Editor’s Note: De-escalation and precision tailoring of neoadjuvant therapy have become major trends in the management of HER2-positive early breast cancer, yet accurately predicting pathological response at an early stage remains a key clinical challenge.
At the 2025 San Antonio Breast Cancer Symposium (SABCS), Professor Liu Yunjiang and colleagues from The Fourth Hospital of Hebei Medical University presented results from a prospective study (Abstract No. PS1-06-30) investigating the value of a novel tracer-based imaging modality—⁶⁸Ga-HER2 PET/CT—for predicting pathological response to neoadjuvant therapy in HER2-positive breast cancer.
By dynamically monitoring changes in tracer uptake before and during treatment, the study successfully established early imaging thresholds predictive of pathological complete response (pCR). These findings provide important evidence for individualized treatment decisions and may help move neoadjuvant response assessment toward a more precise, biology-driven era. Oncology Frontier invited Professor Liu to introduce and discuss this research.
**Q1
Oncology Frontier:** Your study prospectively applied the novel tracer ⁶⁸Ga-HER2 PET/CT to predict response to neoadjuvant therapy in HER2-positive breast cancer. What initially motivated you to choose this imaging approach? Compared with conventional imaging modalities, what theoretical advantages or potential clinical value does ⁶⁸Ga-HER2 PET/CT offer—particularly in assessing response to HER2-targeted therapy?
Professor Liu Yunjiang: Neoadjuvant therapy is an essential treatment strategy in breast cancer, especially for patients with more advanced disease or tumors that are highly treatment-sensitive. It also serves as an in vivo drug-sensitivity testing platform, which is particularly important for HER2-positive and triple-negative breast cancer. Patients who achieve pathological complete response (pCR) generally have better long-term outcomes, whereas those who do not achieve pCR often require treatment intensification afterward.
Traditional methods for evaluating response to neoadjuvant therapy—such as ultrasound, CT, MRI, and even ¹⁸F-FDG PET/CT—all have limitations. Their assessments do not always align well with pathological pCR. Meanwhile, antibody–drug conjugates (ADCs) are rapidly evolving, and ⁶⁸Ga-HER2 PET/CT is based on a similar principle: it uses an anti-HER2 antibody labeled with the radionuclide ⁶⁸Ga.
This approach specifically targets HER2-positive breast cancer and is theoretically more precise in reflecting tumor functional status and cellular-level tracer uptake. Our goal in conducting this study was to evaluate whether ⁶⁸Ga-HER2 PET/CT could reliably predict pathological response to neoadjuvant therapy in HER2-positive breast cancer.
From our initial experience, the tracer demonstrated good safety, with no treatment-related toxicities observed. It was also specifically taken up by HER2-positive tumors, clearly delineating tumor lesions. Importantly, ⁶⁸Ga-HER2 PET/CT was able to detect occult distant micrometastases that were not identified by CT or other conventional imaging modalities. This capability was a key motivation for undertaking the study.
**Q2
Oncology Frontier:** Could you walk us through the main findings of this study?
Professor Liu Yunjiang: Previous studies have suggested that ⁶⁸Ga-HER2 PET/CT can capture early changes in tracer uptake during neoadjuvant therapy and may have potential for predicting pCR. In our exploratory study, we initially enrolled 45 patients. One patient was excluded after liver metastases were detected during follow-up, leaving 44 patients for final analysis, including both HER2-positive and HR+/HER2+ cases.
Patients underwent ⁶⁸Ga-HER2 PET/CT at three time points:
- Before neoadjuvant therapy (PET1),
- After completion of the second treatment cycle (PET2),
- Preoperatively (PET3).
The maximum standardized uptake value (SUVmax) of the primary tumor and involved lymph nodes was measured. Changes in SUVmax were calculated as follows:
- ΔSUVmax₁ = (SUVmax at PET2 − SUVmax at PET1) / SUVmax at PET1 × 100%
- ΔSUVmax₂ = (SUVmax at PET3 − SUVmax at PET1) / SUVmax at PET1 × 100%
Overall, 70.45% of patients (31/44) achieved pCR, while 29.55% were classified as non-pCR. No significant differences in pCR rates were observed according to age at diagnosis, menopausal status, clinical stage, ER expression, PR expression, Ki-67 index, neoadjuvant regimen, type of breast surgery, or axillary management. In contrast, HER2 status showed a statistically significant association with pCR (P = 0.025).
At baseline (PET1), there was no significant difference in primary tumor SUVmax between the pCR and non-pCR groups (3.76 ± 1.97 vs 3.79 ± 2.71, P = 0.349). However, at both subsequent time points, the pCR group demonstrated significantly lower SUVmax values:
- PET2: 0.45 ± 0.71 vs 2.01 ± 2.36 (P = 0.008)
- PET3: 0.12 ± 0.39 vs 1.67 ± 2.94 (P = 0.014)
The optimal cut-off values for predicting pCR were:
- Primary tumor SUVmax ≤ 1.15 at PET2 (AUC = 0.738),
- SUVmax ≤ 0.50 at PET3 (AUC = 0.735),
- Absolute ΔSUVmax reduction ≥ 61.14% at PET2 (AUC = 0.742),
- Absolute ΔSUVmax reduction ≥ 71.63% at PET3 (AUC = 0.743).
Using PET2-based SUVmax and ΔSUVmax thresholds to identify treatment-sensitive patients, the pCR rate reached 84.62%, which was 14.17% higher than the overall pCR rate without this imaging-guided assessment.
This finding has clear clinical implications: insufficient early decline in tracer uptake may indicate resistance to the current regimen, prompting clinicians to adjust treatment in a timely manner and potentially enabling more patients to achieve pCR.
**Q3
Oncology Frontier:** Your study introduces a promising functional imaging tool for predicting response to neoadjuvant therapy in HER2-positive breast cancer. What key advice would you offer to clinicians interested in conducting similar translational research? And what further validation steps or challenges must be addressed before this technology can be widely adopted in routine clinical practice?
Professor Liu Yunjiang: Our exploratory study has demonstrated encouraging preliminary value, and we are now advancing a phase III clinical trial. One of its core objectives is to validate the ability of ⁶⁸Ga-HER2 PET/CT to predict pCR early during treatment.
If, after two treatment cycles, SUVmax decreases below 1.15 or declines by more than 60% from baseline, the patient is highly likely to achieve pCR. Conversely, failure to meet these thresholds suggests that treatment modification may be necessary.
Similarly, when ⁶⁸Ga-HER2 PET/CT is repeated at the end of neoadjuvant therapy, prior to surgery, a SUVmax below 0.5 or a reduction of more than 70% from baseline predicts pCR with a sensitivity exceeding 95%. This allows clinicians to assess, even before surgery, whether pCR has likely been achieved—an insight with major implications for surgical planning.
When combined with biopsy and other comprehensive assessments, patients predicted to have achieved pCR may be candidates for breast-conserving surgery, omission of axillary lymph node dissection, or sentinel lymph node biopsy alone, in line with current trends toward less extensive surgery. Such strategies could significantly improve quality of life and reduce physical and psychological burden.
These are key objectives of our ongoing phase III trial. I believe that, with further validation, ⁶⁸Ga-HER2 PET/CT has strong potential to be integrated into routine clinical practice as a precision tool for evaluating neoadjuvant treatment response in HER2-positive breast cancer.
Professor Liu Yunjiang
