TriangleNCT00004205 · CITED IN SOURCE DOCUMENTS
Letrozole or Tamoxifen in Treating Postmenopausal Women With Breast Cancer
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2017-12-12
RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by reducing the production of estrogen. Hormone therapy using tamoxifen may fight breast cancer by blocking the uptake of estrogen by the tumor cells. If is not yet known which treatment regimen is most effective for breast cancer. PURPOSE: Randomized double-blind phase III trial to compare the effectiveness of letrozole with that of tamoxifen in treating postmenopausal women who have breast cancer that has been surgically removed.
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What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
No posted result sections were captured. Registered plans do not establish that a treatment works.
Who could take part
- eligibility Criteria
- DISEASE CHARACTERISTICS: * Histologically confirmed resectable adenocarcinoma of the breast * pT1, pT2, pT3, or minimal dermal involvement on pathology only * pN0, pN1, pN2, or M0 * Negative nodal status * At least 8 nodes are negative * Unknown nodal status * Less than 8 nodes examined and no pathological finding * Positive nodal status * Any positive finding independent of the number of nodes examined * Negative sentinel node or no prior nodal dissection allowed if all other criteria met * Must have had total mastectomy, lumpectomy, or quadrantectomy * Should have prior chest wall radiotherapy after segmental mastectomy or histopathologic T4 dermal involvement * Stage I, II, or IIIa allowed if the tumor is completely removed macroscopically and margins of the resected tumor are microscopically free of tumor * Must undergo chest wall radiotherapy or second resection if microscopic disease at the mastectomy margins * No bilateral disease except in situ disease, either ductal or lobular of the contralateral breast * Postmenopausal * Regardless of prior hormonal replacement therapy (HRT) or hysterectomy: * Bilateral oophorectomy and any age * Radiologic castration and amenorrheic for at least 3 months and any age * Not postmenopausal at the start of adjuvant chemotherapy AND and completed at least 6 courses of prior cyclophosphamide, methotrexate, and fluorouracil (CMF) or at least 4 courses of prior anthracycline-cyclophosphamide continuation therapy and at least age 45 with follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) postmenopausal levels * No prior HRT: * Prior hysterectomy and less than age 55 with FSH/LH/E2 postmenopausal levels * Prior hysterectomy and at least age 55 * No prior HRT or hysterectomy: * Amenorrhea more than 1 year and less than age 50 * Amenorrhea more than 6 months and at least age 50 * Prior HRT regardless of hysterectomy: * At least 1 month since prior HRT and less than age 55 with FSH/LH/E2 postmenopausal levels * At least 1 month since prior HRT and at least age 55 * FSH/LH/E2 postmenopausal levels and uncategorized * No distant metastases, including bone scans showing hot spots unconfirmed as benign disease or skeletal pain of unknown cause * At least 10% hormone receptor-positive tumor cells * Hormone receptor status: * Estrogen receptor positive AND/OR * Progesterone receptor positive PATIENT CHARACTERISTICS: Age: * 30 and over Sex: * Female Menopausal status: * Postmenopausal Performance status: * Not specified Life expectancy: * Not specified Hematopoietic: * WBC greater than 3,000/mm\^3 * Platelet count at least 100,000/mm\^3 * Hemoglobin greater than 10 g/dL Hepatic: * Bilirubin less than 3.0 mg/dL * SGOT or SGPT less than 1.5 times upper limit of normal * No hepatic disease that would preclude study Renal: * Creatinine less than 1.8 mg/dL * No renal disease that would preclude study Cardiovascular: * No cardiovascular disease that would preclude study * Prior deep vein thrombosis allowed if medically stable Pulmonary: * No lung embolism Other: * No other prior or concurrent malignancy within the past 5 years except adequately treated basal or squamous cell skin cancer or carcinoma in situ of the cervix * No prior noncompliance to medical regimens * No other nonmalignant systemic diseases that would preclude follow-up * HIV negative PRIOR CONCURRENT THERAPY: Biologic