Anatomic Stage 0 Breast Cancer AJCC v8Phase 3LoTamNCT06671912
Testing Low Dose Tamoxifen for Invasive Breast Cancer, LoTam Trial
A Phase 3 study testing Anastrozole, Letrozole and Exemestane in people with Anatomic Stage 0 Breast Cancer AJCC v8 and Anatomic Stage 1 Breast Cancer AJCC v8, run by Alliance for Clinical Trials in Oncology at 732 sites in 2 countries.
Trial summary
This phase III trial compares the effect of low dose tamoxifen to usual hormonal therapy, including aromatase inhibitors, in treating post-menopausal women with hormone positive, HER2 negative early stage breast cancer. Tamoxifen is in a class of medications known as antiestrogens. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anatomic Stage 0 Breast Cancer AJCC v8, Anatomic Stage 1 Breast Cancer AJCC v8, Anatomic Stage IIA Breast Cancer AJCC v8
- What is being tested?
- Anastrozole, Letrozole and Exemestane
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,556 participants
- Where
- 732 sitesin 2 countries
- Study dates
- 19 Feb 2025to 30 Nov 2031
- Phase
- Phase 3
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Unilateral invasive adenocarcinoma of the breast that is histologically confirmed
- Invasive breast cancer is estrogen receptor positive in ≥ 10% of cells
- HER2 negative by current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines
- The patient must have a multigene assay with a low-risk score, including any of the following (if more than one genomic assay was obtained, both are required to be low-risk):
- Oncotype DX recurrence score ≤ 25
- Mamma Print low risk
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- Prosigna risk of recurrence ≤ 40 Patients with pathologic tumor size ≤ 0.5cm who meet all other eligibility criteria are eligible for enrollment without multigene assay testing. The total number of enrolled patients with tumor size ≤ 0.5cm without genomic testing will be limited
- Tumor size must be ≤ 3 cm by pathologic evaluation. Multifocal tumors are permitted if the largest focus of disease is ≤ 3 cm
- Adequate surgical removal of all clinically evident disease in the breast with either breast conserving surgery or mastectomy. Negative margins on final pathology are required. Additional excisions may be performed to obtain clear margins before registration
- No clinical (cN1, cN2, cN3) or pathologic (pN1mi, pN1, pN2, or pN3) evidence of lymph node involvement on either needle biopsy or surgical lymph node assessment. Patients with pN0(i+) or pN0 (mol+) are eligible
- Surgical axillary staging (sentinel lymph node biopsy ± axillary lymph node dissection) is completed according to physician discretion
- For patients age <70, clinicians may selectively choose to forego surgical axillary staging if an Ipsilateral axillary ultrasound or preop MRI shows no lymph node involvement with no evidence of lymphadenopathy or suspicious thickening is required in this scenario
- For patients age ≥ 70 without surgical axillary staging, axillary ultrasound is not required in this scenario but may be obtained at the discretion of the treating investigator
- No tumors that are considered pT4
- No definitive clinical or radiologic evidence of metastatic disease
- No palpable or radiographically suspicious axillary, supraclavicular, infraclavicular, or internal mammary lymph nodes, unless there is histologic confirmation that these lymph nodes are negative for tumor
- No suspicious microcalcifications, densities, or palpable abnormalities in the ipsilateral or contralateral breast, unless biopsied and found to be benign
- An interval of no more than 20 weeks between the date of surgery and the date of registration
- Must have had a bilateral mammogram or MRI within 9 months prior to registration
- Must be intending to take endocrine therapy for 5 years duration
- No prior treatment with endocrine therapy or chemotherapy for the currently diagnosed breast cancer prior to registration. (Short course endocrine therapy of ≤ 6 weeks duration is acceptable after core biopsy and before surgery, if genomic testing is assessed on the biopsy core and meets eligibility requirements for a low-risk score.)
- No use of oral hormone replacement therapy or transdermal estrogen replacement therapy (patch) within 7 days prior to registration
- Age ≥ 18 years and female
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Postmenopausal status confirmed as one of the following:
- No spontaneous menses ≥ 1 year or
- No menses for < 1 year with follicle stimulating hormone (FSH) and estradiol levels within a postmenopausal range according to institutional standards or
- Previous bilateral surgical oophorectomy
- None of the following conditions:
- Abnormal or dysfunctional uterine bleeding within 1 year prior to study enrollment or
- Any patient with known atypia or endometrial pathology that the opinion of the treating investigator would place the patient at undue risk of endometrial cancer with tamoxifen or
- Any patient with a known hypercoagulable state that in the opinion of the treating investigator would put the patient at undue risk of venous thromboembolism with tamoxifen
- No history of breast or thoracic radiotherapy for any previous condition. Patients may complete radiotherapy for the currently diagnosed breast cancer prior to registering for the study. In this scenario, registration must be completed within 12 weeks of completing breast radiotherapy
- No previous history of ipsilateral invasive breast cancer or ipsilateral ductal carcinoma in situ (DCIS), regardless of the disease-free interval
- No synchronous or previous history of contralateral invasive breast cancer or DCIS
- 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
- No current treatment with any endocrine therapy for breast cancer prevention or osteoporosis, including raloxifene, tamoxifen, or other selective estrogen receptor modulator. Patients intending to continue oral hormone replacement are not eligible
- HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
Who cannot join
None listed.
