Comparative Effectiveness of Adjuvant Chemotherapy in Early-Stage Breast Cancer: A Network Meta-analysis

Preethi John, Mikala C. Osani, Abhigna Kodali, Rachel Buchsbaum, Raveendhara R. Bannuru, John K. Erban

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Background: There are several regimens recommended by the National Comprehensive Cancer Network (NCCN) for HER2-negative operable breast cancer. To our knowledge, no trials have yet been performed comparing these regimens head to head. We performed a network meta-analysis comparing the efficacy of NCCN-recommended chemotherapy regimens. Methods: We searched Medline, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and World Health Organization (WHO) International Clinical Trials Registry Platform from inception to February 2020. We included randomized clinical trials comparing adjuvant regimens in predominantly node-positive operable breast cancer patients. We compared (1) DDACT, (2) TCx4 cycles, (3) TAC, and (4) ACWKT. Common comparators were (5) AC, (6) ACT, and (7) ACD. Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed. The Cochrane risk of bias tool assessed quality of the studies. Odds ratios (ORs) were calculated as measures of treatment effects with AC as reference. We used Bayesian hierarchical random-effects models with noninformative priors for mixed multiple treatment comparisons. Effectiveness was estimated by disease-free and overall survival using ORs. Sensitivity analyses were performed. Safety outcomes included febrile neutropenia. Results: We identified 7 randomized controlled trials with 16,332 patients. TC (odds ratio [95% confidence interval], 0.71 [0.36-1.40]), TAC (0.77 [0.37-1.57]), ACWKT (0.68 [0.34-1.38]), and DDACT (0.72 [0.35-1.42]) were similar for overall survival. TC (0.64 [0.36-1.14]), TAC (0.67 [0.39-1.15]), ACWKT (0.63 [0.37-1.07]), and DDACT (0.59 [0.35-1.01]) had similar disease-free survival benefit. With regard to toxicity, TAC (2.67 [0.30-21.04]) had the highest odds of febrile neutropenia. Conclusion: The current generation of regimens are similar in efficacy. Given the lower toxicity of TCx4 comparatively, it is an acceptable alternative for lower-risk early-stage HER2-negative breast cancers. National guidelines recommend several adjuvant chemotherapies for HER2-negative breast cancer that have not been compared in clinical trials. Our network meta-analysis of 7 randomized clinical trials showed that contemporary anthracycline-based regimens have similar efficacy compared to each other and to N-anthracycline–based regimens. These findings suggest that clinicians can tailor therapy toward patient preferences and tolerability without compromising benefit.

Original languageEnglish (US)
Pages (from-to)e22-e37
JournalClinical breast cancer
Issue number1
StatePublished - Feb 2021
Externally publishedYes


  • Adjuvant therapy
  • Breast malignancy
  • Chemotherapy
  • Clinical effectiveness
  • Early stage breast cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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