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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Completed	over 50	NCI	NSABP-B-16 MAOP-1684, NCOG-NSABP-B-16

Objectives

I.  Compare the failure rates in patients aged of 50-70 years with potentially 
curable carcinoma of the breast treated postoperatively with ACT 
(doxorubicin/cyclophosphamide/tamoxifen) vs. PAFT 
(melphalan/doxorubicin/fluorouracil/tamoxifen) vs. tamoxifen alone.

Entry Criteria

Disease Characteristics:

Histologically proven invasive carcinoma of the breast
definitively removed by either:
  Total mastectomy with axillary node dissection
  Segmental mastectomy with axillary node dissection

No more than 35 days between mastectomy and randomization, with
radiotherapy planned on study for patients who underwent
segmental mastectomy

No more than 4 weeks between diagnosis and mastectomy

Histology established by excisional, incisional, or needle
biopsy and aspiration cytology

Tumor clinically confined to the breast or breast and
ipsilateral axilla and movable relative to the underlying
muscle, chest wall, and skin

Histologic proof of ipsilateral axillary node involvement
required
  Involved nodes clinically must be movable in relation to
  each other, the chest wall, and the neurovascular bundle

  Nodes no greater than 2 cm in largest diameter

Palpable contralateral axillary nodes or palpable
supraclavicular or infraclavicular nodes must be biopsy-proven
benign

Hormone receptor status:
  PgR at least 10 fmol/mg (any ER level) and age 50-59
  Any ER/PgR status and age 60 or over
  Quantitative receptor data must be available prior to
     randomization

The following exclude:
  Ulceration
  Erythema
  Infiltration of the skin
  Peau d'orange or any degree of skin edema
  Satellite breast nodules
  Parasternal nodules
  Edema of the arm
  Infiltration of the skin
     Tethering, skin dimpling, and nipple inversion are
     not to be interpreted as skin infiltration and
     patients with these conditions are eligible
  Inflammatory carcinoma
  Histologies other than carcinoma
  Bilateral breast cancer
     Any mass in the contralateral breast must be biopsy-
     proven benign
  Metastatic disease
     Patients with bone pain with negative bone scan
     and/or x-rays are eligible

Segmental mastectomy patients must additionally meet the
following criteria:
  Tumor clinically no greater than 5 cm in greatest diameter
     Mammography preferred

  No more than 1 malignant mass in the breast
     Other masses must be biopsy-proven benign

  Breast is of a size to allow a cosmetically acceptable
  resection

  Breast sufficiently small to permit satisfactory irradiation

  No breast irradiation prior to randomization

Prior/Concurrent Therapy:

Biologic therapy:
  No prior immunotherapy for breast cancer

Chemotherapy:
  No prior chemotherapy for breast cancer

Endocrine therapy:
  No  prior hormonal therapy for breast cancer
  No prior oophorectomy for malignancy (oophorectomy for other
     reasons allowed)
  No prior radiation castration
  Hormonal therapy other than that stipulated by protocol
     (e.g., birth control, replacement therapy) must be
     discontinued on entry

Radiotherapy:
  No prior radiotherapy for breast cancer

Surgery:
  See Disease Characteristics

Patient Characteristics:

Age:
  Over 50

Sex:
  Female only

Menopausal status:
  Not specified

Performance status:
  Not specified

Life expectancy:
  At least 10 years exclusive of breast cancer

Hematopoietic:
  (obtained postoperatively)
  WBC at least 4,000
  Platelets at least 100,000

Hepatic:
  (obtained postoperatively)
  Bilirubin no greater than 1.5 mg/dl
  SGOT no greater than 60 IU/ml

Renal:
  (obtained postoperatively)
  Creatinine no greater than 1.5 mg/dl

Cardiovascular:
  No documented MI
  No angina pectoris requiring antianginal medication
  No documented history of CHF
  No arrhythmia associated with heart failure or dysfunction
  No valvular disease with documented cardiac function
     compromise
  No cardiomegaly on chest x-ray
  No ventricular hypertrophy on EKG
  No poorly controlled hypertension, i.e., diastolic pressure 
     greater than 100 (hypertension well controlled on
     medication allowed)

Other:
  No psychiatric or addictive disorder that would preclude
     informed consent
  No nonmalignant systemic disease that would preclude any
     protocol therapy or prolonged follow-up
  No second malignancy except:
     Curatively treated nonmelanomatous skin cancer
     In situ cervical cancer treated by surgery only
  No pregnancy

Expected Enrollment

Accrual as of November, 1988, was 1,221 of a total accrual target of 1,400.

Outline

Randomized study.  Patients are randomized to Arms I, II, and III.  All 
patients who had segmental mastectomy receive radiotherapy on Regimen A.

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

Arm II:  2-Drug Combination Chemotherapy plus Antiestrogen Therapy.  ACT:  
Doxorubicin, DOX, NSC-123127; Cyclophosphamide, CTX, NSC-26271; plus TMX.

Arm III:  3-Drug Combination Chemotherapy plus Antiestrogen Therapy.  PAFT:  
Melphalan, L-PAM, NSC-8806; DOX; Fluorouracil, 5-FU, NSC-19893; plus TMX.

Regimen A:  Radiotherapy.  Irradiation of the involved breast using Co60 or 
linear accelerators.

Fisher B, Redmond C, Legault-Poisson S, et al.: Postoperative chemotherapy and tamoxifen compared with tamoxifen alone in the treatment of positive-node breast cancer patients aged 50 years and older with tumors responsive to tamoxifen: results from the National Surgical Adjuvant Breast and Bowel Project B-16. J Clin Oncol 8 (6): 1005-18, 1990.[PUBMED Abstract]

Wapnir IL, Anderson SJ, Mamounas EP, et al.: Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences in five National Surgical Adjuvant Breast and Bowel Project node-positive adjuvant breast cancer trials. J Clin Oncol 24 (13): 2028-37, 2006.[PUBMED Abstract]

Taghian A, Jeong JH, Mamounas E, et al.: Patterns of locoregional failure in patients with operable breast cancer treated by mastectomy and adjuvant chemotherapy with or without tamoxifen and without radiotherapy: results from five National Surgical Adjuvant Breast and Bowel Project randomized clinical trials. J Clin Oncol 22 (21): 4247-54, 2004.[PUBMED Abstract]

Wickerham L: Tamoxifen--an update on current data and where it can now be used. Breast Cancer Res Treat 75 (Suppl 1): S7-12; discussion S33-5, 2002.[PUBMED Abstract]

McCaskill-Stevens W, Bryant J, Costantino J, et al.: Incidence of contralateral breast cancer (CBC), endometrial cancer (EC), and thromboembolic events (TE) in African American (AA) women receiving tamoxifen for treatment of primary breast cancer. [Abstract] Proceedings of the American Society of Clinical Oncology 19: A269, 2000.

Wapnir I, Anderson S, Tan-Chiu E, et al.: Ipsilateral breast tumor recurrence (IBTR) and survival in NSABP node-positive breast cancer protocols. [Abstract] Proceedings of the American Society of Clinical Oncology 19: A315, 2000.

Trial Contact Information

Trial Lead Organizations

National Surgical Adjuvant Breast and Bowel Project

Norman Wolmark, MD, Protocol chair		Ph: 412-359-3336; 866-680-0004

Mid-Atlantic Oncology Program

Patrick Byrne, MD, Protocol chair(Contact information may not be current)		Ph: 703-560-3205

Clinical Research Program - Northern California Cancer Center

Robert Carlson, MD, Protocol chair		Ph: 650-725-6457; 800-756-9000