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Predicting neoadjuvant chemotherapy treatment response in hormone-receptor-positive/HER2-negative breast cancer – results from the Swedish SCAN-B population-based cohort

Loman, Niklas LU ; Saghir, Hani LU and Kimbung, Siker LU (2025) In Acta Oncologica 64. p.1577-1589
Abstract

Background and purpose: Hormone-receptor-positive/HER2-negative (HR+/HER2-) early-stage breast cancers (EBCs) display heterogenous responses to neoadjuvant chemotherapy (NACT) warranting biomarkers to tailor optimal treatment for individual patients. Patients/material and methods: Women with HR+/HER2-EBC (N = 178) included in the Swedish Sweden Cancerome Analysis Network-Breast (SCAN-B) population-based cohort (2010–2019) treated with NACT were included. We analyzed rates of pathologic complete response (pCR), objective response (OR), breast conserving surgery (BCS), and recurrence-free interval (RFI) in subgroups defined by baseline clinicopath-ological and molecular characteristics. Results: The pCR rate was low (6%); nonetheless,... (More)

Background and purpose: Hormone-receptor-positive/HER2-negative (HR+/HER2-) early-stage breast cancers (EBCs) display heterogenous responses to neoadjuvant chemotherapy (NACT) warranting biomarkers to tailor optimal treatment for individual patients. Patients/material and methods: Women with HR+/HER2-EBC (N = 178) included in the Swedish Sweden Cancerome Analysis Network-Breast (SCAN-B) population-based cohort (2010–2019) treated with NACT were included. We analyzed rates of pathologic complete response (pCR), objective response (OR), breast conserving surgery (BCS), and recurrence-free interval (RFI) in subgroups defined by baseline clinicopath-ological and molecular characteristics. Results: The pCR rate was low (6%); nonetheless, after a median follow-up of 5.41 years, all patients who achieved pCR remained recurrence-free despite uniform baseline predicted high PAM50 risk of recurrence (ROR). Younger age (≤ 40 years), cT1, ER% positivity (≤ 66%), and negative PR (≤ 10%) were conventional clinicopathological factors positively associated with increased pCR. Molecular predictors of pCR included negative HR status by gene-expression signatures and non-luminal PAM50 subtypes. Tumor shrinkage ≥ 30%, i.e., OR and BCS, was achieved in 59% and 34%, respectively. No factor was significantly associated with ORR, whereas non-lobular histology and cT1 were positively associated with BCS. In addition, only 1/49 patients who underwent BCS experienced a recurrence during follow-up. Low/intermediate ER% pos-itivity, PR negativity, and non-luminal PAM50 subtype were baseline factors univariately prognostic for inferior long-term outcome in case of residual disease. Interpretation: Baseline characteristics indicative of reduced hormonal signaling and non-luminal tumor biology assessed more precisely using mRNA profiling can guide optimal tailoring of NACT for patients with high-risk HR+/HER2-tumors. Baseline molecular biology did not predict surgical outcomes following NACT.

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author
; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
endocrine responsiveness, hormone-receptor-positive, Neoadjuvant chemotherapy, optimal response, personalized treatment
in
Acta Oncologica
volume
64
pages
13 pages
publisher
Taylor & Francis
external identifiers
  • scopus:105022315076
  • pmid:41261821
ISSN
0284-186X
DOI
10.2340/1651-226X.2025.44201
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2025 The Author(s).
id
1b0781ca-83ed-418d-b8f8-5c4e3581b867
date added to LUP
2026-01-22 09:46:08
date last changed
2026-01-23 03:00:18
@article{1b0781ca-83ed-418d-b8f8-5c4e3581b867,
  abstract     = {{<p>Background and purpose: Hormone-receptor-positive/HER2-negative (HR+/HER2-) early-stage breast cancers (EBCs) display heterogenous responses to neoadjuvant chemotherapy (NACT) warranting biomarkers to tailor optimal treatment for individual patients. Patients/material and methods: Women with HR+/HER2-EBC (N = 178) included in the Swedish Sweden Cancerome Analysis Network-Breast (SCAN-B) population-based cohort (2010–2019) treated with NACT were included. We analyzed rates of pathologic complete response (pCR), objective response (OR), breast conserving surgery (BCS), and recurrence-free interval (RFI) in subgroups defined by baseline clinicopath-ological and molecular characteristics. Results: The pCR rate was low (6%); nonetheless, after a median follow-up of 5.41 years, all patients who achieved pCR remained recurrence-free despite uniform baseline predicted high PAM50 risk of recurrence (ROR). Younger age (≤ 40 years), cT1, ER% positivity (≤ 66%), and negative PR (≤ 10%) were conventional clinicopathological factors positively associated with increased pCR. Molecular predictors of pCR included negative HR status by gene-expression signatures and non-luminal PAM50 subtypes. Tumor shrinkage ≥ 30%, i.e., OR and BCS, was achieved in 59% and 34%, respectively. No factor was significantly associated with ORR, whereas non-lobular histology and cT1 were positively associated with BCS. In addition, only 1/49 patients who underwent BCS experienced a recurrence during follow-up. Low/intermediate ER% pos-itivity, PR negativity, and non-luminal PAM50 subtype were baseline factors univariately prognostic for inferior long-term outcome in case of residual disease. Interpretation: Baseline characteristics indicative of reduced hormonal signaling and non-luminal tumor biology assessed more precisely using mRNA profiling can guide optimal tailoring of NACT for patients with high-risk HR+/HER2-tumors. Baseline molecular biology did not predict surgical outcomes following NACT.</p>}},
  author       = {{Loman, Niklas and Saghir, Hani and Kimbung, Siker}},
  issn         = {{0284-186X}},
  keywords     = {{endocrine responsiveness; hormone-receptor-positive; Neoadjuvant chemotherapy; optimal response; personalized treatment}},
  language     = {{eng}},
  pages        = {{1577--1589}},
  publisher    = {{Taylor & Francis}},
  series       = {{Acta Oncologica}},
  title        = {{Predicting neoadjuvant chemotherapy treatment response in hormone-receptor-positive/HER2-negative breast cancer – results from the Swedish SCAN-B population-based cohort}},
  url          = {{http://dx.doi.org/10.2340/1651-226X.2025.44201}},
  doi          = {{10.2340/1651-226X.2025.44201}},
  volume       = {{64}},
  year         = {{2025}},
}