title: Dose-dense adjuvant chemotherapy for primary breast cancer.
abstract: Adjuvant chemotherapy has been proven to reduce significantly the risk for relapse and death in women with operable breast cancer. Nevertheless, the prognosis for patients presenting with extensive axillary lymph node involvement remains suboptimal. In an attempt to improve on the efficacy of existing chemotherapy, a phase III intergroup trial led by the Cancer and Leukemia Group B (CALGB 97-41) was designed, which tested a mathematical model of tumor growth based on the Norton-Simon hypothesis. This hypothesis, developed about 3 decades ago, and the kinetic model derived from it, created the basis of the concepts of dose density and sequential therapy, both of which were tested in CALGB 97-41. This large prospective randomized trial demonstrated that shortening the time interval between each chemotherapy cycle while maintaining the same dose size resulted in significant improvements in disease-free and overall survival in patients with node-positive breast carcinoma. This finding is highly relevant and has immediate implications for clinical practice.
authors.affiliation: Breast Cancer Medicine Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. fornierm@mskcc.org
authors.forename: Monica
authors.initials: M
authors.lastname: Fornier
authors.forename: Larry
authors.initials: L
authors.lastname: Norton
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic
references.citation: J Clin Oncol. 1997 May;15(5):1858-69
references.pmid: 9164196
references.citation: JAMA. 1995 Feb 15;273(7):542-7
references.pmid: 7837388
references.citation: CA Cancer J Clin. 2004 Jan-Feb;54(1):8-29
references.pmid: 14974761
references.citation: J Clin Oncol. 2003 Apr 15;21(8):1431-9
references.pmid: 12668651
references.citation: N Engl J Med. 2003 Jul 3;349(1):7-16
references.pmid: 12840087
references.citation: Cancer Treat Rep. 1986 Jan;70(1):3-7
references.pmid: 3943114
references.citation: Ann Oncol. 2004 Sep;15(9):1425-31
references.pmid: 15319250
references.citation: J Clin Oncol. 1999 Apr;17(4):1118
references.pmid: 10561169
references.citation: J Clin Oncol. 2005 Jun 1;23(16):3686-96
references.pmid: 15897552
references.citation: Cancer Treat Rep. 1979 Nov-Dec;63(11-12):1727-33
references.pmid: 526911
references.citation: J Clin Oncol. 2001 Feb 1;19(3):602-11
references.pmid: 11157009
references.citation: Lancet. 1998 Sep 19;352(9132):930-42
references.pmid: 9752815
references.citation: J Clin Oncol. 2003 Mar 15;21(6):976-83
references.pmid: 12637460
references.citation: Cancer Res. 1988 Dec 15;48(24 Pt 1):7067-71
references.pmid: 3191483
references.citation: Clin Cancer Res. 2004 Sep 1;10(17):5754-61
references.pmid: 15355903
references.citation: J Clin Oncol. 1999 Nov;17(11):3374-88
references.pmid: 10550131
references.citation: J Clin Oncol. 1999 Jan;17(1):93-100
references.pmid: 10458222
references.citation: Clin Cancer Res. 2001 Dec;7(12):3934-41
references.pmid: 11751485
references.citation: J Clin Oncol. 1986 Aug;4(8):1162-70
references.pmid: 3525765
references.citation: J Clin Oncol. 2003 Mar 1;21(5):843-50
references.pmid: 12610183