Trial locations and contacts
732 sites in 2 countries.
304 sites in 2 countries
United States300 sites
Hawaii Cancer Care - Westridge
‘Aiea, Hawaii, 96701
Pali Momi Medical Center
‘Aiea, Hawaii, 96701
The Queen's Medical Center - West Oahu
‘Ewa Beach, Hawaii, 96706
UM Upper Chesapeake Hematology and Oncology - Aberdeen
Aberdeen, Maryland, 21001
Summa Health System - Akron Campus
Akron, Ohio, 44304
Phoebe Putney Memorial Hospital
Albany, Georgia, 31701
Mayo Clinic Health System in Albert Lea
Albert Lea, Minnesota, 56007
Lovelace Medical Center-Saint Joseph Square
Albuquerque, New Mexico, 87102
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106
Lovelace Women's Hospital
Albuquerque, New Mexico, 87109
Presbyterian Kaseman Hospital
Albuquerque, New Mexico, 87110
The Don and Sybil Harrington Cancer Center
Amarillo, Texas, 79106
Mary Greeley Medical Center
Ames, Iowa, 50010
McFarland Clinic - Ames
Ames, Iowa, 50010
Community Hospital of Anaconda
Anaconda, Montana, 59711
Katmai Oncology Group
Anchorage, Alaska, 99508
UI Health Care Mission Cancer and Blood - Ankeny Clinic
Ankeny, Iowa, 50023
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109
Aspirus Cancer Care-Antigo-Volm Cancer Center
Antigo, Wisconsin, 54409
ThedaCare Regional Cancer Center
Appleton, Wisconsin, 54911
Ascension Northeast Wisconsin-Saint Elizabeth Cancer Center-Appleton
Appleton, Wisconsin, 54915
AdventHealth Infusion Center Asheville
Asheville, North Carolina, 28803
Duluth Clinic Ashland
Ashland, Wisconsin, 54806
Northwest Wisconsin Cancer Center
Ashland, Wisconsin, 54806
University Cancer and Blood Center LLC
Athens, Georgia, 30607
Emory University Hospital Midtown
Atlanta, Georgia, 30308
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322
Emory Saint Joseph's Hospital
Atlanta, Georgia, 30342
Harold Alfond Center for Cancer Care
Augusta, Maine, 04330
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045
Rush-Copley Medical Center
Aurora, Illinois, 60504
Advocate Outpatient Center - Aurora
Aurora, Illinois, 60506
IU Health West Hospital
Avon, Indiana, 46123
Saint Alphonsus Cancer Care Center-Baker City
Baker City, Oregon, 97814
Mercy Oncology and Hematology - Clayton-Clarkson
Ballwin, Missouri, 63011
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201
Greater Baltimore Medical Center
Baltimore, Maryland, 21204
Sinai Hospital of Baltimore
Baltimore, Maryland, 21215
Kaiser Permanente-Woodlawn Medical Center
Baltimore, Maryland, 21244
Summa Health System - Barberton Campus
Barberton, Ohio, 44203
Advocate Good Shepherd Hospital
Barrington, Illinois, 60010
Louisiana Hematology Oncology Associates LLC
Baton Rouge, Louisiana, 70809
Bronson Battle Creek
Battle Creek, Michigan, 49017
Northwell Health Imbert Cancer Center
Bay Shore, New York, 11706
Houston Methodist San Jacinto Hospital
Baytown, Texas, 77521
Beaufort Memorial Hospital
Beaufort, South Carolina, 29902
UPMC-Heritage Valley Health System Beaver
Beaver, Pennsylvania, 15009
UM Upper Chesapeake Medical Center
Bel Air, Maryland, 21014
Nebraska Medicine-Bellevue
Bellevue, Nebraska, 68123
FHCC Overlake
Bellevue, Washington, 98004
Sanford Joe Lueken Cancer Center
Bemidji, Minnesota, 56601
Saint Charles Health System
Bend, Oregon, 97701
UCSF Cancer Center - Berkeley
Berkeley, California, 94702
Central Vermont Medical Center/National Life Cancer Treatment
Berlin Corners, Vermont, 05602
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889-5600
University of Iowa Healthcare Cancer Services Quad Cities
Bettendorf, Iowa, 52722
Beverly Hospital
Beverly, Massachusetts, 01915
Tower Cancer Research Foundation
Beverly Hills, California, 90211
Billings Clinic Cancer Center
Billings, Montana, 59101
Saint Vincent Frontier Cancer Center
Billings, Montana, 59102
Sanford Bismarck Medical Center
Bismarck, North Dakota, 58501
Illinois CancerCare-Bloomington
Bloomington, Illinois, 61704
Saint Joseph's/Candler - Bluffton Campus
Bluffton, South Carolina, 29910
Prisma Health Cancer Institute - Spartanburg
Boiling Springs, South Carolina, 29316
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, 83706
