Biomarker dynamics affecting neoadjuvant therapy response and outcome of HER2-positive breast cancer subtype
Abstract 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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-40071-2 |
| _version_ | 1827634309134024704 |
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| author | Sandra Orrù Emanuele Pascariello Barbara Pes Vincenzo Rallo Raffaele Barbara Marta Muntoni Francesca Notari Gianfranco Fancello Cristina Mocci Maria Rosaria Muroni Paolo Cossu-Rocca Andrea Angius Maria Rosaria De Miglio |
| author_facet | Sandra Orrù Emanuele Pascariello Barbara Pes Vincenzo Rallo Raffaele Barbara Marta Muntoni Francesca Notari Gianfranco Fancello Cristina Mocci Maria Rosaria Muroni Paolo Cossu-Rocca Andrea Angius Maria Rosaria De Miglio |
| author_sort | Sandra Orrù |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-09T15:11:34Z |
| format | Article |
| id | doaj.art-36a1b443ba6641c4a88d18e2637049d3 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T15:11:34Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-36a1b443ba6641c4a88d18e2637049d32023-11-26T13:19:55ZengNature PortfolioScientific Reports2045-23222023-08-0113111410.1038/s41598-023-40071-2Biomarker dynamics affecting neoadjuvant therapy response and outcome of HER2-positive breast cancer subtypeSandra Orrù0Emanuele Pascariello1Barbara Pes2Vincenzo Rallo3Raffaele Barbara4Marta Muntoni5Francesca Notari6Gianfranco Fancello7Cristina Mocci8Maria Rosaria Muroni9Paolo Cossu-Rocca10Andrea Angius11Maria Rosaria De Miglio12Department of Pathology, “A. Businco” Oncologic Hospital, ARNA S BrotzuDepartment of Pathology, “A. Businco” Oncologic Hospital, ARNA S BrotzuDipartimento di Matematica e Informatica, University of Cagliari, Palazzo delle ScienzeIstituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, CNR, Cittadella Universitaria di CagliariDepartment of Radiotherapy, “A. Businco” Oncologic Hospital, ARNAS BrotzuDepartment of Pathology, “A. Businco” Oncologic Hospital, ARNA S BrotzuDepartment of Pathology, “A. Businco” Oncologic Hospital, ARNA S BrotzuBreast Surgery Department, “A. Businco” Oncologic Hospital, ARNAS BrotzuDepartment of Pathology, “A. Businco” Oncologic Hospital, ARNA S BrotzuDepartment of Medicine, Surgery and Pharmacy, University of SassariDepartment of Medicine, Surgery and Pharmacy, University of SassariIstituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, CNR, Cittadella Universitaria di CagliariDepartment of Medicine, Surgery and Pharmacy, University of SassariAbstract 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.https://doi.org/10.1038/s41598-023-40071-2 |
| spellingShingle | Sandra Orrù Emanuele Pascariello Barbara Pes Vincenzo Rallo Raffaele Barbara Marta Muntoni Francesca Notari Gianfranco Fancello Cristina Mocci Maria Rosaria Muroni Paolo Cossu-Rocca Andrea Angius Maria Rosaria De Miglio Biomarker dynamics affecting neoadjuvant therapy response and outcome of HER2-positive breast cancer subtype Scientific Reports |
| title | Biomarker dynamics affecting neoadjuvant therapy response and outcome of HER2-positive breast cancer subtype |
| title_full | Biomarker dynamics affecting neoadjuvant therapy response and outcome of HER2-positive breast cancer subtype |
| title_fullStr | Biomarker dynamics affecting neoadjuvant therapy response and outcome of HER2-positive breast cancer subtype |
| title_full_unstemmed | Biomarker dynamics affecting neoadjuvant therapy response and outcome of HER2-positive breast cancer subtype |
| title_short | Biomarker dynamics affecting neoadjuvant therapy response and outcome of HER2-positive breast cancer subtype |
| title_sort | biomarker dynamics affecting neoadjuvant therapy response and outcome of her2 positive breast cancer subtype |
| url | https://doi.org/10.1038/s41598-023-40071-2 |
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