Detection of HER2-Positive Metastases in Patients with HER2-Negative Primary Breast Cancer

Posted May 19, 2017

Gary A. Ulaner, M.D., Ph.D., Memorial Sloan Kettering Cancer Center

Gary A. Ulaner, M.D., Ph.D., Memorial Sloan Kettering Cancer Center
Gary A. Ulaner, M.D., Ph.D.
Memorial Sloan Kettering Cancer Center

The presence or absence of specific receptors on tumor cells influences treatment plans for women diagnosed with breast cancer. For example, human epidermal growth factor receptor 2 (HER2)-targeted therapies are given to patients diagnosed with HER2-positive breast cancer. Women who progress to metastatic disease are usually offered treatment based on the receptor status of their primary disease. For this reason, a majority of metastatic breast cancer patients diagnosed with a HER2-negative primary malignancy do not receive HER2-targeted treatments.

In recent years, research has shown that HER2 expression at metastatic sites can differ from HER2 expression at the primary site in breast cancer patients, highlighting the heterogeneity of tumors and illustrating important decision-making in using the appropriate targeted therapies for metastatic disease. With support from a Fiscal Year 2013 Breast Cancer Research Program Breakthrough Award, Dr. Ulaner and a team of researchers at Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College investigated the use of 89Zr-trastuzumab PET/CT to detect HER2-positive metastatic lesions in patients with HER2-negative primary breast cancer. Upon detection and confirmation of HER2-positive lesions, treatment plans were altered to incorporate HER2-targeted therapies.

In a prospective clinical trial published in the Journal of Nuclear Medicine, Dr. Ulaner and his team showed that 89Zr-trastuzumab could detect HER2-positive metastases in patients diagnosed with HER2-negative primary tumors, and these patients responded to HER2-targeted therapies. Nine patients were enrolled in Dr. Ulaner’s study, all of whom had been diagnosed with estrogen receptor-positive HER2-negative primary tumors and had at least one site of metastatic disease. HER2-negative status of their primary disease was confirmed prior to 89Zr-trastuzumab imaging for potential HER2-positive metastatic foci. Five patients showed evidence of HER2-positive metastases, and image-guided biopsy results confirmed HER2-positive status in two patients. Both patients received trastuzumab, pertuzumab, and paclitaxel, as well as concomitant taxane antimitotic chemotherapy. Their response to treatment was observed in 18F-FDG PET/CT imaging. One patient showed complete response after two months of treatment, where CT scans showed resolution of previously enlarged lymph nodes and the absence of new lesions. The second patient showed decreased size and avidity of metastases after three months of treatment.

This proof-of-concept clinical trial conducted by Dr. Ulaner and his team highlights the impact of HER2-targeted imaging on identifying patients that could benefit from systemic HER2-targeted therapy. In addition, using funds from this award, Dr. Ulaner has developed a second radiotracer that has just entered a Phase I clinical trial ( to try to improve the accuracy of the imaging procedure to diagnosis of HER-2 positive metastatic disease. Targeted imaging may help physicians create individualized therapy to overcome tumor heterogeneity and improve patient outcomes. This study lays the groundwork for future HER2-targeted imaging techniques, as well as larger clinical studies evaluating the benefit of screening patient populations for administration of HER2-targeted therapeutics.

Consortium Group Photo
Left: MIP image from a 89Zr-pertuzumab PET demonstrating avid intracranial foci.

Left middle: Axial fused 89Zr-pertuzumab PET/CT through the brain demonstrating foci localize to brain parenchyma.

Right middle: Axial T1 post gadolinium MR demonstrate enhancing brain metastases, which correspond to the 89Zr-pertuzumab foci on PET/CT.

Right (optional): Axial 89Zr-pertuzumab PET through the brain demonstrating foci.


Ulaner GA, Hyman DM, Ross DA, et al. 2016. Detection of HER2-positive metastases in patients with HER2-negative primary breast cancer using 89Zr-trastuzumab PET/CT. J Nucl Med 57:1523-1528.


Public and Technical Abstracts: Could HER2 Heterogeneity Open New Therapeutic Options in Patients with HER2- Primary Breast Cancer?

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Last updated Monday, January 3, 2022