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712
McFarland Clinic - Boone
Boone, Iowa, 50036
Tufts Medical Center
Boston, Massachusetts, 02111
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Bozeman Health Deaconess Hospital
Bozeman, Montana, 59715
Essentia Health Saint Joseph's Medical Center
Brainerd, Minnesota, 56401
Lafayette Family Cancer Center-EMMC
Brewer, Maine, 04412
Intermountain Health Platte Valley Hospital
Brighton, Colorado, 80601
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton, Michigan, 48114
University of Michigan - Brighton Center for Specialty Care
Brighton, Michigan, 48116
Ascension Southeast Wisconsin Hospital-Elmbrook Campus-Brookfield
Brookfield, Wisconsin, 53045
New York-Presbyterian/Brooklyn Methodist Hospital
Brooklyn, New York, 11215
Henry Ford Cancer Institute-Downriver
Brownstown, Michigan, 48183
MaineHealth Cancer Care and IV Therapy - Brunswick
Brunswick, Maine, 04011
Mid Coast Hospital
Brunswick, Maine, 04011
Keck Medicine of USC Buena Park
Buena Park, California, 90621
Roswell Park Cancer Institute
Buffalo, New York, 14263
UCSF Cancer Center Burlingame
Burlingame, California, 94010
Lahey Clinic
Burlington, Massachusetts, 01805
University of Vermont Medical Center
Burlington, Vermont, 05401
University of Vermont and State Agricultural College
Burlington, Vermont, 05405
Aurora Cancer Care-Southern Lakes VLCC
Burlington, Wisconsin, 53105
Minnesota Oncology - Burnsville
Burnsville, Minnesota, 55337
Saint Alphonsus Cancer Care Center-Caldwell
Caldwell, Idaho, 83605
Marshall Cancer Center
Cameron Park, California, 95682
Hematology Oncology Associates of CNY at Camillus
Camillus, New York, 13031
Illinois CancerCare-Canton
Canton, Illinois, 61520
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton, Michigan, 48188
Aultman Health Foundation
Canton, Ohio, 44710
Saint Francis Medical Center
Cape Girardeau, Missouri, 63703
AtlantiCare Health Park-Cape May Court House
Cape May Court House, New Jersey, 08210
Carlisle Regional Cancer Center
Carlisle, Pennsylvania, 17015
IU Health North Hospital
Carmel, Indiana, 46032
Mercy Cancer Center - Carmichael
Carmichael, California, 95608
Mercy San Juan Medical Center
Carmichael, California, 95608
Saint Anthony Regional Hospital
Carroll, Iowa, 51401
Illinois CancerCare-Carthage
Carthage, Illinois, 62321
Duke Cancer Center Cary
Cary, North Carolina, 27518
Waverly Hematology Oncology
Cary, North Carolina, 27518
Mercy Hospital
Cedar Rapids, Iowa, 52403
Oncology Associates at Mercy Medical Center
Cedar Rapids, Iowa, 52403
Miami Valley Hospital South
Centerville, Ohio, 45459
WellSpan Medical Oncology and Hematology
Chambersburg, Pennsylvania, 17201
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Medical University of South Carolina
Charleston, South Carolina, 29425
Novant Health Presbyterian Medical Center
Charlotte, North Carolina, 28204
Sentara Martha Jefferson Hospital
Charlottesville, Virginia, 22911
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea, Michigan, 48118
Jefferson Cherry Hill Hospital
Cherry Hill, New Jersey, 08002
Mount Sinai Hospital Medical Center
Chicago, Illinois, 60608
Northwestern University
Chicago, Illinois, 60611
John H Stroger Jr Hospital of Cook County
Chicago, Illinois, 60612
University of Illinois
Chicago, Illinois, 60612
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Advocate Illinois Masonic Medical Center
Chicago, Illinois, 60657
Enloe Medical Center
Chico, California, 95926
Ascension Calumet Hospital-Chilton
Chilton, Wisconsin, 53014
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, 45219
Good Samaritan Hospital - Cincinnati
Cincinnati, Ohio, 45220
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376
Michigan Healthcare Professionals Clarkston
Clarkston, Michigan, 48346
Morton Plant Hospital
Clearwater, Florida, 33756
Wake Forest University at Clemmons
Clemmons, North Carolina, 27012
Cleveland Clinic Cancer Center/Fairview Hospital
Cleveland, Ohio, 44111
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Henry Ford Macomb Hospital-Clinton Township
Clinton Township, Michigan, 48038
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
Clive, Iowa, 50325
AdventHealth Infusion Center Haywood
Clyde, North Carolina, 28721
Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho, 83814
Baptist Memorial Hospital and Cancer Center-Collierville
Collierville, Tennessee, 38017
UCHealth Memorial Hospital Central
Colorado Springs, Colorado, 80909
Memorial Hospital North
Colorado Springs, Colorado, 80920
Baptist Memorial Hospital and Cancer Center-Golden Triangle
Columbus, Mississippi, 39705
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
New Hampshire Oncology Hematology PA-Concord
Concord, New Hampshire, 03301
UT MD Anderson - The Woodlands
Conroe, Texas, 77384
Mercy Hospital
Coon Rapids, Minnesota, 55433
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146
UM Sylvester Comprehensive Cancer Center at Coral Springs
Coral Springs, Florida, 33065
City of Hope Corona
Corona, California, 92882
Good Samaritan Hospital
Corvallis, Oregon, 97330
Northshore Oncology Associates-Covington
Covington, Louisiana, 70433
Ochsner Hematology Oncology North Shore - Covington (West Region)
Covington, Louisiana, 70433
UPMC Hillman Cancer Center - Passavant - Cranberry
Cranberry Township, Pennsylvania, 16066
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141
Northwest Cancer Center - Crown Point
Crown Point, Indiana, 46307
UChicago Medicine Northwest Indiana
Crown Point, Indiana, 46307
AMG Crystal Lake - Oncology
Crystal Lake, Illinois, 60014
Aurora Saint Luke's South Shore
Cudahy, Wisconsin, 53110
UPMC Western Maryland
Cumberland, Maryland, 21502
Houston Methodist Cypress Hospital
Cypress, Texas, 77429
Hamilton Medical Center - Peeples Cancer Institute
Dalton, Georgia, 30720
Danbury Hospital
Danbury, Connecticut, 06810
Carle at The Riverfront
Danville, Illinois, 61832
Geisinger Medical Center
Danville, Pennsylvania, 17822
Mercy Fitzgerald Hospital
Darby, Pennsylvania, 19023-1291
Miami Valley Hospital
Dayton, Ohio, 45409
Premier Blood and Cancer Center
Dayton, Ohio, 45409
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
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442
Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois, 60115
UCHealth - Cherry Creek
Denver, Colorado, 80206
Saint Joseph Hospital - Cancer Centers of Colorado
Denver, Colorado, 80218
Smilow Cancer Hospital-Derby Care Center
Derby, Connecticut, 06418
Iowa Methodist Medical Center
Des Moines, Iowa, 50309
UI Health Care Mission Cancer and Blood - Des Moines Clinic
Des Moines, Iowa, 50309
Broadlawns Medical Center
Des Moines, Iowa, 50314
UI Health Care Mission Cancer and Blood - Laurel Clinic
Des Moines, Iowa, 50314
Henry Ford Hospital
Detroit, Michigan, 48202
Henry Ford Health Saint John Hospital
Detroit, Michigan, 48236
Geisinger Cancer Center Dickson City
Dickson City, Pennsylvania, 18519
Illinois CancerCare-Dixon
Dixon, Illinois, 61021
UM Sylvester Comprehensive Cancer Center at Doral
Doral, Florida, 33166
Bayhealth Hospital Kent Campus
Dover, Delaware, 19901
Advocate Good Samaritan Hospital
Downers Grove, Illinois, 60515
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
Kaiser Permanente Dublin
Dublin, California, 94568
Essentia Health Cancer Center
Duluth, Minnesota, 55805
Saint Luke's Hospital of Duluth
Duluth, Minnesota, 55805
Duke University Medical Center
Durham, North Carolina, 27710
Northwest Oncology LLC
Dyer, Indiana, 46311
Prisma Health Cancer Institute - Easley
Easley, South Carolina, 29640
Henry Ford River District Hospital
East China Township, Michigan, 48054
Hematology Oncology Associates of Central New York-East Syracuse
East Syracuse, New York, 13057
Marshfield Medical Center-EC Cancer Center
Eau Claire, Wisconsin, 54701
Mayo Clinic Health System-Eau Claire Clinic
Eau Claire, Wisconsin, 54701
Fairview Southdale Hospital
Edina, Minnesota, 55435
Swedish Cancer Institute-Edmonds
Edmonds, Washington, 98026
Shaw Cancer Center
Edwards, Colorado, 81632
Carle Physician Group-Effingham
Effingham, Illinois, 62401
Crossroads Cancer Center
Effingham, Illinois, 62401
AtlantiCare Surgery Center
