, California, United States, 90033
    - Los Angeles General Medical Center
  - Modesto, California, United States, 95355
    - Memorial Medical Center
  - Modesto, California, United States, 95356
    - Kaiser Permanente-Modesto
  - Mountain View, California, United States, 94040
    - Palo Alto Medical Foundation-Camino Division
  - Oakland, California, United States, 94611
    - Kaiser Permanente-Oakland
  - Oakland, California, United States, 94611
    - Kaiser Permanente Oakland-Broadway
  - Orange, California, United States, 92868
    - UC Irvine Health/Chao Family Comprehensive Cancer Center
  - Palo Alto, California, United States, 94304
    - Stanford Cancer Institute Palo Alto
  - Palo Alto, California, United States, 94301
    - Palo Alto Medical Foundation Health Care
  - Pomona, California, United States, 91767
    - Pomona Valley Hospital Medical Center
  - Rancho Cordova, California, United States, 95670
    - Kaiser Permanente-Rancho Cordova Cancer Center
  - Redwood City, California, United States, 94063
    - Kaiser Permanente- Marshall Medical Offices
  - Richmond, California, United States, 94801
    - Kaiser Permanente-Richmond
  - Rohnert Park, California, United States, 94928
    - Rohnert Park Cancer Center
  - Roseville, California, United States, 95678
    - The Permanente Medical Group-Roseville Radiation Oncology
  - Roseville, California, United States, 95661
    - Kaiser Permanente-Roseville
  - Roseville, California, United States, 95661
    - Sutter Cancer Centers Radiation Oncology Services-Roseville
  - Roseville, California, United States, 95661
    - Sutter Roseville Medical Center
  - Sacramento, California, United States, 95816
    - Sutter Medical Center Sacramento
  - Sacramento, California, United States, 95817
    - University of California Davis Comprehensive Cancer Center
  - Sacramento, California, United States, 95814
    - Kaiser Permanente Downtown Commons
  - Sacramento, California, United States, 95823
    - Kaiser Permanente-South Sacramento
  - Sacramento, California, United States, 95823
    - South Sacramento Cancer Center
  - San Francisco, California, United States, 94115
    - Kaiser Permanente-San Francisco
  - San Francisco, California, United States, 94115
    - California Pacific Medical Center-Pacific Campus
  - San Jose, California, United States, 95119
    - Kaiser Permanente-Santa Teresa-San Jose
  - San Jose, California, United States, 95124
    - Stanford Cancer Center South Bay
  - San Leandro, California, United States, 94577
    - Kaiser Permanente San Leandro
  - San Luis Obispo, California, United States, 93401
    - Pacific Central Coast Health Center-San Luis Obispo
  - San Rafael, California, United States, 94903
    - Kaiser San Rafael-Gallinas
  - Santa Barbara, California, United States, 93105
    - Ridley-Tree Cancer Center
  - Santa Clara, California, United States, 95051
    - Kaiser Permanente Medical Center - Santa Clara
  - Santa Maria, California, United States, 93444
    - Mission Hope Medical Oncology - Santa Maria
  - Santa Rosa, California, United States, 95403
    - Kaiser Permanente-Santa Rosa
  - Santa Rosa, California, United States, 95403
    - Sutter Pacific Medical Foundation
  - South Pasadena, California, United States, 91030
    - City of Hope South Pasadena
  - South San Francisco, California, United States, 94080
    - Kaiser Permanente Cancer Treatment Center
  - South San Francisco, California, United States, 94080
    - Kaiser Permanente-South San Francisco
  - Stockton, California, United States, 95210
    - Kaiser Permanente-Stockton
  - Sunnyvale, California, United States, 94086
    - Palo Alto Medical Foundation-Sunnyvale
  - Tarzana, California, United States, 91356
    - Cedars-Sinai Cancer - Tarzana
  - Torrance, California, United States, 90505
    - Torrance Memorial Physician Network - Cancer Care
  - Torrance, California, United States, 90503
    - City of Hope South Bay
  - Upland, California, United States, 91786
    - City of Hope Upland
  - Vacaville, California, United States, 95688
    - Kaiser Permanente Medical Center-Vacaville
  - Vallejo, California, United States, 94589
    - Kaiser Permanente-Vallejo
  - Walnut Creek, California, United States, 94596
    - Kaiser Permanente-Walnut Creek
- Colorado
  - Aurora, Colorado, United States, 80045
    - UCHealth University of Colorado Hospital
  - Colorado Springs, Colorado, United States, 80907
    - Penrose-Saint Francis Healthcare
  - Colorado Springs, Colorado, United States, 80909
    - UCHealth Memorial Hospital Central
  - Colorado Springs, Colorado, United States, 80907
    - Rocky Mountain Cancer Centers-Penrose
  - Colorado Springs, Colorado, United States, 80920
    - Memorial Hospital North
  - Colorado Springs, Colorado, United States, 80923
    - Saint Francis Cancer Center
  - Fort Collins, Colorado, United States, 80524
    - Poudre Valley Hospital
  - Fort Collins, Colorado, United States, 80528
