The Journal of Clinical Oncology recently published significant secondary results from the ECOG-ACRIN Cancer Research Group’s CompassHER2-pCR clinical trial (EA1181, NCT04266249). The findings will be highlighted in a podcast on Thursday, October 8, 2026, featuring lead investigator Nadine M. Tung, MD . The results help identify which early-stage HER2-positive (HER2+) breast cancers may be most likely to respond to less intensive chemotherapy than the current standard.
Patients with early-stage HER2+ breast cancer usually receive multi-agent chemotherapy with anti-HER2 drugs before surgery. In CompassHER2-pCR, 2,175 patients with stage II-IIIA disease instead received 12 weeks of a treatment called THP, which combines a single chemotherapy drug (taxane) with two HER2-targeted drugs (trastuzumab and pertuzumab).
Those who had a pathologic complete response (pCR), defined as no invasive cancer in the breast or lymph nodes at surgery, received no additional chemotherapy and continued dual HER2 blockade to complete one year of treatment. The trial is continuing to follow patients with a pCR to assess 3-year recurrence-free survival, its primary endpoint.
“Our goal is not simply to give patients less treatment. It is to determine whether we can give each patient the treatment they need to achieve the best possible outcome while avoiding chemotherapy that may not be necessary. The recurrence-free survival results will be critical,” said Dr. Tung, a medical oncologist at Beth Israel Deaconess Medical Center in Boston.
Overall, among 2,141 HER2+ patients who began treatment, 43.8% had a pCR. The rate was 63.7% among patients with estrogen receptor-negative (ER-) breast cancer and 32.4% among those with ER-positive (ER+) disease. Characteristics associated with a greater likelihood of pCR included ER-negative or low ER-expressing tumors, low or no progesterone receptor expression, HER2 IHC 3+ tumors, and weekly paclitaxel treatment.
“These results show that a substantial proportion of patients can have a pathologic complete response after just 12 weeks of THP, particularly those with HER2-positive, ER-negative breast cancer. The more accurately we can identify patients who are likely to benefit, the better we may be able to determine who could be treated with less intensive and more individualized chemotherapy,” said Dr. Tung.
CompassHER2-pCR is the largest prospective trial of 12-week neoadjuvant THP in stage II-IIIA HER2+ breast cancer. It is also the only trial in this setting powered to evaluate survival outcomes.
Researchers also evaluated HER2DX, a molecular test designed specifically for HER2+ breast cancer. Diagnostic tumor samples from a representative subset of 569 participants were centrally analyzed using the validated and standardized HER2DX test, blinded to clinical outcomes.
The pCR rate was 68% in the group with high HER2DX pCR scores, compared with 19% in those with low scores, an observed difference of 49 percentage points. The high-versus-low difference exceeded 30 percentage points in both ER-positive (58% vs 18%) and ER-negative (70% vs 31%) disease. A high HER2DX pCR score remained independently associated with pCR after adjustment for clinical and pathologic factors and type of taxane.
“Together, the findings suggest that combining information routinely available about a patient’s tumor with molecular biomarkers may improve the ability to identify patients most likely to have pCR with a less intensive chemotherapy approach,” said Dr. Tung. “Further research is needed to determine how these factors should be used to guide treatment decisions.”
The paper, “ Pathologic Complete Response (pCR) Rate and Predictors of Response to Taxane, Trastuzumab, and Pertuzumab in HER2‑Positive Breast Cancer: Secondary Analyses of EA1181/CompassHER2 pCR ,” was published August 20, 2026, in the Journal of Clinical Oncology (DOI: 10.1200/JCO-25-02255).
The National Cancer Institute (NCI), part of the National Institutes of Health, is funding the study through its National Clinical Trials Network (NCTN). ECOG-ACRIN is leading and conducting the study, with participation from other NCTN groups. The Breast Cancer Research Foundation and Susan G. Komen provided additional funding.
About the CompassHER2 Program
This trial is part of the CompassHER2 (Comprehensive Use of Pathologic Response Assessment to Optimize Therapy in HER2-Positive Breast Cancer) Trial Program. It is a collaboration between the ECOG-ACRIN Cancer Research Group and the Alliance for Clinical Trials in Oncology, two cooperative research groups in the NCTN.
About ECOG-ACRIN
The ECOG-ACRIN Cancer Research Group is one of the world’s leading scientific organizations, known for innovative multicenter clinical trials involving adults with cancer or at risk of developing it. Its expansive membership includes over 1,400 hospitals and cancer centers across the United States and around the world, involving nearly 21,000 researchers and advocates. Its research is funded primarily by the US National Institutes of Health through its National Cancer Institute. To learn more, visit www.ecog-acrin.org , follow us on X , Facebook , LinkedIn , YouTube , Instagram , and Bluesky , or call 215-789-3631.
Journal of Clinical Oncology
Randomized controlled/clinical trial
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Pathologic Complete Response (pCR) Rate and Predictors of Response to Taxane, Trastuzumab, and Pertuzumab in HER2‑Positive Breast Cancer: Secondary Analyses of EA1181/CompassHER2 pCR
20-Aug-2026