Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2012 Nov 20;30(33):4071-6.
doi: 10.1200/JCO.2011.40.6405. Epub 2012 Jul 23.

Six Cycles of Doxorubicin and Cyclophosphamide or Paclitaxel Are Not Superior to Four Cycles as Adjuvant Chemotherapy for Breast Cancer in Women With Zero to Three Positive Axillary Nodes: Cancer and Leukemia Group B 40101

Affiliations
Free PMC article
Clinical Trial

Six Cycles of Doxorubicin and Cyclophosphamide or Paclitaxel Are Not Superior to Four Cycles as Adjuvant Chemotherapy for Breast Cancer in Women With Zero to Three Positive Axillary Nodes: Cancer and Leukemia Group B 40101

Lawrence N Shulman et al. J Clin Oncol. .
Free PMC article

Abstract

Purpose: The ideal duration of adjuvant chemotherapy for patients with lower risk primary breast cancer is not known. Cancer and Leukemia Group B trial 40101 was conducted using a phase III factorial design to define whether six cycles of a chemotherapy regimen are superior to four cycles. We also sought to determine whether paclitaxel (T) is as efficacious as doxorubicin/cyclophosphamide (AC), but with reduced toxicity.

Patients and methods: Between 2002 and 2008, the study enrolled women with operable breast cancer and zero to three positive nodes. Patients were randomly assigned to either four or six cycles of either AC or T. Study stratifiers were estrogen receptor/progesterone receptor (ER/PgR), human epidermal growth factor receptor 2 (HER2), and menopausal status. After 2003, all treatment was administered in dose-dense fashion. The primary efficacy end point was relapse-free survival (RFS).

Results: A total of 3,171 patients were enrolled; 94% were node-negative and 6% had one to three positive nodes. At a median follow-up of 5.3 years, the 4-year RFS was 90.9% and 91.8% for six and four cycles, respectively. The adjusted hazard ratio (HR) of six to four cycles regarding RFS was 1.03 (95% CI, 0.84 to 1.28; P=.77). The 4-year OS was 95.3% and 96.3% for six and four cycles, respectively, with an HR of six to four cycles of 1.12 (95% CI, 0.84 to 1.49; P=.44). There was no interaction between treatment duration and chemotherapy regimen, ER/PgR, or HER2 status on RFS or OS.

Conclusion: For women with resected primary breast cancer and zero to three positive nodes, we found no evidence that extending chemotherapy regimens of AC or single-agent T from four to six cycles improves clinical outcome.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
CONSORT diagram showing patients registered, treatment arm assignments, and exclusions. AC, doxorubicin and cyclophosphamide; T, paclitaxel.
Fig 2.
Fig 2.
(A) Relapse-free and (B) overall survival comparing four cycles versus six cycles of therapy. HR, hazard ratio.

Similar articles

See all similar articles

Cited by 30 articles

See all "Cited by" articles

Publication types

MeSH terms

Feedback