FEATURED , Research , Breast Cancer

Alan Stolier, MD/


PSMA in Breast 1

Editorial comment: It has not likely to go unnoticed that in the last few weeks, the FDA gave approval for 68 Ga-PSMA-11 PET scans for detection of subclinical disease in prostate cancer.

Staging of prostate cancer is usually done with CT, MRI, and bone scans which suffer from low sensitivity. Gallium tagged prostate specific membrane antigen (PSMA) benefits from being a low molecular size and that over the last 4 years a substantial amount of data has accrued supporting its use and FDA approval in initial staging in intermediate to high grade prostate cancer as well as in those with a biochemical recurrence. The detection rate for PSAs < 2.o was 64%. For values of 2.0-5.0, the detection rate was 89% whereas for values > 5 it was 95%. Even for PSAs of <0.2, several papers reported detection rates of 40%! It occurred to us that should PSMA also be detectable in breast cancer, 68 Ga-PSMA-11 PET may be a useful tool in extent of disease evaluation prior to surgery and post treatment evaluation, potentially with rising tumor markers. A recent study in 2013 by Wernicke et al. from Weill Cornell Medical examined breast cancers for the presence and detection of PSMA.

Wernicke et al. found that PSMA was indeed expressed in breast cancer. In a large cohort of 106 patients, they found that PSMA was expressed only in the breast tumor microvessels. Tumor microvessels in 90 of 92 cases studied (98%) were found to express PSMA. Normal breast parenchymal cells and carcinoma cells were PSMA-negative in all cases. Neovascular PSMA expression levels appear to differ among different tumor types. Their data indicated that PSMA expression in the neovasculature of primary breast cancers (74%) as well as (distant) metastatic disease (100%) is largely restricted to endothelial cells within the pathologically defined tumor area. This is consistent with prior experiences with gastric, colorectal, and head and neck cancers.

The authors also noted that cancers with poor prognostic factors, such as ER/PR negativity, and high Ki67 had significantly higher PSMA expression. If confirmed, this may be valuable in patient selection for evaluation of metastatic disease prior to definitive surgery. In one patient they found the same degree of PSMA expression in both the metastatic disease and primary tumor. If consistent going forward, this would allow for evaluation of PSMA expression in the primary tumor, suggesting the use of 68Ga-PSMA-11 PET -11 PET for extent of disease workup as well as tagging the 68Ga-PSMA-11 PET with chemotherapy or radiation agent for exquisite, targeted therapy.

This topic has not been laid to rest. In a more recent study from Germany, Kasoha et al. studied 70 breast cancers for PSMA expression. These researchers found PSMA expression in tumor cells in 72% of patients studied and in 46% of tumor associated neovasculature. They also found that 75% of the 12 cases of distant metastasis expressed PSMA. In fact, they found that distant metastases had significantly stronger staining I tumor neovasculature than the primary tumor. Overall, they found that PSMA staining was more intense in tumor-associated neovascular than in metastatic tumor cells (see image above).

In summary, PSMA appears to have a propensity for the endothelial cells in breast cancer neovasculature. As a result, , 68Ga-PSMA-11 PET may have utility in breast cancer patients in 2 circumstances. First, as an extent of disease workup in patients with high-grade or locally advanced breast cancer. And secondly, as part of the workup for chemical recurrence with elevated breast cancer markers.

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