Anastrozole or Fulvestrant in Treating Postmenopausal Patients With Breast Cancer

OBJECTIVES:

Primary

• Evaluate clinical tumor response at 6 months in patients with hormone-sensitive non-metastatic breast cancer treated with neoadjuvant anastrozole and fulvestrant.

Secondary

• Evaluate tumor regression by mammography and ultrasound in these patients.
• Evaluate the rate of breast conservation at 6 months of treatment in these patients.
• Evaluate the tolerability of these regimens.
• Estimate the relapse-free survival at 5 years.
• Identify molecular signatures predictive of response in these patients.
• Identify genes implicated in response in these patients.
• Identify changes in mRNA splicing of genes involved in breast tumorigenesis.

OUTLINE: This is a non-comparative multicentre randomised phase II study in which patients from three French centres were randomly assigned in a 1 : 1 ratio to receive either anatrozole or fulvestrant.

All patients undergo biopsy at baseline. Patients are randomized between the two treatment arms.

• Arm I: Patients receive oral anastrozole once daily for 6 months.
• Arm II: Patients receive fulvestrant intramuscularly on days 1, 14, and 28 and then once a month at 2-6 months.

Within 8 days after completion of hormone therapy, all patients undergo surgical resection of the residual lesion followed by radiotherapy. Patients then receive oral anastrozole once daily for 5 years.

Tissue samples from biopsy and surgery are analyzed to assess molecular signatures and sensitivity to treatment, and to compare gene expression variation with response.

DISEASE CHARACTERISTICS:

• Histologically confirmed invasive breast cancer, meeting 1 of the following criteria:

• SBR grade I-II disease (patients < 65 years of age)
• SBR grade I-III disease (patients > 65 years of age)
• T2 (2-5 cm), T3, or T4B, and N0-1 disease
• No metastatic disease
• Breast lesion not amenable to breast-conserving resection
• No inflammatory breast cancer
• No prior breast cancer
• Hormone receptor status:

• Estrogen receptor- and/or progesterone receptor-positive

PATIENT CHARACTERISTICS:

• Postmenopausal
• No other cancer within the past 5 years except for adequately treated skin carcinoma or carcinoma in situ of the cervix
• No contraindication to anti-hormonal treatment
• No psychological, familial, social, or geographical reasons that would preclude follow up

PRIOR CONCURRENT THERAPY:

• At least 8 days since prior hormone replacement therapy
• No concurrent anti-vitamin K treatment