therapy: * Prior immunotherapy or biological response modifiers (e.g., interferon) allowed Chemotherapy: * See Disease Characteristics * Prior adjuvant or neoadjuvant chemotherapy allowed * Concurrent adjuvant chemotherapy allowed Endocrine therapy: * See Disease Characteristics * Prior neoadjuvant hormonal therapy allowed (e.g., antiestrogens, progestins, or aromatase inhibitors) if no more than 4 months duration and no disease progression * Prior corticosteroids allowed * At least 4 weeks since prior HRT * Prior adjuvant antiestrogen therapy allowed if less than 1 month duration and immediately after surgery, radiotherapy, and/or chemotherapy * Prior antiestrogens for chemoprevention allowed if at least 18 months between completion of chemoprevention and diagnosis * No other concurrent antiestrogens or aromatase inhibitors * No concurrent raloxifene * No concurrent systemic HRT with or without progestins of more than 3 months duration Radiotherapy: * See Disease Characteristics * Concurrent radiotherapy allowed Surgery: * See Disease Characteristics Other: * At least 30 days since prior systemic investigational drugs * At least 7 days since prior topical investigational drugs * Concurrent bisphosphonates allowed
- healthy Volunteers
- false
- maximum Age
- 120 Years
- minimum Age
- 30 Years
- sex
- FEMALE
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Tamoxifen for 5 years after randomization.
- intervention Names
- Drug: tamoxifen citrate
- label
- Tamoxifen
- type
- EXPERIMENTAL
- description
- Letrozole for 5 years after randomization.
- intervention Names
- Drug: letrozole
- label
- Letrozole
- type
- EXPERIMENTAL
- description
- Tamoxifen for 2 years after randomization, then letrozole for the next 3 years.
- intervention Names
- Drug: letrozole
- Drug: tamoxifen citrate
- label
- Tamoxifen, then letrozole
- type
- EXPERIMENTAL
- description
- Letrozole for 2 years after randomization, then tamoxifen for the next 3 years.
- intervention Names
- Drug: letrozole
- Drug: tamoxifen citrate
- label
- Letrozole, then tamoxifen
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Letrozole
- Letrozole, then tamoxifen
- Tamoxifen, then letrozole
- description
- Letrozole 2.5 mg daily oral administration.
- name
- letrozole
- type
- DRUG
- arm Group Labels
- Letrozole, then tamoxifen
- Tamoxifen
- Tamoxifen, then letrozole
- description
- Tamoxifen 20 mg daily oral administration.
- name
- tamoxifen citrate
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- QUADRUPLE
- who Masked
- PARTICIPANT
- CARE_PROVIDER
- INVESTIGATOR
- OUTCOMES_ASSESSOR
- primary Purpose
- TREATMENT
Enrollment
- count
- 8028
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- Time from randomization to recurrence (including recurrence restricted to the breast after breast conserving treatment), metastasis, appearance of a second primary tumor, or death from any cause, whichever occurs first, assessed up to end of year 2015, for a maximum of 17 years
- measure
- Disease free survival.
- time Frame
- Up to end of year 2015
- secondary Outcomes
- description
- Time from randomization to death from any cause, assessed up to end of year 2015, for a maximum of 17 years
- measure
- Overall survival
- time Frame
- Up to end of year 2015
- description
- Morbidity information will be recorded using the Adverse Event Form (AE).
- measure
- Safety
- time Frame
- 5 years after randomization.
- description
- Time from randomization to appearance of any recurrent or metastatic disease in sites other than the local mastectomy scar, the ipsilateral breast in case of breast conservation, or the contralateral breast, assessed up to end of year 2015, for a maximum of 17 years
- measure
- Systemic relapse
- time Frame
- Up to end of year 2015
Full study description
- brief Summary
- RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by reducing the production of estrogen. Hormone therapy using tamoxifen may fight breast cancer by blocking the uptake of estrogen by the tumor cells. If is not yet known which treatment regimen is most effective for breast cancer. PURPOSE: Randomized double-blind phase III trial to compare the effectiveness of letrozole with that of tamoxifen in treating postmenopausal women who have breast cancer that has been surgically removed.
