Exemestane, Letrozole, or Anastrozole in Treating Postmenopausal Women Who Are Undergoing Surgery for Stage II or Stage III Breast Cancer

This study is ongoing, but not recruiting participants.
National Cancer Institute (NCI)
Cancer and Leukemia Group B
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
First received: December 14, 2005
Last updated: July 23, 2015
Last verified: July 2015

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using exemestane, letrozole, or anastrozole, may fight breast cancer by lowering the amount of estrogen the body makes. Giving exemestane, letrozole, or anastrozole before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known whether exemestane, letrozole, or anastrozole is more effective in treating breast cancer.

PURPOSE: This randomized phase III trial is studying exemestane, letrozole, and anastrozole to compare how well they work in treating postmenopausal women who are undergoing surgery for stage II or stage III breast cancer.

Condition Intervention Phase
Breast Cancer
Drug: anastrozole
Drug: exemestane
Drug: letrozole
Procedure: Therapeutic Conventional Surgery
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase III Trial Comparing 16 to 18 Weeks of Neoadjuvant Exemestane (25 mg Daily), Letrozole (2.5 mg), or Anastrozole (1 mg) in Postmenopausal Women With Clinical Stage II and III Estrogen Receptor Positive Breast Cancer

Resource links provided by NLM:

Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Clinical response (complete or partial response) rate (cohort A) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  • Anti-tumor effect in terms of pathologic CR (pCR) rate to neoadjuvant chemotherapy (Cohort B) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Radiological response rate (RRR) by Response Evaluation Criteria in Solid Tumors criteria Cohort A & B [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  • Incidence of adverse events as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (Cohort A and B) [ Time Frame: Up to 30 days after drug therapy ] [ Designated as safety issue: Yes ]
  • Progression-free survival (PFS) (Cohort A and B) [ Time Frame: assessed up to 10 years ] [ Designated as safety issue: No ]
  • Rate of improvement in surgical outcome (Cohort A) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  • Rate of downstaging to stage I determined by sentinel node evaluation (Cohort A) [ Time Frame: At time of surgery ] [ Designated as safety issue: No ]
  • Rate of lymph node involvement (LNI) (Cohort A) [ Time Frame: At time of surgery ] [ Designated as safety issue: No ]
  • PCR rate defined as no histologic evidence of invasive tumor cells in the surgical breast specimen and axillary or sentinel lymph nodes (Cohort A) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  • Clinical response rate (cohort B) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]

Enrollment: 610
Study Start Date: January 2006
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive oral exemestane once daily for up to 16-18 weeks.
Drug: exemestane
Given PO
Procedure: Therapeutic Conventional Surgery
Undergo partial or radical mastectomy or lumpectomy with or without lymph node dissection
Experimental: Arm II
Patients receive oral letrozole once daily for up to 16-18 weeks.
Drug: letrozole
Given PO
Procedure: Therapeutic Conventional Surgery
Undergo partial or radical mastectomy or lumpectomy with or without lymph node dissection
Experimental: Arm III
Patients receive oral anastrozole once daily for up to 16-18 weeks.
Drug: anastrozole
Given PO
Procedure: Therapeutic Conventional Surgery
Undergo partial or radical mastectomy or lumpectomy with or without lymph node dissection

  Show Detailed Description


Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No


  • Diagnosis of breast cancer

    • T2-T4c, any N, M0 disease
  • Clinically staged, as documented by the treating physician, as 1 of the following:

    • T4a-c disease for which modified radical mastectomy with negative margins is the goal
    • T2 or T3 disease for which conversion from needing mastectomy to breast conservation is the goal
    • T2 disease for which lumpectomy at first attempt is the goal
  • Primary tumor must be palpable and measure > 2 cm by tape, ruler, or caliper measurements in at least one dimension
  • Must agree to undergo mastectomy or lumpectomy after neoadjuvant aromatase inhibitor therapy
  • No inflammatory breast cancer, defined as clinically significant erythema of the breast and/or documented dermal lymphatic invasion (not direct skin invasion by tumor or peau d'orange without erythema)
  • No distant metastasis (M1)

    • Isolated ipsilateral supraclavicular node involvement allowed
  • No diagnosis that was established by incisional biopsy
  • Must have estrogen receptor (ER) positive tumor with an Allred score of 6, 7 or 8

    • Patients with > 66.66% (two-thirds) of cells staining positive and have a minimum Allred score of 6 are eligible


  • ECOG/Zubrod performance status of ≤ 2
  • Female
  • Patient must be postmenopausal, verified by 1 of the following:

    • Bilateral surgical oophorectomy
    • No spontaneous menses ≥ 1 year
    • No menses for < 1 year with FSH and estradiol levels in postmenopausal range
  • No other malignancies within the past 5 years, except for successfully treated cervical carcinoma in situ; lobular carcinoma in situ of the breast; contralateral ductal carcinoma in situ that was treated with mastectomy or lumpectomy with radiotherapy (without tamoxifen); or non-melanoma skin cancer with no evidence of recurrence

    • Must have undergone potentially curative therapy for all prior malignancies AND deemed to be at low risk for recurrence, according to the treating physician


  • No prior treatment for invasive breast cancer, including radiotherapy, endocrine therapy, chemotherapy, or investigational agents
  • No prior sentinel lymph node biopsy (cohort B only)
  • At least 1 week since prior agents with estrogenic or putatively estrogenic properties, including herbal preparations
  • At least 1 week since prior hormone replacement therapy of any type, megestrol acetate, or raloxifene
  • No concurrent enrollment in another neoadjuvant clinical trial for treatment of the existing breast cancer
  • No other concurrent anti-neoplastic therapy, including chemotherapy or radiotherapy
  • No concurrent agents or herbal products that alter ER function
  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 ClinicalTrials.gov identifier: NCT00265759

United States, Missouri
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
Saint Louis, Missouri, United States, 63110
United States, Texas
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
Doctor's Hospital of Laredo
Laredo, Texas, United States, 78041
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Cancer and Leukemia Group B
Study Chair: Matthew J. Ellis, MD, PhD, FRCP Washington University Siteman Cancer Center
  More Information

Additional Information:
Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00265759     History of Changes
Obsolete Identifiers: NCT00698971
Other Study ID Numbers: ACOSOG-Z1031, ACOSOG-Z1031, CDR0000456382
Study First Received: December 14, 2005
Last Updated: July 23, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Alliance for Clinical Trials in Oncology:
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
estrogen receptor-positive breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms by Site
Skin Diseases
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 07, 2015