Letrozole in Preventing Cancer in Postmenopausal Women Who Have Received 4-6 Years of Hormone Therapy for Hormone Receptor-Positive, Lymph Node-Positive, Early-Stage Breast Cancer (SOLE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00553410
Recruitment Status : Active, not recruiting
First Posted : November 5, 2007
Last Update Posted : March 6, 2018
Breast International Group
Information provided by (Responsible Party):
International Breast Cancer Study Group

Brief Summary:

RATIONALE: Estrogen can cause the growth of breast cancer cells. Letrozole may fight breast cancer by lowering the amount of estrogen the body makes. It is not yet known which regimen of letrozole is more effective in postmenopausal women who have received hormone therapy for early-stage breast cancer.

PURPOSE: This randomized phase III trial is comparing two different regimens of letrozole in preventing cancer in postmenopausal women who have received 4-6 years of hormone therapy for hormone receptor-positive, lymph node-positive, early-stage breast cancer.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Letrozole Phase 3

Detailed Description:



  • Compare the disease-free survival (DFS) of postmenopausal women treated with continuous letrozole for 5 years vs intermittent letrozole over a 5-year period.


  • Compare overall survival of patients treated with these two regimens.
  • Compare distant DFS of these patients.
  • Compare breast cancer-free interval of these patients.
  • Compare sites of first DFS failure in these patients.
  • Compare second (nonbreast) malignancies in these patients.
  • Compare deaths without prior cancer events in these patients.
  • Compare adverse events resulting from these two regimens.

OUTLINE: This is a multicenter study. Patients are stratified according to treatment center and type of prior endocrine therapy (selective estrogen receptor modulators [SERMs] alone vs aromatase inhibitors [AIs] alone vs both SERMs and AIs each for at least 1 month). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral letrozole daily for 5 years.
  • Arm II: Patients receive oral letrozole daily for the first 9 months of years 1 through 4, followed by 12 months in year 5.

After completion of study therapy, patients are followed annually.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4884 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: SOLE, Study of Letrozole Extension, A Phase III Trial Evaluating the Role of Continuous Letrozole Versus Intermittent Letrozole Following 4 to 6 Years of Prior Adjuvant Endocrine Therapy for Postmenopausal Women With Hormone-Receptor Positive, Node Positive Early Stage Breast Cancer
Study Start Date : August 2007
Estimated Primary Completion Date : April 2019
Estimated Study Completion Date : April 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Letrozole

Arm Intervention/treatment
Active Comparator: Continuous letrozole
Continuous letrozole: 5 years continuously (2.5 mg Letrozole daily)
Drug: Letrozole
Film-coated tablet, oral use, 2.5 mg Letrozole daily for 5 years continuously

Experimental: Intermittent letrozole
Intermittent letrozole: 48 months over 5 yrs: 4 x 9 months (9 mo followed by 3 mo treatment-free interval in yrs 1-4, -> 36 mo) plus 1 x 12 mo in yr 5 -> 48 months
Drug: Letrozole
Film-coated tablet, oral use, 2.5 mg daily, 48 months over 5 yrs: 4 x 9 months (9 mo followed by 3 mo treatment-free interval in yrs 1-4, -> 36 mo) plus 1 x 12 mo in yr 5 -> 48 months

Primary Outcome Measures :
  1. Disease-free survival (DFS) [ Time Frame: estimated 10 years after first patient in ]

Secondary Outcome Measures :
  1. Overall survival [ Time Frame: estimated 10 years after first patient in ]
  2. Distant DFS [ Time Frame: estimated 10 years after first patient in ]
  3. Breast cancer-free interval [ Time Frame: estimated 10 years after first patient in ]
  4. Sites of first DFS failure [ Time Frame: estimated 10 years after first patient in ]
  5. Second (nonbreast) malignancies [ Time Frame: estimated 10 years after first patient in ]
  6. Deaths without prior cancer events [ Time Frame: estimated 10 years after first patient in ]
  7. Adverse events [ Time Frame: estimated 10 years after first patient in ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No


