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Dynamic assessment of proliferation to guide response-adapted therapy in the setting of neoadjuvant chemotherapy in ER+/HER2- breast cancer

Saghir, Hani LU ; Veerla, Srinivas LU orcid ; Loman, Niklas LU and Kimbung, Siker LU (2025) In Translational Oncology 63. p.1-11
Abstract

Biomarkers for evaluating response to neoadjuvant chemotherapy (NACT) in ER+/HER2- breast cancer remain limited. This study explores the impact of NACT on tumor proliferation dynamics and its association with relapse-free interval (RFI) among 175 patients with early ER+/HER2- breast tumors. Proliferation was assessed at baseline, after completing two NACT cycles, and in the residual tumor using Ki67 immunohistochemistry (IHC) and two gene expression assays (GEAs): SSP-Ki67 and AURKA score. Slight to moderate agreement was observed between IHC and GEAs, with IHC-Ki67 consistently classifying more tumors as highly proliferative compared to SSP-Ki67 at both baseline and surgery. Proliferation status at baseline was not prognostic for RFI... (More)

Biomarkers for evaluating response to neoadjuvant chemotherapy (NACT) in ER+/HER2- breast cancer remain limited. This study explores the impact of NACT on tumor proliferation dynamics and its association with relapse-free interval (RFI) among 175 patients with early ER+/HER2- breast tumors. Proliferation was assessed at baseline, after completing two NACT cycles, and in the residual tumor using Ki67 immunohistochemistry (IHC) and two gene expression assays (GEAs): SSP-Ki67 and AURKA score. Slight to moderate agreement was observed between IHC and GEAs, with IHC-Ki67 consistently classifying more tumors as highly proliferative compared to SSP-Ki67 at both baseline and surgery. Proliferation status at baseline was not prognostic for RFI using either IHC-Ki67 or SSP-Ki67 in our cohort. However, patients with persistently high proliferation after two NACT cycles or in the residual tumor following NACT were at increased risk of relapse, with SSP-Ki67 outperforming IHC-Ki67 in identifying patients with a poorer prognosis. Our results demonstrate that tumor proliferation status measured after brief exposure to NACT or in the residual tumor post-NACT holds prognostic value and may inform the tailoring of post-neoadjuvant treatment strategies in patients with early luminal breast cancer, and that relying on IHC-Ki67 to evaluate treatment response may potentially lead to overtreatment.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
Translational Oncology
volume
63
article number
102597
pages
1 - 11
publisher
Neoplasia Press
external identifiers
  • pmid:41242143
ISSN
1936-5233
DOI
10.1016/j.tranon.2025.102597
language
English
LU publication?
yes
additional info
Copyright © 2025. Published by Elsevier Inc.
id
bb361c7c-ef8c-490d-8565-0c6036bf46dd
date added to LUP
2025-11-19 13:41:52
date last changed
2025-11-19 14:49:29
@article{bb361c7c-ef8c-490d-8565-0c6036bf46dd,
  abstract     = {{<p>Biomarkers for evaluating response to neoadjuvant chemotherapy (NACT) in ER+/HER2- breast cancer remain limited. This study explores the impact of NACT on tumor proliferation dynamics and its association with relapse-free interval (RFI) among 175 patients with early ER+/HER2- breast tumors. Proliferation was assessed at baseline, after completing two NACT cycles, and in the residual tumor using Ki67 immunohistochemistry (IHC) and two gene expression assays (GEAs): SSP-Ki67 and AURKA score. Slight to moderate agreement was observed between IHC and GEAs, with IHC-Ki67 consistently classifying more tumors as highly proliferative compared to SSP-Ki67 at both baseline and surgery. Proliferation status at baseline was not prognostic for RFI using either IHC-Ki67 or SSP-Ki67 in our cohort. However, patients with persistently high proliferation after two NACT cycles or in the residual tumor following NACT were at increased risk of relapse, with SSP-Ki67 outperforming IHC-Ki67 in identifying patients with a poorer prognosis. Our results demonstrate that tumor proliferation status measured after brief exposure to NACT or in the residual tumor post-NACT holds prognostic value and may inform the tailoring of post-neoadjuvant treatment strategies in patients with early luminal breast cancer, and that relying on IHC-Ki67 to evaluate treatment response may potentially lead to overtreatment.</p>}},
  author       = {{Saghir, Hani and Veerla, Srinivas and Loman, Niklas and Kimbung, Siker}},
  issn         = {{1936-5233}},
  language     = {{eng}},
  month        = {{11}},
  pages        = {{1--11}},
  publisher    = {{Neoplasia Press}},
  series       = {{Translational Oncology}},
  title        = {{Dynamic assessment of proliferation to guide response-adapted therapy in the setting of neoadjuvant chemotherapy in ER+/HER2- breast cancer}},
  url          = {{http://dx.doi.org/10.1016/j.tranon.2025.102597}},
  doi          = {{10.1016/j.tranon.2025.102597}},
  volume       = {{63}},
  year         = {{2025}},
}