• Recurrence-free rate [ Time Frame: The observation period is designated as 10 years from the commencement of treatment. ] [ Designated as safety issue: No ]
  

• Survival rate [ Time Frame: The observation period is designated as 10 years from the commencement of treatment. ] [ Designated as safety issue: No ]
  
• Drug adverse events [ Time Frame: The observation period is designated as 10 years from the commencement of treatment. ] [ Designated as safety issue: Yes ]
  
• Bone metabolism markers (BAP, NTx) [ Time Frame: Pretreatment, and post-treatment at 3, 6, 12, and 24 months. ] [ Designated as safety issue: No ]
  
• BMD (DXA method): Lumbar vertebrae, femoral neck [ Time Frame: Pretreatment, and post-treatment at 12 months and 24 months. ] [ Designated as safety issue: No ]
  
• Laboratory values of lipid metabolism (TC, LDL, HDL, Lp(a), TG) [ Time Frame: Pretreatment, and post-treatment at 3, 6, 12, and 24 months. ] [ Designated as safety issue: No ]
  
• Compliance [ Time Frame: Compliance status will be entered into the database in the data center every time the study doctor prescribes drugs to the patient (1 to 3 months). ] [ Designated as safety issue: No ]
  

To investigate the benefit of postoperative adjuvant therapy using sequential administration of the hormone, toremifene citrate (TOR) or anastrozole (ANA), after chemotherapy in breast cancer.

TOR is reported to be as effective, or more effective, than TAM on both DFS and OS for postoperative adjuvant therapy. The incidence rate and severity of its adverse effects are similar to those of TAM as shown in two clinical trials, the Finnish Breast Cancer Group (FBCG) and the International Breast Cancer Study Group (IBCSG). Although no significant difference was observed in these trials, other studies report that TOR produced a lower number of thromboembolism events compared with TAM, a undesirable side effect seen in patients treated with TAM. Additionally, compared with TAM, TOR showed less endometrial hypertrophy which is induced by estrogen.

Endometrial cancer remains one of the significant problems associated with TAM. A TAM metabolite binds to DNA and forms DNA adducts which damage cells. It is reported that TAM has an expanded ability to form DNA adducts compared with TOR in vitro. 　A recent study compared endometrial cells collected from patients in which TAM or TOR had been administered. The k-ras gene mutation was investigated in these cases, and it showed that TAM held a higher frequency of gene mutation. Although we still need to discuss whether or not k-ras mutation is directly related to the development of endometrial cancer, TAM seems to have a higher risk of inducing cancer compared with TOR.

In the IBCSG14-93 trials, two chemotherapy protocols were studied subsequent to administration of TOR. They were doxorubicin and cyclophosphamide (AC) and cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). These two chemotherapy protocols were administered in the following sequence: AC four times followed by CMF three times after administration of TOR. The findings revealed that in estrogen-receptor (ER) positive cases, DFS equaled 73% in the TOR group, 65% in the TAM group; hormone receptor (HR=0.80 (0.57-1.11); P=0.18). OS was found to total 88% in the TOR group, 84% in the TAM group; HR=0.78 (0.48-1.27); p=0.32). Although there was no significant difference in two groups, the TOR group has showed somewhat improved survival.

Based on the information provided above, we consider TAM and TOR to have similar efficacy with less adverse effects, and this trial will compare the two drugs, TOR and ANA.