- detailed Description
- OBJECTIVES: * Compare adjuvant letrozole vs tamoxifen administered for 5 years in postmenopausal women with operable, hormone receptor-positive breast cancer. * Compare these treatment regimens given sequentially vs continuously in this patient population. * Compare these treatment regimens in terms of overall survival, disease-free and systemic-free survival, safety, and tolerability in this patient population. OUTLINE: This is a randomized, double-blind, multicenter study. Patients are stratified according to adjuvant chemotherapy (prior therapy vs no prior or concurrent therapy vs concurrent therapy), prior surgery (modified radical mastectomy vs a lesser surgical procedure), and participating center. Patients are randomized to one of four treatment arms. * Arm I: Patients receive adjuvant oral tamoxifen daily for 5 years. * Arm II: Patients receive adjuvant oral letrozole daily for 5 years. * Arm III: Patients receive adjuvant oral tamoxifen daily for 2 years followed by adjuvant oral letrozole daily for 3 years. * Arm IV: Patients receive adjuvant oral letrozole daily for 2 years followed by adjuvant oral tamoxifen daily for 3 years. Patients may receive concurrent radiotherapy. Some patients receive concurrent adjuvant chemotherapy beginning within 8 weeks after surgery and continuing for no more than 6 months. Patients are followed annually. PROJECTED ACCRUAL: A total of 5,180 patients (1,295 per treatment arm) will be accrued for this study within 6 years.
Source references
- references
- citation
- Lipsitz M, Delea TE, Guo A. Cost effectiveness of letrozole versus anastrozole in postmenopausal women with HR+ early-stage breast cancer. Curr Med Res Opin. 2010 Oct;26(10):2315-28. doi: 10.1185/03007995.2010.510784.
- pmid
- 20731528
- type
- BACKGROUND
- citation
- Skedgel C, Rayson D, Younis T, et al.: Direct and indirect economic evaluation of upfront and sequential adjuvant treatment in postmenopausal women with breast cancer based on the BIG 1-98 trial. [Abstract] J Clin Oncol 27 (Suppl 15): A-6594, 2009.
- type
- BACKGROUND
- citation
- Delea TE, El-Ouagari K, Karnon J, Sofrygin O. Cost-effectiveness of letrozole versus tamoxifen as initial adjuvant therapy in postmenopausal women with hormone-receptor positive early breast cancer from a Canadian perspective. Breast Cancer Res Treat. 2008 Apr;108(3):375-87. doi: 10.1007/s10549-007-9607-7. Epub 2007 Jul 26.
- pmid
- 17653859
- type
- BACKGROUND
- citation
- Delea TE, Karnon J, Sofrygin O, Thomas SK, Papo NL, Barghout V. Cost-effectiveness of letrozole versus tamoxifen as initial adjuvant therapy in hormone receptor-positive postmenopausal women with early-stage breast cancer. Clin Breast Cancer. 2007 Jun;7(8):608-18. doi: 10.3816/CBC.2007.n.018.
- pmid
- 17592673
- type
- BACKGROUND
- citation
- Buzdar A, Chlebowski R, Cuzick J, Duffy S, Forbes J, Jonat W, Ravdin P. Defining the role of aromatase inhibitors in the adjuvant endocrine treatment of early breast cancer. Curr Med Res Opin. 2006 Aug;22(8):1575-85. doi: 10.1185/030079906X120940.
- pmid
- 16870082
- type
- BACKGROUND
- citation
- Scott LJ, Keam SJ. Letrozole : in postmenopausal hormone-responsive early-stage breast cancer. Drugs. 2006;66(3):353-62. doi: 10.2165/00003495-200666030-00010.
