Breast CancerPhase 3NCT00265759
Exemestane, Letrozole, or Anastrozole in Treating Postmenopausal Women Who Are Undergoing Surgery for Stage II or Stage III Breast Cancer
A Phase 3 study testing anastrozole, exemestane and letrozole in people with Breast Cancer, run by Alliance for Clinical Trials in Oncology at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- anastrozole, exemestane and letrozole
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 622 participants
- Where
- 3 sitesUnited States
- Study dates
- Jan 2006to 27 Nov 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, 77030-4009
Doctor's Hospital of Laredo
Laredo, Texas, 78041
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
St Louis, Missouri, 63110
About this study
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
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.
Read the detailed description
OBJECTIVES:
Primary
- 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])
Secondary
- Compare the neoadjuvant treatment regimens relative to the rates of improvement in surgical outcome for patients considered marginal for Breast Conservation Surgery prior to therapy. (Cohort A)
- Compare the neoadjuvant treatment regimens relative to the rates of improvement in surgical outcome for patients designated as candidates for Mastectomy prior to therapy. (Cohort A)
- Compare the relative safety of the neoadjuvant treatment regimens in terms of reported adverse events. (Cohort A)
- To compare the tumor pathologic size between the neoadjuvant treatment regimens, to compare the rates of pathological complete response. (Cohort A)
- To compare the tumor pathologic size between the neoadjuvant treatment regimens, to compare the rates of down-staging to stage I. (Cohort A)
- 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. (Cohort A)
- Compare the neoadjuvant treatment regimens relative to clinical response rate. (Cohort B)
- Compare the neoadjuvant treatment regimens relative to progression-free survival. (Cohort A and B)
- Compare the neoadjuvant treatment regimens relative to overall survival. (Cohort A and B)
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.
- Conditions
- Breast Cancer
- Being tested
- anastrozole, exemestane, letrozole, Therapeutic Conventional Surgery
- Keywords
- stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, estrogen receptor-positive breast cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anastrozoleDrug
Given PO
exemestaneDrug
Given PO
letrozoleDrug
Given PO
Therapeutic Conventional SurgeryProcedure or surgery
Undergo partial or radical mastectomy or lumpectomy with or without lymph node dissection
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | Patients receive oral exemestane once daily for up to 16-18 weeks. Receives: Drug: exemestane; Procedure: Therapeutic Conventional Surgery |
| Arm II | Experimental | Patients receive oral letrozole once daily for up to 16-18 weeks. Receives: Drug: letrozole; Procedure: Therapeutic Conventional Surgery |
| Arm III | Experimental | Patients receive oral anastrozole once daily for up to 16-18 weeks. Receives: Drug: anastrozole; Procedure: Therapeutic Conventional Surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Up to 18 weeks
Secondary outcomes (9)
Toxicity (Cohort A)
Incidence of the most common grade 3+ toxicities reported to be probably, possibly, or definitely related to treatment as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (Cohort A) At each treatment evaluation, the type, severity, and attribution of each adverse event reported will be assessed using the NCI-CTCAE definitions. For each treatment, the percentage of patients who developed a severe (grade 3+) toxicity considered possibly, probably or definitively related to treatment will be determined.
Measured: Up to 30 days after drug therapy
Disease-free Survival (DFS) (Cohort A and B)
Disease-free survival (DFS) is the time from surgery to the first of the following events: local, regional or distant recurrence, second primary disease, contralateral invasive breast cancer, or death due to any cause. The 5 year DFS rate and 95% confidence interval will be calculated.
Measured: 5 years
Rate of Improved Surgical Outcome for Patients Considered Marginal for Breast Conservation Surgery Prior to Therapy (Cohort A)
The rate (percentage) of improved surgical outcome for patients considered marginal for breast conservation surgery prior to therapy for Cohort A is reported below for each treatment arm. Breast conservation surgery (not mastectomy) as the most extensive surgery performed for a patient is considered an improvement in surgical outcome.