  • Confirmed diagnosis of prior operable, noninflammatory breast cancer meeting the following criteria:

    • Steroid hormone receptor-positive tumors (estrogen receptor and/or progesterone receptor), determined by immunohistochemistry, after primary surgery and before commencement of prior endocrine therapy
    • Prior local treatment including surgery with or without radiotherapy for primary breast cancer with no known clinical residual loco-regional disease
    • Following primary surgery, eligible patients must have had evidence of lymph node involvement either in the axillary or internal mammary nodes, but not supraclavicular nodes
    • Clinically disease-free
  • Must have completed 4-6 years of prior adjuvant selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs), or a sequential combination of both

    • When calculating 4-6 years, neoadjuvant endocrine therapy should not be included
  • No evidence of recurrent disease or distant metastatic disease
  • No prior bilateral breast cancer


  • Female
  • Must be postmenopausal by any of the following criteria:

    • Patients of any age who have had a bilateral oophorectomy (including radiation castration AND amenorrheic for > 3 months)
    • Patients 56 years old or older with any evidence of ovarian function must have biochemical evidence of definite postmenopausal status (defined as estradiol, luteinizing hormone [LH], and follicle-stimulating hormone [FSH] in the postmenopausal range)
    • Patients 55 years old or younger must have biochemical evidence of definite postmenopausal status (defined as estradiol, LH, and FSH in the postmenopausal range)

      • Patients who have received prior luteinizing-hormone releasing-hormone (LHRH) analogues within the last year are eligible if they have definite evidence of postmenopausal status as defined above
  • Clinically adequate hepatic function
  • No bone fracture due to osteoporosis at any time during the 4-6 years of prior therapy
  • No prior or current malignancy except adequately treated basal cell or squamous cell carcinoma of the skin, in situ carcinoma of the cervix or bladder, or contra- or ipsilateral in situ breast carcinoma
  • No other nonmalignant systemic diseases (cardiovascular, renal, lung, etc.) that would prevent prolonged follow-up
  • No psychiatric, addictive, or any other disorder that compromises compliance with protocol requirements


  • See Disease Characteristics
  • More than 12 months since prior and no other concurrent endocrine SERM/AI therapy
  • Any type of prior adjuvant therapy allowed including, but not limited to, any of the following:

    • Neoadjuvant chemotherapy
    • Neoadjuvant endocrine therapy
    • Adjuvant chemotherapy
    • Trastuzumab (Herceptin®)
    • Ovarian ablation
    • Gonadotropin releasing hormone analogues
    • Lapatinib ditosylate
  • No concurrent hormone-replacement therapy, bisphosphonates (except for treatment of bone loss), or any other investigational agent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00553410