    - Cancer Care and Hematology-Fort Collins
  - Greeley, Colorado, United States, 80631
    - UCHealth Greeley Hospital
  - Highlands Ranch, Colorado, United States, 80129
    - UCHealth Highlands Ranch Hospital
  - Loveland, Colorado, United States, 80538
    - Medical Center of the Rockies
- Florida
  - Atlantis, Florida, United States, 33462
    - John Fitzgerald Kennedy Medical Center
  - Clearwater, Florida, United States, 33756
    - Morton Plant Hospital
  - Fort Myers, Florida, United States, 33905
    - Regional Cancer Center-Lee Memorial Health System
  - Fort Myers, Florida, United States, 33901
    - Lee Memorial Health System
  - N. Venice, Florida, United States, 34275
    - Sarasota Memorial Hospital-Venice
  - Ocoee, Florida, United States, 34761
    - Health Central
  - Orlando, Florida, United States, 32806
    - Orlando Health Cancer Institute
  - Plantation, Florida, United States, 33324
    - GenesisCare USA - Plantation
  - Sarasota, Florida, United States, 34239
    - Sarasota Memorial Hospital
  - Sarasota, Florida, United States, 34232
    - Florida Cancer Specialists - Sarasota
  - Sarasota, Florida, United States, 34236
    - Florida Cancer Specialists - Sarasota Downtown
  - Sarasota, Florida, United States, 34239
    - First Physicians Group - Urology Robotic and Minimally Invasive Surgery
  - Sarasota, Florida, United States, 34243
    - Sarasota Memorial Health Care Center at University Parkway
  - Sarasota, Florida, United States, 34239
    - First Physicians Group-Sarasota
  - Sarasota, Florida, United States, 34232
    - Intercoastal Medical Group - Cattleridge II
  - Tampa, Florida, United States, 33612
    - Moffitt Cancer Center
  - Tampa, Florida, United States, 33607
    - Moffitt Cancer Center-International Plaza
  - Tampa, Florida, United States, 33612
    - Moffitt Cancer Center - McKinley Campus
  - Venice, Florida, United States, 34285
    - Florida Cancer Specialists - Venice Island
  - Venice, Florida, United States, 34275
    - Florida Cancer Specialists - Venice Pinebrook
  - Wesley Chapel, Florida, United States, 33544
    - Moffitt Cancer Center at Wesley Chapel
- Georgia
  - Atlanta, Georgia, United States, 30308
    - Emory University Hospital Midtown
  - Atlanta, Georgia, United States, 30322
    - Emory University Hospital/Winship Cancer Institute
  - Atlanta, Georgia, United States, 30342
    - Emory Saint Joseph's Hospital
  - Atlanta, Georgia, United States, 30303
    - Grady Health System
  - Atlanta, Georgia, United States, 30308
    - Emory Proton Therapy Center
  - Decatur, Georgia, United States, 30033
    - Emory Decatur Hospital
  - Johns Creek, Georgia, United States, 30097
    - Emory Johns Creek Hospital
  - Newnan, Georgia, United States, 30265
    - CTCA at Southeastern Regional Medical Center
  - Valdosta, Georgia, United States, 31602
    - South Georgia Medical Center/Pearlman Cancer Center
- Hawaii
  - Honolulu, Hawaii, United States, 96813
    - Queen's Medical Center
  - Honolulu, Hawaii, United States, 96813
    - Hawaii Cancer Care Inc - Waterfront Plaza
  - Honolulu, Hawaii, United States, 96813
    - Queen's Cancer Cenrer - POB I
  - Honolulu, Hawaii, United States, 96813
    - Straub Clinic and Hospital
  - Honolulu, Hawaii, United States, 96813
    - University of Hawaii Cancer Center
  - Honolulu, Hawaii, United States, 96817
    - Kuakini Medical Center
  - Honolulu, Hawaii, United States, 96817
    - Queen's Cancer Center - Kuakini
  - Honolulu, Hawaii, United States, 96826
    - Kapiolani Medical Center for Women and Children
  - Kailua, Hawaii, United States, 96734
    - Castle Medical Center
  - Lihue, Hawaii, United States, 96766
    - Wilcox Memorial Hospital and Kauai Medical Clinic
  - ‘Aiea, Hawaii, United States, 96701
    - Hawaii Cancer Care - Westridge
  - ‘Aiea, Hawaii, United States, 96701
    - Pali Momi Medical Center
  - ‘Aiea, Hawaii, United States, 96701
    - Queen's Cancer Center - Pearlridge
  - ‘Aiea, Hawaii, United States, 96701
    - The Cancer Center of Hawaii-Pali Momi
  - ‘Ewa Beach, Hawaii, United States, 96706
    - The Queen's Medical Center - West Oahu
- Idaho
  - Boise, Idaho, United States, 83712
    - Saint Luke's Cancer Institute - Boise
  - Fruitland, Idaho, United States, 83619
    - Saint Luke's Cancer Institute - Fruitland
  - Meridian, Idaho, United States, 83642
    - Saint Luke's Cancer Institute - Meridian
  - Nampa, Idaho, United States, 83687
    - Saint Luke's Cancer Institute - Nampa
  - Twin Falls, Idaho, United States, 83301
    - Saint Luke's Cancer Institute - Twin Falls
- Illinois
  - Aurora, Illinois, United States, 60504
    - Rush-Copley Medical Center
  - Centralia, Illinois, United States, 62801
    - Centralia Oncology Clinic
  - Centralia, Illinois, United States, 62801
    - Saint Mary's Hospital
  - Chicago, Illinois, United States, 60611
    - Northwestern University
  - Chicago, Illinois, United States, 60637
    - University of Chicago Comprehensive Cancer Center
