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RecruitingInterventionalPhase 3

CAMBRIA-2: A Phase III, Open-Label, Randomised Study to Assess the Efficacy and Safety of Camizestrant (AZD9833, a Next Generation, Oral Selective Estrogen Receptor Degrader) vs Standard Endocrine Therapy (Aromatase Inhibitor or Tamoxifen) as Adjuvant Treatment for Patients With ER+/HER2- Early Breast Cancer and an Intermediate-High or High Risk of Recurrence Who Have Completed Definitive Locoregional Treatment and Have No Evidence of Disease

NCT ID: NCT05952557Sponsor: AstraZenecaLast updated: 2026-05-28

Summary

This is a Phase III open-label study to assess if camizestrant improves outcomes compared to standard adjuvant endocrine therapy for patients with ER+/HER2- early breast cancer with intermediate-high or high risk for disease recurrence who completed definitive locoregional therapy (with or without chemotherapy). The planned duration of treatment in either arm within the study will be 7 years.

Detailed description

This is a Phase III open-label study to assess if camizestrant improves outcomes compared to standard adjuvant endocrine therapy for patients with ER+/HER2- early breast cancer with intermediate-high or high risk for disease recurrence who completed definitive locoregional therapy (with or without chemotherapy). The planned duration of treatment in either arm of the study is 7 years. Eligible patients must have intermediate-high or high risk of recurrence as defined by specified clinical and biologic criteria. Concurrent use of abemaciclib is permitted in both arms. The primary endpoint of the study is Invasive breast cancer-free survival (IBCFS) and main secondary endpoints include Invasive disease-free survival (IDFS), Distant relapse-free survival (DRFS), Overall survival (OS), Safety and Clinical Outcome Assessments (COAs). Patients will be followed for 10 years from randomization of the last patient.

Arms & interventions

  • DrugCamizestrant

    Camizestrant. Experimental. Administered orally

  • DrugTamoxifen

    Tamoxifen. Comparator. Administered orally

  • DrugAnastrozole

    Anastrozole. Comparator. Administered orally

  • DrugLetrozole

    Letrozole. Comparator. Administered orally

  • DrugExemestane

    Exemestane. Comparator. Administered orally

  • DrugAbemaciclib

    Abemaciclib adjuvant treatment Administered orally

Outcome measures

Primary

  • Invasive breast cancer-free survival (IBCFS)

    IBCFS is defined as time from randomisation until date of first occurrence of: * Invasive ipsilateral breast tumour recurrence * Locoregional invasive breast cancer recurrence * Distant recurrence * Contralateral invasive breast cancer * Death attributable to any cause.

    Time frame: Up to 14 years

Secondary

  • Invasive disease-free survival (IDFS)

    Time frame: Up to 14 years

  • Distant relapse-free survival (DRFS)

    Time frame: Up to 14 years

  • Overall survival (OS)

    Time frame: Up to 14 years

  • Incidence and Severity of Adverse Events, with Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI-CTCAE v5.0)

    Time frame: Until 28 days after the final dose of study treatment (up to 7 years)

  • Proportion of time on study treatment with high side-effect burden as measured by the PGI-TT.

    Time frame: Until 28 days after the final dose of study treatment (up to 7 years)

  • Change from baseline and time to deterioration of health-related quality of life as measured by the 2 global QoL items from the EORTC IL-311

    Time frame: Until 28 days after the final dose of study treatment (up to 7 years)

  • Pharmacokinetics (PK)

