Study of Anastrozole, Letrozole, or Exemestane With or Without Tamoxifen in Treating Postmenopausal Women With Hormone-Responsive Breast Cancer That Has Been Completely Removed By Surgery

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2007 by National Cancer Institute (NCI)
Information provided by:
National Cancer Institute (NCI) Identifier:
First received: October 5, 2007
Last updated: August 23, 2013
Last verified: October 2007

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using tamoxifen may fight breast cancer by blocking use of estrogen by the tumor cells. Anastrozole, letrozole, and exemestane may fight breast cancer by lowering the amount of estrogen the body makes. It is not yet known whether giving tamoxifen followed by anastrozole, letrozole, or exemestane is more effective than giving anastrozole, letrozole, or exemestane alone in treating breast cancer.

PURPOSE: This randomized phase III trial is studying giving tamoxifen followed by either anastrozole, letrozole, or exemestane to see how well it works compared to anastrozole, letrozole, or exemestane alone in treating postmenopausal women with hormone-responsive invasive breast cancer that has been completely removed by surgery.

Condition Intervention Phase
Breast Cancer
Drug: anastrozole
Drug: exemestane
Drug: letrozole
Drug: tamoxifen citrate
Procedure: adjuvant therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Study Comparing Anastrozole, Letrozole and Exemestane, Upfront (for 5 Years) or Sequentially (for 3 Years After 2 Years of Tamoxifen), as Adjuvant Treatment of Postmenopausal Patients With Endocrine-responsive Breast Cancer

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Disease-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall Survival [ Designated as safety issue: No ]
  • Distant metastasis-free survival [ Designated as safety issue: No ]
  • Cumulative incidence of contralateral breast cancer as first event [ Designated as safety issue: No ]
  • Breast cancer-free survival [ Designated as safety issue: No ]
  • Cumulative incidence and type of second non-breast invasive cancer [ Designated as safety issue: No ]
  • Effects on lipid profile [ Designated as safety issue: No ]
  • Toxicity as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]

Estimated Enrollment: 10000
Study Start Date: March 2007
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Detailed Description:


  • To compare sequential tamoxifen for 2 years followed by anastrozole, letrozole, or exemestane for 3 years vs anastrozole, letrozole, or exemestane for 5 years in terms of disease-free survival in postmenopausal women with nonrecurrent, nonmetastatic invasive endocrine-responsive breast cancer.
  • To compare disease-free survival in patients treated with anastrozole vs letrozole vs exemestane.

OUTLINE: This is a multicenter study. Patients are stratified according to hormone receptor status (estrogen receptor [ER]-positive and progesterone [PgR] receptor-positive disease vs ER-positive and PgR-negative disease vs ER-negative and PgR-positive disease vs ER- or PgR-positive disease or ER or PgR status unknown), HER-2/neu status (positive [3+ by IHC or positive by fluorescence in situ hybridization ( FISH)] vs negative vs unknown), prior chemotherapy (none vs adjuvant vs neoadjuvant vs both adjuvant and neoadjuvant), and nodal status (pN0 vs pN1 vs pN2 vs pN3). Patients are randomized to 1 of 6 treatment arms.

  • Arm I: Patients receive oral anastrozole once daily for 5 years.
  • Arm II: Patients receive oral exemestane once daily for 5 years.
  • Arm III: Patients receive oral letrozole once daily for 5 years.
  • Arm IV: Patients receive oral tamoxifen citrate once daily for 2 years followed by oral anastrazole once daily for 3 years.
  • Arm V: Patients receive oral tamoxifen citrate once daily for 2 years followed by oral exemestane once daily for 3 years.
  • Arm VI: Patients receive oral tamoxifen citrate once daily for 2 years followed by oral letrozole once daily for 3 years.

Treatment in all arms continues in the absence of disease recurrence or unacceptable toxicity.

After completion of study therapy, patients are followed periodically.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No


  • Histologically confirmed invasive breast cancer completely removed by surgery

    • Any T, any N
    • No recurrent or metastatic disease
  • Estrogen or progesterone receptor-positive disease in primary tumor, as defined by 1 of the following:

    • At least 10% of tumor cells positive by immunohistochemistry
    • At least 10 fmol/mg cytosol protein by ligand binding assay
  • Patients with HER-2/neu positive tumors are eligible provided they receive trastuzumab (Herceptin®) according to the registered schedule


  • Female
  • Postmenopausal, defined by ≥ 1 of the following:

    • Age ≥ 60 years
    • Age 45-59 and satisfying 1 or more of the following criteria:

      • Amenorrhea for ≥ 12 months AND intact uterus
      • Amenorrhea (secondary to hysterectomy, hormone replacement therapy (HRT), or chemotherapy) for < 12 months AND follicle-stimulating hormone within the postmenopausal range
    • Underwent prior bilateral oophorectomy at any age >18 years
  • No concurrent illness that contraindicates adjuvant endocrine treatment
  • No other invasive breast cancer or invasive malignancy within the past 10 years, except adequately cone-biopsied squamous cell or basal cell skin cancer or carcinoma in situ of the cervix
  • No concurrent disease that would place the patient at unusual risk


  • See Disease Characteristics
  • Adjuvant or neoadjuvant chemotherapy must be completed prior to study entry
  • At least 1 month since prior and no concurrent HRT
  • More than 30 days since prior systemic investigational drugs
  • No prior tamoxifen as part of any breast cancer prevention study
  • Prior or concurrent locoregional radiotherapy allowed
  • No other concurrent experimental drugs
  • No concurrent bisphosphonates, unless indicated as treatment for osteoporosis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00541086

Federico II University Medical School Recruiting
Naples, Italy, 80131
Contact: Sabino De Placido, MD    39-081-746-3660   
Istituto Nazionale per lo Studio e la Cura dei Tumori Recruiting
Naples, Italy, 80131
Contact: Francesco Perrone, MD    39-81-590-3571      
Seconda Universita di Napoli Recruiting
Naples, Italy, 80138
Contact: Ciro Gallo    39-81-566-6021      
Arcispedale S. Maria Nuova Recruiting
Reggio Emilia, Italy, 42100
Contact: Corrado Boni, MD    39-522-296-546   
Istituti Fisioterapici Ospitalieri - Roma Recruiting
Rome, Italy, 00128
Contact: Francesco Cognetti, MD    39-06-5266-6919   
Sponsors and Collaborators
Gruppo Italiano Mammella (GIM)
Study Chair: Sabino De Placido, MD Federico II University
  More Information

Additional Information:
No publications provided Identifier: NCT00541086     History of Changes
Other Study ID Numbers: CDR0000570041, GIM-3-FATA, EUDRACT-2006-004018-42, EU-20764
Study First Received: October 5, 2007
Last Updated: August 23, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
stage IA breast cancer
stage IB breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
estrogen receptor-positive breast cancer
progesterone receptor-positive breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Selective Estrogen Receptor Modulators
Bone Density Conservation Agents processed this record on October 16, 2014