468P - Impact of low HER2 status on CDK4/6 inhibitor and endocrine therapy in metastatic HR+ breast cancer: A retrospective multicenter study

Background

CDK4/6 inhibitors combined with endocrine therapy have revolutionized the treatment of metastatic HR+ breast cancer. However, the influence of low HER2 expression on treatment response and progression-free survival (PFS) remains unclear.

Methods

We conducted a multicenter retrospective study including 204 HR+ breast cancer patients who received a combination of CDK4/6 inhibitor and endocrine therapy. Among them, 138 (68%) patients exhibited HER2-zero disease, while 66 (32%) patients had HER2-low disease. We analyzed treatment-related characteristics and clinical outcomes, with a median follow-up of 22 months.

Results

In the HER2-low group, the objective response rate (ORR) was 72.7%, compared to 66.6% in the HER2-zero group (p=0.54). Median PFS did not significantly differ between the HER2-low and HER2-zero groups (19 months vs. 18 months, p=0.89). Notably, a trend towards longer PFS was observed in the HER2-low group for first-line treatment (24 months progression-free survival rate: 63% vs. 49%). For recurrent disease, the median PFS was 25 months in the HER2-low group and 12 months in the HER2-zero group (p=0.08), while in de novo metastatic disease, the median PFS was 18 months in the HER2-low group and 27 months in the HER2-zero group (p=0.16). Independent variables affecting PFS were identified as the order of CDK4/6 inhibitor use and the presence of visceral metastasis.

Conclusions

Low HER2 expression did not significantly impact treatment response or PFS in HR+ breast cancer patients treated with a CDK4/6 inhibitor and endocrine therapy. Because of the conflicting results in the literature, further prospective studies are needed to evaluate the clinical significance of HER2 expression in HR+ breast cancer.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.