Measured: At time of surgery up to 18 weeks
Rate of Downstaging to Stage I Determined by Sentinel Node Evaluation (Cohort A)
The rate downstaging to Stage I of a given treatment is defined as 100 times the number of eligible patients randomized to that treatment whose surgically findings are such that the maximum dimension of the invasive lesion contained in their surgical specimen is at most 2 cm and their lymph nodes are negative (by Hematoxylin \& Eosin Staining) divided by the total number of eligible patients randomized to that treatment. For each neo-adjuvant endocrine treatment pair, a 95% binomial confidence interval will be constructed for the true difference in the rate of downstaging to Stage I between these 2 treatments.
Measured: At time of surgery up to 18 weeks
Rate of Lymph Node Involvement (LNI) (Cohort A)
For those patients who undergo a sentinel lymph node dissection or an axillary lymph node dissection (at least 6 nodes examined with Hematoxylin \& Eosin Staining), the LNI rate (percentage) is defined as 100 times the proportion of eligible patients randomized to that treatment with at least one positive node. For each neo-adjuvant endocrine treatment, a 95% binomial confidence interval will be constructed for its true LNI rate.
Measured: At time of surgery up to 18 weeks
The Pathologic Complete Response (pCR) Rate (Cohort A)
The pathologic complete response is defined as no histologic evidence of invasive tumor cells in the surgical breast specimen and axillary or sentinel lymph nodes. The pathologic complete response rate (percentage) of a given treatment is defined as 100 times the number of eligible patients randomized to that treatment whose surgical specimen is such that there is no histologic evidence of invasive tumor cells in the surgical breast specimen and axillary or sentinel lymph nodes divided by the total number of eligible patients randomized to that treatment. For each neo-adjuvant endocrine treatment pair, a 95% binomial confidence interval will be constructed for the true difference in the pCR between these 2 treatments.
Measured: At time of surgery up to 18 weeks
Clinical Response Rate (Cohort B)
The clinical response rate is defined as 100 times the number of eligible patients whose disease meets the WHO criteria for complete or partial response prior to surgery divided by the total number of eligible patients. A 90% binomial confidence interval will be constructed for the true clinical response rate.
Measured: Up to 18 weeks
Rate of Improved Surgical Outcome for Patients Designated as Candidates for Mastectomy Prior to Therapy (Cohort A)
Rate (percentage) of Improved surgical outcome for patients designated as candidates for mastectomy prior to therapy (Cohort A). Breast conservation surgery (not mastectomy) as the most extensive surgery performed for a patient is considered an improvement in surgical outcome.
Measured: At time of surgery up to 18 weeks
Percentage of Participants With Overall Survival (Cohort A and B)
Overall survival (OS) will be measured from the date of randomization until the date of death. The distribution of overall survival times will be estimated using the Kaplan-Meier method. The 5 year OS rate and 95% confidence interval will be calculated.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2005 (estimated)
- Study startJan 2006
- Primary completionAug 2012
- Study completion27 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Alliance for Clinical Trials in OncologyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 622 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alliance for Clinical Trials in Oncology
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Cancer and Leukemia Group B
- Responsible party
- Sponsor
- Investigators
- Matthew J. Ellis, MD, PhD, FRCP, Study chair, Washington University Siteman Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00265759
- Sponsor's protocol ID
- ACOSOG-Z1031
- Other IDs
- ACOSOG-Z1031, CDR0000456382
- Status last verified
- Apr 2025
- First submitted
- 14 Dec 2005
- Last updated
- 23 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 21555689Ellis 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.
PubMed 28045625Punturi 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.
