A major prospective clinical trial has identified clinical and molecular characteristics that may help determine which patients with early-stage HER2-positive breast cancer are most likely to achieve a pathologic complete response (pCR) after a shorter, less intensive chemotherapy regimen.
The findings come from the ECOG-ACRIN Cancer Research Group’s CompassHER2-pCR trial (EA1181/NCT04266249) and were published in the Journal of Clinical Oncology on August 20, 2026. The results are also being featured in a JCO podcast with lead investigator Nadine M. Tung, MD.
12 Weeks of THP Evaluated
Patients with stage II-IIIA HER2-positive breast cancer commonly receive multi-agent chemotherapy together with HER2-targeted therapy before surgery. In the CompassHER2-pCR trial, however, patients received just 12 weeks of THP—a combination of a taxane chemotherapy drug with trastuzumab and pertuzumab.
The trial enrolled 2,175 patients, making it the largest prospective study evaluating 12-week neoadjuvant THP in stage II-IIIA HER2-positive breast cancer.
Among the 2,141 HER2-positive patients who started treatment, 43.8% achieved a pathologic complete response. A pCR was defined as having no invasive cancer remaining in the breast or lymph nodes at the time of surgery.
Patients who achieved pCR did not receive additional chemotherapy and continued dual HER2-targeted therapy to complete one year of treatment. Researchers are continuing to follow these patients to determine whether the approach can deliver favorable 3-year recurrence-free survival outcomes.
ER-Negative Tumors Showed Higher pCR Rates
The study found a substantial difference in response according to estrogen receptor (ER) status.
The pCR rate was 63.7% among patients with ER-negative disease, compared with 32.4% among patients with ER-positive disease.
Other clinical and pathological characteristics associated with a greater likelihood of achieving pCR included:
- ER-negative or low ER-expressing tumors
- Low or absent progesterone receptor expression
- HER2 IHC 3+ tumors
- Treatment with weekly paclitaxel
These findings suggest that routinely available tumor characteristics may help identify patients who are more likely to respond to a shorter chemotherapy regimen.
HER2DX Molecular Test Further Improved Prediction
Researchers also investigated whether molecular testing could provide additional information about treatment response.
Tumor samples from a representative group of 569 participants were analyzed using HER2DX, a molecular test developed specifically for HER2-positive breast cancer. The testing was performed centrally using a validated and standardized assay, with researchers blinded to clinical outcomes.
The results showed a major difference in pCR rates based on the HER2DX pCR score.
Patients with a high HER2DX pCR score had a 68% pCR rate, compared with only 19% among those with a low score—a difference of 49 percentage points.
The difference remained substantial when patients were analyzed according to ER status. In ER-positive disease, pCR occurred in 58% of patients with high scores versus 18% with low scores. In ER-negative disease, the corresponding rates were 70% versus 31%.
A high HER2DX pCR score remained independently associated with achieving pCR even after researchers adjusted for clinical and pathological characteristics and the type of taxane used.
Toward More Individualized Treatment
According to the researchers, the findings could contribute to a more individualized approach to treating HER2-positive breast cancer.
Rather than automatically exposing every patient to the same intensity of chemotherapy, combining clinical characteristics with molecular biomarkers may eventually help identify patients who are most likely to achieve a complete response with a shorter treatment approach.
However, the researchers emphasized that further evidence is needed before these factors can be routinely used to determine treatment intensity.
The most important remaining question is whether patients who achieve pCR after the 12-week THP regimen maintain favorable long-term outcomes. The ongoing CompassHER2-pCR study is specifically designed to evaluate survival outcomes, with 3-year recurrence-free survival as its primary endpoint.
Largest Prospective Study of Short-Course THP
CompassHER2-pCR is part of the CompassHER2 Program, which aims to use pathologic response to optimize treatment for patients with HER2-positive breast cancer.
The trial is a collaboration between the ECOG-ACRIN Cancer Research Group and the Alliance for Clinical Trials in Oncology, both of which are part of the National Clinical Trials Network.
The study is funded by the National Cancer Institute through the NCTN, with additional support from the Breast Cancer Research Foundation and Susan G. Komen.
