LAUSR

We thankKadri for his discussion of our recent article entitled “Change in HER2 status after neoadjuvant chemotherapy and the prognostic impact in patients with primary breast cancer.” The questions posed by Kadri et al question whether 33 patients with HER2 loss after NAC might have not received adjuvant trastuzumab. In the article, we have described that, of the 33 patients who had HER2-positive tumors changed to HER2-negative, 23 patients (70%) were administered trastuzumab in the adjuvant setting while 10 patients (30%) were not because of no coverage by Japanese national insurance during the period. In other words, the rate of HER2 loss was 43% (12/28) in HER2-positive patients who received trastuzumab and 30% (21/71) in those who did not in neoadjuvant setting. It showed that use of trastuzumab was not associated with the rate of HER2 loss in our study. The important issue in clinical practice is whether we could omit adjuvant trastuzumab for these patients having HER2 loss after neoadjuvant chemotherapy. Kadri also suggested that patients with HER2positive tumor at the initial diagnosis should still be treated with HER2-targeted therapy at adjuvant treatment regardless of the biological discordance related to intra-tumor heterogeneity. We agreed with this opinion based on the evidence showing that 1 year of trastuzumab is standard treatment for primary breast cancer patients. There is no evidence to omit adjuvant trastuzumab for patients achieving pathologic complete response or HER2 loss after neoadjuvant chemotherapy. We also showed the change of HER2 status was not associated with prognosis if trastuzumab was used for primary HER2-positive tumors. Prospective studies are warranted to study the prognostic impact of omitting adjuvant trastuzumab for such a population who might achieve little benefit from the treatment. ORCID