Improved staging of lobular breast cancer with novel amino acid metabolic
and tumor neovasculature receptor imaging
Project Summary / Abstract
Invasive lobular breast cancer (ILC) accounts for approximately 10-15% of breast malignancies and has an
underlying metastatic rate of up to 43%. ILC has discohesive growth making metastasis difficult to visualize
with conventional imaging modalities such as computed tomography (CT), bone scan, and magnetic
resonance imaging (MR). Suboptimal imaging adversely impacts accurate staging upon which therapeutic
decisions are based. While fluorodeoxyglucose (FDG) PET has been shown to clinically upstage patients with
locally advanced IDC, this is not so with ILC, which has been described as “initially indolent but slowly
progressive”. There are no accurate imaging techniques for staging ILC. Our goal is to address an
unmet public health need by improved staging of ILC, specifically detection of metastatic disease.
Amino acid transporters are upregulated in breast cancer cells. We and others have successfully imaged
breast cancer with fluciclovine (18F) PET, an FDA approved synthetic amino acid radiotracer originally
developed at Emory for imaging of cerebral glioma and prostate cancer. In exploratory studies conducted at
Emory and Memorial Sloan Kettering in 39 women with breast cancer (13 patients with ILC), fluciclovine PET
demonstrated promising results in detection of ILC in primary tumors and locoregional metastases. Distant
disease was not studied.
There is emerging data that imaging with prostate specific membrane antigen (PSMA) PET may improve
detection of breast cancer, including ILC. Prostate-specific is actually a misnomer as PSMA receptors are
upregulated in tumor neovasculature in many cancers including breast cancer. PSMA targeting of lobular
breast cancer for more effective staging has been strongly encouraged by experts in the field.
We hypothesize that metabolic imaging with amino acid transporter PET will improve staging of
ILC, particularly for distant metastases, compared to conventional imaging. We also hypothesize that
receptor directed PSMA imaging of tumor associated neovasculature in ILC will reveal unique
information to complement metabolic interrogation with fluciclovine PET.
To test these hypotheses with the highest scientific rigor, we propose an early phase trial with fluciclovine
and PSMA PET strategies centered on detection of metastasis in patients with advanced ILC using histology
as the gold standard. As an exploratory aim, we will also correlate the occurrence of circulating tumor DNA
(ctDNA) mutations including PIK3CA, ESR1, HER2, and AKT1 with presence of metastasis and tumor burden.
We expect this study will generate sufficient preliminary data to determine feasibility for a definitive NIH
sponsored multi-center trial developing more accurate staging techniques to alter current practice for imaging