Egg Harbor, New Jersey, 08234
Advocate Sherman Hospital
Elgin, Illinois, 60123
Trinitas Hospital and Comprehensive Cancer Center - Williamson Street Campus
Elizabeth, New Jersey, 07207
Mercy Cancer Center - Elk Grove
Elk Grove, California, 95758
Stanford Cancer Center Emeryville
Emeryville, California, 94608
Ephrata Cancer Center
Ephrata, Pennsylvania, 17522
UPMC Hillman Cancer Center Erie
Erie, Pennsylvania, 16505
OSF Saint Francis Hospital and Medical Group
Escanaba, Michigan, 49829
Illinois CancerCare-Eureka
Eureka, Illinois, 61530
Smilow Cancer Hospital Care Center-Fairfield
Fairfield, Connecticut, 06824
Essentia Health Cancer Center-South University Clinic
Fargo, North Dakota, 58103
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
UPMC Cancer Center at UPMC Horizon
Farrell, Pennsylvania, 16121
Augusta Health Center for Cancer and Blood Disorders
Fishersville, Virginia, 22939
Cancer Hematology Centers - Flint
Flint, Michigan, 48503
Genesee Hematology Oncology PC
Flint, Michigan, 48503
Genesys Hurley Cancer Institute
Flint, Michigan, 48503
Hurley Medical Center
Flint, Michigan, 48503
The New York Hospital Medical Center of Queens
Flushing, New York, 11355
Poudre Valley Hospital
Fort Collins, Colorado, 80524
Cancer Care and Hematology-Fort Collins
Fort Collins, Colorado, 80528
McFarland Clinic - Trinity Cancer Center
Fort Dodge, Iowa, 50501
Mercy Hospital Fort Smith
Fort Smith, Arkansas, 72903
Atrium Medical Center-Middletown Regional Hospital
Franklin, Ohio, 45005-1066
Reiman Cancer Center-Ascension Wisconsin Health Center-Rawson
Franklin, Wisconsin, 53132
CentraState Medical Center
Freehold, New Jersey, 07728
Kaiser Permanente-Fremont
Fremont, California, 94538
Washington Health
Fremont, California, 94538
Kaiser Permanente Fresno Orchard Plaza
Fresno, California, 93720
Kaiser Permanente-Fresno
Fresno, California, 93720
Saint Luke's Cancer Institute - Fruitland
Fruitland, Idaho, 83619
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610
Kaiser Permanente-Gaithersburg Medical Center
Gaithersburg, Maryland, 20879
Illinois CancerCare-Galesburg
Galesburg, Illinois, 61401
University of Texas Medical Branch
Galveston, Texas, 77555-0565
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois, 60134
Aurora Health Care Germantown Health Center
Germantown, Wisconsin, 53022
Adams Cancer Center
Gettysburg, Pennsylvania, 17325
Arizona Center for Cancer Care - Gilbert
Gilbert, Arizona, 85297
Smilow Cancer Hospital Care Center at Glastonbury
Glastonbury, Connecticut, 06033
Glens Falls Hospital
Glens Falls, New York, 12801
Northwestern Medicine Glenview Outpatient Center
Glenview, Illinois, 60026
Addison Gilbert Hospital
Gloucester, Massachusetts, 01930
Lutheran Hospital - Cancer Centers of Colorado
Golden, Colorado, 80401
CTCA at Western Regional Medical Center
Goodyear, Arizona, 85338
Aurora Cancer Care-Grafton
Grafton, Wisconsin, 53024
Saint Mary's Hospital and Regional Medical Center
Grand Junction, Colorado, 81501
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
Grand Rapids, Michigan, 49503
Trinity Health Grand Rapids Hospital
Grand Rapids, Michigan, 49503
Three Rivers Community Hospital
Grants Pass, Oregon, 97527
Northwestern Medicine Grayslake Outpatient Center
Grayslake, Illinois, 60030
Benefis Sletten Cancer Institute
Great Falls, Montana, 59405
UCHealth Greeley Hospital
Greeley, Colorado, 80631
Saint Vincent Hospital Cancer Center Green Bay
Green Bay, Wisconsin, 54301
Saint Vincent Hospital Cancer Center at Saint Mary's
Green Bay, Wisconsin, 54303
Aurora BayCare Medical Center
Green Bay, Wisconsin, 54311
Northwell Health Cancer Institute at Huntington
Greenlawn, New York, 11740
UPMC Cancer Centers - Arnold Palmer Pavilion
Greensburg, Pennsylvania, 15601
Miami Valley Cancer Care and Infusion
Greenville, Ohio, 45331
Prisma Health Cancer Institute - Butternut
Greenville, South Carolina, 29605
Prisma Health Cancer Institute - Faris
Greenville, South Carolina, 29605
Prisma Health Cancer Institute - Eastside
Greenville, South Carolina, 29615
Smilow Cancer Hospital Care Center at Greenwich
Greenwich, Connecticut, 06830
