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

Alternate Title

Tamoxifen and Ovarian Ablation in Treating Patients With Node-Negative, Receptor-Positive Breast Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Completed premenopausal NCI E-3193 CLB-9494, NCCTG-933252, SWOG-9347, INT-0142, E3193

Objectives

I.  Compare overall and disease-free survival and toxicity in premenopausal 
women with axillary lymph node-negative, hormone receptor-positive breast 
cancer measuring 3 cm or less randomized to adjuvant therapy with tamoxifen 
(TMX) alone vs. TMX with ovarian ablation.

II.  Obtain tumor tissue for future biologic studies of relevance to this 
patient population.

III.  Compare menopausal symptoms, sexual function, and quality of life in 
these patients.

Entry Criteria

Disease Characteristics:

Primary, invasive, adenocarcinoma of the breast, including the following
histologies:
  Colloid                 Mucinous
  Ductal                  Tubular
  Lobular                 Papillary
  Medullary

Negative axillary nodes (at least 6 nodes sampled)

Complete resection required, as follows:
 Total mastectomy/lumpectomy with axillary node dissection
 No residual disease noted on the surgery and pathology reports

No evidence of disseminated disease on chest x-ray

Tumor in pathology section no greater than 3 cm in maximum diameter, including
invasive and intraductal components
 Size determined from the largest lesion with an invasive component

Hormone receptor status:
 Estrogen receptor and/or progesterone receptor positive
  Receptor positive defined as at least 10 fmol/mg cytosol protein or by 
   immunohistochemistry

Lumpectomy patients also must meet the following criteria:
 Tumor freely mobile and mammography confirms:
  No contact with the chest wall
  No involvement of the skin
  No multiple tumors
  No diffuse microcalcifications
 Radiotherapy planned within 12 weeks following surgery
  Brachytherapy at lumpectomy allowed

No contralateral breast cancer (mammogram required)

No prior invasive breast cancer
 History of intraductal carcinoma or lobular carcinoma in situ eligible
  provided patient is currently disease free

No sarcoma or lymphoma

No apocrine, adenocystic, or squamous cell histology

No locally advanced disease, e.g.:
 No fixed tumors
 No peau d'orange
 No skin ulceration
 No inflammatory breast cancer

Randomization within 84 days of definitive surgery required

Prior/Concurrent Therapy:

No prior systemic therapy for any cancer

Biologic therapy:
 Not specified

Chemotherapy:
 No prior chemotherapy for breast cancer

Endocrine therapy:
 Up to 12 weeks of prior tamoxifen allowed
 No concomitant estrogen therapy

Radiotherapy:
 Concomitant postmastectomy radiotherapy allowed

Surgery:
 See Disease Characteristics

Patient Characteristics:

Age:
 Not specified

Sex:
 Women only

Menopausal status:
 Premenopausal, defined by 1 of the following:
  No more than 6 months since last menstrual period and no prior bilateral
   ovariectomy
  55 years or less with a prior hysterectomy provided:
   1 or both ovaries remain
   Estradiol level in normal premenopausal range

Performance status:
 Not specified

Hematopoietic:
 Hematopoietic function adequate for surgery

Hepatic:
 Bilirubin no greater than 1.5 times normal

Renal:
 Renal function adequate for surgery

Cardiovascular:
 Cardiac function adequate for surgery

Other:
 Health adequate for long-term follow-up
 No serious disease other than breast cancer
 No pregnant or nursing women
 Effective barrier or other nonhormonal contraception required of fertile
  women

Chemistries to determine eligibility completed within 4 weeks prior to
randomization; imaging studies completed within 12 weeks prior to
randomization

Expected Enrollment

A total of 1,600 evaluable patients will be accrued over 4 years.  If after 2 
years accrual is below expectations, the study objectives, sample size, and 
feasibility of continuing will be reassessed.

Outline

This is a randomized study.  Patients are stratified by participating 
institution, hormone receptor status, tumor size, and method of ovarian 
ablation.

Hormonal therapy must begin within 12 weeks of definitive surgery.  When 
planned, radiotherapy must be initiated within 12 weeks of surgery and may 
begin concurrently with hormonal therapy.

Patients in the first group receive oral tamoxifen daily for 5 years. 

Patients in the second group receive tamoxifen as above in addition to ovarian 
ablation.  Ovarian ablation may be accomplished with radiation to the pelvis 
over 2 weeks or medically with either leuprolide or goserelin every 4 weeks 
for 5 years.

Patients discontinue treatment for unacceptable toxicity or disease recurrence 
at any site.  All patients are followed every 6 months for 5 years, then 
yearly.

Hughes LL, Gray RJ, Solin LJ, et al.: Efficacy of radiotherapy for ovarian ablation: results of a breast intergroup study. Cancer 101 (5): 969-72, 2004.[PUBMED Abstract]

Robert NJ, Wang M, Cella D, et al.: Phase III comparison of tamoxifen versus tamoxifen with ovarian ablation in premenopausal women with axillary node-negative receptor-positive breast cancer ? 3 cm . [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-16, 2003.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Nicholas Robert, MD, Protocol chair		Ph: 703-698-2302

Southwest Oncology Group

Silvana Martino, DO, Protocol chair		Ph: 310-582-7900 Email: martinos@jwci.org

Cancer and Leukemia Group B

Debasish Tripathy, MD, Protocol chair(Contact information may not be current)		Ph: 415-885-3700

North Central Cancer Treatment Group

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