Biomarkers of immunotherapy response in breast cancer beyond PD-L1

Chic, Núria; Brasó-Maristany, Fara; Prat, Aleix

doi:10.1007/s10549-021-06421-2

Cited by 11 publications

(15 citation statements)

References 108 publications

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“…Tumor development and progression generally occur along with the acquisition and accumulation of mutations ( 45 ). Neoantigens generated by mutations may lead to T-cell infiltration, thereby better response to immunotherapy ( 48 ). In fact, several studies have attempted to evaluate somatic mutations as biomarkers for predicting ICB response in OC ( Table 1 ).…”

Section: Mutation and Genomics Alterationsmentioning

confidence: 99%

The current landscape of predictive and prognostic biomarkers for immune checkpoint blockade in ovarian cancer

Zuo

Wang

et al. 2022

Front. Immunol.

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Immune checkpoint blockade (ICB) therapy has evoked a prominent shift in anticancer therapy. Durable clinical antitumor activity to ICB has been observed in patients with ovarian cancer (OC). However, only a subset of patients derive clinical benefit, and immune-related adverse events (irAEs) caused by ICB therapy can lead to permanent tissue damage and even fatal consequences. It is thus urgent to develop predictive biomarkers to optimize patient outcomes and minimize toxicity risk. Herein, we review current predictive and prognostic biomarkers for checkpoint immunotherapy in OC and highlight emerging biomarkers to guide treatment with ICB. The prevalent biomarkers, such as PD-L1 expression status, tumor-infiltrating lymphocytes, mutational burden, and immune gene signatures, are further discussed. We provide a state-of-the-art survey on prognostic and predictive biomarkers for checkpoint immunotherapy and offer valuable information for guiding precision immunotherapy

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Section: Mutation and Genomics Alterationsmentioning

confidence: 99%

The current landscape of predictive and prognostic biomarkers for immune checkpoint blockade in ovarian cancer

Zuo

Wang

et al. 2022

Front. Immunol.

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“…Finally, the APOBEC family of zinc‐coordinating enzymes convert cytosine to uracil and are essential for innate immune responses. APOBEC‐mediated mutational signatures are enriched in breast cancer, and durable responses to immune therapy have been reported in TMB high breast cancers with APOBEC activity, including PD‐L1‐negative tumours 108 …”

Section: Testing For Immunotherapy For Breast Cancermentioning

confidence: 99%

“…An association between TILs score and benefit from ICIs has been demonstrated in the metastatic setting, with improved survival with intermediate/high TILs and PD-L1 positivity in the Impassion 130 trial and in HER2 + disease in the PANACEA and KATE2 trials. 108 In the neoadjuvant setting there is a similar problem to PD-L1 in that high TILs are associated with improved pCR rates and better prognosis even in the absence of immunotherapy. In the GeparNuevo and Neo-TRIPaPD-L1 trials, higher TILs showed increased pCR rates in both arms.…”

Section: U M O U R -I N F I L T R a T I N G L Y M P H O C Y T E Smentioning

confidence: 99%

“…In the GeparNuevo trial, high TMB was associated with improved pCR across both arms, again highlighting the difficulty in identifying specific markers of immune therapy benefit. 108 High TMB in breast cancer can be linked to defects in DNA-damaged repair pathways. The strongest evidence exists for mismatch repair deficiency (dMMR) resulting in microsatellite instability with durable responses to ICIs seen in dMMR tumours across several primary sites, including colorectal and endometrial carcinomas.…”

Section: G E N E E X P R E S S I O N S I G N a T U R E Smentioning

confidence: 99%

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Pathology of neoadjuvant therapy and immunotherapy testing for breast cancer

