What is the role of taxanes in the adjuvant therapy for breast cancer?

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

Taxanes are among the most active and commonly used chemotherapeutic agents for the treatment of early-stage breast cancer. However, questions have lingered as to whether taxanes are the most effective chemotherapeutic agent to use in this setting and, if so, which is the best dosing schedule.  Although they are gernally better tolerated than the anthracyclines, they can have considerable toxicity:  peripheral neuropathy, myelosuppression, myalgias, and the risk of infusions reactions.

A Cochrane meta-analysis showed a statistically significant overall survival and disease-free survival for the taxane-containing regimens compared with the nontaxane regimens. The meta-analysis included 12 studies and more than 21,000 patients in evaluating the role of taxanes in the adjuvant treatment of operable breast cancer (stages I-III). However, this meta-analysis did not identify any subgroups of patients within the evaluated studies in which a taxane-containing regimen would be more effective. [18]

The Cancer and Leukemia Group B (CALGB) 9344 study demonstrated a survival benefit for the sequential use of paclitaxel following Adriamycin (doxorubicin) and cyclophosphamide (AC) chemotherapy. This investigation was one of the largest trials to evaluate taxanes in the adjuvant setting for early-stage breast cancer, with more than 3000 women with node-positive breast cancer. [16]

In a retrospective analysis of CALGB 9344 testing for HER2 status using 1322 original participant tumor blocks, HER2 positivity irrespective of estrogen receptor status predicted a significant benefit from paclitaxel in terms of reduced disease recurrence. Patients with ER-positive, HER2-negative, node-positive breast cancer did not seem to benefit from the addition of a taxane. [19]

However, the National Cancer Institute of Canada MA.21 [20] and UK TACT trials, [21] which used taxane- and nontaxane-based chemotherapeutic regimens in early-stage breast cancer patients, did not demonstrate a benefit in using taxanes. Although the precise role of adjuvant taxane therapy remains controversial, the optimal scheduling of taxane administration has been determined.

The Eastern Coast Oncology Group (ECOG) 1199 study demonstrated that paclitaxel weekly and docetaxel every 3 weeks were superior to two other regimens in terms of disease-free survival after a median follow-up of 64 months. This trial randomized 4950 women with lymph node-positive or high-risk lymph node–negative early-stage breast cancer to four cycles of AC followed by four different taxane regimens: paclitaxel at 175 mg/m2 q3wk; paclitaxel at 80 mg/m2 weekly; docetaxel (Taxotere) at 100 mg/m2 q3wk; and docetaxel at 35 mg/m2 weekly. [22]

Similarly, the TAX 311 trial, performed by the US Oncology Group in patients with advanced breast cancer that had progressed after an anthracycline-containing chemotherapy regimen, showed that every-3-week docetaxel at 100 mg/m2 improved time to progression (TTP) and overall survival when compared with paclitaxel at 175 mg/m2 given every 3 weeks. [23]

Thus, taxane-based regimens still have use in the treatment of early-stage breast cancer and should be considered in treating women, especially those with HER2-positive disease, using either the weekly paclitaxel or every-3-week docetaxel dosing schedules.


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