Molecular imaging demonstrates promise for predicting complete pathologic response in HER2-positive breast cancer

Molecular imaging with ⁶⁸Ga-HER2 PET/CT may provide an early, targeted measure of how well treatment is working in patients with HER2-positive breast cancer.

According to new research published in the October issue of The Journal of Nuclear Medicine, ⁶⁸Ga-HER2 PET/CT can detect changes in HER2-positive breast cancer after only two cycles of neoadjuvant treatment, giving physicians information that could support earlier discussions about subsequent treatment and surgical planning.

Limits of current response monitoring

HER2-positive tumors, which represent 20% to 25% of all breast cancer cases, are aggressive and associated with poorer outcomes. Neoadjuvant therapy is often given to patients before surgery in an attempt to shrink the tumor. Currently, physicians have limited ability to know early on whether a patient is responding well to this presurgical therapy.

“Ultrasound offers cost-effective assessment of lymph nodes but is operator-dependent; mammography detects calcifications well but poorly measures tumor size; MRI, the standard neoadjuvant therapy monitoring modality, faces challenges in differentiating between fibrosis and tumors; and clinical examination, although rapid, lacks accuracy,” said Yunjiang Liu, M.D., Ph.D., a professor at the Fourth Hospital of Hebei Medical University and Hebei Provincial Tumor Hospital in Shijiazhuang, China. “This trade-off between accuracy and timeliness drives the need for novel approaches.”

Tracking HER2 changes during treatment

Recently, ⁶⁸Ga-HER2 PET/CT has emerged as a promising molecular imaging modality for the noninvasive, whole-body visualization of HER2 expression. To further evaluate its potential, researchers conducted a prospective study to assess the ability of ⁶⁸Ga-HER2 PET/CT to predict pathologic response to neoadjuvant therapy in patients with HER2-positive breast cancer.

The study included 44 patients with biopsy-confirmed HER2-positive breast cancer. All patients received at least four cycles of neoadjuvant therapy, although the specific treatment regimens varied, followed by surgery. ⁶⁸Ga-HER2 PET/CT was performed at baseline, after the second therapy cycle and before surgery. Researchers measured changes in tracer uptake in primary breast tumors and lymph nodes across the imaging time points and analyzed whether these changes were associated with pathologic complete response.

The baseline scan did not distinguish patients who would or would not achieve a pathologic complete response. However, after only two treatment cycles, a substantial reduction in tracer uptake in the primary breast tumor was associated with a pathologic response at surgery. Patients whose primary tumor tracer uptake decreased by at least 61% after the second treatment cycle had an 85% rate of pathologic complete response, compared with 38% among patients whose uptake decreased by less than 61%.

Clinical use needs further validation

“These findings provide preliminary prospective evidence that changes in HER2-targeted tracer uptake can predict treatment response at a very early stage,” said Xinming Zhao, M.D., Ph.D., director of the Department of Nuclear Medicine at the Fourth Hospital of Hebei Medical University and Hebei Provincial Tumor Hospital. “For patients, the potential importance is that treatment response may be assessed much earlier. If future studies confirm our findings, imaging could provide earlier information to support discussions about alternative treatment strategies or surgical timing.”

The authors noted that the study was limited by its small sample size, single-center design and variation in neoadjuvant treatment regimens. The study was designed to evaluate diagnostic performance and did not test whether changing treatment on the basis of PET/CT findings improves outcomes.

Provided by
Society of Nuclear Medicine and Molecular Imaging

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