This intriguing phenomenon further suggests better efficacy of concurrent schedule than sequential use of trastuzumab. On the other hand, our findings first provide Ophiopogonin D indirect evidence for the hypothesis just as mentioned above that superiority of concurrent schedule in preventing non-CNS recurrence contributes to a relatively extended life span so that metastatic propensity to CNS, usually occurring late in the course of the disease, is augmented as a natural consequence. Nonetheless, our findings are only for hypothesis generation and need to be confirmed through welldesigned and well-executed randomized clinical trials. Additionally, we demonstrated unfortunately in the present analysis that trastuzumab had no bearing on the risk reduction of contralateral breast cancer. But curiously enough, adjuvant endocrine therapy including tamoxifen and aromatase inhibitors brought about a definite and highly significant decrease in the incidence of contralateral breast cancer for women with estrogen receptor – positive or ER-unknown disease. As far as we know, this marked divergence had never been described before; nor had its underlying mechanism been elucidated. Whether it is attributed to the dissimilar function in carcinogenesis or metastasis between ER and HER2 still remains suspended and requires intensive study. In conclusion, this analysis provides the NDB latest and overwhelming evidence for the outstanding efficacy of adjuvant trastuzumab administration in reducing the risk of extracranial recurrence as well as prolonging the DFS and overall survival. More importantly, our findings first corroborate that concurrent trastuzumab outweighs sequential use as concerns overall survival advantage. Besides, we further certify the postulation that the rising level of CNS recurrence actually accompanies the life extension by treatment with trastuzumab vs. observation. Current fashion of administration might insufficiently maximize the prophylactic function of trastuzumab on CNS metastasis in the adjuvant setting rather than increase its incidence.