Self Regional Healthcare
Greenwood, South Carolina, 29646
Prisma Health Cancer Institute - Greer
Greer, South Carolina, 29650
Baptist Cancer Center-Grenada
Grenada, Mississippi, 38901
Legacy Mount Hood Medical Center
Gresham, Oregon, 97030
Henry Ford Saint John Hospital - Academic
Grosse Pointe Woods, Michigan, 48236
Henry Ford Saint John Hospital - Breast
Grosse Pointe Woods, Michigan, 48236
Henry Ford Saint John Hospital - Van Elslander
Grosse Pointe Woods, Michigan, 48236
Smilow Cancer Hospital Care Center - Guilford
Guilford, Connecticut, 06437
Hackensack University Medical Center
Hackensack, New Jersey, 07601
The Cancer Institute of New Jersey Hamilton
Hamilton, New Jersey, 08690
UPMC Pinnacle Cancer Center/Community Osteopathic Campus
Harrisburg, Pennsylvania, 17109
Smilow Cancer Hospital Care Center at Saint Francis
Hartford, Connecticut, 06105
Ingalls Memorial Hospital
Harvey, Illinois, 60426
HaysMed
Hays, Kansas, 67601
Essentia Health-Hayward Clinic
Hayward, Wisconsin, 54843
Advocate South Suburban Hospital
Hazel Crest, Illinois, 60429
Margaret R Pardee Memorial Hospital
Hendersonville, North Carolina, 28791
AdventHealth Hendersonville
Hendersonville, North Carolina, 28792
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
University of North Carolina-Hillsborough Campus
Hillsborough, North Carolina, 27278
South Carolina Cancer Specialists PC
Hilton Head Island, South Carolina, 29926-3827
UChicago Medicine AdventHealth Cancer Institute Hinsdale
Hinsdale, Illinois, 60521
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
Queen's Cancer Center - Kuakini
Honolulu, Hawaii, 96817
Puerto Rico4 sites
Doctors Cancer Center
Manati, 00674
Centro Comprensivo de Cancer de UPR
San Juan, 00927
PROncology
San Juan, 00927
San Juan City Hospital
San Juan, 00936
About this study
Official title: LoTam: A Randomized, Phase III Clinical Trial of Low-Dose Tamoxifen for Selected Patients With Molecular Low-Risk Early-Stage Breast Cancer
This phase III trial compares the effect of low dose tamoxifen to usual hormonal therapy, including aromatase inhibitors, in treating post-menopausal women with hormone positive, HER2 negative early stage breast cancer. Tamoxifen is in a class of medications known as antiestrogens. It blocks the activity of estrogen (a female hormone) in the breast. This may stop the growth of some breast tumors that need estrogen to grow. Aromatase inhibitors, such as anastrozole, letrozole, and exemestane, prevent the formation of estradiol, a female hormone, by interfering with an aromatase enzyme. Aromatase inhibitors are used as a type of hormone therapy to treat postmenopausal women with hormone-dependent breast cancer. Giving low dose tamoxifen may be more effective compared to usual hormone therapy in treating post-menopausal women with hormone-positive, HER2 negative early stage breast cancer.
Read the detailed description
The primary and secondary objectives of the study:
PRIMARY OBJECTIVE:
- To evaluate whether the recurrence-free interval (RFI) with low-dose tamoxifen is non-inferior to standard-of-care endocrine therapy among post-menopausal women with early-stage, low molecular risk breast cancer.
SECONDARY OBJECTIVES:
- To compare endocrine therapy nonadherence rates between treatment arms. II. To compare the incidence of adverse events between treatment arms, including osteoporosis, fracture, endometrial carcinoma, stroke, and deep vein thrombosis.
III. To compare endocrine therapy-related patient reported symptoms between treatment arms.
IV. To compare the invasive disease-free survival between treatment arms. V. To compare the locoregional breast cancer recurrence between treatment arms. VI. To compare distant recurrence free survival between treatment arms. VII. To compare overall survival between treatment arms. VIII. To compare ductal carcinoma in situ (DCIS) incidence (ipsilateral and contralateral) between treatment arms.
IX. To evaluate the association between radiotherapy modality (no radiation, partial breast radiation, and whole breast radiation) and RFI in each arm.
