HER2-positive tumors account for 20 to 25 percent of all breast cancer cases and are among the most aggressive forms of the disease, associated with poorer outcomes when not effectively treated. Neoadjuvant therapy is frequently administered before surgery with the goal of shrinking the tumor, sometimes to the point where surgeons find no residual invasive cancer at all—a result known as pathologic complete response, which carries important prognostic weight. The problem, according to the researchers behind the new study, is that the tools currently used to monitor treatment response each fall short in some way.

“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, MD, PhD, 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.”

That is where molecular imaging enters the picture. 68Ga-HER2 PET/CT uses a radioactive tracer engineered to bind specifically to HER2 receptors on the surface of cancer cells, allowing physicians to visualize HER2 expression throughout the entire body noninvasively. Unlike anatomical imaging, which measures the size of a tumor, molecular imaging measures biological activity—how much of the HER2 target is actually present and accessible. When treatment begins to work, HER2 expression and tumor metabolism can change before the tumor itself measurably shrinks, potentially offering an earlier window into therapeutic success or failure.

To test this concept rigorously, the research team conducted a prospective study of 44 patients with biopsy-confirmed HER2-positive breast cancer. Every patient received at least four cycles of neoadjuvant therapy, though the specific regimens varied from patient to patient, followed by surgery. The researchers performed 68Ga-HER2 PET/CT scans at three time points: at baseline before treatment began, after the second therapy cycle, and again before surgery. They then measured how tracer uptake in the primary breast tumors and in lymph nodes changed across these imaging sessions and analyzed whether those changes correlated with pathologic complete response when the surgical specimens were examined under the microscope.

The results were striking in one respect and sobering in another. The baseline scan, performed before any treatment, did not distinguish between patients who would go on to achieve a pathologic complete response and those who would not. But after only two cycles of therapy, a clear signal emerged. Patients whose primary tumor tracer uptake dropped by at least 61 percent after the second treatment cycle had an 85 percent rate of pathologic complete response at surgery. Among patients whose uptake fell by less than that threshold, the complete response rate was just 38 percent. In other words, a single early scan nearly doubled the predictive separation between responders and non-responders.

The imaging findings from a representative case illustrate the principle vividly. At baseline, one patient’s scan showed a soft-tissue lesion measuring approximately 2.3 by 2.2 centimeters in the upper outer quadrant of the left breast, with marked radiotracer uptake and a maximum standardized uptake value of 10.1—a measure of how intensely the tracer accumulated in the tumor. At the end of the second treatment cycle, the residual lesion measured approximately 2.2 by 1.0 centimeters, but crucially, no abnormal radiotracer accumulation remained. By the preoperative scan, the lesion had shrunk further to approximately 2.0 by 0.6 centimeters, again with no abnormal tracer uptake detected. The biological signal had vanished well before the anatomical lesion did.

“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, MD, PhD, 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 clinical implications could be substantial. If an early 68Ga-HER2 PET/CT scan shows that a patient’s tumor is not responding—tracer uptake remaining stubbornly high after two cycles—physicians could consider switching to an alternative treatment strategy sooner, or move directly to surgery rather than continuing a regimen that appears ineffective. Conversely, patients showing a dramatic drop in uptake could proceed with confidence that their current therapy is working. This kind of early, biologically grounded feedback addresses precisely the trade-off that Liu described: the existing modalities are either accurate but slow, or fast but imprecise.

The authors are careful to note the limitations of their work. The study was small, conducted at a single center, and included variation in neoadjuvant treatment regimens among patients. Moreover, the study was designed to evaluate diagnostic performance only—it did not test whether actually changing treatment based on PET/CT findings improves patient outcomes, which would require a different kind of trial. Those caveats mean the 61 percent uptake-reduction threshold and the response rates reported here should be considered preliminary rather than definitive. Still, as a prospective study with serial imaging and surgical confirmation, it provides some of the strongest evidence to date that HER2-targeted molecular imaging can serve as an early biomarker of treatment response. Larger, multicenter trials will be needed to validate the findings and determine whether early 68Ga-HER2 PET/CT can genuinely change the course of care for patients with this aggressive form of breast cancer.

Subject of Research: Using 68Ga-HER2 PET/CT molecular imaging to predict pathologic complete response in HER2-positive breast cancer during neoadjuvant therapy

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

Article References: Molecular imaging demonstrates promise for predicting complete pathologic response in HER2-positive breast cancer. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: HER2-positive breast cancer, 68Ga-HER2 PET/CT, molecular imaging, neoadjuvant therapy, pathologic complete response, PET imaging, radiotracer, breast cancer treatment, nuclear medicine, treatment response prediction, oncology, The Journal of Nuclear Medicine