Long-term prognostic significance of HER2-low and HER2-zero in node-negative breast cancer

Recently, novel antibody––drug conjugates (ADCs) showed clinical activity in a subset of advanced human epidermal growth factor receptor 2 (HER2)-negative patients. We investigated the prognostic significance of HER2-low and HER2-zero tumours. The retrospective cohort study included 410 consecutive...

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Published in:European journal of cancer (1990) 2022-09, Vol.173, p.10-19
Main Authors: Almstedt, Katrin, Heimes, Anne-Sophie, Kappenberg, Franziska, Battista, Marco J., Lehr, Hans-Anton, Krajnak, Slavomir, Lebrecht, Antje, Gehrmann, Mathias, Stewen, Kathrin, Brenner, Walburgis, Weikel, Wolfgang, Rahnenführer, Jörg, Hengstler, Jan G., Hasenburg, Annette, Schmidt, Marcus
Format: Article
Language:English
Subjects:
Antibodies
Breast cancer
Early breast cancer
Epidermal growth factor
ErbB-2 protein
Gene expression
Growth factors
HER2 gene expression
HER2 overexpression
HER2-low
HER2-zero
Hybridization
Immunohistochemistry
Medical prognosis
Prognosis
Receptors
Regression analysis
Survival
Tumors
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Summary:Recently, novel antibody––drug conjugates (ADCs) showed clinical activity in a subset of advanced human epidermal growth factor receptor 2 (HER2)-negative patients. We investigated the prognostic significance of HER2-low and HER2-zero tumours. The retrospective cohort study included 410 consecutive node-negative breast cancer patients without adjuvant systemic therapy treated between 1985 and 2000 (median follow-up: 16.73 [IQR 8.58–23.45] years). 351 (85.6%) were HER-2 negative and subdivided into HER2-zero (immunohistochemistry [IHC] score 0) and HER2-low (IHC score 1+ or 2+/in situ hybridisation [ISH]-negative). HER2 gene expression was available in 170 (48.4%) patients. Differences in HER2 status for immunohistochemistry, gene expression and clinico-pathologic parameters were assessed using Fisher's exact test, Pearson's correlation and Mann–Whitney test. Prognosis was investigated using the Kaplan–Meier method and Cox regression analyses. Of the 351 HER2-negative patients, 198 (56.4%) had HER2-low tumours and 153 (43.6%) were HER2-zero. Significant differences between HER2-zero and HER2-low tumours were found in histologic grading (P = 0.001), Ki-67 (P = 0.013) and HER2 gene expression (P = 0.002). HER2-low patients had significantly longer disease-free survival (DFS) (15-year rate: 67.5% [95% CI 61.0–74.7] vs. 47.3% [95% CI 39.9–56.1], P 
ISSN:0959-8049
1879-0852
DOI:10.1016/j.ejca.2022.06.012