    Time frame: Until 6 months from treatment start

Eligibility criteria

Sex: AllAge: 18 Years to 130 YearsHealthy volunteers: No
Inclusion Criteria: * Women and Men; ≥18 years at the time of screening (or per national guidelines) * Histologically confirmed ER+/HER2- early-stage resected invasive breast cancer with absence of any evidence of metastatic disease as defined in the protocol. * Completed adequate (definitive) locoregional therapy (surgery with or without radiotherapy) for the primary breast tumour(s), with or without (neo)adjuvant chemotherapy. * Patients must be randomised within 12 months of definitive breast surgery. * Patients may have received up to 12 weeks of endocrine therapy prior to randomisation. * Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 * Adequate organ and bone marrow function Exclusion Criteria: * Inoperable locally advanced or metastatic breast cancer * Pathological complete response following treatment with neoadjuvant therapy * History of any other cancer (except non-melanoma skin cancer or carcinoma in situ of the cervix or considered a very low risk of recurrence per investigator judgement) unless in complete remission with no therapy for a minimum of 5 years from the date of randomisation * Any evidence of severe or uncontrolled systemic diseases which, in the investigator's opinion precludes participation in the study or compliance " * Known LVEF \<50% with heart failure NYHA Grade ≥2. * Mean resting QTcF interval \> 480 ms at screening * Concurrent exogenous reproductive hormone therapy or non topical hormonal therapy for non-cancer-related conditions * Any concurrent anti-cancer treatment not specified in the protocol with the exception of bisphosphonates (e.g. zoledronic acid) or RANKL inhibitors ( eg, denosumab) * Previous treatment with camizestrant, investigational SERDs/investigational ER targeting agents, or fulvestrant * Currently pregnant (confirmed with positive serum pregnancy test) or breastfeeding. * Patients with known hypersensitivity to active or inactive excipients of camizestrant or drugs with a similar chemical structure or class to camizestrant. In pre-/peri-menopausal female and male patients, known hypersensitivity or intolerance to LHRH agonists that would preclude the patient from receiving any LHRH agonist.

Study locations (148)

Research Site

Dothan, Alabama, 36303

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Phoenix, Arizona, 85054

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Tucson, Arizona, 85745

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Fayetteville, Arkansas, 72703

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Duarte, California, 91010

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Fountain Valley, California, 92708

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Greenbrae, California, 94904

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Irvine, California, 92618

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La Jolla, California, 92093

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Los Angeles, California, 90017

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Monterey, California, 93940

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Walnut Creek, California, 94598

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West Hollywood, California, 90048

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Aurora, Colorado, 80045

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Littleton, Colorado, 80120

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Littleton, Colorado, 80129

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New Haven, Connecticut, 06510

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Newark, Delaware, 19713

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Washington D.C., District of Columbia, 20016

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Clearwater, Florida, 33756

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Fort Myers, Florida, 33901

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Gainesville, Florida, 32610

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Jacksonville, Florida, 32224

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Orlando, Florida, 32806

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Pembroke Pines, Florida, 33028

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Plantation, Florida, 33322

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Plantation, Florida, 33324

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St. Petersburg, Florida, 33705

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St. Petersburg, Florida, 33709

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Tallahassee, Florida, 32308

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West Palm Beach, Florida, 33401

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Atlanta, Georgia, 30318

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Atlanta, Georgia, 30322

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Columbus, Georgia, 31904

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Marietta, Georgia, 30060

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Savannah, Georgia, 31404

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Thomasville, Georgia, 31792

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Chicago, Illinois, 60637

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Elmhurst, Illinois, 60126

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Naperville, Illinois, 60540

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Park Ridge, Illinois, 60068

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Plainfield, Illinois, 60585

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Urbana, Illinois, 61801

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Fort Wayne, Indiana, 46804

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Des Moines, Iowa, 50309

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Fairway, Kansas, 66205

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Louisville, Kentucky, 40202

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New Orleans, Louisiana, 70121

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Scarborough, Maine, 04074

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Annapolis, Maryland, 21401

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Baltimore, Maryland, 21201

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Baltimore, Maryland, 21287

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Bethesda, Maryland, 20817

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Lutherville, Maryland, 21093

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Towson, Maryland, 21204

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Boston, Massachusetts, 02111

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Boston, Massachusetts, 02115

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Hyannis, Massachusetts, 02601

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Worcester, Massachusetts, 01655

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Detroit, Michigan, 48202

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Flint, Michigan, 48503

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Ypsilanti, Michigan, 48197

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Minneapolis, Minnesota, 55416

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Rochester, Minnesota, 55905

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Kansas City, Missouri, 64111

