GCC 1366 is a prospective randomized window trial to evaluate the anti-proliferative response in obese and overweight breast cancer patients treated with neoadjuvant non-steroidal aromatase inhibitors. Post-menopausal women over the age of 18 years with estrogen receptor positive Her 2 neu negative stage II-III breast cancer are eligible. Participants will be randomized according to BMI to neoadjuvant treatment with Arimidex or Letrozole.
A total of 90 patients will be enrolled with 15 patients in each cohort below.
* Cohort 1: Patients with BMI \< 25.0 kg/m2 treating with anastrozole
* Cohort 2: Patients with BMI ≥ 25.0-29.9 kg/m2 treating with anastrozole
* Cohort 3: Patients with BMI ≥ 30 kg/m2 treating with anastrozole
* Cohort 4: Patients with BMI \< 25.0 kg/m2 treating with letrozole
* Cohort 5: Patients with BMI ≥ 25.0-29.9 kg/m2 treating with letrozole
* Cohort 6: Patients with BMI ≥ 30 kg/m2 treating with letrozole
Based on the patients' calculated BMI, patients in each BMI category (normal, overweight, and obese) will be enrolled in the different cohorts as described above. The first 15 patients in each BMI category will be treated with anastrozole. After completion of enrollment in cohorts 1, 2, and 3, subsequent patients will be treated with letrozole in cohorts 4, 5, and 6.
Anastrozole 1 mg or Letrozole 2.5 mg oral daily will be administered and continued for a minimum of 14 days and a maximum of 28 days (2-4 weeks). Surgery will be performed between weeks 2-3 of treatment unless there are compelling medical or personal reasons that prevent a patient from having surgery during this time. In those cases, patients may continue anastrozole or letrozole up to 4 weeks before surgery. Surgery should be performed within 36 hours of the last dose of anastrozole or letrozole.
Tumor tissue that is obtained for diagnosis or to assess response to initial AI therapy will be utilized for correlative studies. A patient may be continued on anastrozole or letrozole beyond 4 weeks (up to 18 weeks) if in the opinion of the treating physician, the patient will benefit from extended endocrine therapy. In this context, patients will have a core needle biopsy performed at 2-4 weeks after treatment to assess Ki67 response to AI therapy. Patients with an appropriate response to treatment as determined by a decrease in Ki67 levels (≤10%) will be continued on AI treatment. Patients without an appropriate decrease in Ki67 levels will be recommended to have immediate surgery or a switch to neoadjuvant chemotherapy if desired by the patient and treating physician.
Patients on extended AI neoadjuvant treatment having core biopsy at 2-4 weeks for Ki67 determination for clinical decision making will be approached and consented for additional research tissues to be taken at the same time as the biopsy for Ki67 determination. Blood samples will be collected prior to starting treatment and within 3 days or on the day of surgery. Additional blood samples will be obtained as clinically necessary.
Clinical assessment will be performed prior to enrollment and within 3 days or on the day of surgery. For patients who continue neoadjuvant endocrine therapy past 4 weeks, clinical assessment will be performed at the time of clinical biopsy and every 4-6 weeks thereafter. For clinical evidence of progression, patients will be offered immediate surgery or switch to neoadjuvant chemotherapy at the discretion of the treating physician.
Radiological assessment including mammogram, ultrasound, and breast MRI will be performed as per standard of care.
Patients will be followed for 30 days on study after the last dose of anastrozole or letrozole prior to surgery. For patients who receive extended neoadjuvant therapy with anastrozole or letrozole and for patients who receive other primary treatment after anastrozole or letrozole administration prior to surgery, patients will be followed for 30 days on study after the last dose of anastrozole or letrozole. Patients continuing to experience adverse events attributable to anastrozole or letrozole will be followed as needed until resolution or stabilization of the adverse events. Patients who are either found to be ineligible or refuse to start treatment after consenting will not be followed and will be replaced. Their information will not be collected. After 30 days after the last dose of anastrozole or letrozole, if there are no continuing adverse events attributable to treatment, patients will be off study.
