Relationship between HER2-low status and efficacy of CDK4/6 inhibitors in advanced breast cancer: a real-world study

• Published in: International journal of clinical oncology Vol. 29; no. 7; pp. 972 - 984
• Main Authors: Önder, T., Ateş, Ö., Öner, İ., Karaçin, C.
• Format: Journal Article
• Language: English
• Published: Singapore Springer Nature Singapore 01.07.2024; Springer Nature B.V
• Subjects: Breast cancer; Cancer Research; Cyclin-dependent kinase 4; Cyclin-dependent kinases; Disease control; ErbB-2 protein; Kinases; Medicine; Medicine & Public Health; Metastases; Oncology; Original Article; Patients; Statistical analysis; Surgical Oncology; Survival; HER2-low; Breast cancer; HER2-zero; CDK 4/6 inhibitor
• ISSN: 1341-9625; 1437-7772; 1437-7772
• DOI: 10.1007/s10147-024-02528-w

Aims and objectives Human epidermal growth factor receptor 2 (HER2)-low breast cancer (BC) is a new entity considered a biologically distinct subtype from HER2-zero BC. However, the importance of HER2 low expression on the activity of cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) remains unclear. Methods/materials We conducted a single-center retrospective study including hormone receptor-positive (HR +) /HER2- metastatic BC (mBC) patients treated with CDK4/6i plus endocrine treatment (ET) as first-line therapy. Clinical outcomes were analyzed according to HER2 expression. Results 258 women were analyzed with a median follow-up of 25.4 months; 39.9% had HER2 low, and 60.1% had HER2 zero BC. Median progression-free survival (mPFS) in the HER2-low group was 27.6 months compared with 44.3 months in the HER2-zero group (p = 0.341). In patients receiving ribociclib, the mPFS in the HER2-low group was 24.2 months compared with 53.1 months in the HER2-zero group (multivariate-adjusted HR: 1.981, 95 Cl 1.094–3.586; p = 0.024). The survival probabilities at 24, 36 and 48 months for the HER2 low and HER2 zero groups were 82%, 69%, 69% and 83%, 75% and 69%, respectively (p = 0.336). Objective response rate (p = 0.179) and disease control rate (p = 0.338) did not significantly differ between HER-2-low and HER-2-zero groups. Conclusions The mPFS in the Her2-zero group was almost twice that of the Her2-low group, but the difference was not statistically significant. mPFS was significantly longer in the HER2-zero group compared to the HER2-low group in patients receiving ribociclib. More prospective studies are needed to understand the actual consequences of this biomarker.