The study was internally monitored by certified HeCOG personnel. Patients were examined at the Clinic every three months following the discontinuation of the Ginsenoside-F4 treatment with ixabepilone. All imaging material pertinent to treatment response was assessed centrally by one of the authors after the completion of the study. The consort diagram of the study is shown in Figure 1. Unfortunately, the study was closed prematurely due to a low rate of accrual. This was probably due to the reluctance of physicians and patients to further participate in the study following the decision of Bristol-Myers Squibb, in March 2009, to withdraw the application to the European Medicines Agency for a centralized marketing authorization for ixabepilone and arrest its development in Chlorhexidine hydrochloride Europe. The ORR of the 3-weekly and weekly schedules was 47% and 50%, respectively, which is in the range of that reported in some of the phase II studies, albeit higher than that achieved in others. It is worthy of note, that in a randomized phase II study comparing the approved dose with that of 16 mg/m2 on days 1, 8 and 15 every 28 days, the ORR was 14% for the 3-weekly and 8% for the weekly schedule. In the registration phase III trial, the combination of 
ixabepilone and capecitabine demonstrated significantly improved ORR compared to capecitabine monotherapy with longer PFS. Importantly, in a recent phase III trial, weekly ixabepilone was found to have inferior PFS and greater toxicity compared to weekly paclitaxel, both given on a 3-weeks on, 1-week off schedule to chemotherapy na? ��ve MBC patients. Nevertheless, it has to be kept in mind that cross-study comparisons of response rates is frequently misleading, since differences in important patient or tumor characteristics, study sample size, ethnicity and previous treatments in combination with other confounding factors may influence the results. In general, ixabepilone, given as first line chemotherapy, has a manageable safety profile with neutropenia, sensory neuropathy, arthralgias/myalgias and fatigue being the most prominent adverse events incidence of severe neuropathy compared to the 3-weekly schedule. Likewise, in the present study, grade III sensory neuropathy occurred in 4/34 of the patients treated with the 3-weekly and in 8/30 with the weekly schedule. However, in all patients, except one, sensory neuropathy showed complete resolution to baseline or grade I after the completion of ixabepilone treatment. The main route of metabolism of ixabepilone is via CYP3A4, with substances that inhibit CYP3A4 activity decreasing its metabolism. The tumors examined here, however, expressed very low to undetectable CYP3A4 mRNA, while all patients carried the ancestral C-allele for rs12721627 in the same gene. It seems therefore unlikely that the CYP3A4 gene or its derivatives may have influenced the effect of ixabepilone in the present patient series. CYP2C8 is another cytochrome P450 gene that has been implicated in taxane metabolism but has not as yet been explored in epothilones. In comparison to CYP3A4, CYP2C8 transcripts were detected at variable levels in our breast carcinoma samples and were preferentially high in tumors with low proliferation rates, as indicated by low Ki67 scores. A new variation was identified, concerning a T-insertion in the 3rd intron of CYP2C8, which was strongly associated with increased expression of this gene. These observations may be useful when assessing the role of CYP2C8 in breast cancer, especially during treatment with taxanes or epothilones. Other than the above cytochrome P450 components, all ABCB1 polymorphisms tested were associated with patient survival.