New Research Shows Pre-Operative THP Achieves pCR in 64% of Early-Stage HER2+ Breast Cancer Patients

Recent findings from a significant study indicate that pre-operative therapy using a regimen known as THP can lead to a pathologic complete response (pCR) in 64% of patients suffering from early-stage HER2-positive, estrogen receptor-negative (ER-) breast cancer. This promising result was shared at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, highlighting the potential benefits of a less intensive chemotherapy approach for these patients.

The study, conducted by the ECOG-ACRIN Cancer Research Group, evaluated a treatment protocol involving a combination of taxane chemotherapy and HER2-targeting agents, trastuzumab and pertuzumab. This treatment, referred to as THP, is already established as a standard for managing metastatic HER2+ breast cancer, but its application in early-stage cases is now being extensively explored.

Lead investigator Dr. Nadine M. Tung, a medical oncologist at Beth Israel Deaconess Medical Center, emphasized that the findings demonstrate a marked increase in pCR rates for early-stage HER2+ breast cancer, particularly among patients with ER-negative tumors. In contrast, patients with ER-positive tumors achieved a pCR rate of only 33%. Moreover, the study found that within the subset of ER-positive breast cancers, those with lower levels of ER expression were associated with higher pCR rates.

The CompassHER2 pCR trial, which is the first large-scale investigation of this treatment approach, enrolled a total of 2,175 participants from February 2020 to October 2023, despite interruptions caused by the COVID-19 pandemic. Notably, only 16 patients (0.7%) experienced disease progression during THP treatment, suggesting a strong initial efficacy for the regimen.

Patients who achieved a pCR after undergoing THP were not subjected to further chemotherapy but continued with HER2-directed antibodies post-surgery, along with radiation therapy and endocrine treatment if necessary. The primary goal of the trial is to evaluate the three-year recurrence-free survival rate, which will require more extended follow-up to ascertain.

The study also analyzed a subset of 569 patients through biopsies that employed the HER2DX pCR-score, a laboratory test that assesses tumor gene expression. This analysis identified several predictors of pCR, including:

• ER-negative status
• Lower ER expression (<=70%) in ER-positive tumors
• HER2 IHC score of 3+ compared to IHC 2+/ISH+
• Utilization of weekly paclitaxel instead of docetaxel administered every three weeks
• Higher HER2DX pCR scores regardless of ER status

Interestingly, the analysis did not reveal any correlation between the baseline clinical stage of the disease and pCR rates.

While THP is associated with some adverse effects, it is generally less toxic than traditional chemotherapy regimens that involve multiple drugs. Dr. Tung noted that the insights gained from this trial may assist healthcare providers in identifying patients with HER2+ breast cancer who could potentially avoid the harsher side effects of more intensive chemotherapy treatments.