  - Chicago, Illinois, United States, 60612
    - John H Stroger Jr Hospital of Cook County
  - Danville, Illinois, United States, 61832
    - Carle at The Riverfront
  - DeKalb, Illinois, United States, 60115
    - Northwestern Medicine Cancer Center Kishwaukee
  - Decatur, Illinois, United States, 62526
    - Decatur Memorial Hospital
  - Decatur, Illinois, United States, 62526
    - Cancer Care Specialists of Illinois - Decatur
  - Effingham, Illinois, United States, 62401
    - Crossroads Cancer Center
  - Effingham, Illinois, United States, 62401
    - Carle Physician Group-Effingham
  - Elmhurst, Illinois, United States, 60126
    - Elmhurst Memorial Hospital
  - Geneva, Illinois, United States, 60134
    - Northwestern Medicine Cancer Center Delnor
  - Glenview, Illinois, United States, 60026
    - Northwestern Medicine Glenview Outpatient Center
  - Grayslake, Illinois, United States, 60030
    - Northwestern Medicine Grayslake Outpatient Center
  - Harvey, Illinois, United States, 60426
    - Ingalls Memorial Hospital
  - Lake Forest, Illinois, United States, 60045
    - Northwestern Medicine Lake Forest Hospital
  - Mattoon, Illinois, United States, 61938
    - Carle Physician Group-Mattoon/Charleston
  - Maywood, Illinois, United States, 60153
    - Loyola University Medical Center
  - Naperville, Illinois, United States, 60540
    - Edward Hospital/Cancer Center
  - New Lenox, Illinois, United States, 60451
    - UC Comprehensive Cancer Center at Silver Cross
  - Normal, Illinois, United States, 61761
    - Carle Cancer Institute Normal
  - O'Fallon, Illinois, United States, 62269
    - Cancer Care Center of O'Fallon
  - O'Fallon, Illinois, United States, 62269
    - HSHS Saint Elizabeth's Hospital
  - Orland Park, Illinois, United States, 60462
    - University of Chicago Medicine-Orland Park
  - Orland Park, Illinois, United States, 60462
    - Northwestern Medicine Orland Park
  - Springfield, Illinois, United States, 62702
    - Southern Illinois University School of Medicine
  - Springfield, Illinois, United States, 62702
    - Springfield Clinic
  - Springfield, Illinois, United States, 62781
    - Springfield Memorial Hospital
  - Urbana, Illinois, United States, 61801
    - Carle Cancer Center
  - Warrenville, Illinois, United States, 60555
    - Northwestern Medicine Cancer Center Warrenville
  - Zion, Illinois, United States, 60099
    - Midwestern Regional Medical Center
- Indiana
  - Crown Point, Indiana, United States, 46307
    - Northwest Cancer Center - Main Campus
  - Crown Point, Indiana, United States, 46307
    - UChicago Medicine Northwest Indiana
  - Dyer, Indiana, United States, 46311
    - Northwest Oncology LLC
  - Goshen, Indiana, United States, 46526
    - Goshen Center for Cancer Care
  - Hobart, Indiana, United States, 46342
    - Northwest Cancer Center - Hobart
  - Hobart, Indiana, United States, 46342
    - Saint Mary Medical Center
  - Munster, Indiana, United States, 46321
    - The Community Hospital
  - Munster, Indiana, United States, 46321
    - Women's Diagnostic Center - Munster
  - Richmond, Indiana, United States, 47374
    - Reid Health
  - South Bend, Indiana, United States, 46601
    - Memorial Hospital of South Bend
  - Valparaiso, Indiana, United States, 46383
    - Northwest Cancer Center - Valparaiso
- Iowa
  - Ames, Iowa, United States, 50010
    - Mary Greeley Medical Center
  - Ames, Iowa, United States, 50010
    - McFarland Clinic - Ames
  - Ankeny, Iowa, United States, 50023
    - UI Health Care Mission Cancer and Blood - Ankeny Clinic
  - Cedar Rapids, Iowa, United States, 52402
    - Physicians' Clinic of Iowa PC
  - Clive, Iowa, United States, 50325
    - Mercy Cancer Center-West Lakes
  - Clive, Iowa, United States, 50325
    - UI Health Care Mission Cancer and Blood - West Des Moines Clinic
  - Creston, Iowa, United States, 50801
    - Greater Regional Medical Center
  - Des Moines, Iowa, United States, 50309
    - Iowa Methodist Medical Center
  - Des Moines, Iowa, United States, 50314
    - Mercy Medical Center - Des Moines
  - Des Moines, Iowa, United States, 50309
    - UI Health Care Mission Cancer and Blood - Des Moines Clinic
  - Des Moines, Iowa, United States, 50314
    - UI Health Care Mission Cancer and Blood - Laurel Clinic
  - Waukee, Iowa, United States, 50263
    - UI Health Care Mission Cancer and Blood - Waukee Clinic
  - West Des Moines, Iowa, United States, 50266
    - Mercy Medical Center-West Lakes
- Kansas
  - Kansas City, Kansas, United States, 66160
    - University of Kansas Cancer Center
  - Olathe, Kansas, United States, 66061
    - The University of Kansas Cancer Center - Olathe
  - Overland Park, Kansas, United States, 66210
    - University of Kansas Cancer Center-Overland Park
  - Overland Park, Kansas, United States, 66211
    - University of Kansas Hospital-Indian Creek Campus
  - Salina, Kansas, United States, 67401
    - Salina Regional Health Center
  - Topeka, Kansas, United States, 66606
