Highlights
- •Trastuzumab deruxtecan showed to prolong survival in HER2-low breast cancer (BC).
- •No data exist on the clinical role of HER2-low expression in inflammatory BC (IBC).
- •We found more ER-expressing tumours among stage III HER2-low (versus HER2-zero) IBC.
- •As in non-IBC, no clear prognostic role emerged for HER2-low expression in IBC.
- •Our results do not support HER2-low as a distinct subtype of IBC.
Abstract
Background
HER2)-low expression is a predictive biomarker for novel anti-HER2 antibody-drug conjugates.
However, little is known about its clinical significance in inflammatory breast cancer
(IBC).
Methods
Patients diagnosed with HER2-negative IBC between December 1999 and December 2020
were identified from the Dana-Farber Cancer Institute IBC registry. Patients were
divided into HER2-low (IHC 1+ or 2+/ISH–) and HER2-zero (IHC 0), comparing clinicopathologic
features and disease outcomes between the two subgroups.
Results
The study included 276 patients. Among patients with stage III (n = 209) and stage
IV (n = 67) IBC, 54% and 39% had HER2-low tumours, respectively. Oestrogen receptor
(ER)-expressing tumours were more common in patients with HER2-low versus HER2-zero
stage III IBC (65% versus 38%, p < 0.01). Among stage III patients undergoing surgery
(n = 182), pathologic complete response (pCR) rates were higher for HER2-zero versus
HER2-low IBC (11% versus 6%, OR: 1.8, 95%CI:0.6–5.3), but minimal differences persisted
when separately analysing pCR by ER status. Similar invasive disease-free survival
(iDFS) outcomes were observed among ER-positive HER2-zero versus HER2-low IBC (48-month
iDFS: 63% versus 63%, HR: 1.10, 95%CI:0.57–2.13) and ER-negative HER2-zero versus
HER2-low IBC (48-month iDFS: 28% versus 25%, HR: 1.19, 95%CI:0.69–2.04). Differences
in overall survival (OS) were small, both among ER-positive HER2-zero versus HER2-low
IBC (48-month OS: 80% versus 81%, HR: 0.82, 95%CI:0.39–1.73) and ER-negative HER2-zero
versus HER2-low IBC (48-month OS: 34% versus 47%, HR: 1.34, 95%CI: 0.74–2.41).
Conclusions
Marginal differences in clinicopathologic features and outcomes were observed in HER2-low
versus HER2-zero IBC when controlling for ER status, not supporting the definition
of HER2-low as a distinct subtype of IBC.
Keywords
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Article info
Publication history
Accepted:
July 1,
2022
Received in revised form:
June 30,
2022
Received:
May 27,
2022
Identification
Copyright
© 2022 Elsevier Ltd. All rights reserved.
