NCI HIGH PRIORITY CLINICAL TRIAL --- Phase III Randomized Trial of Adjuvant Tamoxifen vs Placebo Following Breast Irradiation in Patients Who Have Undergone Lumpectomy for Noninvasive Intraductal Carcinoma (DCIS) of the Breast
Basic Trial Information
I. Determine, in a Phase III setting, the efficacy of lumpectomy followed by breast irradiation with vs. without adjuvant tamoxifen in preventing the subsequent occurrence of ipsilateral and contralateral invasive breast cancer in patients with noninvasive intraductal cancer (DCIS). II. Determine the efficacy of prolonged adjuvant tamoxifen vs. placebo following lumpectomy and breast irradiation in preventing subsequent occurrence of ipsilateral and contralateral noninvasive (DCIS or LCIS) breast cancers in these patients.
Histologically proven, noninvasive intraductal carcinoma (DCIS) of the breast, including mixed intraductal and lobular in situ (LCIS) disease Breast-conserving definitive surgery must be performed within 8 weeks of histologic diagnosis Bilateral malignancy excludes Contralateral mass excludes unless proven benign on biopsy Axillary dissection not required; if performed, all nodes must be histologically negative Suspicious palpable ipsilateral or contralateral axillary nodes and palpable supra- or infraclavicular nodes must be biopsied and must be negative for malignancy The following disease distributions are eligible for randomization provided surgical margins are free of grossly evident disease (microscopic involvement of the margins with DCIS or LCIS permitted, if so determined by the pathologist and/or surgeon): Single mass or cluster of calcifications detected clinically or mammographically More than 1 mass or cluster of calcifications in the same or separate quadrants provided cosmetically acceptable surgery is possible Single or multiple masses or single or multiple clusters of calcifications with mammographic evidence of scattered calcifications considered by the radiologist to be of an indeterminate nature (suspicious scattered calcifications permitted without biopsy confirmation; if biopsied, must be noninvasive) Diffuse scattered microcalcifications determined radiologically to be suspicious permitted provided DCIS is demonstrated on biopsy Randomization must occur within 56 days after surgery Hormone receptor status: Not specified
Biologic therapy: No prior immunotherapy for present disease allowed Chemotherapy: No prior chemotherapy for present disease allowed Endocrine therapy: No prior endocrine therapy for present disease allowed Radiotherapy: No prior radiotherapy for present disease allowed Surgery: Breast conservation surgery for present disease required Re-excision to obtain histologically clear margins allowed Randomization must occur no more than 56 days after surgery Other: Prior oophorectomy allowed for reasons other than malignancy Sex hormones (e.g., birth control pills, replacement therapy) must be discontinued while on protocol
Age: 18 to 75 Sex: Females only Menopausal status: Pre- and postmenopausal Performance status: Not specified Life expectancy: At least 10 years excluding the breast cancer Hematopoietic: WBC at least 4,000/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.5 mg/dL or within normal limits SGOT no greater than 60 IU/mL or within normal limits Renal: Not specified Other: No prior or concurrent other malignancy except: Adequately treated nonmelanomatous skin cancer Surgically treated in situ cervical cancer No nonmalignant systemic disease that would preclude randomization to either arm or prevent prolonged follow-up No psychiatric or addictive disorder that would preclude informed consent Not pregnant
1,800 patients will be randomized. The accrual rate is anticipated to be 360 patients/year.
Randomized, double-blind study. Arm I: Radiotherapy plus Antiestrogen Therapy. Irradiation of remaining breast tissue using Co60 or linear accelerators with a minimum energy of 4 MV, with electrons, superficial, or orthovoltage equipment with energies of 100-300 KV used to boost the operative area; plus Tamoxifen, TMX, NSC-180973. Arm II: Radiotherapy plus Placebo. Irradiation as in Arm I; plus Placebo.
Allred DC, Anderson SJ, Paik S, et al.: Adjuvant tamoxifen reduces subsequent breast cancer in women with estrogen receptor-positive ductal carcinoma in situ: a study based on NSABP protocol B-24. J Clin Oncol 30 (12): 1268-73, 2012.[PUBMED Abstract]
Fisher ER, Land SR, Saad RS, et al.: Pathologic variables predictive of breast events in patients with ductal carcinoma in situ. Am J Clin Pathol 128 (1): 86-91, 2007.[PUBMED Abstract]
Allred D, Bryant J, Land S, et al.: Estrogen receptor expression as a predictive marker of the effectiveness of tamoxifen in the treatment of DCIS: findings from NSABP Protocol B-24. [Abstract] Breast Cancer Res Treat 76 (Suppl 1): A-30, 2002.
Fisher B, Land S, Mamounas E, et al.: Prevention of invasive breast cancer in women with ductal carcinoma in situ: an update of the national surgical adjuvant breast and bowel project experience. Semin Oncol 28 (4): 400-18, 2001.[PUBMED Abstract]
Fisher B, Dignam J, Wolmark N, et al.: Tamoxifen in treatment of intraductal breast cancer: National Surgical Adjuvant Breast and Bowel Project B-24 randomised controlled trial. Lancet 353 (9169): 1993-2000, 1999.[PUBMED Abstract]
Petrelli F, Barni S: Tamoxifen added to radiotherapy and surgery for the treatment of ductal carcinoma in situ of the breast: a meta-analysis of 2 randomized trials. Radiother Oncol 100 (2): 195-9, 2011.[PUBMED Abstract]
Wapnir IL, Dignam JJ, Fisher B, et al.: Long-term outcomes of invasive ipsilateral breast tumor recurrences after lumpectomy in NSABP B-17 and B-24 randomized clinical trials for DCIS. J Natl Cancer Inst 103 (6): 478-88, 2011.[PUBMED Abstract]
Julian TB, Land SR, Fourchotte V, et al.: Is sentinel node biopsy necessary in conservatively treated DCIS? Ann Surg Oncol 14 (8): 2202-8, 2007.[PUBMED Abstract]
Vogel VG, Costantino JP, Wickerham DL, et al.: National surgical adjuvant breast and bowel project update: prevention trials and endocrine therapy of ductal carcinoma in situ. Clin Cancer Res 9 (1 Pt 2): 495S-501S, 2003.[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]
Trial Contact Information
Trial Lead Organizations
National Surgical Adjuvant Breast and Bowel Project
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.