1 Progression-free survival in all patients. interval [CI], 3.46C8.17), and the median overall survival was 35.3?months (95% CI, 20.0C46.7). Of the 28 patients, partial response was observed in 1 (4%), stable disease in 17 (61%), and progressive disease in 10 (36%) patients. The disease control rate Lamotrigine was 64%. Adverse events of grade??3 were not observed. Conclusions Trastuzumab and fulvestrant combination therapy showed moderate clinical efficacy and no severe toxicity after standard anti-HER2 treatment, which is a reasonable treatment option for patients with hormone receptor- and HER2-positive metastatic breast cancer. These data contribute to understanding the efficacy of trastuzumab and fulvestrant combination therapy as control data for further development of anti-HER2 agents plus hormone therapy. value of ?0.05 was considered statistically significant. Statistical analysis was performed using JMP version 14.3.0 (SAS Institute Inc., Cary, NC, USA) and SPSS Statistics 27.0 (IBM corporation, New York, USA). This study was approved by the institutional review board (# 2020C1280). Comprehensive consent was obtained from accusable patients in our institution. Results The data of 1612 patients with recurrent or metastatic breast cancer during the targeted period were reviewed and 118 patients with histologically documented HR?+?HER2+ breast cancer were identified. Of these, 28 patients received trastuzumab and fulvestrant combination therapy. The patient characteristics are presented in Table?1. The median age was 66 (range, 50C80) years. Of these 28 patients, 7 (25%) had de novo stage IV and 21 (75%) had recurrent disease. Before trastuzumab and fulvestrant combination therapy, the median Rabbit polyclonal to ZNF484 treatment line for advanced breast cancer was 6. Six patients had a treatment line of 2, and the remaining 22 patients were treated on the third treatment line or later. Trastuzumab was previously administered for advanced breast cancer to all patients, pertuzumab to four patients, and trastuzumab emtansine (T-DM1) to 10 patients. Of all patients, 21 (75%) had visceral metastasis, including liver and brain metastases. Table 1 Patient characteristics thead th rowspan=”1″ colspan=”1″ Characteristics /th th rowspan=”1″ colspan=”1″ em N /em ?=?28 (%) /th /thead Age (years)? median66 (range: 50C80)Stage? De novo stage IV7 (25)? recurrent disease21 (75)Subtype? HR+ HER2+28 (100)? others0Number of treatment line? median6? 1 or 26 (21)? 3C69 (32)? 7C109 (32)? ?104 (14)Prior treatment for recurrent or metastatic breast cancer? Trastuzumab28 (100)? Pertuzumab4 (14)? T-DM110 (36)? Trastuzumab deruxtecan (T-DXd)2 (7)Visceral metastasis? Yes21 (75)? No7 (25)Liver metastasis? Yes11 (39)? No17 (61)Brain metastasis? Yes4 (14)? No24 (86) Open in a separate window Efficacy Complete response (CR) was not observed in any patient. Partial response (PR) was observed in 1, stable disease (SD) in 17, and progressive disease in 10 patients. The overall response rate was 4%, and the disease control rate (DCR?=?CR?+?PR?+?SD) was 64%. The median PFS was 6.4?months (95% CI, 3.46C8.17), and median OS was 35.3?months (95% CI, 20.0C46.7) (Figs.?1 and ?and2).2). Subgroup analysis depending on patient characteristics is shown in Fig.?3, which suggested that no Lamotrigine significant difference in PFS was observed in any subgroup analysis. PFS in patients who received trastuzumab and fulvestrant combination therapy as 3rd line treatment or did not have liver metastasis tended to be better compared to those in patients who received the treatment in later line or with liver metastasis. Median PFS was 7.3?months (95% CI, 1.53C18.67) and median OS was not achieved in patients receiving trastuzumab and fulvestrant combination therapy as 3rd line treatment. In contrast, the median PFS was 5.2?months (95% CI, 2.57C8.17), and median OS was 34.8?months (95% CI, 14.5C45.1) in patients who received the therapy as 3rd line treatment. The PFS and OS of this subgroup were not significantly different (log-rank test, em p /em ?=?0.4299 Lamotrigine and em p /em ?=?0.2550, respectively) (PFS data in Fig.?4). Additionally, PFS in patients with liver metastasis tended to be worse than that in patients without liver metastasis, and median PFS was 3.5?months (95% CI, 1.17C8.93) and 6.9?months (95% CI, 3.93C8.17), respectively (log rank test, em p /em ?=?0.3573) (Fig.?5). No adverse events of grade 3 were observed. Open in a separate window Fig. 1 Progression-free survival in all patients. KaplanCMeier curve of progression-free survival (PFS) of fulvestrant and trastuzumab combination therapy in patients with hormone receptor- and human epidermal growth factor receptor 2-positive metastatic breast cancer Open in a separate window Fig. 2 Overall survival in all patients. KaplanCMeier curve of OS of fulvestrant and trastuzumab combination therapy in patients with hormone receptor- and human epidermal growth factor receptor 2-positive metastatic breast cancer Open in.