CTSU ACOSOG Z1031 - "A Randomized Phase III Trial Comparing 16 to 18 Weeks of Neoadjuvant Exemestane (25mg daily), Letrozole (2.5mg), or Anastrozole (1mg) in Postmenopausal Women with Clinical Stage II and III Estrogen Receptor Positive Breast Cancer"

Treatment Plan    (Supplied Drug:  None)

Arm 1

Exemestane:  25mg/day, PO, x 16-18 wks (followed by surgery)

Arm 2

Letrozole:  2.5mg/day, PO, x 16-18 wks (followed by surgery)

Arm 3

Anastrozole:  1mg/day, PO, x 16-18 wks (followed by surgery)

 â

SURGERY

 â

Follow x 10 yrs.  Continue Anastrozole or Tamoxifen x 5 yrs at physician's discretion.

Eligibility

• ECOG/Zubrod perf status <2.

• Clinically staged T2-T4c, any N, M0 breast cancer.  Prim tumor must be palpable and >2cm by caliper in >1 dimension.

• Post-menopausal, verified by:  bilat surgical oophorectomy OR no spontaneous menses >1 yr OR no menses <1 yr w/FSH & estradiol levels in post-menopausal range (by instit standards).

• Clinically staged by operating surgeon as 1 of following:

  • T4 a-c and modified radical mastectomy w/negative margins is goal

  • T2 or T3 and conversion from needing mastectomy to breast conservation is goal

  • T2 and lumpectomy at 1st attempt is goal

• ER+ tumor w/Allred score 6-8.

• Mammogram and ultrasound w/i 42 days pre-regist.

• If pt is a cancer survivor, all of following must be met:

  • Has undergone potentially curative therapy for all prior malignancies

  • No prior malignancies or recurrence w/i past 5 yrs (except successfully treated in situ  cervical carcinoma, in situ  lobular breast carcinoma, or non-melanoma skin cancer)

  • Low risk for recurrence from prior malignancies (treating physician's opinion)

• No inflammatory breast cancer &/or documented dermal lymphatic invasion.

• No prior tx for breast cancer.

• No HRT of any type, megestrol acetate, or raloxifene w/i 1 wk pre-regist.

• No M1, excluding isolated ipsilateral supraclavicular node involvement.

• Must agree to mastectomy or lumpectomy after neoadjuv aromatase inhibitor therapy.

• No enrollment on another neoadjuv clinical trial for tx of existing breast cancer.

• PRESTUDY REQUIREMENTS:

  • TN stage, ECOG/Zubrod PS, menopausal status, surgery status, ER+ status by Allred

  • Breast mass msmt (tape, ruler, or caliper)*

  • Gyn exam w/i 1 yr pre-study regist (if applicable)

  • Cessation of prohibited meds (1 wk pre-regist & tumor, serum, & plasma harvest) - see protocol list

  • Mammogram/US of breast mass; US of axilla mass (mammogram & US w/tumor msmts <42 days pre-regist)

  • Concomitant therapies & meds (No HRT, megestrol acetate, or raloxifene allowed)

  • Biopsies/tissue (stop prohibited meds 1 wk prior)** - CONTACT KCCOP FOR KIT

  • Serum & plasma (stop prohibited meds 1 wk prior)** - CONTACT KCCOP FOR KIT

  *     Pre-regist & w/i 14 days of start of study drug.  Pre-regist msmt may be used in lieu of baseline msmt if obtained w/i 14 day window.

  **   Tissue:  2 core bxs frozen in separate OCT blocks & 2 core bxs in 10% buffered formalin.  Serum/Plasma/Whole Blood:  One 10cc red-top Vacutainer & two 10cc Vacutainers containing EDTA of perip blood.  Process per protocol.  Freeze serum & plasma in -80^oC freezer (do not use liquid nitrogen).  Do not freeze whole blood.  Ship all samples w/i 1 business day of collection via overnight delivery (send Mon-Fri) to:  Mark Watson, MD, PhD; ACOSOG Central Specimen Bank; Barnes-Jewish Hospital North; St. Louis, MO.  Ship formalin-fixed samples at 15^oC and OCT-embedded tumor, serum, & plasma on dry ice.  

• Signed informed consent & HIPAA (PRIOR to 1st study related procedure being performed).