Tumor Markers Help Predict Response to Less Intensive HER2+ Chemotherapy

HER2-positive breast cancer is commonly treated before surgery with multiagent chemotherapy and HER2-targeted drugs. In early-stage disease, a key challenge is identifying which tumors may respond well enough to allow treatment de-escalation. Pathologic complete response (pCR), defined as no invasive cancer in the breast or lymph nodes at surgery, is an important measure of response. New findings show that tumor markers and molecular testing may help identify patients likely to benefit from a less intensive approach.

ECOG-ACRIN Cancer Research Group investigators evaluated the CompassHER2-pCR clinical trial in patients with stage II–IIIA HER2-positive breast cancer. The treatment approach, known as THP, combined a single taxane chemotherapy drug with two HER2-targeted agents, trastuzumab and pertuzumab, for 12 weeks before surgery. Patients who achieved pathologic complete response (pCR) received no additional chemotherapy and continued dual HER2 blockade to complete one year of treatment.

Image: The treatment approach combines taxane chemotherapy with trastuzumab and pertuzumab for 12 weeks before surgery. Patients achieving pCR receive no further chemotherapy and continue dual HER2 blockade for one year (Image Credit: Shutterstock)

Among 2,141 HER2-positive patients who began treatment, 43.8% achieved pCR. Response rates differed by hormone receptor status, reaching 63.7% in patients with estrogen receptor-negative (ER-) disease and 32.4% in those with estrogen receptor-positive (ER+) disease. Tumor characteristics associated with a greater likelihood of pCR included ER- or low estrogen receptor-expressing tumors, low or absent progesterone receptor expression, HER2 immunohistochemistry 3+ status, and treatment with weekly paclitaxel.

Researchers also evaluated HER2DX, a molecular test developed specifically for HER2-positive breast cancer, to determine whether it could further identify patients likely to respond to the de-escalated regimen. Diagnostic tumor samples from a representative subset of 569 participants were centrally analyzed using the validated and standardized HER2DX test, with results blinded to clinical outcomes. The pCR rate was 68% among tumors with high HER2DX pCR scores, compared with 19% among those with low scores. The difference between high and low scores exceeded 30 percentage points in both ER+ and ER-  disease.

The secondary results were published in the Journal of Clinical Oncology. CompassHER2-pCR is described as the largest prospective trial of 12-week neoadjuvant THP in stage II–IIIA HER2-positive breast cancer and the only trial in this setting powered to evaluate survival outcomes. The trial is continuing to follow patients with pCR to assess three-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 Nadine Tung, medical oncologist at Beth Israel Deaconess Medical Center in Boston.

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ECOG-ACRIN Cancer Research Group