Discussion
tumor, SD, DFS/DDFS, Tumors, PD
TUMOR, BREAST CANCER, PROLIFERATION, ADVERSE EVENTS, TUMORS, ADVERSE EVENT, EVENTS
To the best of our knowledge, this was the first study to assess the value of response-guided therapy using NET. We found no difference in survival outcomes of patients with ER+EBC treated with NET, excluding patients with PD, compared with previous data for the same population [We considered that patients with luminal-type EBC who had PD following NET might have worse outcomes than those with CR, PR, and SD, based on the poorer prognosis of patients with endocrine primary resistance compared with those with a good response in patients with ER+metastatic breast cancer, and we therefore planned a randomized controlled trial to compare CT+ET and ET alone in patients with CR, PR, and SD, excluding PD, after NET. Previous small studies found different response outcomes to ET [The prognostic value of the clinical response to NET has previously been examined in small-scale studies [The results of this study show that it is difficult to decide whether to administer adjuvant CT based solely on the effect of NET. Among patients with CR, PR, or SD (excluding PD) following NET, the CT+ET group had better outcomes compared with the ET alone group, as demonstrated by the 8-year DFS/DDFS rates, especially among patients aged < 60 years or with clinical T2 or high proliferation. In a previous report, tumor size and high proliferation factors were shown to be predictive markers for benefit from CT [The definitions of PR and SD used in this study were equivalent to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and a reduced tumor size ≤ 30% and an increased tumor size ≤ 20% were both classified as SD. However, the possible differences in DFS and DDFS rates between these two groups in patients with SD should be investigated in future studies.In this study DFS/DDFS were significantly better in the CT+ET compared with the ET alone group in patients aged < 60 years. The benefit of additional CT in patients aged < 60 years might be a result of the CT regimen, with more patients aged > 60 years receiving the cyclophosphamide, methotrexate, and fluorouracil regimen compared with the docetaxel and cyclophosphamide regimen (data not shown).A previous study showed that Ki67 down-regulation at an early phase during NET and a preoperative endocrine prognostic index score were predictive markers for survival benefit in patients with ER+EBC [Based on the results of a large-scale trial [No patients in this study experienced any serious adverse events or discontinued the study due to an adverse event during NET (data not shown), indicating that NET was safe and well-tolerated in these patients. The results of our previous study demonstrating that NET had no impact on health-related quality of life in EBC patients [This study had some limitations, including low power due to the low incidence of DFS events, with 8-year DFS and OS rates of > 90% and > 95%, respectively, in the overall population, regardless of the relatively long follow-up period (7.8 years). There were many patients in this study who did not receive the prescribed treatment after randomization. In particular, 67 of the patients assigned to CT+ET did not receive chemotherapy (Supplementary Table S1). Of those who did receive chemotherapy, 63 received cyclophosphamide, methotrexate, and 5-fluorouracil (Supplementary Table S1). This may be one of the reasons why we could not show the benefit of receiving chemotherapy.