The difference in efficacy of the endocrine therapy between the HER2-low and HER2-zero metastatic breast cancer: A single-center retrospective study.

3 Background: HER2-low expression breast cancer is a new classification and began to receive attention after trastuzumab deruxtecan showed its effect on this classification. As for endocrine therapies, HER2-low expression seemed not to affect the efficacy of CDK4/6 inhibitors in a few retrospective studies. However, previous data on the effectiveness of endocrine therapies other than CDK4/6 inhibitors for HER2-low metastatic breast cancer (mBC) are still limited. This study aims to evaluate the difference in endocrine therapy between HER2-low and HER2-zero mBC. Methods: We retrospectively reviewed the clinical data of mBC patients prescribed aromatase inhibitors, tamoxifen or fulvestrant, and/or CDK4/6 inhibitors at our department between May 2012 and December 2022. Patients were excluded if they received chemotherapy before endocrine therapy, lacked data on HER2 score, or discontinued treatment before the first image evaluation. The data cutoff date was 15th March 2023. We analyzed the difference in progression-free survival (PFS) of the first-line endocrine monotherapy and the first-line CDK4/6 inhibitors between HER2-low and HER2-zero mBC by logrank analysis. Results: Of 126 patients who received the first-line endocrine monotherapy, 22 were HER2-zero, and 104 were HER2-low. In the HER2-zero group, six patients received tamoxifen, and 16 received AIs. In the HER2-low group, 29 patients received tamoxifen, 63 received AIs, and 12 received fulvestrant. The median PFS was 27.7 months with the HER2-zero group and 15.6 months with the HER2-low group. This was not statistically significant (P=0.196), but the Kaplan-Meier curve showed that PFS tended to be longer with the HER2-zero group. This trend was also observed in patients who received AIs. Of 52 patients who received CDK4/6 inhibitors as a first-line treatment, ten were HER2-zero, and 42 were HER2-low. The median PFS was NA with the HER2-zero group and 22.8 months with the HER2-low group, and no significant differences were detected. Conclusions: In this study, there were no statistically significant differences in the PFS of the first-line endocrine monotherapy and CDK4/6 inhibitors between HER2-low and HER2-zero mBC. However, the Kaplan-Meier curve showed that the PFS of endocrine therapy tended to be longer in the HER2-zero group. Further studies are warranted.