Clinical trial NCT00003678: Tamoxifen in Treating Women With Breast Cancer
Official title: A Large, Uniquely Simple, Randomised Study to Assess Much More Reliably the Balance of Benefits and Risks of Prolonging Adjuvant Tamoxifen Treatment in Early Breast Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Breast Cancer
Keywords: stage I breast cancer
stage II breast cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 20000
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using tamoxifen may fight breast cancer by blocking the uptake of estrogen by the tumor cells.

PURPOSE: Randomized phase III trial to compare the effectiveness of at least 2 years of tamoxifen with that of 5 additional years of tamoxifen in treating women who have breast cancer that has been surgically removed.

Detailed description: OBJECTIVES:

* Compare the disease-free and overall survival of women with early breast cancer who are randomized to discontinue adjuvant tamoxifen vs those randomized to continue for at least 5 additional years.

OUTLINE: This is a randomized study. Patients are stratified for analysis according to duration of tamoxifen given before randomization (2-3 years vs 4-5 years vs 6-7 years vs 8-9 years vs 10 years and over), age (less than 49 vs over 50), and important prognostic factors, including tumor type and grade and nodal and estrogen receptor status. Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients discontinue tamoxifen after at least 2 years of prior treatment.
* Arm II: Patients continue treatment with tamoxifen for at least 5 additional years in the absence of unacceptable toxicity or disease progression.

Patients are followed annually.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 8,000-20,000 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed breast carcinoma that has been completely excised

  * Clinically relapse free
* Must have completed at least two years of adjuvant therapy with tamoxifen for early breast cancer AND have no clear indication for or against receiving further tamoxifen
* No significant endometrial hyperplasia
* No patients with negligibly low risk of breast cancer death
* Hormone receptor status:

  * Any status allowed

PATIENT CHARACTERISTICS:

Age:

* Not specified

Sex:

* Female

Menopausal status:

* Any status allowed

Performance status:

* Not specified

Life expectancy:

* Not specified

Hematopoietic:

* Not specified

Hepatic:

* Not specified

Renal:

* Not specified

Other:

* No other life threatening disease
* No retinopathy
* No psychiatric disorder or other condition that would preclude study compliance
* No serious toxicity (e.g., depression) thought to be due to tamoxifen
* Not pregnant or nursing
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* Not specified

Endocrine therapy:

* See Disease Characteristics

Radiotherapy:

* Not specified

Surgery:

* See Disease Characteristics

Other:

* Any primary treatment allowed

Primary outcomes:
measure: All-cause mortality
Secondary outcomes:
measure: Disease recurrence
measure: Death due to breast cancer, other primary tumors, or cardiovascular causes
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: Cancer Research UK Clinical Trials Unit - Birmingham
state: England
Study officials:
affiliation: University Hospital Birmingham
name: Daniel Rea, MD
role: STUDY_CHAIR
References:
citation: Gray R, Davies C, Perry P. Tamoxifen for early breast cancer: better late than never. Ann Oncol. 2000 May;11(5):505-7. doi: 10.1023/a:1008323116265. No abstract available.
citation: Rea D, Poole C, Gray R. Adjuvant tamoxifen: how long before we know how long? BMJ. 1998 May 16;316(7143):1518-9. doi: 10.1136/bmj.316.7143.1518. No abstract available.
citation: Earl H, Gray R, Kerr D, Lee M. The optimal duration of adjuvant tamoxifen treatment for breast cancer remains uncertain: randomize into aTTom. Clin Oncol (R Coll Radiol). 1997;9(3):141-3. doi: 10.1016/s0936-6555(97)80067-2. No abstract available.
citation: Earl H, Baker P, Kerr D, Lee M, Gray R, Baum M. Adjuvant treatment with tamoxifen. Recruitment into studies assessing optimum duration of treatment must continue. BMJ. 1996 Apr 20;312(7037):1036-7. doi: 10.1136/bmj.312.7037.1036b. No abstract available.
citation: Gray R. Tamoxifen: how boldly to go where no women have gone before. J Natl Cancer Inst. 1993 Sep 1;85(17):1358-60. doi: 10.1093/jnci/85.17.1358. No abstract available.
citation: Poterala JE, Wisinski KB. Abbreviated endocrine therapy duration for low estrogen receptor-positive breast cancer: The counter to extended endocrine therapy. Cancer. 2022 May 1;128(9):1724-1726. doi: 10.1002/cncr.34158. Epub 2022 Feb 25. No abstract available.
citation: Bartlett JMS, Sgroi DC, Treuner K, Zhang Y, Ahmed I, Piper T, Salunga R, Brachtel EF, Pirrie SJ, Schnabel CA, Rea DW. Breast Cancer Index and prediction of benefit from extended endocrine therapy in breast cancer patients treated in the Adjuvant Tamoxifen-To Offer More? (aTTom) trial. Ann Oncol. 2019 Nov 1;30(11):1776-1783. doi: 10.1093/annonc/mdz289.