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Neoadjuvant Letrozole in Treating Postmenopausal Women With Estrogen-Receptor Positive and/or Progesterone-Receptor Positive Stage II, Stage IIIA, or Stage IIIB Breast Cancer

A Phase 2 Trial Of 4 Months Preoperative Letrozole 2.5 mg Daily For Postmenopausal Women With Estrogen Receptor Positive And/Or Progesterone Receptor Positive T2, T3, T4a-c, N0-2, M0 Breast Cancer- Novel Biomarkers for Aromatase Inhibitor Therapy

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00084396
Enrollment
115
Registered
2004-06-11
Start date
2003-10-31
Completion date
2016-09-30
Last updated
2016-09-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Breast Cancer

Keywords

stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer

Brief summary

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.

Detailed description

OBJECTIVES: Primary * 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. Secondary * 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 drug. * 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 years. PROJECTED ACCRUAL: A total of 150 patients will be accrued for this study.

Interventions

DRUGletrozole
PROCEDUREconventional surgery

Sponsors

National Cancer Institute (NCI)
CollaboratorNIH
Washington University School of Medicine
Lead SponsorOTHER

Study design

Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

DISEASE CHARACTERISTICS: * Histologically confirmed infiltrating adenocarcinoma of the breast by core needle biopsy * 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 breast-conserving surgery * 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 criteria * No inflammatory carcinoma (defined as peau d' orange affecting at least one third of the breast) * Direct extension of the tumor to the skin allowed * No metastatic breast disease, except isolated ipsilateral supraclavicular lymphadenopathy * Hormone receptor status: * Estrogen- and/or progesterone-receptor positive disease based on 10% or more nuclear staining of the invasive component of the tumor PATIENT CHARACTERISTICS: Age * Postmenopausal Sex * Female Menopausal status * 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 Performance status * ECOG 0-2 Life expectancy * Not specified Hematopoietic * Not specified Hepatic * No severe liver dysfunction that would preclude study participation Renal * Not specified Other * 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 compliance * No other concurrent active and progressive invasive malignancies * No other concurrent severe disease that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy * No concurrent immunotherapy or biological response modifiers for breast cancer Chemotherapy * No prior chemotherapy for breast cancer * No concurrent chemotherapy for breast cancer Endocrine therapy * 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 Radiotherapy * No prior radiotherapy for breast cancer * No concurrent radiotherapy for breast cancer Surgery * Prior sentinel node biopsy allowed * No other concurrent surgery for breast cancer Other * More than 30 days since prior non-approved or experimental drugs * Concurrent bisphosphonates for osteoporosis allowed * No other concurrent treatment for breast cancer

Design outcomes

Primary

MeasureTime frame
Predictive model for response as assessed by gene expression profiling

Secondary

MeasureTime frame
Changes in Ki67 proliferation rates
Rate of improvement in surgical outcomes
Response rate
Safety
Mechanisms of resistance
Long-term outcomes

Countries

United States

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026