    - University of Kansas Health System Saint Francis Campus
  - Westwood, Kansas, United States, 66205
    - University of Kansas Hospital-Westwood Cancer Center
- Kentucky
  - Louisville, Kentucky, United States, 40202
    - The James Graham Brown Cancer Center at University of Louisville
  - Louisville, Kentucky, United States, 40245
    - UofL Health Medical Center Northeast
- Maryland
  - Baltimore, Maryland, United States, 21204
    - Greater Baltimore Medical Center
  - Baltimore, Maryland, United States, 21201
    - University of Maryland/Greenebaum Cancer Center
  - Bel Air, Maryland, United States, 21014
    - UM Upper Chesapeake Medical Center
  - Columbia, Maryland, United States, 21044
    - Central Maryland Radiation Oncology in Howard County
  - Easton, Maryland, United States, 21601
    - University of Maryland Shore Medical Center at Easton
  - Glen Burnie, Maryland, United States, 21061
    - UM Baltimore Washington Medical Center/Tate Cancer Center
  - Largo, Maryland, United States, 20774
    - UM Capital Region Medical Center
- Michigan
  - Battle Creek, Michigan, United States, 49017
    - Bronson Battle Creek
  - Brownstown, Michigan, United States, 48183
    - Henry Ford Cancer Institute-Downriver
  - Caro, Michigan, United States, 48723
    - Caro Cancer Center
  - Clarkston, Michigan, United States, 48346
    - Michigan Healthcare Professionals Clarkston
  - Clinton Township, Michigan, United States, 48038
    - Henry Ford Macomb Hospital-Clinton Township
  - Dearborn, Michigan, United States, 48126
    - Henry Ford Medical Center-Fairlane
  - Detroit, Michigan, United States, 48202
    - Henry Ford Hospital
  - Escanaba, Michigan, United States, 49829
    - OSF Saint Francis Hospital and Medical Group
  - Farmington Hills, Michigan, United States, 48334
    - Michigan Healthcare Professionals Farmington
  - Flint, Michigan, United States, 48503
    - Hurley Medical Center
  - Flint, Michigan, United States, 48503
    - Genesys Hurley Cancer Institute
  - Grand Rapids, Michigan, United States, 49503
    - Trinity Health Grand Rapids Hospital
  - Grand Rapids, Michigan, United States, 49503
    - Corewell Health Grand Rapids Hospitals - Butterworth Hospital
  - Grand Rapids, Michigan, United States, 49503
    - Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
  - Jackson, Michigan, United States, 49201
    - Allegiance Health
  - Macomb, Michigan, United States, 48044
    - Michigan Healthcare Professionals Macomb
  - Madison Heights, Michigan, United States, 48071
    - Michigan Healthcare Professionals Madison Heights
  - Marlette, Michigan, United States, 48453
    - Saint Mary's Oncology/Hematology Associates of Marlette
  - Novi, Michigan, United States, 48377
    - Henry Ford Medical Center-Columbus
  - Pontiac, Michigan, United States, 48341
    - Trinity Health Saint Joseph Mercy Oakland Hospital
  - Royal Oak, Michigan, United States, 48073
    - Corewell Health William Beaumont University Hospital
  - Saginaw, Michigan, United States, 48604
    - Oncology Hematology Associates of Saginaw Valley PC
  - Saginaw, Michigan, United States, 48601
    - MyMichigan Medical Center Saginaw
  - Tawas City, Michigan, United States, 48764
    - MyMichigan Medical Center Tawas
  - Troy, Michigan, United States, 48098
    - Michigan Healthcare Professionals Troy
  - Troy, Michigan, United States, 48085
    - Corewell Health Beaumont Troy Hospital
  - West Bloomfield, Michigan, United States, 48322
    - Henry Ford West Bloomfield Hospital
  - West Branch, Michigan, United States, 48661
    - Saint Mary's Oncology/Hematology Associates of West Branch
  - Wyoming, Michigan, United States, 49519
    - University of Michigan Health - West
- Minnesota
  - Bemidji, Minnesota, United States, 56601
    - Sanford Joe Lueken Cancer Center
  - Brainerd, Minnesota, United States, 56401
    - Essentia Health Saint Joseph's Medical Center
  - Coon Rapids, Minnesota, United States, 55433
    - Mercy Hospital
  - Deer River, Minnesota, United States, 56636
    - Essentia Health - Deer River Clinic
  - Duluth, Minnesota, United States, 55805
    - Saint Luke's Hospital of Duluth
  - Duluth, Minnesota, United States, 55805
    - Essentia Health Cancer Center
  - Duluth, Minnesota, United States, 55805
    - Essentia Health Saint Mary's Medical Center
  - Duluth, Minnesota, United States, 55805
    - Miller-Dwan Hospital
  - Edina, Minnesota, United States, 55435
    - Fairview Southdale Hospital
  - Hibbing, Minnesota, United States, 55746
    - Essentia Health Hibbing Clinic
  - Minneapolis, Minnesota, United States, 55407
    - Abbott-Northwestern Hospital
  - Monticello, Minnesota, United States, 55362
    - Monticello Cancer Center
  - Saint Cloud, Minnesota, United States, 56303
    - Coborn Cancer Center at Saint Cloud Hospital
  - Saint Paul, Minnesota, United States, 55101
    - Regions Hospital
  - Saint Paul, Minnesota, United States, 55102
    - United Hospital
  - Sandstone, Minnesota, United States, 55072
    - Essentia Health Sandstone
  - Shakopee, Minnesota, United States, 55379
    - Saint Francis Regional Medical Center
  - Stillwater, Minnesota, United States, 55082
    - Lakeview Hospital
  - Virginia, Minnesota, United States, 55792
    - Essentia Health Virginia Clinic
  - Waconia, Minnesota, United States, 55387
    - Ridgeview Medical Center
- Mississippi
  - Columbus, Mississippi, United States, 39705
    - Baptist Memorial Hospital and Cancer Center-Golden Triangle
  - Grenada, Mississippi, United States, 38901
    - Baptist Cancer Center-Grenada
  - New Albany, Mississippi, United States, 38652
    - Baptist Memorial Hospital and Cancer Center-Union County
  - Oxford, Mississippi, United States, 38655
    - Baptist Memorial Hospital and Cancer Center-Oxford
  - Southhaven, Mississippi, United States, 38671
    - Baptist Memorial Hospital and Cancer Center-Desoto
- Missouri
  - Cape Girardeau, Missouri, United States, 63703
    - Saint Francis Medical Center
  - Farmington, Missouri, United States, 63640
    - Parkland Health Center - Farmington
  - Kansas City, Missouri, United States, 64154
    - University of Kansas Cancer Center - North
  - Lee's Summit, Missouri, United States, 64064
    - University of Kansas Cancer Center - Lee's Summit
  - North Kansas City, Missouri, United States, 64116
    - University of Kansas Cancer Center at North Kansas City Hospital
  - Sainte Genevieve, Missouri, United States, 63670
    - Sainte Genevieve County Memorial Hospital
  - Springfield, Missouri, United States, 65804
    - Mercy Hospital Springfield
  - St Louis, Missouri, United States, 63131
    - Missouri Baptist Medical Center
  - St Louis, Missouri, United States, 63141
    - Mercy Hospital Saint Louis
  - St Louis, Missouri, United States, 63128
    - Mercy Hospital South
  - Sullivan, Missouri, United States, 63080
    - Missouri Baptist Sullivan Hospital
  - Sunset Hills, Missouri, United States, 63127
    - BJC Outpatient Center at Sunset Hills
- Montana
  - Billings, Montana, United States, 59101
    - Billings Clinic Cancer Center
  - Bozeman, Montana, United States, 59715
    - Bozeman Health Deaconess Hospital
- Nebraska
  - Bellevue, Nebraska, United States, 68123
    - Nebraska Medicine-Bellevue
  - Kearney, Nebraska, United States, 68847
    - CHI Health Good Samaritan
  - Lincoln, Nebraska, United States, 68516
    - Cancer Partners of Nebraska
  - Omaha, Nebraska, United States, 68198
    - University of Nebraska Medical Center
  - Omaha, Nebraska, United States, 68118
    - Nebraska Medicine-Village Pointe
- Nevada
  - Henderson, Nevada, United States, 89052
    - OptumCare Cancer Care at Seven Hills
  - Las Vegas, Nevada, United States, 89144
    - Summerlin Hospital Medical Center
  - Las Vegas, Nevada, United States, 89102
    - OptumCare Cancer Care at Charleston
  - Las Vegas, Nevada, United States, 89106
    - Radiation Oncology Centers of Nevada Central
  - Las Vegas, Nevada, United States, 89119
    - Radiation Oncology Centers of Nevada Southeast
  - Las Vegas, Nevada, United States, 89128
    - OptumCare Cancer Care at MountainView
  - Las Vegas, Nevada, United States, 89135
    - Alliance for Childhood Diseases/Cure 4 the Kids Foundation
  - Las Vegas, Nevada, United States, 89148
    - Comprehensive Cancer Centers of Nevada
  - Las Vegas, Nevada, United States, 89148
    - OptumCare Cancer Care at Fort Apache
- New Hampshire
  - Lebanon, New Hampshire, United States, 03756
    - Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
- New Jersey
  - Basking Ridge, New Jersey, United States, 07920
    - Memorial Sloan Kettering Basking Ridge
  - Middletown, New Jersey, United States, 07748
    - Memorial Sloan Kettering Monmouth
  - Montvale, New Jersey, United States, 07645
    - Memorial Sloan Kettering Bergen
- New York
  - Bay Shore, New York, United States, 11706
    - Northwell Health Imbert Cancer Center
  - Canandaigua, New York, United States, 14424
    - Sands Cancer Center
  - Commack, New York, United States, 11725
    - Memorial Sloan Kettering Commack
  - Dansville, New York, United States, 14437
    - Noyes Memorial Hospital/Myers Cancer Center
  - Greenlawn, New York, United States, 11740
    - Northwell Health Cancer Institute at Huntington
  - Harrison, New York, United States, 10604
    - Memorial Sloan Kettering Westchester
  - Lake Success, New York, United States, 11042
    - Northwell Health/Center for Advanced Medicine
  - Mount Kisco, New York, United States, 10549
    - Northern Westchester Hospital
  - New York, New York, United States, 10065
    - Memorial Sloan Kettering Cancer Center
  - New York, New York, United States, 10032
    - NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
  - Oswego, New York, United States, 13126
    - Upstate Cancer Center at Oswego
  - Oswego, New York, United States, 13126
    - Upstate Cancer Center Radiation Oncology at Oswego
  - Rochester, New York, United States, 14642
