Hormone Receptor Status, HER2DX Score Predict Response to Neoadjuvant THP

Hormone receptor status and HER2DX pathologic complete response (pCR) scores may help identify patients with HER2-positive breast cancer who are more likely to respond to less intensive neoadjuvant chemotherapy, according to secondary findings from the CompassHER2-pCR trial (EA1181; NCT04266249) published in the Journal of Clinical Oncology.^1,2

Among 2141 patients who initiated neoadjuvant taxane, trastuzumab (Herceptin), and pertuzumab (Perjeta; THP), the overall pCR rate was 43.8%. Rates were higher among patients with HER2-positive/estrogen receptor (ER)-negative tumors than among those with ER-positive disease (63.7% vs 32.4%). A high HER2DX pCR score was also independently associated with a greater likelihood of pCR after adjustment for clinicopathologic factors and taxane type.

About CompassHER2-pCR

CompassHER2-pCR (NCT04266249) is a single-arm trial evaluating neoadjuvant THP in patients with clinical stage II to IIIA HER2-positive breast cancer.³ A total of 2175 patients are enrolled, including 781 with HER2-positive/ER-negative disease and 1394 with HER2-positive/ER-positive disease. Patients received 4 cycles of trastuzumab and pertuzumab with either weekly paclitaxel for 12 weeks or docetaxel every 3 weeks for 4 cycles, followed by surgery.

Investigators assessed clinicopathologic characteristics associated with pCR and evaluated HER2DX pCR scores using diagnostic biopsy samples from a representative subset of 569 patients. HER2DX is a genomic assay that integrates clinicopathologic characteristics, including tumor size and nodal status, with genomic features related to immune response, luminal differentiation, tumor cell proliferation, and ERBB2 expression. Its pCR likelihood score estimates the probability of achieving pCR following anti-HER2–based treatment.

Additional Findings

Higher pCR rates were observed in tumors with low ER expression, low or absent progesterone receptor (PR) expression, and HER2 immunohistochemistry (IHC) 3+ status. Patients treated with weekly paclitaxel also had higher pCR rates than those receiving docetaxel every 3 weeks.

Tumor stage was not broadly associated with response. T3 disease was associated with a lower pCR rate among patients with ER-negative tumors, whereas other tumor and nodal stage categories were not significantly associated with pCR.

The association between HER2DX scores and pCR was observed across hormone receptor subgroups. Among patients with ER-positive disease, pCR rates were 58% with high HER2DX scores and 18% with low scores. Among those with ER-negative disease, rates were 70% and 31%, respectively. These findings suggest that the score may provide additional information about treatment response beyond hormone receptor status alone.

Refining Patient Selection for Treatment De-escalation

The findings support further evaluation of clinical and molecular factors to identify patients who may be candidates for less intensive neoadjuvant treatment. The independent association between HER2DX pCR scores and response suggests that molecular profiling may complement established clinicopathologic factors when assessing the likelihood of pCR.

“These findings should help optimize risk stratification and treatment personalization for patients with HER2-positive breast cancer,” study authors Tung et al wrote.

However, pCR does not establish long-term disease control. The trial's primary end point is 3-year recurrence-free survival among patients achieving pCR, the data for which remain pending. These data will be important in determining whether the regimen provides durable disease control and in clarifying the potential role of response-associated factors in treatment selection.

REFERENCES

1. Tung N, Zhao F, DeMichele A, et al. 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. J Clin Oncol. Published online August 20, 2026. doi:10.1200/jco-25-02255

2. Major HER2+ breast cancer trial identifies factors associated with pathologic complete response to less intensive chemotherapy. News release. ECOG-ACRIN Cancer Research Group. October 6, 2026. Accessed October 9, 2026. https://tinyurl.com/mvf36d2b

3. CompassHER2-pCR: Decreasing Chemotherapy for Breast Cancer Patients After Pre-surgery Chemo and Targeted Therapy. ClinicalTrials.gov. Updated September 14, 2026. Accessed October 9, 2026. https://clinicaltrials.gov/study/NCT04266249