- To explore important measures of quality of life that would reasonably be expected to vary by study arm, including global quality of life and reasons for nonadherence.
XI. To compare change in mammographic density at two years between treatment arms.
XII. To conduct a within patient comparison of automated versus (vs) semi-automated mammographic density determination.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive standard of care endocrine therapy per physician choice with either anastrozole orally (PO), letrozole PO, exemestane PO or standard dose tamoxifen PO once daily (QD) for up to 5 years in the absence of disease progression or unacceptable toxicity. Patients may also undergo mammogram or magnetic resonance imaging (MRI), dual X-ray absorptiometry (DEXA), and blood sample collection on study.
ARM II: Patients receive low-dose tamoxifen PO every other day (QOD) for up to 5 years in the absence of disease progression or unacceptable toxicity. Patients may also undergo mammogram or MRI, DEXA, and blood sample collection on study.
After completion of study treatment, patients are followed up for 10 years after registration.
- Conditions
- Anatomic Stage 0 Breast Cancer AJCC v8, Anatomic Stage 1 Breast Cancer AJCC v8, Anatomic Stage IIA Breast Cancer AJCC v8, Estrogen Receptor-Positive Breast Carcinoma, HER2-Negative Breast Carcinoma, Breast Ductal Carcinoma In Situ
- Being tested
- Anastrozole, Letrozole, Exemestane, Tamoxifen, Mammogram
- Medical subject headings
- Breast Carcinoma In Situ, Carcinoma, Intraductal, Noninfiltrating
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AnastrozoleDrug
Given PO
LetrozoleDrug
Given PO
ExemestaneDrug
Given PO
TamoxifenDrug
Given PO
MammogramProcedure or surgery
Undergo mammogram
Magnetic Resonance ImagingProcedure or surgery
Undergo MRI
Dual X-ray AbsorptiometryBiological
Undergo DEXA
Biospecimen CollectionProcedure or surgery
Undergo blood sample collection
Questionnaire AdministrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Arm I (anastrozole, letrozole, exemestane, tamoxifen) | Active comparator | Patients receive standard of care endocrine therapy per physician choice with either anastrozole PO, letrozole PO, exemestane PO or standard dose tamoxifen PO QD for up to 5 years in the absence of disease progression or unacceptable toxicity. Patients may also undergo mammogram or MRI, DEXA, and blood sample collection on study. Receives: Drug: Anastrozole; Drug: Letrozole; Drug: Exemestane; Drug: Tamoxifen; Procedure: Mammogram; Procedure: Magnetic Resonance Imaging; Biological: Dual X-ray Absorptiometry; Procedure: Biospecimen Collection; Other: Questionnaire Administration |
| Arm II (low dose tamoxifen) | Experimental | Patients receive low-dose tamoxifen PO QOD for up to 5 years in the absence of disease progression or unacceptable toxicity. Patients may also undergo mammogram or MRI, DEXA, and blood sample collection on study. Receives: Drug: Tamoxifen; Procedure: Mammogram; Procedure: Magnetic Resonance Imaging; Biological: Dual X-ray Absorptiometry; Procedure: Biospecimen Collection; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recurrence-free interval (RFI)
The Kaplan-Meier method will be used to estimate the distribution of RFI times and a stratified log-rank test for non-inferiority will be used to assess whether RFI with low-dose tamoxifen is non-inferior to standard-of-care endocrine therapy in this patient population. Stratified Cox modeling will be used to estimate the hazard ratio and corresponding one-sided 95% confidence interval (CI).
Measured: From randomization to the first of the following breast cancer events: invasive ipsilateral breast or chest wall recurrence, regional recurrence, distant recurrence, and death from breast cancer up to 5 years
Secondary outcomes (10)
Endocrine therapy extent of nonadherence
The proportion of patients who stopped treatment early will be compared between the two treatment arms with a chi-square test. Additional analyses will be performed with respect to nonadherence. The proportion of patients who report any nonadherence will be compared between the two treatment arms using generalized estimating equations for logistic regression
Measured: Up to 5 years
Physician reported incidence of adverse events (AEs)
AEs will be evaluated and graded using the Common Terminology Criteria for Adverse Events version 5.0 with special focus on the incidence of fracture, osteoporosis, stroke and thromboembolic events.
Measured: Up to 10 years
Patient reported toxicities
Patient reported symptoms assessed using Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE). The proportion of patients with a maximum post-baseline score greater than 0 will be compared between arms using Fisher's exact test. The proportion of patients with a maximum post-baseline score greater than or equal to 3 will be compared between arms using Fisher's exact test. The same procedure will be applied to patients' maximum baseline-adjusted scores. Patients' maximum baseline-adjusted scores will be calculated using the method described by Dueck et al. The proportion of patients who report a grade 3 or higher AEs using PRO-CTCAE will be compared between the two treatment arms with a chi-square test. The proportion of patients with reported grade 3 or higher endocrine-related adverse event (any one of fracture, stroke, or deep vein thrombosis) will be compared with a chi-square test or Fisher's exact test, whichever is more appropriate.
