difference was statistically signiﬁcant only in patients with node-positive disease (p 0.05). The study was not powered to detect differences in subgroups. The North American Breast Cancer Intergroup Trial E1199 compared the effectiveness of adjuvant paclitaxel with docetaxel, and the effectiveness of 3-weekly with weekly adjuvant taxane therapy in 4988 patients with operable breast cancer. Patients received 4 cycles of AC (60 mg/m2 and 600 mg/m2 respectively) every 3 weeks, followed by either: paclitaxel 175 mg/m2 every 3 weeks × 4, paclitaxel 80 mg/m2 weekly × 12, docetaxel 100 mg/m2 every 3 weeks × 4, or docetaxel 35 mg/m2 weekly × 12. Most patients (88%) had lymph node-positive disease. After a median follow-up of 46.5 months, there were no signiﬁcant differences in HR comparing taxane (0.985; p = 0.83) or schedule (1.043; p = 0.54) for DFS. In an exploratory analysis, weekly paclitaxel was found to have superior DFS compared with 3-weekly paclitaxel (HR 1.20, p 0.06). The docetaxel arms did not differ signiﬁcantly from 3-weekly paclitaxel but had more Grade III and IV hematological toxicities. Combinations with trastuzumab Trastuzumab is a humanized monoclonal antibody against the HER2 protein, which is overexpressed in 15%–25% of breast carcinomas. The role of trastuzumab is established in metastatic breast cancer where it improves survival when administered with chemotherapy (Slamon et al 2001). This beneﬁt extended to the adjuvant setting with 2 large phase III randomized placebo-controlled trials demonstrating a signiﬁcant improvement in DFS with the addition of trastu- zumab to conventional chemotherapy (Piccart-Gebhart et al 2005; Romond et al 2005). Interestingly, data obtained from in vitro experiments show that docetaxel exhibits synergistic effects against breast cancer cells when administered with trastuzumab, in contrast to the additive effects it exhibits when given with paclitaxel. In early trials of trastuzumab with chemotherapy, 27% of patients treated concurrently with trastuzumab and anthra- cyclines, 13% with trastuzumab and paclitaxel, and 5% with trastuzumab alone had cardiotoxic events (Slamon et al 2001). To overcome the risk of cardiotoxicity, the BCIRG 006 trial randomized patients into 3 arms: comparing doxorubicin and cyclophosphamide followed by docetaxel (AC→T) with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab (AC→TH) with docetaxel, carboplatin, and trastuzumab (TCH). The combination of docetaxel and trastuzumab was well tolerated. After a median follow-up of Therapeutics and Clinical Risk Management 2008:4(2) Docetaxel for post-surgery treatment of breast cancer patients 36 months, both AC→TH and TCH signiﬁcantly improved the DFS and OS over the control (Slamon et al 2005). A prospectively designed subgroup analysis of the BCIRG 001 trial showed that Her 2-neu positive patients treated with TAC had a signiﬁcant reduction in risk (0.60, CI 0.41–0.88) compared with FAC (Trudeau et al 2005). To date, there is insufﬁcient evidence to conclude that HER 2-neu positive breast cancer patients derive superior beneﬁt from this combination and it still remains to be tested in well-designed randomized clinical trials. Conclusions Adjuvant trials with docetaxel have demonstrated a signiﬁ- cant reduction in recurrence and longer disease-free interval in patients with node-positive breast cancer (Martin et al 2005). The survival beneﬁt was more apparent in patients with fewer than 3 axillary lymph nodes and in women older than 50 years of age (Martin et al 2005; Roché et al 2006). The most common side effect is myelosuppression and neutropenic fevers. The incidence of this can be reduced by prophylaxis with growth factors. Hypersensitive reactions and ﬂuid retention are minimized by administration of dexa- methasone and histamine receptor antagonists. Addition of trastuzumab to docetaxel appears promis- ing. Combination of docetaxel with antiangiogeneic agents and trastuzumab is currently under investigation. Further studies are needed to deﬁne the most effective and safe dos- ing regimen of docetaxel to maximize beneﬁt and reduce the incidence of neutropenic complications in patients with node-positive breast cancer. References Bissery MC, Nohynek G, Sanderink GJ, et al. 1995. Docetaxel (Taxotere): a review of preclinical and clinical experience. Part I: Preclinical experi- ence. Anticancer Drugs, 6:339–55, 363–8. Bridgewater. 2004. Taxotere prescribing information. Aventis Pharma- ceuticals Inc. NJ. Cortes JE and Pazdur R. 1995. Docetaxel. J Clin Oncol, 13:2643–55. Crown JP, Francis P, Di Leo A, et al. 2006. 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