  Hide Study Locations
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Faulkner Hospital
Boston, Massachusetts, United States, 02130-3400
Australia, New South Wales
Armidale Hospital
Armidale, New South Wales, Australia, 2350
Bankstown - Lidcombe Hospital
Bankstown, New South Wales, Australia, 2200
Southern Highlands Cancer Center
Bowral, New South Wales, Australia, 2576
Concord Repatriation General Hospital
Concord, New South Wales, Australia, 2139
Breast Center
Gateshead, New South Wales, Australia, 2290
Port Mcquarie Base Hospital
Port Macquarie, New South Wales, Australia, 2444
Prince of Wales Private Hospital
Randwick, New South Wales, Australia, 2031
Tamworth Base Hospital
Tamworth, New South Wales, Australia, 2340
Tweed Heads Hospital
Tweed Heads, New South Wales, Australia, 2485
Calvary Mater Newcastle
Waratah, New South Wales, Australia, 2310
Australia, Tasmania
North West Regional Hospital
Burnie, Tasmania, Australia, 7320
Royal Hobart Hospital
Hobart, Tasmania, Australia, 7000
Australia, Victoria
Box Hill Hospital
Box Hill, Victoria, Australia, 3128
Peter MacCallum Cancer Centre
East Melbourne, Victoria, Australia, 3002
Austin Health
Heidelberg, Victoria, Australia, 3084
Maroondah Hospital
Melbourne, Victoria, Australia, 3135
Australia, Western Australia
Royal Perth Hospital
Perth, Western Australia, Australia, 6000
Landeskrankenhaus Feldkirch
Feldkirch, Austria, A-6807
Medizinische Universitaet Graz
Graz, Austria, A-8036
Innsbruck Universitaetsklinik
Innsbruck, Austria, A-6020
Krankenhaus BHS Linz
Linz, Austria, A-4010
Allgemeines Krankenhaus Linz
Linz, Austria, A-4021
St. Johanns-Spital
Salzburg, Austria, A-5020
Medical University of Vienna
Vienna, Austria, 1090
Allgemeines Krankenhaus - Universitatskliniken
Vienna, Austria, A-1090
Krankenhaus Lainz
Vienna, Austria, A-1130
Vienna, Austria, A-1140
LKH Villach
Villach, Austria, 9500
Klinikum Kreuzschwestern Wels GmbH
Wels, Austria, 4600
Ziekenhuis Netwerk Antwerpen Middelheim
Antwerpen, Belgium, B-2020
Cliniques du Sud Luxembourg
Arlon, Belgium, 6700
Imelda vzw, Ziekenhuis
Bonheiden, Belgium, 2820
AZ Klina
Brasschaat, Belgium, 2930
Institut Jules Bordet
Brussels, Belgium, 1000
Academisch Ziekenhuis der Vrije Universiteit Brussel
Brussels, Belgium, 1090
Cliniques Universitaires Saint-Luc
Brussels, Belgium, 1200
Centre Hospitalier Universitaire Brugmann
Brussels, Belgium, B 1020
Algemeen Ziekenhuis Sint-Maarten - Campus Rooiberg
Duffel, Belgium, 2570
Universitair Ziekenhuis Gent
Ghent, Belgium, B-9000
Hopital de Jolimont
Haine Saint Paul, Belgium, 7100
Virga Jesse Hospital
Hasselt, Belgium, 3500
Centre Hospitalier Hutois
Huy, Belgium, 4500
AZ Groeninge - Oncologisch Centrum
Kortrijk, Belgium, 8500
U.Z. Gasthuisberg
Leuven, Belgium, B-3000
Centre Hospitalier de l'Ardenne
Libramont, Belgium, 6800
Centre Hospitalier Regional de la Citadelle
Liege, Belgium, 4000
Clinique Saint-Joseph
Liege, Belgium, B 4000
CHU Liege - Domaine Universitaire du Sart Tilman
Liege, Belgium, B-4000
Jan Palfijn Hospital
Merksem, Belgium, B-2170
AZ Damiaan
Oostende, Belgium, 8400
Clinique Saint-Pierre
Ottignies, Belgium, B-1340
Clinique Saint Vincent
Rocourt, Belgium, 4000
AZ Nikolaas - Sint-Niklaas
Sint-Niklaas, Belgium, 9100
Turnhout, Belgium, 2300
Centre Hospitalier Peltzer-La Tourelle
Verviers, Belgium, B-4800
Hospital Santiago Oriente Dr. Luis Tisne Brousse
Penalolen, Chile, 2005
