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AzTrials

Breast CancerPhase 3NCT00003140

Letrozole After Tamoxifen in Treating Women With Breast Cancer

A Phase 3 study testing letrozole in people with Breast Cancer, run by NCIC Clinical Trials Group at 57 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. PURPOSE: This randomized phase III trial is studying letrozole to see how well it works in treating women with breast cancer who have received tamoxifen… Read more about this study

Who is it for?
Ages 0 to 120 years, women only
Conditions the study is for
Breast Cancer
What is being tested?
letrozole
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
5,187 participants
Where
57 sitesin 2 countries
Study dates
24 Aug 1998to Oct 2003
Phase
Phase 3
Are there results?
None posted in the registry

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 0 to 120 years
  • Women only
  • No healthy volunteers
  • Child, Adult, Older adult

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed primary invasive breast carcinoma resected at time of original diagnosis
  • No ductal carcinoma in situ
  • Axillary lymph node negative, positive, or unknown
  • No evidence of metastases
  • No localized or distant breast cancer recurrence
  • Not registered on protocol NCCTG-893052, any other IBCSG protocol, or protocol SWOG-S9623
  • Hormone receptor status:
  • Estrogen or progesterone receptor positive as defined by tumor receptor content at least 10 fmol/mg protein or receptor positive by ERICA or PgRICA
  • Unknown status allowed if effort to determine status has been made by immunocytochemistry
  • No contralateral breast cancer

PATIENT CHARACTERISTICS:

Age:

  • Postmenopausal

Sex:

  • Female

Menopausal status:

  • Postmenopausal defined by one of the following:
  • Age 50 or over at start of adjuvant tamoxifen
  • Under age 50 and considered postmenopausal by treating physician at start of adjuvant tamoxifen
  • Under age 50 at start of adjuvant tamoxifen and had bilateral oophorectomy (surgical or radiation)
  • Under age 50 and premenopausal at start of adjuvant tamoxifen, but became amenorrheic during tamoxifen and remained amenorrheic for at least 1 year
  • Considered postmenopausal by physician with LH/FSH levels under the treatment center's postmenopausal limits

Performance status:

  • ECOG 0-2

Life expectancy:

  • At least 5 years

Hematopoietic:

  • WBC ≥ 3,000/mm^3 OR
  • Granulocyte count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3

Hepatic:

  • AST and/or ALT < 2 times upper limit of normal (ULN) (unless imaging examinations have ruled out metastatic disease)
  • Alkaline phosphatase < 2 times ULN (unless imaging examinations have ruled out metastatic disease)

Renal:

  • Not specified

Other:

  • No concurrent medical or psychiatric condition that would preclude study participation
  • No other malignancy within the past 5 years except adequately treated superficial squamous cell or basal cell skin cancer or carcinoma in situ of the cervix
  • Able to swallow study drug
  • Adequate oral intake

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • Prior adjuvant chemotherapy allowed
  • No concurrent chemotherapy

Endocrine therapy:

  • Completed at least 4.5 but no more than 6 years of adjuvant tamoxifen after resection
  • Completed at least 4.5-6 years of adjuvant aromatase inhibitor as initial therapy or after tamoxifen
  • No more than 3 months since prior adjuvant tamoxifen
  • No concurrent hormone replacement therapy (e.g., megestrol)
  • No concurrent selective estrogen-receptor modulators (e.g., raloxifene or idoxifene)
  • Concurrent intermittent vaginal estrogens (e.g., Estring) allowed if other local measures for intractable vaginal atrophy are insufficient
  • No other concurrent aromatase inhibitors
  • No more than 2 years since prior aromatase inhibitor therapy (re-randomization)

Radiotherapy:

  • Prior radiotherapy allowed

Surgery:

  • See Disease Characteristics

Other:

  • At least 1 month since prior investigational drugs
  • Prior treatment on a clinical trial for breast cancer allowed if permission has been obtained from the sponsors of the original study for their patient to participate on MA.17/JMA.17/BIG-97-01
  • No prior placebo on core protocol
  • No concurrent anticancer therapy
  • Concurrent thyroid medication, calcium, vitamin D, and bisphosphonates allowed

Trial locations and contacts

57 sites in 2 countries.

57 sites in 2 countries

Canada53 sites

  • The Royal Victoria Hospital

    Barrie, Ontario, L4M 6M2

  • PEI Cancer Treatment Centre,Queen Elizabeth Hospital

    Charlottetown, Prince Edward Island, C1A 8T5

  • Centre de Sante et de services sociaux de Gatineau

    Gatineau, Quebec, J8P 7H2

  • Regional Cancer Program of the Hopital Regional

    Greater Sudbury, Ontario, P3E 5J1

  • QEII Health Sciences Center

    Halifax, Nova Scotia, B3H 1V7

  • Juravinski Cancer Centre at Hamilton Health Sciences

    Hamilton, Ontario, L8V 5C2

  • BCCA - Cancer Centre for the Southern Interior

    Kelowna, British Columbia, V1Y 5L3

  • Cancer Centre of Southeastern Ontario at Kingston

    Kingston, Ontario, K7L 5P9

  • Lethbridge Cancer Centre

    Lethbridge, Alberta, T1J 1W5

  • L'Hotel-Dieu de Levis

    Lévis, Quebec, G6V 3Z1

  • London Regional Cancer Program

    London, Ontario, N6A 4L6

  • Markham Stouffville Hospital

    Markham, Ontario, L6B 1A1

  • Credit Valley Hospital

    Mississauga, Ontario, L5M 2N1

  • The Moncton Hospital

    Moncton, New Brunswick, E1C 6Z8

  • The Vitalite Health Network - Dr. Leon Richard

    Moncton, New Brunswick, E1C 8X3

  • Hopital Maisonneuve-Rosemont

    Montreal, Quebec, H1T 2M4

  • CHUM - Hopital Notre-Dame

    Montreal, Quebec, H2L 4M1

  • McGill University - Dept. Oncology

    Montreal, Quebec, H2W 1S6

  • CHUM - Hotel Dieu du Montreal

    Montreal, Quebec, H2W 1T8

  • CHUM - Pavillon Saint-Luc

    Montreal, Quebec, H3X 3J4

  • Hopital du Sacre-Coeur de Montreal

    Montreal, Quebec, H4J 1C5

  • NRGH - Nanaimo Cancer Clinic

    Nanaimo, British Columbia, V9S 2B7

  • Stronach Regional Health Centre at Southlake

    Newmarket, Ontario, L3Y 2P9

  • Lakeridge Health Oshawa

    Oshawa, Ontario, L1G 2B9

  • Ottawa Health Research Institute - General Division

    Ottawa, Ontario, K1H 8L6

  • Penticton Regional Hospital

    Penticton, British Columbia, V2A 3G6

  • Peterborough Regional Health Centre

    Peterborough, Ontario, K9H 7B6

  • CHUQ-Pavillon Hotel-Dieu de Quebec

    Québec, Quebec, G1R 2J6

  • CHA-Hopital Du St-Sacrement

    Québec, Quebec, G1S 4L8

  • University Institute of Cardiology and

    Québec, Quebec, G1V 4G5

  • Allan Blair Cancer Centre

    Regina, Saskatchewan, S4T 7T1

  • Atlantic Health Sciences Corporation

    Saint John, New Brunswick, E2L 4L2

  • Saskatoon Cancer Centre

    Saskatoon, Saskatchewan, S7N 4H4

  • Algoma District Cancer Program

    Sault Ste. Marie, Ontario, P6B 0A8

  • Centre hospitalier universitaire de Sherbrooke

    Sherbrooke, Quebec, J1H 5N4

  • Niagara Health System

    St. Catharines, Ontario, L2R 7C6

  • Dr. H. Bliss Murphy Cancer Centre

    St. John's, Newfoundland and Labrador, AIB 3V6

  • BCCA - Fraser Valley Cancer Centre

    Surrey, British Columbia, V3V 1Z2

  • Thunder Bay Regional Health Science Centre

    Thunder Bay, Ontario, P7B 6V4

  • North York General Hospital

    Toronto, Ontario, M2K 1E1

  • Toronto East General Hospital

    Toronto, Ontario, M4C 3E7

  • Odette Cancer Centre

    Toronto, Ontario, M4N 3M5

  • St. Michael's Hospital

    Toronto, Ontario, M5B 1W8

  • Mount Sinai Hospital

    Toronto, Ontario, M5G 1X5

  • Univ. Health Network-The Toronto General Hospital

    Toronto, Ontario, M5G 2C4

  • Univ. Health Network-Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

  • St. Joseph's Health Centre

    Toronto, Ontario, M6R 1B5

  • Trillium Health Centre - West Toronto

    Toronto, Ontario, M9C 1A5

  • Humber River Regional Hospital

    Toronto, Ontario, M9N 1N8

  • BCCA - Vancouver Cancer Centre

    Vancouver, British Columbia, V5Z 4E6

  • BCCA - Vancouver Island Cancer Centre

    Victoria, British Columbia, V8R 6V5

  • Windsor Regional Cancer Centre

    Windsor, Ontario, N8W 2X3

  • CancerCare Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

United Kingdom4 sites

  • The Royal Marsden NHS Foundation Trust

    London, SW3 6JJ

  • Wythenshawe Hospital

    Manchester, M23 9LT

  • Christie's Hospital NHS Trust

    Manchester, M2O 4BX

  • The Royal Marsden NHS Foundation Trust - Sutton

    Surrey, SM2 5PT

Other trials in United Kingdom

About this study

Official title: A Phase III Randomized Double Blind Study of Letrozole Versus Placebo in Women With Primary Breast Cancer Completing Five or More Years of Adjuvant Tamoxifen

RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by reducing the production of estrogen.

PURPOSE: This randomized phase III trial is studying letrozole to see how well it works in treating women with breast cancer who have received tamoxifen for at least 5 years.

Read the detailed description

OBJECTIVES:

Primary

  • Compare the disease-free survival and overall survival of postmenopausal women with primary breast cancer who have completed at least five years of adjuvant aromatase inhibitor as initial therapy or after tamoxifen treated with letrozole or placebo.

Secondary

  • Compare the incidence of contralateral breast cancer in patients treated with these regimens.
  • Evaluate the long-term clinical and laboratory safety of letrozole, in terms of lipid profile, cardiovascular morbidity and mortality, incidence of bone fractures, change in bone density, and common toxic effects, in this patient population.
  • Compare the quality of life of patients treated with these regimens. Re-randomization

Primary

  • Compare disease-free survival of patients who, after receiving at least 4.5 years of letrozole, are re-randomized to receive an additional 5 years of letrozole vs placebo.

Secondary

  • Determine whether common genetic polymorphisms for genes encoding proteins involved in pharmacokinetic and/or pharmacodynamic pathways for letrozole contribute to individual variation in toxicity and efficacy of letrozole therapy.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to receptor status (positive vs unknown), lymph node status (negative vs positive vs unknown), prior adjuvant chemotherapy (yes vs no), interval between last dose of aromatase inhibitor therapy and randomization (< 6 months vs 6 months-2 years), and duration of prior tamoxifen use (0 years vs < 2 years vs 2-4.5 years vs > 4.5 years). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral letrozole once daily.
  • Arm II: Patients receive oral placebo once daily. In both arms, treatment continues for 5 years in the absence of disease progression or unacceptable toxicity. Patients in arm II may then be offered oral letrozole once daily for up to 5 years.

Quality of life is assessed at baseline, at 6 months, and then annually for 4.5 years.

  • Double-blind, re-randomization:

Patients who complete ≥ 4.5 years of letrozole (arm I) and who did not experience recurrent disease or new primary breast cancer, including ductal carcinoma in situ, may participate in the double-blind, placebo-controlled, re-randomization portion of the study. Patients are stratified according to lymph node status at enrollment (negative vs positive vs unknown), prior adjuvant chemotherapy (yes vs no), and interval between last dose of letrozole and re-randomization (<6 months vs 6 months to 2 years). Common genetic single nucleotide polymorphisms for genes encoding proteins involved in pharmacokinetic and/or pharmacodynamic pathways for letrozole are analyzed in order to determine if these single nucleotide polymorphisms contribute to individual variation in toxicity and efficacy of letrozole therapy.

Quality of life is assessed as during the first randomization.

Patients are followed annually.

PROJECTED ACCRUAL: A total of 4,700 patients will be accrued for this study.

Conditions
Breast Cancer
Being tested
letrozole, placebo
Keywords
stage I breast cancer, stage II breast cancer, stage IIIA breast cancer
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • letrozoleDrug

    Also called Femara

    Given orally

  • placeboOther

    Given orally

Study groups in NCT00003140
Study groupRoleWhat they receive
Arm IExperimentalPatients receive oral letrozole once daily.
Receives: Drug: letrozole
Arm IIPlacebo comparatorPatients receive oral placebo once daily.
Receives: Other: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Disease-free survival

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2003 (estimated)
  2. Study start24 Aug 1998
  3. Primary completion22 Aug 2003
  4. Study completionOct 2003

Resources

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
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
5,187 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00003140
Sponsor's protocol ID
MA17
Other IDs
U10CA025224, CAN-NCIC-MA17, CALGB-49805, E-JMA17, EORTC-10983, IBCSG-BIG97-01, NCCTG-JMA17, SWOG-JMA17
Status last verified
Mar 2012
First submitted
1 Nov 1999
Last updated
27 Mar 2026
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Baum M. Adjuvant endocrine therapy in postmenopausal women with early breast cancer: where are we now? Eur J Cancer. 2005 Aug;41(12):1667-77. doi: 10.1016/j.ejca.2005.05.006.

    PubMed 16046117

  • Baum M. Current status of aromatase inhibitors in the management of breast cancer and critique of the NCIC MA-17 trial. Cancer Control. 2004 Jul-Aug;11(4):217-21. doi: 10.1177/107327480401100402.

    PubMed 15284712

  • Booth CM, Pater JL, Goss PE. Identifying breast cancer patients most likely to benefit from aromatase inhibitor therapy after adjuvant tamoxifen. Cancer. 2007 May 1;109(9):1927-8; author reply 1928. doi: 10.1002/cncr.22613. No abstract available.

    PubMed 17354227

  • 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.

    PubMed 16870082

  • 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.

    PubMed 16526826

  • Vakaet L. Re: Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17. J Natl Cancer Inst. 2006 Aug 16;98(16):1162; author reply 1162-3. doi: 10.1093/jnci/djj323. No abstract available.

    PubMed 16912269

  • 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.

    PubMed 16595026

  • Goss PE, Ingle JN, Martino S, et al.: Outcomes of women who were premenopausal at diagnosis of early stage breast cancer in the NCIC CTG MA17 trial. [Abstract] 32nd Annual San Antonio Breast Cancer Symposium, December 9-13, 2009, San Antonio, Texas. A-13, 2009.

  • Goss PE, Ingle JN, Pater JL, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Cameron DA, Palmer MJ, Tu D. Late extended adjuvant treatment with letrozole improves outcome in women with early-stage breast cancer who complete 5 years of tamoxifen. J Clin Oncol. 2008 Apr 20;26(12):1948-55. doi: 10.1200/JCO.2007.11.6798. Epub 2008 Mar 10.

    PubMed 18332475

  • Ingle JN, Tu D, Pater JL, Muss HB, Martino S, Robert NJ, Piccart MJ, Castiglione M, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Cameron DA, Palmer MJ, Goss PE. Intent-to-treat analysis of the placebo-controlled trial of letrozole for extended adjuvant therapy in early breast cancer: NCIC CTG MA.17. Ann Oncol. 2008 May;19(5):877-82. doi: 10.1093/annonc/mdm566. Epub 2008 Mar 10.

    PubMed 18332043

  • Muss HB, Tu D, Ingle JN, Martino S, Robert NJ, Pater JL, Whelan TJ, Palmer MJ, Piccart MJ, Shepherd LE, Pritchard KI, He Z, Goss PE. Efficacy, toxicity, and quality of life in older women with early-stage breast cancer treated with letrozole or placebo after 5 years of tamoxifen: NCIC CTG intergroup trial MA.17. J Clin Oncol. 2008 Apr 20;26(12):1956-64. doi: 10.1200/JCO.2007.12.6334. Epub 2008 Mar 10.

    PubMed 18332474

  • Chapman JW, Meng D, Shepherd L, et al.: Competing causes of death in breast cancer extended adjuvant endocrine therapy: NCIC CTG MA.17. [Abstract] American Society of Clinical Oncology 2007 Breast Cancer Symposium, 7-8 September 2007, San Francisco, California A-56, 2007.

  • Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Cameron DA, Palmer MJ, Pater JL; National Cancer Institute of Canada Clinical Trials Group MA.17. Efficacy of letrozole extended adjuvant therapy according to estrogen receptor and progesterone receptor status of the primary tumor: National Cancer Institute of Canada Clinical Trials Group MA.17. J Clin Oncol. 2007 May 20;25(15):2006-11. doi: 10.1200/JCO.2006.09.4482. Epub 2007 Apr 23.

    PubMed 17452676

  • Goss P: Breaking the 5-year barrier: results from the MA.17 extended adjuvant trial in women who have completed adjuvant tamoxifen treatment. [Abstract] European Journal of Cancer Supplements 4 (9): 10-5, 2006.

  • Ingle JN, Tu D, Pater JL, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Cameron DA, Palmer MJ, Goss PE. Duration of letrozole treatment and outcomes in the placebo-controlled NCIC CTG MA.17 extended adjuvant therapy trial. Breast Cancer Res Treat. 2006 Oct;99(3):295-300. doi: 10.1007/s10549-006-9207-y. Epub 2006 Mar 16.

    PubMed 16541302

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing letrozole in people with Breast Cancer, run by NCIC Clinical Trials Group at 57 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 57 sites in Canada, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease-free survival (time frame: 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00003140, which also lists 32 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2026.

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