Biomarker dynamics affecting neoadjuvant therapy response and outcome of HER2-positive breast cancer subtype

HER2+ breast cancer (BC) is an aggressive subtype genetically and biologically heterogeneous. We evaluate the predictive and prognostic role of HER2 protein/gene expression levels combined with clinico-pathologic features in 154 HER2+ BCs patients who received trastuzumab-based neoadjuvant chemother...

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Published in:Scientific reports Vol. 13; no. 1; pp. 12869 - 14
Main Authors: Orrù, Sandra, Pascariello, Emanuele, Pes, Barbara, Rallo, Vincenzo, Barbara, Raffaele, Muntoni, Marta, Notari, Francesca, Fancello, Gianfranco, Mocci, Cristina, Muroni, Maria Rosaria, Cossu-Rocca, Paolo, Angius, Andrea, De Miglio, Maria Rosaria
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 08.08.2023
Nature Publishing Group
Nature Portfolio
Subjects:
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Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Breast cancer
Breast Neoplasms - drug therapy
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Cancer therapies
Chemotherapy
Decision making
ErbB-2 protein
Female
Gene expression
Humanities and Social Sciences
Humans
Lymph nodes
Lymphatic system
Lymphocytes, Tumor-Infiltrating
Machine learning
Medical prognosis
Metastases
Microenvironments
Monoclonal antibodies
multidisciplinary
Neoadjuvant Therapy
Receptor, ErbB-2 - genetics
Receptor, ErbB-2 - metabolism
Science
Science (multidisciplinary)
Trastuzumab
Trastuzumab - therapeutic use
Treatment Outcome
Tumor Microenvironment
ISSN:2045-2322, 2045-2322
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Summary:HER2+ breast cancer (BC) is an aggressive subtype genetically and biologically heterogeneous. We evaluate the predictive and prognostic role of HER2 protein/gene expression levels combined with clinico-pathologic features in 154 HER2+ BCs patients who received trastuzumab-based neoadjuvant chemotherapy (NACT). The tumoral pathological complete response (pCR) rate was 40.9%. High tumoral pCR show a scarce mortality rate vs subjects with a lower response. 93.7% of ypT0 were HER2 IHC3+ BC, 6.3% were HER2 IHC 2+/SISH+ and 86.7% of ypN0 were HER2 IHC3+, the remaining were HER2 IHC2+/SISH+. Better pCR rate correlate with a high percentage of infiltrating immune cells and right-sided tumors, that reduce distant metastasis and improve survival, but no incidence difference. HER2 IHC score and laterality emerge as strong predictors of tumoral pCR after NACT from machine learning analysis. HER2 IHC3+ and G3 are poor prognostic factors for HER2+ BC patients, and could be considered in the application of neoadjuvant therapy. Increasing TILs concentrations, lower lymph node ratio and lower residual tumor cellularity are associated with a better outcome. The immune microenvironment and scarce lymph node involvement have crucial role in clinical outcomes. The combination of all predictors might offer new options for NACT effectiveness prediction and stratification of HER2+ BC during clinical decision-making.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-023-40071-2