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

NCT00265759 | Completed Phase 3 Results DMC

• 2 other identifiers: ACOSOG-Z1031CDR0000456382
• Study Type: interventional
• Target: 622
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Breast Cancer

Keywords

stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer; estrogen receptor-positive breast cancer

Outcome Measures

Primary Outcomes (2)

• Clinical Response (Complete or Partial Response) Rate (Cohort A)

  The clinical response rate (percentage) of a given treatment is defined as 100 times the number of eligible patients randomized to that treatment whose disease meets the WHO criteria for complete or partial response prior to surgery divided by the total number of eligible patients randomized to that treatment. For each treatment arm, a 95% binomial confidence interval will be constructed for the true clinical response rate. Complete Response (CR): The disappearance of all known disease based on a comparison between the measurements at baseline and the Week 16 visit. Partial Response (PR): A 50% or greater decrease in the product of the bi-dimensional measurements of the lesion (total tumor size) based on a comparison between the measurements at baseline and the Week 16 visit. In addition there can be no appearance of new lesions or progression of any lesion.

  Up to 18 weeks

• Anti-tumor Effect in Terms of Pathologic CR (pCR) Rate to Neoadjuvant Chemotherapy (Cohort B)

  The primary aim is to assess the anti-tumor effect in terms of pathologic CR rates of neo-adjuvant chemotherapy in patients with T2-T4c, any N, M0 breast cancer (by clinical staging) who are endocrine therapy resistant (that is, their Ki-67 level is \>10 after 2-4 week of neo-adjuvant endocrine therapy alone). The pCR rate (percentage) for neo-adjuvant chemotherapy is defined as 100 times the number of eligible patients with no histologic evidence of invasive tumor cells in the surgical breast specimen and the axillary or sentinel lymph nodes divided by the total number of eligible patients who received neo-adjuvant chemotherapy.

  Up to 18 weeks

Secondary Outcomes (9)

• Toxicity (Cohort A)

  Up to 30 days after drug therapy

• Disease-free Survival (DFS) (Cohort A and B)

  5 years

• Rate of Improved Surgical Outcome for Patients Considered Marginal for Breast Conservation Surgery Prior to Therapy (Cohort A)

  At time of surgery up to 18 weeks

• Rate of Downstaging to Stage I Determined by Sentinel Node Evaluation (Cohort A)

  At time of surgery up to 18 weeks

• Rate of Lymph Node Involvement (LNI) (Cohort A)

  At time of surgery up to 18 weeks

Study Arms (3)

Arm I

EXPERIMENTAL

Patients receive oral exemestane once daily for up to 16-18 weeks.

Drug: exemestane; Procedure: Therapeutic Conventional Surgery

Arm II

EXPERIMENTAL

Patients receive oral letrozole once daily for up to 16-18 weeks.

Drug: letrozole; Procedure: Therapeutic Conventional Surgery

Arm III

EXPERIMENTAL

Patients receive oral anastrozole once daily for up to 16-18 weeks.

Drug: anastrozole; Procedure: Therapeutic Conventional Surgery

Interventions

anastrozole DRUG

Given PO

Arm III

exemestane DRUG

Given PO

Arm I

letrozole DRUG

Given PO

Arm II

Therapeutic Conventional Surgery PROCEDURE

Undergo partial or radical mastectomy or lumpectomy with or without lymph node dissection

Arm I; Arm II; Arm III

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * 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 PATIENT CHARACTERISTICS: * 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 PRIOR CONCURRENT THERAPY: * 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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Alliance for Clinical Trials in Oncology: lead
• National Cancer Institute (NCI): collaborator
• Cancer and Leukemia Group B: collaborator

Study Sites (3)

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, 63110, United States

Location

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, 77030-4009, United States

Location

Doctor's Hospital of Laredo

Laredo, Texas, 78041, United States

Location

Related Publications (3)

• 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. Epub 2011 May 9.

  PMID: 21555689 RESULT

• Ellis MJ, Suman VJ, Hoog J, Goncalves R, Sanati S, Creighton CJ, DeSchryver K, Crouch E, Brink A, Watson M, Luo J, Tao Y, Barnes M, Dowsett M, Budd GT, Winer E, Silverman P, Esserman L, Carey L, Ma CX, Unzeitig G, Pluard T, Whitworth P, Babiera G, Guenther JM, Dayao Z, Ota D, Leitch M, Olson JA Jr, Allred DC, Hunt K. Ki67 Proliferation Index as a Tool for Chemotherapy Decisions During and After Neoadjuvant Aromatase Inhibitor Treatment of Breast Cancer: Results From the American College of Surgeons Oncology Group Z1031 Trial (Alliance). J Clin Oncol. 2017 Apr 1;35(10):1061-1069. doi: 10.1200/JCO.2016.69.4406. Epub 2017 Jan 3.

  PMID: 28045625 RESULT

• Punturi NB, Seker S, Devarakonda V, Mazumder A, Kalra R, Chen CH, Li S, Primeau T, Ellis MJ, Kavuri SM, Haricharan S. Mismatch repair deficiency predicts response to HER2 blockade in HER2-negative breast cancer. Nat Commun. 2021 May 19;12(1):2940. doi: 10.1038/s41467-021-23271-0.

  PMID: 34011995 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Anastrozole; exemestane; Letrozole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Matthew J. Ellis, MB, BChir, BSc., PhD, FRCP
• Organization: Baylor College of Medicine

Matthew.Ellis@bcm.edu

713 798-1999

Study Officials

• Matthew J. Ellis, MD, PhD, FRCP

  Washington University Siteman Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2005
• First Posted: December 15, 2005
• Study Start: January 1, 2006
• Primary Completion: August 1, 2012
• Study Completion: November 27, 2019
• Last Updated: April 23, 2025
• Results First Posted: March 30, 2017

Record last verified: 2025-04

Locations

US (3)