|Phase III||Treatment||Completed||18 and over||NCI||NSABP-B-19|
I. Compare survival and disease-free survival of patients who have undergone curative resection of ER-negative carcinoma of the breast with negative nodes randomly assigned to adjuvant postoperative chemotherapy with sequential methotrexate/5-fluorouracil followed by leucovorin vs. conventional CMF (cyclophosphamide/methotrexate/5-fluorouracil). II. Correlate tumor cell ploidy, kinetics, and pathological variables of tumor differentiation (e.g., nuclear grade) to clinical outcome.
See General Eligibility Criteria
See General Eligibility Criteria
General Eligibility Criteria:
Female patients aged 18 years and over who have undergone total mastectomy and axillary dissection or segmental mastectomy and axillary dissection to be followed (on protocol) by breast irradiation for potentially curable ER-negative breast cancer with negative nodes provided they have received no therapy other than mastectomy for the present breast cancer. No more than 4 weeks may have intervened between establishment of histologic diagnosis (excisional, incisional, or needle biopsy and aspiration cytology) and definitive surgery, and protocol treatment must begin within 35 days of definitive surgery. The tumor must be confined to the breast on clinical examination and must be movable in relation to the overlying skin and to the underlying muscle and chest wall. There must be no ulceration, erythema, or peau d'orange of any magnitude and no satellite breast nodules, parasternal nodules, edema of the arm, or inflammatory carcinoma; suspected satellite foci of tumor involving the skin must be demonstrated histologically to be tumor-free. The tumor must be invasive on histologic examination, and all axillary nodes must be histologically negative for tumor (patients may have had palpable ipsilateral axillary nodes preoperatively if these are histologically negative). Patients with palpable contralateral axillary or palpable supraclavicular or infraclavicular nodes are ineligible unless these nodes are histologically demonstrated to be free of tumor. Patients with bone pain may be entered only if a bone scan and/or radiographic examination reveals no evidence of metastatic disease. Patients with bilateral breast cancer are not eligible, and those with a mass in the contralateral breast must have biopsy evidence that the mass is not malignant. Quantitative analyses of ER and PgR content must have been carried out on tumor tissue by a laboratory that conforms to NSABP quality control requirements; patients with any PgR status are eligible, but the ER content must be less than 10 fmol/mg cytosol protein (patients with an ER content of 10 fmol/mg cytosol protein or greater are eligible for NSABP-B-20). Patients may have undergone a previous oophorectomy for reasons other than treatment of breast cancer, but patients who have had radiation castration are ineligible. Patients who are currently on hormonal therapy (e.g., birth control medication) must discontinue such therapy while on protocol until the first recurrence. Exclusive of breast cancer, the life expectancy must be at least 10 years. Adequate postoperative hematopoietic, hepatic, and renal function must be documented by the following: WBC at least 4,000 and platelets at least 100,000; serum bilirubin not greater than 1.5 mg/dl and SGOT not greater than 60 IU/ml; and serum creatinine not greater than 1.5 mg/dl and 24-hour creatinine clearance at least 60 ml/min. A previous or concomitant second malignancy other than effectively treated squamous or basal cell skin cancer and in situ carcinoma of the cervix treated operatively only renders a patient ineligible. There must be no nonmalignant systemic disease (e.g., cardiovascular, renal, hepatic) that would preclude protocol treatment or follow-up, and no psychiatric or addictive disorders that would preclude informed consent. Pregnancy excludes. In addition to fulfilling the foregoing entry criteria, patients who have undergone segmental resection must also satisfy the following requirements: the tumor must have been 5 cm or less in greatest diameter on clinical examination; the breast must be of sufficient size to allow a cosmetically acceptable resection; xeroradiography or mammography must not reveal a diffuse tumor that would not be considered surgically appropriate for segmental mastectomy; a second dominant mass in the same breast must be biopsied and demonstrated to be histologically benign; and the resection specimen margins must be demonstrated to be histologically free of invasive and noninvasive tumor. If the resection margins are positive for tumor histologically, one and only one additional surgical procedure is allowed in order to obtain clear margins, even if axillary dissection has been performed, but the same time constraints still pertain: no more than 4 weeks may intervene between diagnosis and definitive surgery. Patients with positive margins after a second surgical procedure must undergo total mastectomy.
1,020 patients will be entered over about 3 years.
Randomized study. Patients on either arm who have undergone segmental resection receive breast irradiation as described under Regimen A concurrently with chemotherapy. Arm I: 2-Drug Sequential Combination Chemotherapy plus Leucovorin Rescue. Methotrexate, MTX, NSC-740; followed by 5-Fluorouracil, 5-FU, NSC-19893; plus Leucovorin calcium, Citrovorum Factor, CF, NSC-3590. Arm II: 3-Drug Combination Chemotherapy. CMF: Cyclophosphamide, CTX, NSC-26271; MTX; 5-FU. Regimen A: Radiotherapy. Irradiation of the remaining ipsilateral breast tissue with Co60 or linear accelerator equipment.Published Results
Fisher B, Jeong JH, Anderson S, et al.: Treatment of axillary lymph node-negative, estrogen receptor-negative breast cancer: updated findings from National Surgical Adjuvant Breast and Bowel Project clinical trials. J Natl Cancer Inst 96 (24): 1823-31, 2004.[PUBMED Abstract]Related Publications
Anderson SJ, Wapnir I, Dignam JJ, et al.: Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences in patients treated by breast-conserving therapy in five national surgical adjuvant breast and bowel project protocols of node-negative breast cancer. J Clin Oncol 27 (15): 2466-73, 2009.[PUBMED Abstract]
Taghian AG, Jeong JH, Mamounas EP, et al.: Low locoregional recurrence rate among node-negative breast cancer patients with tumors 5 cm or larger treated by mastectomy, with or without adjuvant systemic therapy and without radiotherapy: results from five national surgical adjuvant breast and bowel project randomized clinical trials. J Clin Oncol 24 (24): 3927-32, 2006.[PUBMED Abstract]
Fisher B, Jeong JH, Anderson S, et al.: Treatment of axillary lymph node-negative, estrogen receptor-negative breast cancer: updated findings from National Surgical Adjuvant Breast and Bowel Project clinical trials. J Natl Cancer Inst 96 (24): 1823-31, 2004.[PUBMED Abstract]
Fisher B, Dignam J, Tan-Chiu E, et al.: Prognosis and treatment of patients with breast tumors of one centimeter or less and negative axillary lymph nodes. J Natl Cancer Inst 93 (2): 112-20, 2001.[PUBMED Abstract]
Fisher B, Jeong JH, Dignam J, et al.: Findings from recent National Surgical Adjuvant Breast and Bowel Project adjuvant studies in stage I breast cancer. J Natl Cancer Inst Monogr (30): 62-6, 2001.[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.
Fisher B, Dignam J, Mamounas EP, et al.: Sequential methotrexate and fluorouracil for the treatment of node-negative breast cancer patients with estrogen receptor-negative tumors: eight-year results from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-13 and first report of findings from NSABP B-19 comparing methotrexate and fluorouracil with conventional cyclophosphamide, methotrexate, and fluorouracil. J Clin Oncol 14 (7): 1982-92, 1996.[PUBMED Abstract]
Trial Lead Organizations
National Surgical Adjuvant Breast and Bowel Project
|Norman Wolmark, MD, Protocol chair|
Clinical Research Program - Northern California Cancer Center
|Robert Carlson, MD, Protocol chair|
Mid-Atlantic Oncology Program
|James Ahlgren, MD, Protocol chair|
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.