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

Alternate Title

Nutrition Intervention in Treating Women With Breast Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Closed 48 to 78 Other AHF-WINS MRMC-CTCA-9604, WINS-1, NCI-H94-0001, NCT00002564

Objectives

I.  Determine whether dietary fat reduction will effectively prolong 
disease-free and overall survival in women surgically treated for early stage 
breast cancer who are receiving adjuvant therapy with or without either 
tamoxifen, cyclophosphamide, methotrexate, fluorouracil (CMF), doxorubicin, 
cyclophosphamide (AC), fluorouracil, doxorubicin, cyclophosphamide (FAC, CAF), 
or AC followed by paclitaxel. 

II.  Evaluate whether differences in the lipid profile are associated with 
dietary group assignment and dietary fat.

Entry Criteria

Disease Characteristics:

Histologically proven, invasive, localized carcinoma of the breast

Stage I/II/IIIA disease, i.e.:
 Tumor confined to breast on clinical examination
 Overlying skin movable with respect to tumor
 Tumor movable in relation to underlying muscle and chest wall
 Bone scan and/or x-ray required to rule out bone metastases in cases of
  skeletal pain

Tumor size requirements:
 No greater than 5 cm if lymph nodes are positive
 Greater than 1 cm if lymph nodes are negative

Tumor definitively treated by one of the following procedures:
 Total mastectomy with axillary node dissection
 Segmental mastectomy with or without axillary node dissection and/or sentinel 
  node biopsy followed by breast irradiation, provided:
   Surgical margins are histologically free of invasive or noninvasive tumor
 One additional resection allowed to obtain clear margins
  Total mastectomy required if clear margins are not obtained at second
   resection
  
The following conditions exclude:
 Bilateral malignancy or any mass in the contralateral breast unless proven
  nonmalignant by biopsy
 Palpable lymph nodes in the contralateral axilla or probable supraclavicular
  or infraclavicular nodal involvement unless proven nonmalignant by biopsy
 10 or more positive lymph nodes
 Inflammatory breast cancer
 Ulceration or erythema
 Infiltration of the skin or peau d'orange
  Tethering or dimpling of the skin or nipple inversion should not be
   considered skin infiltration
 Satellite breast nodules
 Parasternal nodules
 Edema of the arm

Hormone receptor status:
 Any estrogen receptor (ER) or progesterone receptor (PR) status allowed
  ER assessment required
  PR assessment recommended
 
Less than 365 days between definitive surgery and randomization

Prior/Concurrent Therapy:

No concurrent participation in another adjuvant breast cancer trial that has
disease-free or overall survival as a study endpoint (e.g., a major
cooperative group trial)

Biologic therapy:
 Not specified

Chemotherapy:
 Concurrent adjuvant cyclophosphamide, methotrexate, fluorouracil (CMF), 
  doxorubicin, cyclophosphamide (AC), AC followed by paclitaxel, or
  fluorouracil/doxorubicin/cyclophosphamide (FAC, CAF) allowed
 If ER negative, approved chemotherapy regimen and/or tamoxifen required
 No more than 120 days between definitive surgery and initiation of
  adjuvant systemic chemotherapy

Endocrine therapy:
 Concurrent adjuvant tamoxifen required if ER positive (if ER negative,
  tamoxifen and/or an approved chemotherapy regimen required)
 No more than 180 days between definitive surgery and initiation of
  tamoxifen (if receiving tamoxifen alone)
 If receiving adjuvant CMF, AC, or FAC, CAF, or AC, paclitaxel, tamoxifen 
  begins after completion of adjuvant therapy

Radiotherapy:
 Radiotherapy required within 56 days following segmental mastectomy

Surgery:
 Definitive surgery required
 Prior oophorectomy for reasons other than malignancy allowed

Patient Characteristics:

Age:
 48 to 78

Sex:
 Female

Menopausal status:
 Postmenopausal

Performance status:
 Not specified

Life expectancy:
 At least 10 years (excluding breast cancer)

Hematopoietic:
 WBC at least 3,000/mm3
 Platelet count at least 100,000/mm3

Hepatic:
 Bilirubin no greater than 1.5 mg/dL
 AST no greater than 60 IU/mL (or within 2 times normal)

Renal:
 Creatinine no greater than 1.5 mg/dL

Cardiovascular:
 No active cardiac disease that would preclude doxorubicin in patients
  assigned to adjuvant chemotherapy with doxorubicin

Other:
 Baseline caloric intake at least 20% fat
 Accessible for follow-up and by telephone
 Sufficient memory required to provide food recall data
 Must speak and read English
 Medically and nutritionally eligible for either dietary intervention arm
 No prior or concomitant malignancy except curatively treated nonmelanoma skin 
 cancer or carcinoma in situ of the cervix

Expected Enrollment

Approximately 2,500 women will be accrued for this study.

Outline

This is a randomized, multicenter study.  Patients are stratified by center, 
nodal status, ER status, and type of adjuvant chemotherapy.

The first group receives intensive dietary intervention for reduction of total 
fat intake to 15% of calories, with repeated individual and group counseling 
sessions.

The second group receives USDA/DHHS dietary guidelines and minimal 
intervention.

All patients who are estrogen receptor positive receive concurrent therapy 
with tamoxifen; cyclophosphamide, methotrexate, fluorouracil (CMF) followed by 
tamoxifen; doxorubicin, cyclophosphamide (AC) followed by tamoxifen; 
fluorouracil, doxorubicin, cyclophosphamide (FAC, CAF) followed by tamoxifen; 
or AC, paclitaxel followed by tamoxifen.

Patients are followed annually throughout the study.

Chlebowski RT, Blackburn GL, Thomson CA, et al.: Dietary fat reduction and breast cancer outcome: interim efficacy results from the Women's Intervention Nutrition Study. J Natl Cancer Inst 98 (24): 1767-76, 2006.[PUBMED Abstract]

Chlebowski RT, Blackburn GL, Elashoff RE, et al.: Dietary fat reduction in postmenopausal women with primary breast cancer: phase III Women’s Intervention Nutrition Study (WINS). [Abstract] J Clin Oncol 23 (Suppl 16): A-10, 3s, 2005.

Trial Contact Information

Trial Lead Organizations

Institute for Cancer Prevention

Daniel Nixon, MD, Protocol chair		Ph: 843-792-5336; 800-424-3828 Email: nixond@musc.edu

Registry Information
Official Title		A CLINICAL TRIAL TO DETERMINE THE EFFICACY OF A DIETARY FAT REDUCTION PROGRAM PROVIDED IN ADDITION TO SYSTEMIC ADJUVANT THERAPY IN THE MANAGEMENT OF PATIENTS WITH PRIMARY INVASIVE BREAST CANCER
Trial Start Date		1994-04-01
Registered in ClinicalTrials.gov		NCT00002564
Date Submitted to PDQ		1994-04-01
Information Last Verified		2007-10-15
NCI Grant/Contract Number		CA17613, CA45504