Assay Prediction of pCR in Patients With HER2-Positive Breast Cancer Treated With Neoadjuvant Paclitaxel, Trastuzumab, and Pertuzumab

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In an analysis reported in JAMA Oncology, Waks et al found that the HER2DX assay performed well in predicting the likelihood of pathologic complete response (pCR) in patients with early HER2-positive breast cancer receiving de-escalated neoadjuvant treatment with paclitaxel, trastuzumab, and pertuzumab.

Study Details

In the study, the HER2DX assay was used in pretreatment tumor biopsy samples from 80 of 97 patients in the phase II DAPHNe trial with newly diagnosed stage II to III disease; patients were treated with neoadjuvant paclitaxel weekly for 12 weeks plus trastuzumab and pertuzumab every 3 weeks for four cycles. The primary outcome measure was the ability of the HER2DX pCR likelihood score (continuous variable from 0–100) to predict pCR (ypT0/isN0).

Key Findings

Among the 80 patients, 82.5% were White, 5.0% were Black, 7.5% were Asian, and 5.0% were Hispanic; the mean age was 50.3 years (range = 26.0–78.0) years. The pCR rate among all patients was 60.0%, including 87.0% in patients with hormone receptor–negative disease and 48.2% in those with hormone receptor–positive disease. The proportions of patients in the HER2DX high, medium, and low pCR score categories were 33.7%, 27.5%, and 38.8%, respectively.

As a continuous variable, HER2DX pCR score was significantly associated with pCR (odds ratio [OR] = 1.05, 95% confidence interval [CI] = 1.03–1.08, P < .001). pCR rates in the HER2DX high, medium, and low pCR score groups were 92.6%, 63.6%, and 29.0%, respectively (OR for high vs low = 30.6, P < .001).

The HER2DX pCR score was significantly associated with pCR independent of hormone receptor status, HER2 immunohistochemistry score, HER2DX HER2 expression score, and prediction analysis of microarray 50 HER2-enriched subtype. On multivariate analysis, continuous HER2DX pCR score (OR = 1.03, 95% CI = 1.01–1.07, P = .03) and HER2DX HER2 expression score as a continuous variable (OR = 1.03, 95% CI = 1.00–1.07, P = .04) were the only significant predictors of pCR.

The investigators concluded, “The results of this diagnostic/prognostic study suggest that the HER2DX pCR score assay could predict pCR following treatment with de-escalated neoadjuvant paclitaxel with trastuzumab and pertuzumab in patients with early-stage HER2-positive breast cancer. The HER2DX pCR score might guide therapeutic decisions by identifying patients who are candidates for de-escalated or escalated approaches.”

Elizabeth A. Mittendorf, MD, PhD, of Dana-Farber Cancer Institute, is the corresponding author for the JAMA Oncology article.

Disclosure: The study was supported by the Breast Cancer Research Foundation, Susan G. Komen, Conquer Cancer Foundation of ASCO, and others. For full disclosures of the study authors, visit

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