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. 2021 Dec:60:62-69.
doi: 10.1016/j.breast.2021.08.016. Epub 2021 Aug 26.

Prognostic impact of HER2-low expression in hormone receptor positive early breast cancer

Raz Mutai  1 , Tamar Barkan  1 , Assaf Moore  2 , Michal Sarfaty  2 , Tzippy Shochat  3 , Rinat Yerushalmi  2 , Salomon M Stemmer  2 , Hadar Goldvaser  4
Affiliations

Prognostic impact of HER2-low expression in hormone receptor positive early breast cancer

Raz Mutai et al. Breast. 2021 Dec.

Abstract

Background: Recent data suggest that human epidermal growth factor receptor 2 (HER2)-low breast cancer may represent a distinct entity. We aimed to compare disease characteristics and outcomes between HER2-low and HER2-0 in estrogen receptor (ER) positive, early-stage breast cancer.

Methods: A single center retrospective study comprising all women with ER positive, HER2 negative early breast cancer, for whom an Oncotype DX test was performed between 2005 and 2012. Women were grouped to HER2-low (immunohistochemistry +1 or +2 and in situ hybridization not amplified) or HER2-0. Clinico-pathological features and Oncotype recurrence score (RS) were collected. Data on overall-survival (OS), disease-free survival (DFS) and distant disease-free survival (DDFS) were evaluated according to HER2 expression status.

Results: 608 women were included, of which 304 women had HER2-0 and 304 had HER2-low disease. Lobular subtype was significantly more common in HER-0 compared to HER2-low disease (17% vs. 8%, p = 0.005). The prevalence of other clinic-pathological characteristics and long-term prognosis were comparable between both groups. For women with high genomic risk (RS > 25), HER2-low expression was associated with significantly favorable OS (HR = 0.31, 95% CI 0.11-0.78, p = 0.01), DFS (HR = 0.40, 95% CI 0.20-0.82, p = 0.01) and DDFS (HR = 0.26, 95% CI 0.11-0.63, P = 0.002) compared to women with HER2-0. For women with low genomic risk (RS ≤ 25), long-term prognosis was unrelated to HER2 expression.

Conclusion: The prognostic impact of HER2-low expression in early-stage luminal disease varies across the genomic risk, with significant favorable outcomes of HER2-low expression compared to HER2-0 in women with high genomic risk.

Keywords: Breast cancer; Genomic risk; HER2-Low; Oncotype DX RS; Prognosis.

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Conflict of interest statement

Declaration of competing interest All other authors have no conflicts of interest.

Figures

Fig. 1
Fig. 1
Kaplan-Meier analyses for all study population, according to HER2 expression status: 10-year overall survival (A), 10-year disease-free survival (B), and 10-year distant disease-free survival (C).
Fig. 2
Fig. 2
Kaplan-Meier analyses for overall survival (A), disease-free survival (B) and distant disease-free survival (C) for low risk Oncotype DX Recurrence Score (0-25) according to HER2 expression status.
Fig. 3
Fig. 3
Kaplan-Meier analyses for overall survival (A), disease-free survival (B) and distant disease-free survival (C) for high risk Oncotype DX Recurrence Score (RS ≥ 26) according to HER2 expression status.
Fig. 4
Fig. 4
HER2 status upon disease recurrence; 0; HER2 IHC-0, 1; HER2 IHC 1+, 2; HER2-IHC +2∖ISH negative, 3- HER2-Positive tumor: IHC +3/HER2 +2, ERBB2 amplified by ISH).
See this image and copyright information in PMC

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