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Chemotherapy or Letrozole Before Surgery in Treating Postmenopausal Women With Breast Cancer That Can Be Removed By Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00963729
Recruitment Status : Completed
First Posted : August 21, 2009
Last Update Posted : August 12, 2013
Information provided by:
National Cancer Institute (NCI)

Brief Summary:

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by reducing the production of estrogen. It is not yet known whether giving more than one drug (combination chemotherapy) or giving letrozole before surgery is more effective in treating women with breast cancer.

PURPOSE: This randomized phase III trial is studying giving combination chemotherapy before surgery to see how well it works compared with letrozole given before surgery in treating postmenopausal women with breast cancer that can be removed by surgery.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: cyclophosphamide Drug: docetaxel Drug: epirubicin hydrochloride Drug: fluorouracil Drug: letrozole Phase 3

Detailed Description:


  • To compare the efficacy and tolerability of cytotoxic chemotherapy versus aromatase inhibition for the down-staging of strongly ER+ primary breast cancer in postmenopausal women.
  • To identify biological predictors of response to these two treatment modalities.

OUTLINE: This is a multicenter pilot, feasibility study followed by a randomized study. In the pilot study, a record of all patients screened and invited to participate in the study is compiled. Reasons for failure to recruit will be recorded. Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive fluorouracil IV, epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients who do not achieve at least partial response after 3 courses receive docetaxel IV on day 1 of 3-week courses for an additional 3 courses.
  • Arm II: Patients receive oral letrozole daily for 18-23 weeks until day of surgery.

Patients in both arms undergo surgery at week 18-23. Most patients then receive adjuvant therapy.

Quality of life is assessed at baseline, periodically during study treatment, and then during follow up.

Blood is collected pre-treatment, at mid-treatment, and before surgery. Blood is then collected every 6 months for 2 years. Blood samples and preserved tumor samples are used for correlative studies.

After completion of surgery, patients are followed up at least annually for 10 years.

PROJECTED ACCRUAL: A total of 40 patients for the pilot study and 716 patients for the phase III study will be accrued.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 756 participants
Allocation: Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Neoadjuvant Study of Chemotherapy Versus Endocrine Therapy in Postmenopausal Patients With Primary Breast Cancer
Study Start Date : September 2008
Actual Primary Completion Date : March 2010
Actual Study Completion Date : March 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Letrozole

Arm Intervention/treatment
Experimental: Arm I
Patients receive fluorouracil IV, epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Drug: cyclophosphamide
Given IV

Drug: docetaxel
Given IV

Drug: epirubicin hydrochloride
Given IV

Drug: fluorouracil
Given IV

Experimental: Arm II
Patients receive oral letrozole daily for 18-23 weeks until day of surgery.
Drug: letrozole
Given orally

Primary Outcome Measures :
  1. Feasibility of patient recruitment (pilot)
  2. Feasibility of tissue collection (pilot)
  3. Ultrasound (or mammogram) response rate

Secondary Outcome Measures :
  1. Clinical response rate
  2. Radiologic response rate by ultrasound (pilot)
  3. Quality of life
  4. Pathological complete response rate (pCR) defined as no residual invasive or pre-invasive carcinoma in breast or axilla (pilot)
  5. Plasma DNA changes in relation to treatment response
  6. Rate of conservation surgery
  7. Degree of pathological response
  8. Ki-67 changes and its relationship to treatment response
  9. Length of time to maximum response within the treatment period
  10. Tolerability of the various treatments
  11. Disease-free survival
  12. Overall survival
  13. MRI response

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No


  • Histologically proven primary invasive breast cancer that is thought to be suitable for neoadjuvant treatment

    • No cytological proof of malignancy only
    • T2 tumor or greater (≥ 20 mm by ultrasound) or any T stage with nodal disease ≥ 20 mm diameter on ultrasound assessment
    • No evidence of distant metastatic disease as disclosed by bone scan, liver, and chest imaging
  • Definite indication for neoadjuvant and adjuvant chemotherapy
  • Primary tumor amenable to biopsy
  • No inoperable disease that is judged very unlikely to be rendered operable by neoadjuvant treatment
  • No inflammatory breast cancer
  • No bilateral invasive breast cancer
  • HER-2 positivity is NOT an exclusion criterion in the feasibility (pilot) study
  • Estrogen receptor (ER) positive tumor

    • No ER-poor disease as defined locally (e.g., H-score < 100, Allred 3/4/5)
    • Allred 6/7/8, H-score H ≥100 allowed


  • Postmenopausal, meeting 1 of the following criteria:

    • Over 12 months since last menstrual period
    • Postmenopausal gonadotrophin levels (luteinizing hormone or follicle-stimulating hormone levels above local criteria)
    • Postmenopausal estradiol levels below local criteria
    • Prior bilateral oophorectomy
    • Menopause induced by gonadotrophin-releasing hormone not allowed
  • WHO performance status 0 or 1
  • WBC ≥ 3.0 × 10^9/L
  • ANC ≥ 1.5 × 10^9/L
  • Platelets ≥ 100 × 10^9/L
  • Hemoglobin > 9 g/dL
  • AST/ALT ≤ 1.5 times upper limit of normal (ULN)
  • Serum bilirubin ≤ 1.5 times ULN
  • Alkaline phosphatase ≤ 1.5 times ULN
  • Serum creatinine ≤ 1.5 times ULN
  • No active, uncontrolled infection
  • No malignancy within the past 10 years except for basal cell carcinoma or cervical carcinoma in situ

    • Treatment for previous malignancy confined to resection alone
  • No concomitant medical, psychiatric, or geographic problems that might prevent completion of treatment or follow-up
  • No known severe hypersensitivity to aromatase inhibitors
  • No contraindication to receiving aromatase inhibitors (clinical evidence or recorded history of osteoporosis)
  • No other serious illness or medical condition including any of the following:

    • Congestive heart failure or unstable angina pectoris
    • Myocardial infarction within the past year
    • Uncontrolled hypertension or high-risk uncontrolled arrhythmias
    • History of significant neurologic or psychiatric disorders, including psychotic disorders, dementia, or seizures, that would prohibit the understanding and giving of informed consent
    • Active peptic ulcer
    • Unstable diabetes mellitus
  • No definite contraindications for the use of corticosteroids
  • No contraindication to receiving combination anthracycline/taxane chemotherapy
  • Willing to undergo repeat biopsies


  • No hormone replacement therapy within 4 weeks of starting treatment
  • No chronic oral treatment with corticosteroids unless initiated > 6 months prior to study entry and at low dose (≤ 20 mg methylprednisolone or equivalent)
  • No concurrent warfarin or heparin therapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00963729

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Korea, Republic of
Asan Medical Center - University of Ulsan College of Medicine
Seoul, Korea, Republic of, 138-736
United Kingdom
West Middlesex University Hospital
Isleworth, England, United Kingdom, TW7 6AF
Guy's Hospital
London, England, United Kingdom, SE1 9RT
St. Mary's Hospital
London, England, United Kingdom, W2 1NY
Charing Cross Hospital
London, England, United Kingdom, W6 8RF
Sponsors and Collaborators
Imperial College London
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Study Chair: R. Charles Coombes, MD, MRCP, FRCP, PhD, FMedSci Charing Cross Hospital

Layout table for additonal information Identifier: NCT00963729     History of Changes
Other Study ID Numbers: ICCRU-NEOcent-C-21-07
CDR0000641383 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: August 21, 2009    Key Record Dates
Last Update Posted: August 12, 2013
Last Verified: August 2011
Keywords provided by National Cancer Institute (NCI):
estrogen receptor-positive breast cancer
recurrent breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors