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Pathological response to pembrolizumab-based neoadjuvant therapy in ER-low vs. ER-zero breast cancer : a Swedish population-based cohort study

Steen, Sanna ; Karlsson, Emelie ; Björnheden, Ida LU ; Rask, Gunilla ; Thurfjell, Viktoria ; Nobin, Hampus LU ; Kolodziej, Blanka ; Bodén, Anna ; Bauer, Annette and Einefors, Rickard , et al. (2025) In Breast Cancer Research 27(1).
Abstract

Background: Emerging evidence indicates that estrogen receptor-low (ER-low)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer (BC) may more closely resemble ER-negative (ER-zero, < 1%) rather than ER-positive disease in terms of biological and clinicopathological characteristics. In Sweden, ER-low (ER 1–9%) BC is managed as triple-negative breast cancer (TNBC) and is thus eligible for neoadjuvant chemo-immunotherapy. We aimed to investigate real-world pathological response to neoadjuvant pembrolizumab combined with chemotherapy in ER-low versus ER-zero BC patients within a Swedish population-based multi-center cohort. Methods: BC patients with indication to receive neoadjuvant pembrolizumab in combination with... (More)

Background: Emerging evidence indicates that estrogen receptor-low (ER-low)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer (BC) may more closely resemble ER-negative (ER-zero, < 1%) rather than ER-positive disease in terms of biological and clinicopathological characteristics. In Sweden, ER-low (ER 1–9%) BC is managed as triple-negative breast cancer (TNBC) and is thus eligible for neoadjuvant chemo-immunotherapy. We aimed to investigate real-world pathological response to neoadjuvant pembrolizumab combined with chemotherapy in ER-low versus ER-zero BC patients within a Swedish population-based multi-center cohort. Methods: BC patients with indication to receive neoadjuvant pembrolizumab in combination with chemotherapy in Sweden between 2022 and 2024 were included in the study. Clinicopathological data—including pathological complete response (pCR) status, residual cancer burden (RCB) score, stromal tumor-infiltrating lymphocytes (sTILs) levels, and routine tumor characteristics—were retrieved from laboratory information systems. Associations between categorical variables were assessed using chi-squared (χ2) tests and associations between continuous variables and ER status or pCR were analyzed using Mann–Whitney U-test. Results: The total cohort comprised 441 TNBC cases (ER-zero n = 398; ER-low n = 43). In the ER-zero group, the pCR rate and RCB score 0–1 were 50.5% (95% CI: 45.5% to 55.5%) and 60.8% (95% CI: 55.8% to 65.6%), respectively. In the ER-low group, the corresponding values were 58.1% (95% CI: 42.1% to 73%), and 60.5% (95% CI: 44.4% to 75%), respectively. There were no statistically significant differences in either pCR rate (p = 0.46) or dichotomized RCB score (p = 0.88) between the groups. The ER-low group showed significantly higher sTILs percentage compared to the ER-zero group (median sTILs 25% versus 20%, p = 0.046). However, when sTILs were analyzed as a binary categorical variable using a 30% cut-off, no significant difference was observed (p = 0.33). Conclusions: We observed no significant difference in pathological response to neoadjuvant chemo-immunotherapy with pembrolizumab between ER-zero and ER-low BCs. These findings support previous evidence suggesting that ER-low tumors behave more similarly to ER-zero than ER-positive.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
ER low, Neoadjuvant immunotherapy, Pembrolizumab, Triple negative breast cancer
in
Breast Cancer Research
volume
27
issue
1
article number
213
publisher
BioMed Central (BMC)
external identifiers
  • pmid:41316480
  • scopus:105023453427
ISSN
1465-5411
DOI
10.1186/s13058-025-02179-3
language
English
LU publication?
yes
id
62fe0ae4-d661-47c9-970e-649bde37e94a
date added to LUP
2026-01-14 11:55:33
date last changed
2026-01-14 11:56:12
@article{62fe0ae4-d661-47c9-970e-649bde37e94a,
  abstract     = {{<p>Background: Emerging evidence indicates that estrogen receptor-low (ER-low)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer (BC) may more closely resemble ER-negative (ER-zero, &lt; 1%) rather than ER-positive disease in terms of biological and clinicopathological characteristics. In Sweden, ER-low (ER 1–9%) BC is managed as triple-negative breast cancer (TNBC) and is thus eligible for neoadjuvant chemo-immunotherapy. We aimed to investigate real-world pathological response to neoadjuvant pembrolizumab combined with chemotherapy in ER-low versus ER-zero BC patients within a Swedish population-based multi-center cohort. Methods: BC patients with indication to receive neoadjuvant pembrolizumab in combination with chemotherapy in Sweden between 2022 and 2024 were included in the study. Clinicopathological data—including pathological complete response (pCR) status, residual cancer burden (RCB) score, stromal tumor-infiltrating lymphocytes (sTILs) levels, and routine tumor characteristics—were retrieved from laboratory information systems. Associations between categorical variables were assessed using chi-squared (χ<sup>2</sup>) tests and associations between continuous variables and ER status or pCR were analyzed using Mann–Whitney U-test. Results: The total cohort comprised 441 TNBC cases (ER-zero n = 398; ER-low n = 43). In the ER-zero group, the pCR rate and RCB score 0–1 were 50.5% (95% CI: 45.5% to 55.5%) and 60.8% (95% CI: 55.8% to 65.6%), respectively. In the ER-low group, the corresponding values were 58.1% (95% CI: 42.1% to 73%), and 60.5% (95% CI: 44.4% to 75%), respectively. There were no statistically significant differences in either pCR rate (p = 0.46) or dichotomized RCB score (p = 0.88) between the groups. The ER-low group showed significantly higher sTILs percentage compared to the ER-zero group (median sTILs 25% versus 20%, p = 0.046). However, when sTILs were analyzed as a binary categorical variable using a 30% cut-off, no significant difference was observed (p = 0.33). Conclusions: We observed no significant difference in pathological response to neoadjuvant chemo-immunotherapy with pembrolizumab between ER-zero and ER-low BCs. These findings support previous evidence suggesting that ER-low tumors behave more similarly to ER-zero than ER-positive.</p>}},
  author       = {{Steen, Sanna and Karlsson, Emelie and Björnheden, Ida and Rask, Gunilla and Thurfjell, Viktoria and Nobin, Hampus and Kolodziej, Blanka and Bodén, Anna and Bauer, Annette and Einefors, Rickard and Nilsson, Per and Zerdes, Ioannis and Papakonstantinou, Andri and Foukakis, Theodoros and Fredriksson, Irma and Rantalainen, Mattias and Colón-Cervantes, Eugenia and Kovács, Anikó and Acs, Balazs and Hartman, Johan}},
  issn         = {{1465-5411}},
  keywords     = {{ER low; Neoadjuvant immunotherapy; Pembrolizumab; Triple negative breast cancer}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Breast Cancer Research}},
  title        = {{Pathological response to pembrolizumab-based neoadjuvant therapy in ER-low vs. ER-zero breast cancer : a Swedish population-based cohort study}},
  url          = {{http://dx.doi.org/10.1186/s13058-025-02179-3}},
  doi          = {{10.1186/s13058-025-02179-3}},
  volume       = {{27}},
  year         = {{2025}},
}