Measured: At baseline and up to 10 years
Invasive disease-free survival (iDFS)
IDFS will be defined as local, regional or distant recurrences, or contralateral invasive breast cancer, second non-breast primary cancer, and death from any cause. IDFS will be compared between the treatment arms with a stratified log rank test and a stratified Cox model will be used to generate the hazard ratio estimates (both a point estimate and a 95% CI).
Measured: Up to 10 years
Locoregional recurrence free-survival (LRFS)
LRFS will be defined as the time from randomization until invasive tumor recurs in the ipsilateral breast or chest wall, axillary, supraclavicular, or internal mammary nodes (if before or synchronous with a systemic recurrence), whichever comes first. LRFS will be compared between the treatment arms with a stratified log rank test and a stratified Cox model will be used to generate the hazard ratio estimates (both a point estimate and a 95% CI).
Measured: From randomization until invasive tumor recurs in the ipsilateral breast or chest wall, axillary, supraclavicular, or internal mammary nodes up to 10 years
Distant disease-free survival (DDFS)
DDFS will be defined as the time from randomization until the tumor recurs distantly, or the patient dies, whichever comes first. DDFS will be compared between the treatment arms with a stratified log rank test and a stratified Cox model will be used to generate the hazard ratio estimates (both a point estimate and a 95% CI).
Measured: From randomization until the tumor recurs distantly or death up to 10 years
Overall survival (OS)
OS will be defined as the time from randomization until death due to any cause. OS will be compared between the treatment arms with a stratified log rank test and a stratified Cox model will be used to generate the hazard ratio estimates (both a point estimate and a 95% CI).
Measured: From randomization until death up to 10 years
Cumulative incidence rate of ductal carcinoma in situ (DCIS)
Cumulative incidence rate of DCIS will be measured as the time from randomization until the occurrence of an ipsilateral or contralateral DCIS diagnosis. The cumulative incidence of DCIS will be analyzed with Kaplan-Meier estimates (curve starting at 0 rather than 1) and compared with a log rank test.
Measured: From randomization until the occurrence of an ipsilateral or contralateral DCIS diagnosis up to 10 years
RFI in patients who did not receive radiation therapy
A key analysis will be to report on the updated estimate of the primary endpoint (RFI) after all patients have been followed for 10 years, if the primary analysis took place prior to this time. There are two key subgroup analyses. These analyses will occur once the requisite number of events have been observed within the subgroup or after all patients have been followed for 10 years, whichever occurs first. All endpoints will be evaluated and reported for patients who did not receive radiation therapy. Will also determine whether there is evidence for differential treatment effects in these subgroups by including the subgroup, the treatment arm, and the interaction term. Will compare outcomes by arm and subgroup using Kaplan-Meier curves and Cox models where the control arm and better prognosis group within the grouping variable will be the reference.
Measured: At the time requisite number of events have been observed within the subgroup or after all patients have been followed for 10 years, whichever occurs first
RFI in patients who had an intermediate Oncotype DX score
A key analysis will be to report on the updated estimate of the primary endpoint (RFI) after all patients have been followed for 10 years, if the primary analysis took place prior to this time. There are two key subgroup analyses. These analyses will occur once the requisite number of events have been observed within the subgroup or after all patients have been followed for 10 years, whichever occurs first. All endpoints will be evaluated and reported for patients who had an intermediate Oncotype DX score. Will also determine whether there is evidence for differential treatment effects in these subgroups by including the subgroup, the treatment arm, and the interaction term. Will compare outcomes by arm and subgroup using Kaplan-Meier curves and Cox models where the control arm and better prognosis group within the grouping variable will be the reference.
Measured: At the time requisite number of events have been observed within the subgroup or after all patients have been followed for 10 years, whichever occurs first
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2024
- Study start19 Feb 2025
- Primary completion30 Nov 2030 (estimated)
- Study completion30 Nov 2031 (estimated)
Why it stopped: Amending protocol to increase sample size
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anatomic Stage 0 Breast Cancer AJCC v8Studies of the same condition, open and under way.
- More trials run by Alliance for Clinical Trials in OncologyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Masking
- None (open label)
- Enrolment
- 1,556 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Alliance for Clinical Trials in Oncology
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06671912
- Sponsor's protocol ID
- A012301
- Other IDs
- NCI-2024-06672
- Acronym
- LoTam
- Status last verified
- Sep 2026
- First submitted
- 1 Nov 2024
- Last updated
- 2 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided