Abstract
Background
Pathologic response at the time of surgery after neoadjuvant therapy for HER2 positive
early breast cancer impacts both prognosis and subsequent adjuvant therapy. Comprehensive
descriptions of the tumor microenvironment (TME) in patients with HER2 positive early
breast cancer is not well described. We utilized standard stromal pathologist-assessed
tumor infiltrating lymphocyte (TIL) quantification, quantitative multiplex immunofluorescence,
and RNA-based gene pathway signatures to assess pretreatment TME characteristics associated
pathologic complete response in patients with hormone receptor positive, HER2 positive
early breast cancer treated in the neoadjuvant setting.
Methods
We utilized standard stromal pathologist-assessed TIL quantification, quantitative
multiplex immunofluorescence, and RNA-based gene pathway signatures to assess pretreatment
TME characteristics associated pathologic complete response in 28 patients with hormone
receptor positive, HER2 positive early breast cancer treated in the neoadjuvant setting.
Results
Pathologist-assessed stromal TILs were significantly associated with pathologic complete
response (pCR). By quantitative multiplex immunofluorescence, univariate analysis
revealed significant increases in CD3+, CD3+CD8-FOXP3-, CD8+ and FOXP3+ T-cell densities
as well as increased immune cell aggregates in pCR patients. In subsets of paired
pre/post-treatment samples, we observed significant changes in gene expression signatures
in non-pCR patients and significant decreases in CD8+ densities after treatment in
pCR patients. No RNA based pathway signature was associated with pCR.
Conclusion
TME characterization HER2 positive breast cancer patients revealed several stromal
T-cell densities and immune cell aggregates associated with pCR. These results demonstrate
the feasibility of these novel methods in TME evaluation and contribute to ongoing
investigations of the TME in HER2+ early breast cancer to identify robust biomarkers
to best identify patients eligible for systemic de-escalation strategies.
Keywords
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Article Info
Publication History
Published online: April 17, 2022
Accepted:
April 11,
2022
Received in revised form:
April 5,
2022
Received:
December 13,
2021
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2022 Elsevier Inc. All rights reserved.