    - University of Rochester
  - Rochester, New York, United States, 14620
    - Highland Hospital
  - Rochester, New York, United States, 14606
    - Wilmot Cancer Institute Radiation Oncology at Greece
  - Rochester, New York, United States, 14623
    - Pluta Cancer Center
  - Sleepy Hollow, New York, United States, 10591
    - Phelps Memorial Hospital Center
  - Staten Island, New York, United States, 10305
    - Staten Island University Hospital
  - Stony Brook, New York, United States, 11794
    - Stony Brook University Medical Center
  - Syracuse, New York, United States, 13210
    - State University of New York Upstate Medical University
  - Syracuse, New York, United States, 13215
    - SUNY Upstate Medical Center-Community Campus
  - Syracuse, New York, United States, 13210
    - Upstate Cancer Center at Hill Radiation Oncology
  - The Bronx, New York, United States, 10461
    - Montefiore Medical Center-Einstein Campus
  - The Bronx, New York, United States, 10467
    - Montefiore Medical Center - Moses Campus
  - The Bronx, New York, United States, 10461
    - Montefiore Medical Center-Weiler Hospital
  - Uniondale, New York, United States, 11553
    - Memorial Sloan Kettering Nassau
  - Verona, New York, United States, 13478
    - Upstate Cancer Center at Verona
  - Webster, New York, United States, 14580
    - Wilmot Cancer Institute at Webster
- North Carolina
  - Greenville, North Carolina, United States, 27834
    - East Carolina University
  - Winston-Salem, North Carolina, United States, 27157
    - Wake Forest University Health Sciences
- North Dakota
  - Bismarck, North Dakota, United States, 58501
    - Sanford Bismarck Medical Center
  - Fargo, North Dakota, United States, 58122
    - Sanford Roger Maris Cancer Center
  - Fargo, North Dakota, United States, 58122
    - Sanford Broadway Medical Center
- Ohio
  - Beavercreek, Ohio, United States, 45431
    - Indu and Raj Soin Medical Center
  - Canton, Ohio, United States, 44708
    - Cleveland Clinic Mercy Hospital
  - Centerville, Ohio, United States, 45459
    - Miami Valley Hospital South
  - Centerville, Ohio, United States, 45459
    - Dayton Physicians LLC-Miami Valley South
  - Columbus, Ohio, United States, 43214
    - Riverside Methodist Hospital
  - Columbus, Ohio, United States, 43210
    - Ohio State University Comprehensive Cancer Center
  - Columbus, Ohio, United States, 43228
    - Doctors Hospital
  - Columbus, Ohio, United States, 43215
    - Grant Medical Center
  - Dayton, Ohio, United States, 45409
    - Miami Valley Hospital
  - Dayton, Ohio, United States, 45415
    - Miami Valley Hospital North
  - Dayton, Ohio, United States, 45415
    - Dayton Physician LLC - Englewood
  - Dayton, Ohio, United States, 45409
    - Premier Blood and Cancer Center
  - Delaware, Ohio, United States, 43015
    - Delaware Health Center-Grady Cancer Center
  - Delaware, Ohio, United States, 43015
    - Grady Memorial Hospital
  - Dublin, Ohio, United States, 43016
    - Dublin Methodist Hospital
  - Franklin, Ohio, United States, 45005-1066
    - Atrium Medical Center-Middletown Regional Hospital
  - Franklin, Ohio, United States, 45005
    - Dayton Physicians LLC-Atrium
  - Greenville, Ohio, United States, 45331
    - Miami Valley Cancer Care and Infusion
  - Kettering, Ohio, United States, 45429
    - Kettering Medical Center
  - Mansfield, Ohio, United States, 44903
    - OhioHealth Mansfield Hospital
  - Marion, Ohio, United States, 43302
    - OhioHealth Marion General Hospital
  - Troy, Ohio, United States, 45373
    - Upper Valley Medical Center
  - Troy, Ohio, United States, 45373
    - Dayton Physicians LLC - Troy
- Oklahoma
  - Oklahoma City, Oklahoma, United States, 73104
    - University of Oklahoma Health Sciences Center
  - Oklahoma City, Oklahoma, United States, 73120
    - Mercy Hospital Oklahoma City
- Oregon
  - Bend, Oregon, United States, 97701
    - Saint Charles Health System
  - Clackamas, Oregon, United States, 97015
    - Clackamas Radiation Oncology Center
  - Clackamas, Oregon, United States, 97015
    - Providence Cancer Institute Clackamas Clinic
  - Gresham, Oregon, United States, 97030
    - Legacy Mount Hood Medical Center
  - Newberg, Oregon, United States, 97132
    - Providence Newberg Medical Center
  - Oregon City, Oregon, United States, 97045
    - Providence Willamette Falls Medical Center
  - Portland, Oregon, United States, 97210
    - Legacy Good Samaritan Hospital and Medical Center
  - Portland, Oregon, United States, 97213
    - Providence Portland Medical Center
  - Portland, Oregon, United States, 97225
    - Providence Saint Vincent Medical Center
  - Tualatin, Oregon, United States, 97062
    - Legacy Meridian Park Hospital
- Pennsylvania
  - Hershey, Pennsylvania, United States, 17033-0850
    - Penn State Milton S Hershey Medical Center
  - Pittsburgh, Pennsylvania, United States, 15213
    - UPMC-Magee Womens Hospital
- Rhode Island
  - Providence, Rhode Island, United States, 02905
