Neoadjuvant chemotherapy plus dual HER2 blockade is more effective than endocrine therapy (ET) plus dual HER2 blockade in patients with hormone receptor (HR)-positive, HER2-positive breast cancer, according to research published in JAMA Oncology.

In this phase 2 study, the pathologic complete response (pCR) rate was significantly higher in patients who received paclitaxel plus trastuzumab and pertuzumab than in patients who received ET plus trastuzumab and pertuzumab.

The trial ( identifier: NCT03272477) included 207 patients with HR-positive, HER2-positive breast cancer. The median age of the cohort was 53 (range, 25-83) years, 58% of patients had cT2 to cT4 tumors, 28% had node-positive disease, 66% had stage II-III disease, and 43% had grade 3 tumors.

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The patients were randomly assigned to receive trastuzumab plus pertuzumab with either paclitaxel (n=107) or ET (n=100) for 12 weeks. ET consisted of tamoxifen, anastrozole, letrozole, or exemestane.

The primary endpoint was pCR. The pCR rate was 56.4% in the chemotherapy arm and 23.7% in the ET arm (odds ratio, 0.24; 95% CI, 0.12-0.46; P <.001).

In an exploratory analysis, HER2 expression was an independent predictor of pCR. Among patients with the highest HER2 expression, the pCR rate was 70.0% with chemotherapy and 55.6% with ET. Among patients with the lowest HER2 expression, the pCR rates were 20.0% with chemotherapy and 0.0% with ET.

Patients with a HER2-enriched subtype had higher pCR rates with chemotherapy and ET (60.8% and 34.8%, respectively) than patients with a luminal A/B subtype (40.7% and 3.9%, respectively).

Health-related quality of life remained stable throughout neoadjuvant treatment in the ET arm but decreased in the chemotherapy arm.

There were 23 serious adverse events (AEs) — 10 in the ET arm and 13 in the chemotherapy arm. There were 35 grade 3-4 AEs — 5 in the ET arm and 30 in the chemotherapy arm. The most common grade 3-4 AEs in the chemotherapy arm were diarrhea (4%) and infections (3%). 

Based on these results, the researchers concluded that paclitaxel plus trastuzumab and pertuzumab is a “universally applicable, efficacious, and well-tolerated standard regimen” for patients with intermediate- to high-risk, HR-positive, HER2-positive breast cancer.

Disclosures: This research was supported by Roche Pharma AG. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Gluz O, Nitz UA, Christgen M, et al. Efficacy of endocrine therapy plus trastuzumab and pertuzumab vs de-escalated chemotherapy in patients with hormone receptor–positive/ERBB2-positive early breast cancer: The neoadjuvant WSG-TP-II randomized clinical trial. JAMA Oncol. Published online May 11, 2023. doi:10.1001/jamaoncol.2023.0646