Provenzano

Shaaban

2022

Histopathology

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Neoadjuvant chemotherapy (NACT) has become the standard of care for high-risk breast cancer, including triple-negative (TNBC) and HER2positive disease. As a result, handling and reporting of breast specimens post-NACT is part of routine practice, and it is important for pathologists to recognise the changes in tumour cells, tumour-associated stroma and background breast tissue induced by NACT. Familiarity with characteristic stromal features enables identification of the pre-treatment tumour site and allows confident diagnosis of pathological complete response (pCR) which is important for decisions concerning adjuvant therapy. Neoadjuvant endocrine therapy (NAET) is used less frequently than NACT; however, the SARS-COVID-19 pandemic has changed practice, with increased use as bridging therapy if surgery is delayed. NAET also induces characteristic changes in the tumour and stroma. Changes in the tumour microenvironment following NACT and NAET are also described. Immunotherapy is approved for use in advanced TNBC, and there are several trials exploring its role in early TNBC in the neoadjuvant setting. The current biomarker to determine eligibility for treatment with immune checkpoint inhibitors is programmed death ligand-1 (PD-L1) immunohistochemistry; however, this is complicated by lack of standardisation with different drugs linked to tests using different antibodies with different scoring systems. The situation in the neoadjuvant setting is further complicated by improved pCR rates for PD-L1positive tumours in both immune therapy and placebo arms. Alternative biomarkers are urgently needed to identify which patients will derive benefit from immunotherapy and key candidates are discussed.

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“…Moreover, CD8+TILs have been suggested to be predictive of anthracycline benefit in ER-negative breast cancers [ 27 ], whereas low sTILs predict superiority of trastuzumab over lapatinib in a formal prospective–retrospective analysis of the MA.31 trial of metastatic HER2-positive patients [ 29 ]. Additionally, immune checkpoint biomarkers such as LAG-3 (lymphocyte activation gene-3), PD-1 (programmed cell death protein 1), and PD-L1 (programmed death ligand 1) may also have prognostic value in breast cancer [ 30 , 31 ], and PD-L1 expression on immune cells is being used as a predictive biomarker for immune checkpoint inhibitors in triple-negative breast cancers [ 32 ].…”

Section: Introductionmentioning

confidence: 99%

Neither Tumor-Infiltrating Lymphocytes nor Cytotoxic T Cells Predict Enhanced Benefit from Chemotherapy in the DBCG77B Phase III Clinical Trial

Shenasa

Stovgaard

Jensen

et al. 2022

Cancers

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Recent studies have shown that immune infiltrates in the tumor microenvironment play a role in response to therapy, with some suggesting that patients with immunogenic tumors may receive increased benefit from chemotherapies. We evaluated this hypothesis in early breast cancer by testing the interaction between immune biomarkers and chemotherapy using materials from DBCG77B, a phase III clinical trial where high-risk premenopausal women were randomized to receive chemotherapy or no chemotherapy. Tissue microarrays were evaluated for tumor-infiltrating lymphocytes (TILs) assessed morphologically on hematoxylin and eosin-stained slides, and by immunohistochemistry for CD8, FOXP3, LAG-3, PD-1 and PD-L1. Following REMARK reporting guidelines, data analyses were performed according to a prespecified statistical plan, using 10-year invasive disease-free survival as the endpoint. Differences in survival probabilities between biomarker groups were evaluated by Kaplan–Meier and Cox proportional hazard ratio analyses and prediction for treatment benefit by an interaction test. Our results showed that stromal TILs were associated with an improved prognosis (HR = 0.93; p-value = 0.03), consistent with previous studies. However, none of the immune biomarkers predicted benefit from chemotherapy in the full study set nor within major breast cancer subtypes. Our study indicates that primary tumors with higher immune infiltration do not derive extra benefit from cyclophosphamide-based cytotoxic chemotherapy.

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Biomarkers of immunotherapy response in breast cancer beyond PD-L1

Cited by 11 publications

References 108 publications

The current landscape of predictive and prognostic biomarkers for immune checkpoint blockade in ovarian cancer

The current landscape of predictive and prognostic biomarkers for immune checkpoint blockade in ovarian cancer

Pathology of neoadjuvant therapy and immunotherapy testing for breast cancer

Neither Tumor-Infiltrating Lymphocytes nor Cytotoxic T Cells Predict Enhanced Benefit from Chemotherapy in the DBCG77B Phase III Clinical Trial

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