RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using
letrozole may fight breast cancer by reducing the production of estrogen. Giving letrozole
before surgery may shrink the tumor so that it can be removed.
PURPOSE: This phase II trial is studying how well neoadjuvant letrozole works in treating
postmenopausal women who are undergoing surgery for estrogen-receptor positive or
progesterone-receptor positive stage II, stage IIIA, or stage IIIB breast cancer.
- Develop a predictive model of response (based on gene expression profiling) in
postmenopausal women with estrogen- and/or progesterone-receptor positive stage II,
IIIA, or IIIB breast cancer treated with neoadjuvant letrozole.
- Determine the response rate in patients treated with this drug.
- Determine changes in Ki67 proliferation rates in patients treated with this drug.
- Determine the rate of improvement in surgical outcomes in patients treated with this
- Determine the long-term outcomes in patients treated with this drug.
- Determine the safety of this drug in these patients.
- Determine mechanisms of resistance to this drug in these patients.
OUTLINE: This is a multicenter study.
Patients receive neoadjuvant oral letrozole once daily for 16 weeks in the absence of
disease progression. Patients then undergo breast surgery one day after the last dose of
letrozole. Patients with partial response after 16 weeks may continue to receive letrozole
for an additional 8 weeks before undergoing breast surgery.
Patients are followed within 4 weeks after definitive surgery and then annually for 10
PROJECTED ACCRUAL: A total of 150 patients will be accrued for this study.
- Histologically confirmed infiltrating adenocarcinoma of the breast by core needle
- Clinical stage T2-T4a-c, N0-2, M0
- Palpable and measurable disease
- Previously untreated disease
- Benefits from neoadjuvant therapy that would improve surgical outcome AND meets
criteria for 1 of the following:
- Marginal candidate for lumpectomy (e.g., lumpectomy feasible but patient at risk
for positive margins or poor cosmetic outcome) AND patient desires
- Ineligible for lumpectomy due to size of primary tumor, but modified radical
mastectomy feasible AND patient desires breast-conserving surgery
- Inoperable disease AND systemic therapy required for disease to become operable
by modified radical mastectomy
- Bilateral primary tumors allowed provided both tumors are consistent with entry
- No inflammatory carcinoma (defined as peau d' orange affecting at least one third of
- Direct extension of the tumor to the skin allowed
- No metastatic breast disease, except isolated ipsilateral supraclavicular
- Hormone receptor status:
- Estrogen- and/or progesterone-receptor positive disease based on 10% or more
nuclear staining of the invasive component of the tumor
- Postmenopausal, defined as meeting 1 of the following criteria:
- Cessation of menstrual periods for at least 1 year
- Bilateral surgical oophorectomy
- Follicle-stimulating hormone and estradiol levels in the postmenopausal range
- ECOG 0-2
- Not specified
- Not specified
- No severe liver dysfunction that would preclude study participation
- Not specified
- Willing and able to provide biopsy material
- Willing to undergo breast surgery after neoadjuvant treatment
- No condition (e.g., confusion, infirmity, or alcoholism) that would preclude study
- No other concurrent active and progressive invasive malignancies
- No other concurrent severe disease that would preclude study participation
PRIOR CONCURRENT THERAPY:
- No concurrent immunotherapy or biological response modifiers for breast cancer
- No prior chemotherapy for breast cancer
- No concurrent chemotherapy for breast cancer
- At least 2 weeks since prior hormone replacement therapy or phytoestrogenic herbal,
alternative, or over-the-counter (OTC) sex hormone remedies
- No prior hormonal agents for breast cancer
- No prior aromatase inhibitors, tamoxifen, raloxifene, or other antiestrogen or
selective estrogen receptor modulators
- No concurrent drugs known to affect sex hormone status, including hormone replacement
therapy or phytoestrogenic herbal, alternative, or OTC remedies
- No other concurrent endocrine therapy for breast cancer
- No prior radiotherapy for breast cancer
- No concurrent radiotherapy for breast cancer
- Prior sentinel node biopsy allowed
- No other concurrent surgery for breast cancer
- More than 30 days since prior non-approved or experimental drugs
- Concurrent bisphosphonates for osteoporosis allowed
- No other concurrent treatment for breast cancer