Digitally quantified area of residual tumor after neoadjuvant chemotherapy in HER2-positive breast cancer

TL;DR

This study shows that even small amounts of leftover tumor after chemotherapy in HER2-positive breast cancer patients can affect their prognosis.

Contribution

The study introduces ART (area of residual tumor) as a digital quantification method to predict prognosis in HER2-positive breast cancer patients.

Findings

The ART-Low group had significantly shorter event-free survival compared to the ART-0 group.

The ART-High group showed a trend toward poorer prognosis but not statistically significant.

Minimal residual tumor cells can impact prognosis in HER2-positive breast cancer.

Abstract

The area of residual tumor (ART) is a quantitative method for assessing tumors after neoadjuvant chemotherapy (NAC). This study evaluated whether ART can identify a favorable prognosis group in patients with HER2-positive surgically resected breast cancer and residual tumors post-NAC.

We retrospectively reviewed patients with HER2-positive who underwent surgery after NAC, including trastuzumab, from 2005 to 2022 at our institution. ART was assessed at the maximum cut surface of the residual primary tumor using digital pathology images. Receiver operating characteristic curve analysis determined ART-Low and ART-High cutoffs, excluding ART-0 (0 mm2) patients.

Of the 219 patients, 82 had ART greater than 0 mm2. The median follow-up was 90.2 months. The number of patients in the ART-0, ART-Low (0 < ART ≤ 4.0 mm2), and ART-High (> 4.0 mm2) groups were 137, 39, and 43, respectively. The ART-Low group showed significantly shorter event-free survival compared to the ART-0 group (HR 3.50, 95% CI 1.52–8.06), and the ART-High group also tended toward poorer prognosis (HR 2.31, 95% CI 0.89–5.97). However, there was no significant difference in prognosis between the ART-Low and ART-High groups.

The current study suggests that even minimal residual tumor cells in the primary site can significantly impact on prognosis in HER2-positive early breast cancer.

The online version contains supplementary material available at 10.1007/s12282-025-01694-7.

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