Fundacion Arturo Lopez Perez
Santiago, Chile, 29
Hospital Clinico San Borja Arriaran
Santiago, Chile
Instituto Nacional Del Cancer
Santiago, Chile
IRAM - Chile
Santiago, Chile
Hospital Clinico Regional de Valdivia at University Austral de Chile
Valdivia, Chile
Hospital Carlos Van Buren
Valparaiso, Chile
Aarhus Universitetshospital - Aarhus Sygehus
Aarhus C, Denmark, DK-8000
Copenhagen County Herlev University Hospital
Copenhagen, Denmark, DK-2730
Centralsygehus Esbjerg
Esbjerg, Denmark, DK-6700
Herning Central Hospital
Herning, Denmark, DK-7400
Hillerod Hospital
Hillerod, Denmark, 3400
Naestved Hospital
Naestved, Denmark, 4700
Odense University Hospital
Odense, Denmark, DK-5000
Bornholms Hospital
Ronne, Denmark, 3700
Roskilde Amtssygehuset
Roskilde, Denmark, 4000
Sonderborg Sygehus
Sonderborg, Denmark, 6400
Vejle Sygehus
Vejle, Denmark, DK-7100
Viborg Sygehus
Viborg, Denmark, 8800
Institut Bergonie
Bordeaux, France, 33076
Aalen Breast Center
Aalen, Germany, 73430
Onkologische Schwerpunktpraxis Bielefeld
Bielefeld, Germany, D-33602
Allgemeinen Krankenhaus Celle Kinderklinik
Celle, Germany, 29223
Klinikum Deggendorf
Deggendorf, Germany, 94469
Praxis Dr. Wilke - Onkologie am Klinikum Fuerth
Fuerth, Germany, 90766
Vinzenzkrankenhaus Hannover gGmbH
Hannover, Germany, 30559
Henriettenstiftung Krankenhaus
Hannover, Germany, D-30171
Gynaekologisch-onkologische Praxis Hannover
Hannover, Germany, D-30177
Frauenheilkunde u. Geburtshilfe
Ilsede, Germany, 31241
Asklepios Klinik Lich
Lich, Germany, D-35423
Gemeinschaftspraxis Gynaekologie & Geburtshilfe
Mannheim, Germany, D68161
Klinikum Meiningen GmbH
Meiningen, Germany, 98617
Klinikum Memmingen
Memmingen, Germany, 87700
Klinikum Offenback GmbH
Offenbach, Germany, D-63069
Deaconess Hospital
Schwabisch Hall, Germany, D-74523
Johanniter Kankenhaus Stendal
Stendal, Germany, 39576
SRH Zentralklinikum Suhl GmbH
Suhl, Germany, 98527
Universitaetsklinikum Tuebingen
Tuebingen, Germany, D-72076
National Institute of Oncology - Budapest
Budapest, Hungary, 1122
Szeged University
Szeged, Hungary, H-6720
Tata Memorial Hospital
Mumbai, India, 400012
Centro di Riferimento Oncologico - Aviano
Aviano, Italy, 33081
Ospedale degli Infermi - ASL 12
Biella, Italy, 13900
Azienda Sanitaria di Bolzano
Bolzano, Italy, 39100
Spedali Civili di Brescia
Brescia, Italy, 25123
A. Perrino Hospital
Brindisi, Italy, 72100
Azienda Istituti Ospitalieri
Cremona, Italy, 26100
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
Meldola, Italy, 47014
European Institute of Oncology
Milan, Italy, 20141
Fondazione Salvatore Maugeri
Pavia, Italy, I-27100
Misericordia e Dolce Hospital
Prato, Italy, 59100
Ospedale Civile Rimini
Rimini, Italy, 47900
Ospedale di Circolo e Fondazione Macchi
Varese, Italy, 21100
Osaka Rosai Hospital
Sakai, Osaka, Japan, 1179-3
Sagara Hospital
Kagoshima, Japan
Kumamoto University Faculty of Medical and Pharmaceutical Sciences
Kumamoto, Japan, 860-8556
Kyoto University Hospital
Kyoto, Japan, 606-8507
Niigata Cancer Center Hospital
Niigata, Japan, 951-8566
Yao Municipal Hospital
Osaka, Japan, 581-0069
Tokyo Metropolitan - Komagome Hospital
Tokyo, Japan, 113-8677
New Zealand
Christchurch Hospital
Christchurch, New Zealand, 1
Waikato Hospital
Hamilton, New Zealand, 2020
Instituto Nacional de Enfermedades Neoplasicas
Lima, Peru, 34
Russian Federation
Russian Academy of Medical Sciences Cancer Research Center