- pmid
- 16526826
- type
- BACKGROUND
- citation
- Wardley AM. Emerging data on optimal adjuvant endocrine therapy: Breast International Group trial 1-98/MA.17. Clin Breast Cancer. 2006 Feb;6 Suppl 2:S45-50. doi: 10.3816/cbc.2006.s.003.
- pmid
- 16595026
- type
- BACKGROUND
- citation
- Leyland-Jones B, Gray KP, Abramovitz M, Bouzyk M, Young B, Long B, Kammler R, Dell'Orto P, Biasi MO, Thurlimann B, Harvey V, Neven P, Arnould L, Maibach R, Price KN, Coates AS, Goldhirsch A, Gelber RD, Pagani O, Viale G, Rae JM, Regan MM; BIG 1-98 Collaborative Group. ESR1 and ESR2 polymorphisms in the BIG 1-98 trial comparing adjuvant letrozole versus tamoxifen or their sequence for early breast cancer. Breast Cancer Res Treat. 2015 Dec;154(3):543-55. doi: 10.1007/s10549-015-3634-6. Epub 2015 Nov 21.
- pmid
- 26590813
- type
- RESULT
- citation
- Colleoni M, Giobbie-Hurder A, Regan MM, Thurlimann B, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Lang I, Smith I, Chirgwin J, Pienkowski T, Wardley A, Price KN, Gelber RD, Coates AS, Goldhirsch A. Analyses adjusting for selective crossover show improved overall survival with adjuvant letrozole compared with tamoxifen in the BIG 1-98 study. J Clin Oncol. 2011 Mar 20;29(9):1117-24. doi: 10.1200/JCO.2010.31.6455. Epub 2011 Feb 14.
- pmid
- 21321298
- type
- RESULT
- citation
- De Censi A, Sun Z, Thurlimann BJK, et al.: Bone mineral density (BMD) in participants (pts) of trial BIG 1-98 comparing adjuvant letrozole (L) versus tamoxifen (T) or their sequence. [Abstract] J Clin Oncol 29 (Suppl 15): A-516, 2011.
- type
- RESULT
- citation
- Ejlertsen B, Aldridge J, Nielsen KV, Regan MM, Henriksen KL, Lykkesfeldt AE, Muller S, Gelber RD, Price KN, Rasmussen BB, Viale G, Mouridsen H; Danish Breast Cancer Cooperative Group the BIG 1-98 Collaborative Group and the International Breast Cancer Study Group. Prognostic and predictive role of ESR1 status for postmenopausal patients with endocrine-responsive early breast cancer in the Danish cohort of the BIG 1-98 trial. Ann Oncol. 2012 May;23(5):1138-1144. doi: 10.1093/annonc/mdr438. Epub 2011 Oct 10.
- pmid
- 21986093
- type
- RESULT
- citation
- Huober JB, Cole BF, Wu J, et al.: Symptoms of endocrine treatment and outcome: A retrospective analysis of the monotherapy arms of the BIG 1-98 trial. [Abstract] J Clin Oncol 29 (Suppl 15): A-522, 2011.
- type
- RESULT
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- a href="#cit/section_6.63">63</a>] An updated analysis from the International Breast Cancer Study Group (<a href="/clinicaltrials/NCT00004205">IBCSG-1-98</a> [NCT00004205]) reported results on the 4,922 women who received tamoxifen or letrozole for 5 years at a median follow-up of 51 months.[<a href="#cit/section_6.64">64</a>][<
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- and 86% in the exemestane-alone group (HR, 0.97; 95% CI, 0.88–1.08; <em>P</em> = .60).</li></ul></div></li><li>Similarly in the <a href="/clinicaltrials/NCT00004205">IBCSG 1-98</a> trial (NCT00004205), two sequential arms were compared with 5 years of letrozole.[<a href="#cit/section_6.71">71</a>][<a href="/Common/PopUps/p
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Preserved source evidence · Not medical advice