Plasma IFN-γ may predict pyrotinib efficacy in patients with HER2-positive advanced breast cancer

Pyrotinib has been extensively utilized in the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC), yet few reliable markers for predicting pyrotinib efficacy in these patients have been identified. Therefore, the present study aimed to explore the predictive clinical factors for treating patients with HER2-positive ABC with pyrotinib. To this aim, a prospective observational study was conducted on the prognostic potential of serum cytokines in a cohort of 58 patients with HER2-positive cancer receiving pyrotinib treatment, enrolled from January 2020 to December 2022. Patients were treated with oral pyrotinib (400 mg/day, 30 min after eating) combined with capecitabine (1,000 mg/m² twice daily on days 1-14 of a 21-day cycle) or vinorelbine soft capsules (40 mg/day, 3 times weekly). Peripheral blood was collected from these patients before and 4 weeks after the initial administration of pyrotinib. Plasma cytokine levels (IL-6, IL-8, IL-10, IL-17 and IFN-γ) were measured via multiple microsphere flow cytometry luminescence. Univariate analysis revealed that patients who received pyrotinib as second-line therapy had an improved progression-free survival (PFS) time compared with those who received it as third- or later-line therapy [median PFS (mPFS), 17.0 vs. 9.5 months; P=0.016]. Furthermore, patients with increased plasma IL-8 levels had a poorer PFS time than those with decreased levels (mPFS, 9.4 vs, 14.0 months; P=0.021). Patients with increased plasma IFN-γ levels had a longer PFS time than those with decreased levels (mPFS, 13.0 vs. 11.0 months; P=0.010). Multivariate Cox regression analysis revealed that pyrotinib application beyond third-line therapy and decreased plasma IFN-γ levels were independent risk factors for PFS (P=0.025 and P=0.033, respectively). In conclusion, early application of pyrotinib may improve the PFS time of patients with HER2-positive ABC who are resistant to trastuzumab; however, whether these findings translate into an improved overall survival time requires further investigation. Additionally, plasma IFN-γ has potential prognostic value in patients with HER2-positive ABC treated with pyrotinib.