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St Louis, Missouri, 63110

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St Louis, Missouri, 63131

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Lincoln, Nebraska, 68506

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Omaha, Nebraska, 68124

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Omaha, Nebraska, 68198

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Hooksett, New Hampshire, 03106

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Lebanon, New Hampshire, 03756

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Manchester, New Hampshire, 03103

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New Brunswick, New Jersey, 08901

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Albuquerque, New Mexico, 87109

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Farmington, New Mexico, 87401

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Bay Shore, New York, 11706

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East Syracuse, New York, 13057

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Greenlawn, New York, 11740

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New Hyde Park, New York, 11042

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New York, New York, 10029

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New York, New York, 10065

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New York, New York, 10065

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Stony Brook, New York, 11794

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White Plains, New York, 10601

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Charlotte, North Carolina, 28204

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Durham, North Carolina, 27710

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Greensboro, North Carolina, 27403

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Greenville, North Carolina, 27834

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Pinehurst, North Carolina, 28374

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Raleigh, North Carolina, 27607

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Winston-Salem, North Carolina, 27103

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Blue Ash, Ohio, 45242

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Cincinnati, Ohio, 45255

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Cleveland, Ohio, 44106

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Columbus, Ohio, 43212

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Toledo, Ohio, 43623

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Youngstown, Ohio, 44504

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Oklahoma City, Oklahoma, 73104

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Portland, Oregon, 97210

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Portland, Oregon, 97213

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Portland, Oregon, 97225

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Gettysburg, Pennsylvania, 17325

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Hershey, Pennsylvania, 17033

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Philadelphia, Pennsylvania, 19104

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Pittsburgh, Pennsylvania, 15213

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Sayre, Pennsylvania, 18840

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York, Pennsylvania, 17403

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Charleston, South Carolina, 29425

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Greenville, South Carolina, 29605

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Rock Hill, South Carolina, 29732

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Spartanburg, South Carolina, 29303

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Aberdeen, South Dakota, 57401

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Sioux Falls, South Dakota, 57105

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Chattanooga, Tennessee, 37404

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Knoxville, Tennessee, 37909

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Knoxville, Tennessee, 37920

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Memphis, Tennessee, 38120

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Nashville, Tennessee, 37203

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Nashville, Tennessee, 37232

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Austin, Texas, 78731

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Bedford, Texas, 76022

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Dallas, Texas, 75230

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Dallas, Texas, 75231

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Dallas, Texas, 75246

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El Paso, Texas, 79902

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Flower Mound, Texas, 75028

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Houston, Texas, 77024

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Houston, Texas, 77030

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Plano, Texas, 75075

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San Antonio, Texas, 78217

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Tyler, Texas, 75702

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Salt Lake City, Utah, 84112

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Charlottesville, Virginia, 22908

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Fairfax, Virginia, 22031

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Midlothian, Virginia, 23114

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Norfolk, Virginia, 23502

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Richmond, Virginia, 23219

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Roanoke, Virginia, 24014

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Winchester, Virginia, 22601

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Puyallup, Washington, 98373

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Spokane, Washington, 99202

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Vancouver, Washington, 98684

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Charleston, West Virginia, 25304

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Morgantown, West Virginia, 26505

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Appleton, Wisconsin, 54911

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Madison, Wisconsin, 53792

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Milwaukee, Wisconsin, 53215

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References

  • Hamilton EP, Loibl S, Bachelot T, Gnant M, Niikura N, Park YH, Tolaney SM, Pistilli B, Rastogi P, Saini KS, Gioni I, Johnston S, Nunes R, Quintana A, Stuart M, Syta E, Walding A, Klinowska T, Mayer IA. CAMBRIA-1 & CAMBRIA-2 phase III trials: camizestrant versus standard endocrine therapy in ER+/HER2- early breast cancer. Future Oncol. 2025 Mar;21(7):795-806. doi: 10.1080/14796694.2025.2459548. Epub 2025 Feb 27.(PubMed)
An Adjuvant Endocrine-based Therapy Study of Camizestrant (AZD9833) in ER+/HER2- Early Breast Cancer (CAMBRIA-2) | Cancerify