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A Neoadjuvant Study of Chemotherapy Versus Endocrine Therapy in Postmenopausal Patients With Primary Breast Cancer

Phase 3
18 Years
70 Years
Open (Enrolling)
Breast Cancer

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Trial Information

A Neoadjuvant Study of Chemotherapy Versus Endocrine Therapy in Postmenopausal Patients With Primary Breast Cancer


- To compare the efficacy and tolerability of cytotoxic chemotherapy versus aromatase
inhibition for the down-staging of strongly ER+ primary breast cancer in postmenopausal

- 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

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.

Inclusion Criteria


- 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

Type of Study:


Study Design:

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Feasibility of patient recruitment (pilot)

Safety Issue:


Principal Investigator

R. Charles Coombes, MD, MRCP, FRCP, PhD, FMedSci

Investigator Role:

Study Chair

Investigator Affiliation:

Charing Cross Hospital



Study ID:




Start Date:

September 2008

Completion Date:

Related Keywords:

  • Breast Cancer
  • estrogen receptor-positive breast cancer
  • recurrent breast cancer
  • stage II breast cancer
  • stage IIIA breast cancer
  • stage IIIB breast cancer
  • stage IIIC breast cancer
  • Breast Neoplasms