Purpose: Somatostatin receptor (SSTR) expression has been reported in estrogen receptor-positive (ER +) metastatic breast cancer (mBC) by pathology and immunohistochemistry studies. We aimed to investigate whether SSTR could be a viable target for PET imaging and potential theranostics in ER + mBC.

Methods: Thirty prospectively recruited patients with ER + mBC underwent PET/CT imaging with [F]FDG and [Ga]Ga-DOTATATE (within three weeks). Detection rates (per-patient, per-region), number of lesions detected, SUVmax values, Krenning scores, SSTR-FDG visual scores, and PET-based staging with both radiotracers were compared.

Results: [F]FDG and [Ga]Ga-DOTATATE PET/CT had similar per-patient detection rates (100% vs 96.7%, P = 1.0). Per-region and per-lesion analyses revealed comparable detection of local/breast lesions, nodal, and skeletal metastases. However, [F]FDG outperformed [Ga]Ga-DOTATATE in detecting visceral/other metastases (235 vs 128 lesions, P = 0.003). [Ga]Ga-DOTATATE resulted in a lower PET-based M-stage compared to [F]FDG in 10% of patients, although T-/N-stages were concordant in all patients. HER2- patients showed a trend of higher [Ga]Ga-DOTATATE lesional SUVmax values compared to the HER2 + sub-group (median 9.0 vs 3.8, P = 0.078). 3/30 (10%) participants had a patient-level Krenning score ≥ 3 ([Ga]Ga-DOTATATE uptake higher than liver background in majority of the lesions), potentially making them suitable for SSTR-targeted radionuclide therapy.

Conclusions: SSTR-targeted theranostics may represent a novel potential alternative in a subset of patients with ER + mBC. Its generalized applicability is limited by poor sensitivity for visceral metastases and significant inter-lesion heterogeneity. Future studies must identify how tumor subtype, proliferation, and prior systemic therapies impact SSTR expression levels in these patients to ensure meaningful clinical translation.

Clinical Trial Registration: Clinical Trials Registry-India: CTRI/2023/03/051025 (prospectively registered on 23.03.2023).

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http://dx.doi.org/10.1007/s10549-025-07651-4DOI Listing

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