Anastrozole or Letrozole before Surgery in Treating Patients with Hormone Receptor Positive Stage II-III Breast Cancer That Can Be Removed by Surgery

Status: Active

Description

This pilot early phase I trial studies how well anastrozole or letrozole before surgery work in treating patients with hormone receptor positive stage II-III breast cancer that can be removed by surgery. Estrogen can cause the growth of breast cancer cells. Hormone therapy using anastrozole and letrozole may fight hormone receptor positive breast cancer by lowering the amount of estrogen the body makes and blocking the use of estrogen by the tumor cells.

Eligibility Criteria

Inclusion Criteria

  • Postmenopausal status, defined as no menstrual cycle for 12 months or surgical removal of ovaries
  • Histologically confirmed adenocarcinoma of the breast
  • Evidence of hormone sensitive, ER rich primary tumor defined by an Allred score of >= 6
  • HER2 negative in the primary tumor as defined by: * Grade 0 or 1+ staining intensity (on a scale of 0 to 3) by means of immunohistochemistry (IHC) analysis OR * Grade 2+ staining intensity by means of IHC analysis with gene amplification on fluorescence in situ hybridization (FISH) < 2.0 OR * Gene amplification on fluorescence in situ hybridization (FISH) < 2.0
  • Eastern Cooperative Oncology Group (ECOG) performance status < 3
  • Unresected operable breast cancer stage II-III with primary tumor > 2.0 cm
  • Ability to understand and willingness to sign a written informed consent document
  • Patients must not have received any prior chemotherapy, radiation therapy, or endocrine therapy for their current breast cancer; patients who received tamoxifen or raloxifene or another agent for prevention of breast cancer may be included as long as the patient has discontinued the treatment at least one month prior to baseline study biopsy
  • Patients must have an adequate tumor tissue sample prior to enrollment available for correlative studies as defined below: core needle biopsy or incisional biopsy samples that can provide >= 5 unstained sections of 5 micron thickness; fine needle aspiration (FNA) sample alone is not sufficient
  • Patient must have adequate organ function as defined below: * Total bilirubin within normal institutional limits * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) < 2.5 x institutional upper limit of normal * Creatinine clearance >= 10 mL/min/1.73 m^2

Exclusion Criteria

  • Previous or current systemic malignancy within the past 3 years other than breast cancer or adequately treated cervical carcinoma in situ or basal/squamous carcinoma of the skin
  • Patients may not be receiving any other investigational agent
  • History of allergic reactions or hypersensitivity to compounds of similar chemical or biologic composition to anastrozole or letrozole

Locations & Contacts

Maryland

Baltimore
University of Maryland / Greenebaum Cancer Center
Status: Active
Contact: Emily Catherine Bellavance
Phone: 410-328-7320
Email: ebellavance@som.umaryland.edu
Bel Air
UM Upper Chesapeake Medical Center
Status: Active
Contact: Emily Catherine Bellavance
Phone: 410-328-7320
Email: ebellavance@som.umaryland.edu
Towson
UM Saint Joseph Medical Center
Status: Active
Contact: Emily Catherine Bellavance
Phone: 410-328-7320
Email: ebellavance@som.umaryland.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To evaluate the percent change in proliferative index (Ki67) in the primary breast tumor after neoadjuvant treatment with standard dose anastrozole or letrozole in normal, overweight, and obese patients with estrogen receptor (ER) positive breast cancer (T2-3, N0/1, M0).

SECONDARY OBJECTIVES:

I. To assess estradiol levels at baseline and after treatment with standard dose anastrozole or letrozole in normal, overweight, and obese patients.

II. To evaluate differences in baseline PC cell-derived growth factor (GP88) level and Oncotype Dx assay in primary ER positive breast tumors from normal, overweight, and obese patients.

III. To evaluate the association of aromatase inhibitor (AI)-induced Ki67 response with baseline and post treatment GP88 level and baseline Oncotype Dx assay in normal, overweight, and obese patients.

TERTIARY OBJECTIVES:

I. To assess circulating and infiltrating immunoregulatory cells (IRC) at baseline and after treatment with standard dose anastrozole or letrozole in normal, overweight, and obese patients. (optional when feasible)

II. To evaluate local and circulating pro-inflammatory cytokines at baseline and after treatment with standard dose anastrozole or letrozole in normal, overweight, and obese patients. (optional when feasible)

OUTLINE: Patients are assigned to 1 of 2 arms.

ARM I: Patients receive anastrozole orally (PO) once daily (QD) for 14-28 days in the absence of disease progression or unacceptable toxicity. Treatment may continue for up to 18 weeks at the discretion of the treating physician. Within 36 hours after the last dose of anastrozole, patients undergo surgery.

ARM II: Patients receive letrozole PO QD for 14-28 days in the absence of disease progression or unacceptable toxicity. Treatment may continue for up to 18 weeks at the discretion of the treating physician. Within 36 hours after the last dose of letrozole, patients undergo surgery.

After completion of study treatment, patients are followed up for 30 days.

Trial Phase & Type

Trial Phase

No phase specified

Trial Type

Treatment

Lead Organization

Lead Organization
University of Maryland / Greenebaum Cancer Center

Principal Investigator
Emily Catherine Bellavance

Trial IDs

Primary ID GCC1366
Secondary IDs NCI-2016-01581
Clinicaltrials.gov ID NCT02095184