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. 2019 Sep 15;11(9):6110-6116.
eCollection 2019.

Loss of HER2 and disease prognosis after neoadjuvant treatment of HER2+ breast cancer

Francisco P Branco  1 , Duarte Machado  2 , Filipa F Silva  3 , Saudade André  4 , Ana Catarino  5 , Rosa Madureira  6 , João M Pinto  1 , João P Godinho  1 , Pedro D Simões  1 , Margarida Brito  2 , Mafalda Casa-Nova  1 , António R Moreira  2 , José L Passos-Coelho  1   3
Affiliations

Loss of HER2 and disease prognosis after neoadjuvant treatment of HER2+ breast cancer

Francisco P Branco et al. Am J Transl Res. .

Abstract

Introduction: HER2 overexpression/amplification occurs in 15-20% breast cancers (BC) and is associated with worse prognosis. The addition of anti-HER2 treatment to neoadjuvant chemotherapy significantly improves the pathological complete response (pCR) rate. Changes in HER2 status after neoadjuvant treatment (NAT) have been reported and may affect prognosis. The aim of this study was to assess the efficacy of NAT in patients with HER2+ BC and its influence on HER2 status and associated prognostic impact.

Methods: Retrospective chart review and pathologic evaluation of all consecutive patients with HER2+ BC (defined as IHC 3+ or IHC 2+ confirmed by SISH) submitted to NAT between 2010-2015 in three Portuguese Hospitals.

Results: One hundred eight female patients were included; 40 with stage II, 68 with stage III. Hormone receptors were positive in 70. pCR (ypT0/isN0) was achieved in 48 patients (44%). With a median follow-up of 52 months, there were 5 disease free survival (DFS) events among pCR patients and 19 among non-pCR (P = 0.02). Of the 60 patients with residual disease at surgery, 52 remained HER2+ and 8 (13%) lost HER2 overexpression/amplification. 5y-DFS and 5y-OS was 70% and 84%, respectively, for patients whose residual tumors remained HER2+, and 21% and 50% for patients whose residual tumors became HER2 negative (P = 0.02 and < 0.001).

Discussion: We confirmed the negative prognostic impact of NAT-induced HER2 loss on residual tumor leading to worse DFS and OS. Despite the retrospective design and small sample size, these results suggest that it is important to retest HER2 after NAT, to better refine patient outcome.

Keywords: Breast cancer; HER2; chemotherapy; neoadjuvant therapy; trastuzumab.

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Conflict of interest statement

None.

Figures

Figure 1
Figure 1
Kaplan-Meier disease-free survival curves according pCR status after neoadjuvant treatment. DFS curves according to pCR (ypT0/isN0) status, comparison by log-rank test with 95% CI for the hazard rate (HR) and p-value.
Figure 2
Figure 2
Kaplan-Meier overall survival curves according pCR status after neoadjuvant treatment. OS curves according to pCR (ypT0/isN0) status, comparison by log-rank test with 95% CI for the hazard rate (HR) and p-value.
Figure 3
Figure 3
Kaplan-Meier disease-free survival curves according to residual tumor HER2 status after neoadjuvant treatment (no pCR patients). DFS curves according to loss of HER2 overexpression/amplification after neoadjuvant treatment in patients with residual disease, comparison by log-rank test with 95% CI for the hazard rate (HR) and p-value.
Figure 4
Figure 4
Kaplan-Meier overall survival curves according to residual tumor HER2 status after neoadjuvant treatment (no pCR patients). OS curves according to loss of HER2 overexpression/amplification after neoadjuvant treatment in patients with residual disease, comparison by log-rank test with 95% CI for the hazard rate (HR) and p-value.
See this image and copyright information in PMC

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