SWOG JMA17.R - "A Double Blind Randomization to Letrozole or Placebo for Women Previously Diagnosed with Primary Breast Cancer Completing Five Years of Adjuvant Aromatase Inhibitor Either as Initial Therapy or After Tamoxifen (Including Those in the MA.17 Study)"

Treatment Plan    (Supplied Drug:  Letrozole/placebo)

Eligibility

• Completion of 4.5-6 yrs of aromatase inhibitor therapy (Letrozole, Anastrozole, or Exemestane) as part of MA.17 core protocol.

• No mets or recur disease, contralateral breast cancer, or DCIS in either breast.

• <2 yrs between last day of prior aromatase inhibitor therapy and randomiz.

• Prim tumor at time of dx for pts not previously enrolled on MA.17 core protocol is receptor-positive (i.e., ER &/or PgR positive [tumor receptor content of >10 fmol/mg protein, or receptor positive by immunohistochemistry:  ERICA or PgRICA]).  For MA.17 subjects only, a receptor status unknown is allowed.

• ECOG perf status 0-2 w/i 60 days pre-randomiz.

• Life expectancy >5 yrs.

• No mets or recur disease, contralateral breast cancer, or DCIS in either breast.  Following must be performed: 

  • Clinical exam of breast area, axillae, and neck w/i 60 days pre-randomiz

  • Mammogram w/i 12 mos pre-randomiz

  • CXR w/i 60 days pre-randomiz

  • Bone scan if alk phos >2x normal &/or symptoms of mets disease, and confirmatory xray of bone scan results are questionable w/i 60 days pre-randomiz

  • Abdominal US, liver scan, or CT abdomen w/i 60 days pre-randomiz if SGOT/SGPT or alk phos >2x normal.

• Within 60 days pre re-randomiz:   WBC>3.0x 10⁹/L or granulocytes (polymorphs + bands) >1.5x 10⁹/L; platelets >100x 10⁹/L; SGOT &/or SGPT <2x UNL*; alk phos <2x UNL*.        

  * Unless imaging has r/o mets.

• Quality of Life (optional).

• Must be accessible for tx and follow-up.

• Tx to begin w/i 5 working days of pt randomiz.

• BMD by DEXA of L2-L4 PA spine & hip w/i 4 wks pre-randomiz if not done w/i previous 12 mos.  Perform on hologic or lunar instrumentation in approved center.

• No previous or concurrent malignancy except adequately treated, superficial non-melanoma skin cancer or cervical carcinoma in situ, or any cancer treated >5 yrs prior & presumed cured.

• No current or planned use of a SERM.

• No current use of any anticancer therapy.

• PRESTUDY REQUIREMENTS:

  • H&P (w/medical hx, clinical eval, PS)*

  • CBC/diff/platelets*

  • SGOT &/or SGPT, alk phos*

  • Mammogram (w/i 12 mos pre re-randomiz [not required if bilat mastectomy])

  • CXR*

  • Bone scan* (if alk phos >2x normal &/or symptoms of mets.  Confirmatory xray required if results are questionable.)

  • Abdominal US, liver scan, or CT abdomen* (if SGOT &/or SGPT or alk phos >2 x normal)

  • Baseline toxicity eval*

  • SF-36 Health Survey & Menopause-Specific QOL (optional)*

  • Whole blood (pharmacogenomics)* - two 10-ml EDTA tubes (contact KCCOP for kits)

  • Tumor/Tissue blocks*

  • DEXA of L2-L4 PA spine & hip (w/i 4 wks pre-randomiz if not done w/i previous 12 mos)

  *     Within 60 days pre re-randomiz

• Signed informed consent.