Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Closed postmenopausal NCI NCCTG-893052 MAYO-893052, NCCTG-89-30-52

Objectives

I.  Compare relapse-free and overall survival of postmenopausal women with 
ER-positive breast cancer randomly assigned to adjuvant therapy with tamoxifen 
alone vs. tamoxifen/fluoxymesterone following resection of all known disease.

Entry Criteria

Disease Characteristics:

Histologically confirmed adenocarcinoma of the breast

Tumor excised within 6 weeks of randomization
  Lumpectomy patients should first be considered for protocol NCCTG-923051

One of the following pathologic stage/age combinations required:
  Node-negative T1c (larger than 1-2 cm) T2 N0 M0--any age
  Node-positive T1-2 N1 M0--age 65 and over

No pectoral fascia invasion

No bilateral or previous breast cancer

Hormone receptor status:
  ER-positive (at least 10 fmoles/mg cytosol protein by standard assay or
  positive by immunocytochemical assay)

Prior/Concurrent Therapy:

Biologic therapy:
  No prior systemic therapy for breast cancer

Chemotherapy:
  No prior systemic therapy for breast cancer

Endocrine therapy:
  No prior systemic therapy for breast cancer except up to 14 days of
  tamoxifen

Radiotherapy:
  No prior radiotherapy for breast cancer

  Radiotherapy required on protocol for patients with breast conservation
  therapy

Surgery:
  Excision within 6 weeks, consisting of 1 of the following:
     Modified radical mastectomy OR

     Lumpectomy with microscopically negative margins (allowed only in
     patients with only 1 primary tumor and with largest diameter no greater
     than 5 cm)

   Levels I and II axillary dissection required with pathologic examination of
   at least 6 axillary nodes

Other:
  No current treatment with warfarin (Coumadin)

Patient Characteristics:

Age:
  Not specified

Menopausal status:
  Postmenopausal, i.e.:
     LMP more than 12 months prior to diagnosis

     LMP 4-12 months prior to diagnosis and FSH in the postmenopausal range

     FSH within postmenopausal range after discontinuing postmenopausal
     estrogen therapy

     Bilateral oophorectomy at least 2 months prior to diagnosis

     Hysterectomy without oophorectomy provided patient is over age 60 or has
     postmenopausal levels of FSH

Performance status:
  Not specified

Hematopoietic:
  WBC at least 3,000
  Platelets at least 100,000

Hepatic:
  Total bilirubin or SGOT not greater than 1.5 x ULN

Renal:
  Creatinine not greater than 2 x ULN

Other:
  No active second cancer within 5 years except:
     Resected nonmelanomatous skin cancer
     Adequately treated in situ cervical cancer

Expected Enrollment

257 patients will be required on each arm.

Outline

Randomized study.  Patients with breast conservation surgery must also receive 
radiotherapy on protocol NCCTG-923051 or on Regimen A.

Arm I:  Antiestrogen Therapy.  Tamoxifen, TMX, NSC-180973.

Arm II:  Antiestrogen Therapy plus Androgen Therapy.  TMX; plus 
Fluoxymesterone, FXM, NSC-12165.

Regimen A:  Radiotherapy.  Irradiation of the ipsilateral breast and chest 
wall using megavoltage equipment with peak energies no greater than 6 MeV with 
an electron beam or interstitial boost plus (as indicated) regional lymphatic 
irradiation using megavoltage equipment with peak photon energies no greater 
than 6 MV.

Goetz MP, Moyer AM, Weinshilboum RM, et al.: Role of SULT1A1 copy number in tamoxifen treated breast cancer: findings from the North Central Cancer Treatment Group (NCCTG) adjuvant trial 89-30-52. [Abstract] J Clin Oncol 26 (Suppl 15): A-22041, 2008.

Goetz MP, Suman VJ, Couch FJ, et al.: Cytochrome P450 2D6 and homeobox 13/interleukin-17B receptor: combining inherited and tumor gene markers for prediction of tamoxifen resistance. Clin Cancer Res 14 (18): 5864-8, 2008.[PUBMED Abstract]

Goetz MP, Knox SK, Suman VJ, et al.: The impact of cytochrome P450 2D6 metabolism in women receiving adjuvant tamoxifen. Breast Cancer Res Treat 101 (1): 113-21, 2007.[PUBMED Abstract]

Goetz MP, Suman V, Couch F, et al.: An index based on HOXB13/IL17BR and CYP2D6 for determination of relapse and survival in tamoxifen-treated node negative breast cancer. [Abstract] Breast Cancer Res Treat 100 (Suppl 1): A-1044, S53, 2006.

Goetz MP, Suman VJ, Ingle JN, et al.: A two-gene expression ratio of homeobox 13 and interleukin-17B receptor for prediction of recurrence and survival in women receiving adjuvant tamoxifen. Clin Cancer Res 12 (7 Pt 1): 2080-7, 2006.[PUBMED Abstract]

Ingle JN, Suman VJ, Mailliard JA, et al.: Randomized trial of tamoxifen alone or combined with fluoxymesterone as adjuvant therapy in postmenopausal women with resected estrogen receptor positive breast cancer. North Central Cancer Treatment Group Trial 89-30-52. Breast Cancer Res Treat 98 (2): 217-22, 2006.[PUBMED Abstract]

Goetz MP, Rae JM, Suman VJ, et al.: Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes. J Clin Oncol 23 (36): 9312-8, 2005.[PUBMED Abstract]

Goetz MP, Suman VJ, Ingle JN, et al.: A two-gene expression ratio of HOXB13 and IL-17BR for prediction of recurrence and survival in women receiving adjuvant tamoxifen. [Abstract] Breast Cancer Research and Treatment 94 (Suppl 1): A-312, 2005.

Goetz MP, Rae JM, Suman VJ, et al.: Pharmacogenomic determinants of outcome with tamoxifen therapy: findings from the randomized North Central Cancer Treatment Group adjuvant breast cancer trial 89-30-52. [Abstract] Breast Cancer Res Treat 88 (Suppl 1): A-314, 2004.

Trial Contact Information

Trial Lead Organizations

North Central Cancer Treatment Group

James Mailliard, MD, Protocol chair(Contact information may not be current)		Ph: 402-280-4138

Mayo Clinic Cancer Center

James Ingle, MD, Protocol chair		Ph: 507-284-8432 Email: ingle.james@mayo.edu