    - Women and Infants Hospital
  - Warwick, Rhode Island, United States, 02886
    - Kent Hospital
- South Carolina
  - Charleston, South Carolina, United States, 29425
    - Medical University of South Carolina
  - West Columbia, South Carolina, United States, 29169
    - Lexington Medical Center
- South Dakota
  - Sioux Falls, South Dakota, United States, 57117-5134
    - Sanford USD Medical Center - Sioux Falls
  - Sioux Falls, South Dakota, United States, 57104
    - Sanford Cancer Center Oncology Clinic
- Tennessee
  - Collierville, Tennessee, United States, 38017
    - Baptist Memorial Hospital and Cancer Center-Collierville
  - Memphis, Tennessee, United States, 38120
    - Baptist Memorial Hospital and Cancer Center-Memphis
- Texas
  - Conroe, Texas, United States, 77384
    - MD Anderson in The Woodlands
  - Houston, Texas, United States, 77030
    - M D Anderson Cancer Center
  - Houston, Texas, United States, 77079
    - MD Anderson West Houston
  - League City, Texas, United States, 77573
    - MD Anderson League City
  - Sugar Land, Texas, United States, 77478
    - MD Anderson in Sugar Land
- Utah
  - Farmington, Utah, United States, 84025
    - Farmington Health Center
  - Salt Lake City, Utah, United States, 84112
    - Huntsman Cancer Institute/University of Utah
  - Salt Lake City, Utah, United States, 84106
    - University of Utah Sugarhouse Health Center
- Vermont
  - Burlington, Vermont, United States, 05401
    - University of Vermont Medical Center
  - Burlington, Vermont, United States, 05405
    - University of Vermont and State Agricultural College
  - Saint Johnsbury, Vermont, United States, 05819
    - Dartmouth Cancer Center - North
- Virginia
  - Mechanicsville, Virginia, United States, 23116
    - Bon Secours Memorial Regional Medical Center
  - Midlothian, Virginia, United States, 23114
    - Bon Secours Saint Francis Medical Center
  - Richmond, Virginia, United States, 23226
    - Bon Secours Saint Mary's Hospital
  - Richmond, Virginia, United States, 23230
    - Bon Secours Cancer Institute at Reynolds Crossing
- Washington
  - Edmonds, Washington, United States, 98026
    - Swedish Cancer Institute-Edmonds
  - Issaquah, Washington, United States, 98029
    - Swedish Cancer Institute-Issaquah
  - Kennewick, Washington, United States, 99336
    - Kadlec Clinic Hematology and Oncology
  - Mount Vernon, Washington, United States, 98274
    - Skagit Regional Health Cancer Care Center
  - Seattle, Washington, United States, 98107
    - Swedish Medical Center-Ballard Campus
  - Seattle, Washington, United States, 98122
    - Swedish Medical Center-First Hill
  - Vancouver, Washington, United States, 98686
    - Legacy Salmon Creek Hospital
  - Vancouver, Washington, United States, 98684
    - Legacy Cancer Institute Medical Oncology and Day Treatment
- Wisconsin
  - Antigo, Wisconsin, United States, 54409
    - Langlade Hospital and Cancer Center
  - Ashland, Wisconsin, United States, 54806
    - Duluth Clinic Ashland
  - Ashland, Wisconsin, United States, 54806
    - Northwest Wisconsin Cancer Center
  - Green Bay, Wisconsin, United States, 54301
    - Saint Vincent Hospital Cancer Center Green Bay
  - Hayward, Wisconsin, United States, 54843
    - Essentia Health-Hayward Clinic
  - Madison, Wisconsin, United States, 53792
    - University of Wisconsin Carbone Cancer Center - University Hospital
  - Menomonee Falls, Wisconsin, United States, 53051
    - Froedtert Menomonee Falls Hospital
  - Milwaukee, Wisconsin, United States, 53226
    - Medical College of Wisconsin
  - Mukwonago, Wisconsin, United States, 53149
    - ProHealth D N Greenwald Center
  - New Richmond, Wisconsin, United States, 54017
    - Cancer Center of Western Wisconsin
  - Oak Creek, Wisconsin, United States, 53154
    - Drexel Town Square Health Center
  - Oconomowoc, Wisconsin, United States, 53066
    - ProHealth Oconomowoc Memorial Hospital
  - Rhinelander, Wisconsin, United States, 54501
    - Aspirus Cancer Care - James Beck Cancer Center
  - Sheboygan, Wisconsin, United States, 53081
    - Saint Vincent Hospital Cancer Center at Sheboygan
  - Sheboygan, Wisconsin, United States, 53081
    - Sheboygan Physicians Group
  - Spooner, Wisconsin, United States, 54801
    - Essentia Health-Spooner Clinic
  - Stevens Point, Wisconsin, United States, 54481
    - Aspirus Cancer Care - Stevens Point
  - Sturgeon Bay, Wisconsin, United States, 54235-1495
    - Saint Vincent Hospital Cancer Center at Sturgeon Bay
  - Superior, Wisconsin, United States, 54880
    - Essentia Health Saint Mary's Hospital - Superior
  - Waukesha, Wisconsin, United States, 53188
    - UW Cancer Center at ProHealth Care
  - Wausau, Wisconsin, United States, 54401
    - Aspirus Regional Cancer Center
  - West Bend, Wisconsin, United States, 53095
    - Froedtert West Bend Hospital/Kraemer Cancer Center
  - Wisconsin Rapids, Wisconsin, United States, 54494
    - Aspirus Cancer Care - Wisconsin Rapids

