A Transcriptomic Immunologic Signature Predicts Favorable Outcome in Neoadjuvant Chemotherapy Treated Triple Negative Breast Tumors

Pérez-Peña, Javier; Fekete, János Tibor; Páez, Raquel; Baliu-Piqué, Mariona; García-Barberán, Vanesa; Manzano, Aránzazu; Pérez‐Segura, Pedro; Esparı́s-Ogando, Azucena; Pandiella, Atanasio; Győrffy, Balázs; Ocaña, Alberto

doi:10.3389/fimmu.2019.02802

Cited by 24 publications

(19 citation statements)

References 24 publications

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“…One group has recently developed a 36-gene assay based on Nanostring technology, the MHCII Immune Activation Assay, which identifies TNBC patients with low risk of recurrence; patients with these tumors can be treated by immunotherapy instead of classical cytotoxic therapy 16 . Similarly, high expression of a gene signature containing HLA-DRA , HLA-E , IDO1 , CXCL9 , CXCL10 , STAT1, and GZMB was found to be associated with TNBCs without relapse in 5 years after NAT 33 .…”

Section: Discussionmentioning

confidence: 89%

Recurrence biomarkers of triple negative breast cancer treated with neoadjuvant chemotherapy and anti-EGFR antibodies

et al. 2021

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To find metastatic recurrence biomarkers of triple-negative breast cancer (TNBC) treated by neoadjuvant chemotherapy and anti-EGFR antibodies (NAT), we evaluated tumor genomic, transcriptomic, and immune features, using MSK-IMPACT assay, gene arrays, Nanostring technology, and TIL assessment on H&E. Six patients experienced a rapid fatal recurrence (RR) and other 6 had later non-fatal recurrences (LR). Before NAT, RR had low expression of 6 MHC class I and 13 MHC class II genes but were enriched in upregulated genes involved in the cell cycle-related pathways. Their TIL number before NAT in RR was very low (<5%) and did not increase after treatment. In post-NAT residual tumors, RR cases showed high expression of SOX2 and CXCR4. Our results indicate that high expression of cell cycle genes, combined with cold immunological phenotype, may predict strong TNBC resistance to NAT and rapid progression after it. This biomarker combination is worth validation in larger studies.

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Section: Discussionmentioning

confidence: 89%

Recurrence biomarkers of triple negative breast cancer treated with neoadjuvant chemotherapy and anti-EGFR antibodies

et al. 2021

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“…Identification of genomic correlates of a particular function is a main goal in cancer to better select patients for a given treatment. In the immunotherapy field, transcriptomic signatures to identify hot and pro-active immune tumors have been reported and some were able to predict response to check point inhibitors [ 47 , 48 , 49 , 50 ]. In a similar manner, some signatures have been described to predict response to PARP inhibitors and consensus panels have provided recommendations for assessment [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Genomic Correlates of DNA Damage in Breast Cancer Subtypes

Morafraile

Pérez-Peña

Fuentes-Antrás

et al. 2021

Cancers

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Among the described druggable vulnerabilities, acting on the DNA repair mechanism has gained momentum, with the approval of PARP inhibitors in several indications, including breast cancer. However, beyond the mere presence of BRCA1/BRCA2 mutations, the identification of additional biomarkers that would help to select tumors with an extreme dependence on DNA repair machinery would help to stratify therapeutic decisions. Gene set enrichment analyses (GSEA) using public datasets evaluating expression values between normal breast tissue and breast cancer identified a set of upregulated genes. Genes included in different pathways, such as ATM/ATR, BARD1, and Fanconi Anemia, which are involved in the DNA damage response, were selected and confirmed using molecular alterations data contained at cBioportal. Nineteen genes from these gene sets were identified to be amplified and upregulated in breast cancer but only five of them NBN, PRKDC, RFWD2, UBE2T, and YWHAZ meet criteria in all breast cancer molecular subtypes. Correlation of the selected genes with prognosis (relapse free survival, RFS, and overall survival, OS) was performed using the KM Plotter Online Tool. In last place, we selected the best signature of genes within this process whose upregulation can be indicative of a more aggressive phenotype and linked with worse outcome. In summary, we identify genomic correlates within DNA damage pathway associated with prognosis in breast cancer.

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“…However, most of them basically focused on the characteristics from imaging or laboratory indexes. From molecular perspective, Hamy et al focused on the predictive values of immunological infiltration for the response to NCT in TNBC, while Ocana and colleagues investigated the immunologic phenotypes of TNBC and the potential associations with the clinical outcomes, which was inconsistent with the findings curated from the study conducted by Fournier et al [31][32][33]. Although the heterogenous profiles of TNBC have been extensively discussed, these predictive techniques were primarily centered on the molecular characteristics with few clinical features adopted.…”

Section: Discussionmentioning

confidence: 99%

Novel biomarkers and prediction model for the pathological complete response to neoadjuvant treatment of triple-negative breast cancer

Wang¹,

Xu²

2021

J. Cancer

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A Transcriptomic Immunologic Signature Predicts Favorable Outcome in Neoadjuvant Chemotherapy Treated Triple Negative Breast Tumors

Cited by 24 publications

References 24 publications

Recurrence biomarkers of triple negative breast cancer treated with neoadjuvant chemotherapy and anti-EGFR antibodies

Recurrence biomarkers of triple negative breast cancer treated with neoadjuvant chemotherapy and anti-EGFR antibodies

Genomic Correlates of DNA Damage in Breast Cancer Subtypes

Novel biomarkers and prediction model for the pathological complete response to neoadjuvant treatment of triple-negative breast cancer

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