Moscow, Russian Federation, 115478
South Africa
Tygerberg Hospital
Kapstadt, South Africa, 7505
Sandton Oncology Medical Research
Sandton, South Africa, 2199
Vall d'Hebron University Hospital
Barcelona, Spain, 08035
M. D. Anderson International Espana SA
Madrid, Spain, 28033
Hospital Ramon y Cajal
Madrid, Spain, 28034
Hospital Universitario 12 de Octubre
Madrid, Spain, 28041
Hospital Son Llatzer
Palma De Mallorca, Spain, 07198
Hospital Sant Joan de Reus
Reus, Spain, 43201
Hospital Universitario Virgen Macarena
Sevilla, Spain, 41009
Hospital de Torrevieja
Torrevieja, Spain, 03180
Instituto Valenciano De Oncologia
Valencia, Spain, 46009
Hospital Clinico Universitario de Valencia
Valencia, Spain, 46010
Lasarettet i Boras
Boras, Sweden, 501 15
Malarsjukhuset Hospital
Eskilstuna, Sweden
Sahlgrenska University Hospital
Gothenburg, Sweden, S-413 45
Lidkoping Hospital
Lidkoping, Sweden, S-53185
Skaraborgs Hospital
Skovde, Sweden, 541 85
Karolinska University Hospital - Huddinge
Stockholm, Sweden, S-141 86
Kantonsspital Aarau
Aarau, Switzerland, CH-5001
Kantonsspital Baden
Baden, Switzerland, CH-5404
Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni
Bellinzona, Switzerland, CH-6500
Inselspital Bern
Bern, Switzerland, CH-3010
Oncocare Sonnenhof-Klinik Engeriedspital
Bern, Switzerland, CH-3012
AndreasKlinik Cham Zug
Cham, Switzerland, CH-6330
Kantonsspital Graubuenden
Chur, Switzerland, CH-7000
Brustzentrum Thurgau at Kantonsspital Frauenfeld
Frauenfeld, Switzerland, 8501
Kantonsspital Freiburg
Freiburg, Switzerland, 1708
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland, CH-1011
Lago Maggiore Oncology Foundation
Locarno, Switzerland, 6600
Ospedale "la Carita", Locarno
Locarno, Switzerland, 6600
Ospedale Civico
Lugano, Switzerland, CH-6903
Ospedale Beata Vergine
Mendrisio, Switzerland, CH-6850
Kantonsspital Olten
Olten, Switzerland, CH-4600
Hopital Regional de Sion-Herens-Conthey
Sion, Switzerland, CH -1951
Tumor Zentrum ZeTup St. Gallen und Chur
St. Gallen, Switzerland, CH-9006
Kantonsspital - St. Gallen
St. Gallen, Switzerland, CH-9007
Thun, Switzerland, 3600
Kantonsspital Winterthur
Winterthur, Switzerland, CH-8400
Breast Center
Zurich, Switzerland, CH-8008
City Hospital Triemli
Zurich, Switzerland, CH-8063
UniversitaetsSpital Zuerich
Zurich, Switzerland, CH-8091
United Kingdom
Borders General Hospital
Melrose, England, United Kingdom, TD6 9BS
Dumfries & Galloway Royal Infirmary
Dumfries, Scotland, United Kingdom, DG1 4AP
Sponsors and Collaborators
International Breast Cancer Study Group
Breast International Group
Study Chair: Marco Colleoni, MD European Institute of Oncology

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: International Breast Cancer Study Group Identifier: NCT00553410     History of Changes
Other Study ID Numbers: IBCSG 35-07 / BIG 1-07
2007-001370-88 ( EudraCT Number )
CDR0000574249 ( Registry Identifier: )
First Posted: November 5, 2007    Key Record Dates
Last Update Posted: March 6, 2018
Last Verified: March 2018

Keywords provided by International Breast Cancer Study Group:
stage IA breast cancer
stage IB breast cancer
stage II breast cancer
stage IIIA breast cancer

Additional relevant MeSH terms:
Hormones, Hormone Substitutes, and Hormone Antagonists
Hormone Antagonists
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Physiological Effects of Drugs
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists