Letrozole After Tamoxifen in Treating Women With Breast Cancer

Overview

  • Study type

    Interventional
  • Study phase

    III
  • Study IDs

  • Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

  • Site IRB
    • La Crosse, Wisconsin: 12-004954
    NCT ID: NCT00003140
    Sponsor Protocol Number: MA.17

About this study

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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

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

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

La Crosse, Wis.

Mayo Clinic principal investigator

Paula Gill, M.D.

Closed for enrollment

Contact information:

Research Information Center

800-664-4542

More information

Publications

  • Over the past few years, data have been published concerning the relative efficacy and safety profiles of tamoxifen and the aromatase inhibitors (AIs) in the adjuvant therapy setting for women with early hormone receptor-positive breast cancer. Recently, debate has centred around trials which have studied primary tamoxifen and AI therapy, switching and sequencing strategies and extended adjuvant therapy. Read More on PubMed
  • In recent years, several major trials have studied aromatase inhibitors (AIs)/inactivators as adjuvant therapy for postmenopausal women with early-stage breast cancer. The AIs have demonstrated improved efficacy compared with 5 years of tamoxifen when used as initial therapy or when used sequentially after 2-3 years. They also improve outcomes when used after 5 years of adjuvant tamoxifen in this patient population. In all cases, AIs improve disease-free survival compared with the standard 5 years of adjuvant tamoxifen, leading to a reassessment of the optimal adjuvant endocrine therapy for postmenopausal patients with breast cancer. The American Society of Clinical Oncology now recommends the inclusion of an AI into the adjuvant regimen at some point for most postmenopausal patients with hormone receptor-positive early-stage breast cancer. However, the optimal duration of AI therapy and the comparative efficacy and safety of the alternative strategies for their incorporation remain matters of debate. In addition, the long-term impact of AIs on other organs, such as the bone and cardiovascular systems, is not completely understood, and longer follow-up of patients from these original trials as well as carefully planned future trials with appropriate substudies are essential to determine the optimal endocrine treatment strategy. Read More on PubMed
  • Letrozole is a highly selective, nonsteroidal, third-generation aromatase inhibitor approved for first-line and extended adjuvant therapy in postmenopausal women with hormone-responsive, early-stage breast cancer. Binding of letrozole to the haeme component of the cytochrome P450 subunit of aromatase inhibits estrogen biosynthesis throughout the body. As first-line adjuvant therapy in approximate, equals 8000 postmenopausal women with hormone-responsive, early-stage breast cancer, once-daily letrozole 2.5mg significantly prolonged disease-free survival (DFS; primary endpoint) and reduced the risk of relapse at distant sites relative to once-daily tamoxifen 20mg in the ongoing Breast International Group 1-98, double-blind, multinational trial. The median duration of follow-up for this primary core analysis was 25.8 months. Extended adjuvant therapy with once-daily letrozole 2.5mg significantly prolonged DFS relative to placebo treatment at a median follow-up of 30 months (primary endpoint) in the MA-17 trial in approximate, equals 5000 postmenopausal women who were disease free after 4.5-6 years of tamoxifen therapy for hormone-responsive, early-stage breast cancer. Letrozole treatment for up to 5 years was generally well tolerated in this clinical setting. As first-line treatment, relative to tamoxifen, letrozole was associated with a significantly lower incidence of venous thromboembolitic events, vaginal bleeding, hot flushes and night sweating, whereas the incidence of cardiac failure, bone fractures and arthralgia was higher in letrozole recipients. Read More on PubMed
  • Tamoxifen has been the standard of care for adjuvant endocrine therapy of early breast cancer. In postmenopausal women, data now suggest that alternative agents (aromatase inhibitors [AIs]) may have improved long-term risk:benefit profiles and thus have the potential to improve outcome. The 'Arimidex', Tamoxifen, alone or in combination (ATAC) trial has shown that anastrozole provides improved disease-free survival (DFS) and time to recurrence, significantly reduced time to distant metastases and superior overall tolerability compared with tamoxifen when used as initial adjuvant therapy. Results have already led to a reconsideration of current recommendations for adjuvant therapy. Other ongoing trials include studies that are evaluating the benefits of sequencing of endocrine agents both within the standard 5-year adjuvant treatment period and as additional therapy in the post-adjuvant period. Three recently reported trials have suggested that switching from tamoxifen to an AI after 2-3 years of treatment leads to better outcomes than 5 years of tamoxifen. Finally, the NCIC MA 17 trial has shown that switching to an AI after 5 years of tamoxifen improves DFS compared with placebo. These are momentous discoveries that have improved our biological understanding and will inevitably change the management of breast cancer in the near future. Read More on PubMed
  • The third-generation aromatase inhibitors reduce circulating estrogen levels in postmenopausal women and are well tolerated orally for breast cancer. Their role in the management of advanced breast cancer has already been recognized. This article reviews the evidence for their role in the adjuvant treatment of early-stage disease. Read More on PubMed

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20154107

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