Recent research has found that somatostatin receptor type 2 (SSTR2) is overexpressed in certain types of breast cancer, particularly in estrogen receptor (ER) positive tumors. This discovery paves the way for the potential use of the well-established DOTATATE theranostics to improve the diagnosis and treatment of this type of breast cancer. A study involving both preclinical and phase 2 clinical trials demonstrated highly promising results.

The overexpression of somatostatin receptors (SST) in neuroendocrine tumors (NETs) is well established. This characteristic has been leveraged in nuclear medicine to develop one of the most successful therapies for NETs: ¹⁷⁷Lu-DOTATATE. This therapy uses the somatostatin analogue DOTATATE to deliver targeted radiation — specifically, the beta-emitter Lutetium-177 — directly to cancer cells.

The most recent discovery has shown that certain types of breast cancer, particularly estrogen receptor (ER) positive tumors, also exhibit high densities of SST, specifically somatostatin receptor type 2 (SSTR2). The research consisted of two parts: a preclinical study using tissue samples and a phase 2 clinical trial involving 30 patients. The preclinical study revealed that 51% of ER-positive breast cancer samples expressed SSTR2, compared to only 18% of ER-negative samples. In the clinical trial, DOTATATE PET/CT scans identified high SSTR2 levels in 30% of the participants.

One heavily pretreated patient with metastatic ER-positive breast cancer showing high SSTR2 expression underwent ²²⁵Ac-DOTATATE therapy (using the more potent alpha-emitter Actinium-225 instead of Lutetium-177). Remarkably, the therapy resulted in a near-complete response.

This discovery has the potential to revolutionize breast cancer treatment — the most prevalent cancer among women — similar to how PSMA-targeted therapies transformed prostate cancer treatment.

Recent advancements in applying theranostics to diagnose and treat breast cancer have largely centred around fibroblast activation protein inhibitor (FAPi). While FAPi-based diagnostics have proven very effective, the therapeutic application is still being optimized. Scientists are constantly churning out new ligands that would remain coupled to cancer-associated fibroblast (CAF) cells long enough to achieve optimal therapeutic outcomes. Some have tended to get washed out a touch too quickly. For the moment, DOTATATE is a well-established and proven treatment method that targets cancer cells directly and has been in use for many years.

We have long been offering DOTATATE theranostics to NET patients and are now thrilled to potentially extend this highly effective therapy, known for its minimal side effects, to female patients with breast cancer as well.