PubMed 34011995
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00265759
- Acronym / sponsor ID
- ACOSOG-Z1031
- 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
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 622 participants (actual)
- Lead sponsor
- Alliance for Clinical Trials in OncologyUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Cancer and Leukemia Group B
- Study start
- Jan 2006 (actual)
- Primary completion
- Aug 2012 (actual)
- Study completion
- 27 Nov 2019 (actual)
- First posted
- 15 Dec 2005 (estimated)
- Results
- Posted 30 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
OBJECTIVES:
Primary
- 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])
Secondary
- Compare the neoadjuvant treatment regimens relative to the rates of improvement in surgical outcome for patients considered marginal for Breast Conservation Surgery prior to therapy. (Cohort A)
- Compare the neoadjuvant treatment regimens relative to the rates of improvement in surgical outcome for patients designated as candidates for Mastectomy prior to therapy. (Cohort A)
- Compare the relative safety of the neoadjuvant treatment regimens in terms of reported adverse events. (Cohort A)
- To compare the tumor pathologic size between the neoadjuvant treatment regimens, to compare the rates of pathological complete response. (Cohort A)
- To compare the tumor pathologic size between the neoadjuvant treatment regimens, to compare the rates of down-staging to stage I. (Cohort A)
- 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. (Cohort A)
- Compare the neoadjuvant treatment regimens relative to clinical response rate. (Cohort B)
- Compare the neoadjuvant treatment regimens relative to progression-free survival. (Cohort A and B)
- Compare the neoadjuvant treatment regimens relative to overall survival. (Cohort A and B)
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Drug: exemestane, Procedure: Therapeutic Conventional SurgeryPatients receive oral exemestane once daily for up to 16-18 weeks. |
| Arm II | Experimental | Drug: letrozole, Procedure: Therapeutic Conventional SurgeryPatients receive oral letrozole once daily for up to 16-18 weeks. |
| Arm III | Experimental | Drug: anastrozole, Procedure: Therapeutic Conventional SurgeryPatients receive oral anastrozole once daily for up to 16-18 weeks. |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| anastrozoleGiven PO | Drug | Arm III |
| exemestaneGiven PO | Drug | Arm I |
| letrozoleGiven PO | Drug | Arm II |
| Therapeutic Conventional SurgeryUndergo partial or radical mastectomy or lumpectomy with or without lymph node dissection | Procedure or surgery | Arm I, Arm II, Arm III |
Primary outcome
Clinical Response (Complete or Partial Response) Rate (Cohort A)
Time frame: Up to 18 weeks
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.
Anti-tumor Effect in Terms of Pathologic CR (pCR) Rate to Neoadjuvant Chemotherapy (Cohort B)
Time frame: Up to 18 weeks
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.
9 secondary outcomes
Toxicity (Cohort A)
Time frame: Up to 30 days after drug therapy
Disease-free Survival (DFS) (Cohort A and B)
Time frame: 5 years
Rate of Improved Surgical Outcome for Patients Considered Marginal for Breast Conservation Surgery Prior to Therapy (Cohort A)
Time frame: At time of surgery up to 18 weeks
Rate of Downstaging to Stage I Determined by Sentinel Node Evaluation (Cohort A)
Time frame: At time of surgery up to 18 weeks
Rate of Lymph Node Involvement (LNI) (Cohort A)
Time frame: At time of surgery up to 18 weeks
The Pathologic Complete Response (pCR) Rate (Cohort A)
Time frame: At time of surgery up to 18 weeks
Clinical Response Rate (Cohort B)
Time frame: Up to 18 weeks
Rate of Improved Surgical Outcome for Patients Designated as Candidates for Mastectomy Prior to Therapy (Cohort A)
Time frame: At time of surgery up to 18 weeks
Percentage of Participants With Overall Survival (Cohort A and B)
Time frame: 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 21555689Ellis 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.
- Results publication: PubMed 28045625Ellis 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.
- Derived from this study: PubMed 34011995Punturi 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.
Related trials for Breast Cancer
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthew J. Ellis, MD, PhD, FRCP study chair
Washington University Siteman Cancer Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing anastrozole, exemestane and letrozole in people with Breast Cancer, run by Alliance for Clinical Trials in Oncology at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Response (Complete or Partial Response) Rate (Cohort A) (time frame: Up to 18 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00265759, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2025.