Highlights
- •Prognosis was assessed in patients with HER2-low and HER2-zero early breast cancer.
- •Patients with HER2-low breast cancer had a significantly better prognosis.
- •HER2-low patients had longer disease-free survival and overall survival.
- •Immunohistochemical HER2 subdivision was confirmed by gene expression analysis.
Abstract
Background
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.
Patients and methods
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.
Results
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 < 0.001) and
overall survival (OS) (15-year rate: 75.4% [95% CI 69.4–81.9] vs. 66.8% [95% CI 59.5–74.9],
P = 0.009). The OS difference was observed in hormone receptor (HR)-positive (P = 0.039)
but not HR-negative (P = 0.086) tumours. The results of multivariable analyses confirmed
the independent prognostic significance of HER2 status (DFS: HR, 0.546; 95% CI, 0.402–0.743;
P < 0.001; OS: HR, 0.653; 95% CI, 0.458–0.932; P = 0.019).
Conclusion
HER2-low patients had a better survival than HER2-zero patients.
Keywords
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Article info
Publication history
Published online: July 12, 2022
Accepted:
June 2,
2022
Received in revised form:
May 24,
2022
Received:
March 28,
2022
Identification
Copyright
© 2022 Elsevier Ltd. All rights reserved.
