PSMA PET/CT shows uptake in half of metastatic triple-negative breast cancer patients
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Key Takeaway
Consider PSMA PET/CT investigational for mTNBC; small study shows heterogeneous uptake in 50% of patients.
This prospective single-center imaging study evaluated 20 patients with progressive metastatic triple-negative breast cancer (median age 53.5 years, median 3 prior systemic therapies) using [Ga]Ga-PSMA-11 PET/CT. The study assessed PSMA uptake patterns to evaluate the feasibility of potential PSMA-targeted radioligand therapy (RLT). No comparator imaging modality or treatment was reported.
On visual assessment, 50% of patients (10 of 20) showed PSMA uptake greater than healthy liver in most lesions. At the lesion level, 67% of FDG-avid target lesions (71 of 106) demonstrated quantitative PSMA positivity (SUVmax above liver). However, per-patient analyses revealed lower rates: only 35% of patients (7 of 20) had all target lesions above liver SUVmean, and 30% (6 of 20) had most lesions above this threshold. Heterogeneity was common, with 65% of patients (13 of 20) having at least one lesion below liver background. The scan identified brain metastases in 10% of patients (2 of 20).
Safety and tolerability data were not reported. Key limitations include the small sample size (n=20), single-center design, and lack of reported follow-up. The study did not test actual PSMA-targeted RLT treatment, only imaging feasibility. These results support further investigation of PSMA-targeted RLT in this biomarker-defined population but do not establish treatment efficacy. Clinical application requires validation in larger, multi-center trials with treatment outcomes.
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View Original Abstract ↓
PURPOSE: Radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) improves survival in metastatic castration-resistant prostate cancer. PSMA is also expressed in triple-negative breast cancer (TNBC), a subtype with limited treatment options. This prospective study assessed PSMA uptake on [Ga]Ga-PSMA-11 PET/CT in patients with metastatic TNBC (mTNBC) to evaluate the feasibility of PSMA-targeted RLT.
METHODS: This single-center prospective study enrolled patients with progressive mTNBC. Each patient underwent [F]FDG PET/CT followed by [Ga]Ga-PSMA-11 PET/CT. Visual PSMA positivity was defined as uptake greater than healthy liver in most lesions. For quantitative analysis, target lesions (TLs) ≥ 1.5 cm and PERCIST-measurable on FDG PET/CT were anatomically matched to PSMA PET/CT. SUVmax was measured and compared to liver background.
RESULTS: Twenty patients (median age 53.5 years; median 3 prior systemic therapies) were included. On visual assessment, 50.0% had PSMA uptake exceeding liver in most lesions. Quantitative analysis included 106 FDG-avid TLs; 67.0% showed PSMA SUVmax above liver. On a per-patient basis, 35.0% had all TLs and 30.0% had most TLs above liver SUVmean. However, 65.0% had at least one lesion below liver background, indicating heterogeneity. Higher PSMA uptake was associated with fewer prior treatments, prior immunotherapy, and low androgen receptor expression. PSMA PET/CT identified brain metastases in 10.0% of patients.
CONCLUSION: [Ga]Ga-PSMA-11 PET/CT revealed clinically relevant PSMA expression in a subset of mTNBC patients. These results support further investigation of PSMA-targeted RLT in this biomarker-defined population.
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