Positron-emission tomography utility for progression-free survival prediction in HER2-positive advanced breast cancer patients treated with pertuzumab, trastuzumab, and docetaxel.

Abstract

e13012 Background: Pertuzumab, trastuzumab, and docetaxel (TPH) remain the gold standard for first-line therapy in patients with HER2-positive advanced breast cancer (ABC). However, the therapeutic landscape is evolving rapidly, underscoring the need for predictive markers that can identify patients likely to achieve durable responses on TPH. Fluorodeoxyglucose positron-emission tomography/computed tomography (FDG-PET/CT) is useful for staging in early breast cancer, but its prognostic value in the advanced disease requires further exploration. We aimed to determine whether baseline FDG-PET/CT predicts progression-free survival (PFS) in HER2-positive ABC treated with TPH. Methods: We retrospectively analyzed 195 patients with HER2-positive ABC who received TPH and underwent baseline FDG-PET/CT at our center between 2017 and 2023. The median age was 58 years (range 30–84), and all patients were female. The highest maximum standardized uptake value (SUVmax), obtained from the most FDG-avid lesion—whether the primary breast tumor, a regional lymph node, or a distant metastasis—was the key PET parameter. PFS was estimated by the Kaplan–Meier method with 95% confidence intervals (CIs) and compared using log-rank tests. The optimal SUVmax cut-off was determined by receiver operating characteristic (ROC) analysis using the Youden index. Cox proportional hazards models were applied to assess the effect of baseline SUVmax on PFS, adjusting for oligometastatic vs. polymetastatic disease, de novo vs. recurrent disease, and visceral vs. bone-only metastases. Statistical significance was set at p ≤ 0.05. All analyses were conducted using Stata version 18 (StataCorp, College Station, TX, USA). Results: The median PFS for the entire cohort was 32.3 months, with a 2-year PFS of 60.2% (95% CI 52.7–66.9). Baseline SUVmax as a continuous variable was significantly associated with PFS (HR 1.06; 95% CI 1.01–1.10; p = 0.011). The optimal SUVmax threshold was 9.7 (sensitivity 0.78; specificity 0.56; AUC 0.67). Patients with SUVmax ≤9.7 had a median PFS of 50.3 months, whereas those with SUVmax > 9.7 experienced a median PFS of 21.1 months (p < 0.001). Two-year PFS rates were 78.8% (95% CI 67.8–86.5) vs. 46.9% (95% CI 37.1–56.1) in the ≤9.7 vs. > 9.7 subgroups, respectively. The prognostic impact of SUVmax remained significant after adjusting for oligometastatic status, disease setting, and metastatic site. Conclusions: Baseline FDG-PET/CT appears to be a valuable biomarker for stratifying HER2-positive ABC patients treated with TPH into those likely to achieve long-term benefit versus those at higher risk of early progression. Prospective studies are warranted to validate these findings and refine patient selection for TPH in an era of rapidly evolving therapeutic options.