What is the efficacy of adjuvant therapy for the treatment of breast cancer?

Updated: May 21, 2019
  • Author: Erin V Newton, MD; Chief Editor: Neetu Radhakrishnan, MD  more...
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Answer

Answer

Major chemotherapy clinical trials by the Cancer and Leukemia Group B (CALGB) from the last few decades have consistently shown that chemotherapy produces significantly better disease-free and overall survival in patients with estrogen receptor (ER)–negative disease. These trials included the following:

  • C8541 - Comparison of various doses of CAF (cyclophosphamide, doxorubicin [Adriamycin], and fluorouracil) [15]

  • C9344 - Addition of paclitaxel to standard-dose Adriamycin-cyclophosphamide [AC]) [16]

  • C9741 - Comparison of 3- and 2-week dosing in patients with ER-positive and ER-negative disease [6]

A comparison of the inferior-dose arm of C8541 with the dose-dense arm of C9741 demonstrated a remarkable 63% improvement in disease-free survival and a 59% improvement in overall survival in patients with ER-negative disease, compared with 32% improvement in disease-free survival and 18% improvement in overall survival in patients with ER-positive disease. Overall, the advantages of chemotherapy, particularly in ER-negative disease, were observed across all three trials, irrespective of the chemotherapy regimen used.

The randomized, prospective phase III CALGB 9741 study assigned 2005 subjects to one of 4 arms:

  • Conventional AC x 4 cycles -> T x 4 cycles (all q 3 weeks)
  • AC x 4 cycles --> T x 4cycles  (all q 2 weeks)
  • A x 4 cycles -> T x 4 cycles -> C x 4 cycles (all q 3 weeks)
  • A x 4 cycles -> T x 4 cycles -> C x 4 cycles (all q 2 weeks) 

Dosing was the same in all arms, and the dose-dense groups received peg-filgrastim support on day 2 of each 14-day cycle. The 4-year disease-free survival for the dose dense groups was 82%, versus 75% for the other two.  Subsequent trials have failed to replicate the results of this pivotal trial, so the dose-dense schedule has not emerged as the standard of the care.

In the phase III AZURE trial, the addition of zoledronic acid to standard adjuvant therapy in women with stage II/III breast cancer did not affect disease-free survival. However, zoledronic acid did reduce the development of bone metastases (hazard ratio [HR], 0.78). In women who had entered menopause more than 5 years before trial entry, zoledronic acid improved invasive disease–free survival (HR, 0.77). [17]


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