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Description

Inclusion Criteria:

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.
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.

Exclusion Criteria:

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.
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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Interventional Model: Parallel Assignment
Masking: None (Open Label)

Number of Arms

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard of Care Adjuvant Breast Radiation Patients continue to receive their current planned adjuvant breast radiation and systemic HER2-targeted therapies	Radiation: Standard of Care Adjuvant Breast Radiation adjuvant breast radiotherapy per the current standard of care
Active Comparator: Standard of Care HER2-targeted Therapy Without Adjuvant Breast Radiation Patients continue to receive their current systemic HER2-targeted therapy without breast adjuvant radiation	Drug: Standard of Care HER2-targeted Therapy Without Adjuvant Breast Radiation participants are randomized to continue their standard of care systemic HER2-targeted therapy without adjuvant breast radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
recurrence-free interval (RFI) Time Frame: From randomization to first recurrence event or censoring for the duration of the trial, at 10.5 years	Time to recurrence event or censoring	From randomization to first recurrence event or censoring for the duration of the trial, at 10.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ipsilateral breast recurrence (IBR) for radiation omitting arm Time Frame: From randomization to first recurrence event or censoring for the duration of the trial , measured at year 7	Time to IBTR event or censoring	From randomization to first recurrence event or censoring for the duration of the trial , measured at year 7
ipsilateral breast recurrence (IBR) by treatment arm Time Frame: From randomization to first recurrence event or censoring for the duration of the trial at 10.5 years.	Time to ipsilateral breast recurrence (IBR) by treatment arm.	From randomization to first recurrence event or censoring for the duration of the trial at 10.5 years.
local regional recurrence (LRR) by treatment arm Time Frame: From randomization to first recurrence event or censoring for the duration of the trial at 10.5 years.	Time to local regional recurrence (LRR) by treatment arm.	From randomization to first recurrence event or censoring for the duration of the trial at 10.5 years.
disease-free survival (DFS) by treatment arm. Time Frame: From the time of randomization for the duration of the trial at 10.5 years.	To determine disease-free survival (DFS) by treatment arm.	From the time of randomization for the duration of the trial at 10.5 years.
overall survival (OS) by treatment arm. Time Frame: From the time of randomization for the duration of the trial at 10.5 years.	To determine overall survival (OS) by treatment arm.	From the time of randomization for the duration of the trial at 10.5 years.
patient-reported breast pain by treatment arm using the Breast Cancer Treatment Outcome Scale (BCTOS) Time Frame: At 3 years after randomization	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.	At 3 years after randomization
patient-reported worry about recurrence by treatment arm using a the three-item worry about recurrence score Time Frame: At 3 years after randomization	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.	At 3 years after randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NRG Oncology

Collaborators

National Cancer Institute (NCI)

Alliance for Clinical Trials in Oncology

Eastern Cooperative Oncology Group

SWOG Cancer Research Network

Investigators

Principal Investigator: Norman Wolmark, MD, NRG Oncology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General 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.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 19, 2023

Primary Completion (Estimated)

February 1, 2034

Study Completion (Estimated)

February 1, 2037

Study Registration Dates

First Submitted

January 5, 2023

First Submitted That Met QC Criteria

January 20, 2023

First Posted (Actual)

January 30, 2023

Study Record Updates

Last Update Posted (Actual)

April 27, 2026

Last Update Submitted That Met QC Criteria

April 22, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

NRG-BR008
5U10CA180868 (U.S. NIH Grant/Contract)
NCI-2022-09157 (Other Identifier: NCI)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Studies a U.S. FDA-regulated device product

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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Completed

Frailty Scales for Predicting Chemotherapy Toxicity in Older Adults With Gastrointestinal Cancers (TOX-FRAIL)

Colorectal Cancer | Frailty | Biliary Tract Cancer | Pancreatic Cancer Resectable | Toxicity Due to Chemotherapy | Gastrointestinal Cancers | Malnutrition Elderly | Gastric Cancer (GC) | Sarcopenia in Elderly | Older Adults (65 Years and Older) | Esophageal Cancer (EsC)

Turkey (Türkiye)
Technical University of Munich
German Cancer Aid

Recruiting

Respiratory Training and Relaxation Techniques to Improve Adjuvant Radiation Therapy in DIBH in Breast Cancer (B-REST)

Breast Cancer | Radiotherapy | Relaxation | Breathholding

Germany
UNICANCER

Active, not recruiting

Standard or Hypofractionated Radiotherapy Versus Accelerated Partial Breast Irradiation (APBI) for Breast Cancer (SHARE)

Breast Cancer | Lumpectomy

France

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

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

Study Overview

Status

Conditions

Intervention / Treatment

Detailed Description

Study Type

Enrollment (Estimated)

Phase

Contacts and Locations

Study Locations

Participation Criteria

Eligibility Criteria

Ages Eligible for Study

Accepts Healthy Volunteers

Description

Study Plan

How is the study designed?

Design Details

Number of Arms

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure

Measure Description

Time Frame

Secondary Outcome Measures

Outcome Measure

Measure Description

Time Frame

Collaborators and Investigators

Sponsor

Collaborators

Investigators

Publications and helpful links

General Publications

Study record dates

Study Major Dates

Study Start (Actual)

Primary Completion (Estimated)

Study Completion (Estimated)

Study Registration Dates

First Submitted

First Submitted That Met QC Criteria

First Posted (Actual)

Study Record Updates

Last Update Posted (Actual)

Last Update Submitted That Met QC Criteria

Last Verified

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Studies a U.S. FDA-regulated device product

Clinical Trials on HER2-positive Breast Cancer

Clinical Trials on Standard of Care Adjuvant Breast Radiation

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Medical Conditions

Drug Interventions

CROs by country

CROs in Jordan

Conditions

Rare Diseases

Drug Interventions

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Locations