Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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 Identifier:
First received: December 14, 2005
Last updated: August 11, 2016
Last verified: August 2016

December 14, 2005
August 11, 2016
January 2006
August 2012   (final data collection date for primary outcome measure)
  • 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 ]
Not Provided
Complete list of historical versions of study NCT00265759 on Archive Site
  • 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 ]
Not Provided
Not Provided
Not Provided
Exemestane, Letrozole, or Anastrozole in Treating Postmenopausal Women Who Are Undergoing Surgery for Stage II or Stage III Breast Cancer
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

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.



  • Determine whether anastrozole, exemestane, or letrozole administered for 16 to 18 weeks as neoadjuvant endocrine treatment for postmenopausal patients with stage II or stage III estrogen receptor (ER)-positive breast cancer should be chosen as the aromatase inhibitor arm of a future study that will compare neoadjuvant aromatase inhibitor (AI) treatment with neoadjuvant chemotherapy. (Cohort A)
  • To determine whether patients who have a high Ki-67 value (> 10%) after 2 weeks of neoadjuvant AI treatment experience a higher than expected pathological response rate to neoadjuvant chemotherapy (20%) than would be typically observed for postmenopausal patients with unselected ER+ rich tumors (estimated to be 5%), indicating that an early assessment of proliferation is a useful approach to the identification of a chemotherapy sensitive subgroup of ER+ tumors. (Cohort B [patients enrolled after the 375th patient])


  • Compare the neoadjuvant treatment regimens relative to the rates of improvement in surgical outcome: mastectomy with primary skin closure and negative surgical margins (for T4 a, b, c tumors); breast conserving surgery with negative final margins (for T3 tumors and T2 tumors classified as requiring mastectomy at baseline); breast conserving surgery at first attempt (for T2 tumors classified as potential candidates for breast conservation).
  • Compare and confirm the radiological response rates (mammography and ultrasound by central radiological analysis) between these three neoadjuvant treatment regimens.
  • Compare the relative safety of the neoadjuvant treatment regimens in terms of reported adverse events.
  • To compare the tumor pathologic size between the neoadjuvant treatment regimens, to compare the rates of pathological complete response, and to compare down-staging to stage I.
  • To compare the rate of complete cell cycle response between the three treatment regimens (Ki67 staining of 1% or less in the post treatment sample).
  • Compare the incidence of metastatic lymph node involvement on the three arms of the study in patients who have a lymph node dissection at the end of neoadjuvant treatment.
  • Determine the 10-year incidence of local recurrence in patients treated with these regimens.
  • To collect tumor tissue, serum specimens, and plasma specimens to develop predictive biomarkers that can be used to select tumors for neoadjuvant AI therapy.
  • Collect surgical specimens post-AI neoadjuvant therapy to identify markers of de novo resistence to AI therapy.

OUTLINE: This is a multicenter study comprising cohort A (phase III study) and cohort B (phase II study). Once cohort A accrual is met (375 patients), subsequent patients are enrolled to cohort B. Patients in both cohorts are stratified according to T stage (T2 vs T3 vs T4), and randomized to 1 of 3 aromatase inhibition (AI) treatment arms.

  • Arm I: Patients receive oral exemestane once daily for 16-18 weeks.
  • Arm II: Patients receive oral letrozole once daily for 16-18 weeks.
  • Arm III: Patients receive oral anastrozole once daily for 16-18 weeks. Patients in cohort B undergo breast biopsy after 2-4 weeks of AI treatment for analysis of Ki-67 levels. Patients with Ki-67 level ≤ 10% continue AI treatment. Patients with Ki-67 level > 10% (high) are given the option to switch to neoadjuvant chemotherapy or undergo immediate breast surgery.

After completion of AI therapy, all patients undergo partial or radical mastectomy or lumpectomy with or without lymph node dissection.

After surgery, patients are followed up periodically for 10 years.

PROJECTED ACCRUAL: A total of 610 patients (375 for cohort A and 235 for cohort B) will be accrued for this study.

Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Breast Cancer
  • Drug: anastrozole
    Given PO
  • Drug: exemestane
    Given PO
  • Drug: letrozole
    Given PO
  • Procedure: Therapeutic Conventional Surgery
    Undergo partial or radical mastectomy or lumpectomy with or without lymph node dissection
  • Experimental: Arm I
    Patients receive oral exemestane once daily for up to 16-18 weeks.
    • Drug: exemestane
    • Procedure: Therapeutic Conventional Surgery
  • Experimental: Arm II
    Patients receive oral letrozole once daily for up to 16-18 weeks.
    • Drug: letrozole
    • Procedure: Therapeutic Conventional Surgery
  • Experimental: Arm III
    Patients receive oral anastrozole once daily for up to 16-18 weeks.
    • Drug: anastrozole
    • Procedure: Therapeutic Conventional Surgery
Ellis MJ, Suman VJ, Hoog J, Lin L, Snider J, Prat A, Parker JS, Luo J, DeSchryver K, Allred DC, Esserman LJ, Unzeitig GW, Margenthaler J, Babiera GV, Marcom PK, Guenther JM, Watson MA, Leitch M, Hunt K, Olson JA. Randomized phase II neoadjuvant comparison between letrozole, anastrozole, and exemestane for postmenopausal women with estrogen receptor-rich stage 2 to 3 breast cancer: clinical and biomarker outcomes and predictive value of the baseline PAM50-based intrinsic subtype--ACOSOG Z1031. J Clin Oncol. 2011 Jun 10;29(17):2342-9. doi: 10.1200/JCO.2010.31.6950.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Active, not recruiting
Not Provided
August 2012   (final data collection date for primary outcome measure)


  • 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
Child, Adult, Senior
Contact information is only displayed when the study is recruiting subjects
United States
ACOSOG-Z1031, ACOSOG-Z1031, CDR0000456382
Not Provided
Not Provided
Alliance for Clinical Trials in Oncology
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
Alliance for Clinical Trials in Oncology
August 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP