Immunotherapy in Breast Cancer Patients: A Focus on the Use of the Currently
Available Biomarkers in Oncology

Guerini-Rocco, Elena; Viale, Giulia; Fumagalli, Caterina; Sajjadi, Elham; Venetis, Konstantinos; Piciotti, Roberto; Invernizzi, Marco; Malapelle, Umberto; Fusco, Nicola

doi:10.2174/1871520621666210706144112

Cited by 28 publications

(19 citation statements)

References 154 publications

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“…In breast cancer, PD-L1 expression is often associated with poor clinicopathologic features, high TIL count and triple-negative phenotype [ 45 , 46 , 47 , 48 ]. Thus far, PD-L1+ and treatment-naïve triple-negative breast cancer (TNBC) patients have been the most suitable candidates for ICI therapy in breast cancer [ 49 ].…”

Section: Introductionmentioning

confidence: 99%

Atlas of PD-L1 for Pathologists: Indications, Scores, Diagnostic Platforms and Reporting Systems

Marletta

Fusco

Munari

et al. 2022

JPM

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Background. Innovative drugs targeting the PD1/PD-L1 axis have opened promising scenarios in modern cancer therapy. Plenty of assays and scoring systems have been developed for the evaluation of PD-L1 immunohistochemical expression, so far considered the most reliable therapeutic predictive marker. Methods. By gathering the opinion of acknowledged experts in dedicated fields of pathology, we sought to update the currently available evidence on PD-L1 assessment in various types of tumors. Results. Robust data were progressively collected for several anatomic districts and leading international agencies to approve specific protocols: among these, TPS with 22C3, SP142 and SP263 clones in lung cancer; IC with SP142 antibody in breast, lung and urothelial tumors; and CPS with 22C3/SP263 assays in head and neck and urothelial carcinomas. On the other hand, for other malignancies, such as gastroenteric neoplasms, immunotherapy has been only recently introduced, often for particular histotypes, so specific guidelines are still lacking. Conclusions. PD-L1 immunohistochemical scoring is currently the basis for allowing many cancer patients to receive properly targeted therapies. While protocols supported by proven data are already available for many tumors, dedicated studies and clinical trials focusing on harmonization of the topic in other still only partially explored fields are surely yet advisable.

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Section: Introductionmentioning

confidence: 99%

Atlas of PD-L1 for Pathologists: Indications, Scores, Diagnostic Platforms and Reporting Systems

Marletta

Fusco

Munari

et al. 2022

JPM

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“…Accurate biomolecular analysis is of great significance to make treatment options and to evaluate functional outcomes and quality of life of breast cancer patients in the era of precise medicine ( 2 , 29 – 31 ). However, with limited knowledge on the consequences of molecular heterogeneity for therapeutic decision-making, it has been accepted that biomarkers can be assessed only in the largest individual tumor focus ( 32 ).…”

Section: Discussionmentioning

confidence: 99%

Association of Molecular Biomarker Heterogeneity With Treatment Pattern and Disease Outcomes in Multifocal or Multicentric Breast Cancer

Wu²,

Huang³

et al. 2022

Front. Oncol.

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PurposeThis study aimed to evaluate the rates of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 heterogeneity in multifocal or multicentric breast cancer (MMBC) and its association with treatment pattern and disease outcomes.MethodsMMBC patients with ER, PR, HER2, and Ki67 results for each tumor focus were retrospectively analyzed using Kappa test and categorized into the homogeneous group (Homo group) and the heterogeneous group (Hetero group). Chi-square tests were performed to compare the clinical features and treatment options between the groups. Disease-free survival (DFS) and overall survival (OS) rates were estimated from Kaplan–Meier curves and compared between two groups.ResultsA total of 387 patients were included, and 93 (24.0%) were classified into the Hetero group. Adjuvant endocrine therapy was more frequently assigned for patients in the Hetero group than in the Homo group (84.9% vs. 71.7%, p = 0.046). There was no difference in terms of adjuvant anti-HER2 therapy (28.3% vs. 19.6%, p = 0.196) and chemotherapy (69.9% vs. 69.8%, p = 0.987) usage between the two groups. At a median follow-up of 36 months, DFS rates were 81.2% for the Hetero group and 96.5% for the Homo group (p = 0.041; adjusted HR, 2.95; 95% CI, 1.04–8.37). The estimated 3-year OS rates for the groups were 95.8% and 99.5%, respectively (p = 0.059; adjusted HR, 5.36; 95% CI, 0.97–29.69).ConclusionHeterogeneity of ER, PR, HER2, or Ki67 was present in 24.0% patients with MMBC. Biomarkers heterogeneity influenced adjuvant endocrine therapy usage and was associated with worse disease outcomes, indicating further clinical evaluation.

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“…Then, CD4 and FOXP3 were recorded as dichotomous variables based on the cut of the value of 1%, while CD8 was categorized as negative (<1%), low (1–30%), intermediate (31–50%), and high (>50%). Finally, PD-L1 analysis was based on the combined positive score (CPS), determined as the number of PD-L1 positive tumor cells, lymphocytes, and macrophages divided by the total number of viable tumor cells, multiplied by 100 [ 36 , 37 , 38 ]. Necrotic areas, as well as intraductal components, were excluded from the analysis.…”

Section: Methodsmentioning

confidence: 99%

Breast Cancer during Pregnancy as a Special Type of Early-Onset Breast Cancer: Analysis of the Tumor Immune Microenvironment and Risk Profiles

Sajjadi

Venetis

Noale

et al. 2022

Cells

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Breast cancer during pregnancy (PrBC) is a rare tumor with only a little information on its immune landscape. Here, we sought to characterize the cellular composition of the tumor microenvironment (TME) of PrBC and identify its differences from early-onset breast cancer (EOBC) in non-pregnant women. A total of 83 PrBC and 89 EOBC were selected from our Institutional registry and subjected to tumor-infiltrating lymphocytes (TILs) profiling and immunohistochemistry for CD4, CD8, forkhead box P3 (FOXP3), and programmed death-ligand 1 (PD-L1) (clone 22C3). A significantly lower frequency of hormone receptor (HR)-positive tumors was observed in PrBC. The prevalence of low/null PD-L1 and CD8+TILs was higher in PrBC than in the controls, specifically in HR+/HER2– breast cancers. PrBC had a significantly higher risk of relapse and disease-related death, compared to EOBC. The presence of TILs and each TIL subpopulation were significantly associated with disease relapse. Moreover, the death rate was higher in PrBC with CD8+ TILs. The TME of PrBC is characterized by specific patterns of TIL subpopulations with significant biological and prognostic roles. Routine assessment of TILs and TILs subtyping in these patients would be a valid addition to the pathology report that might help identify clinically relevant subsets of women with PrBC.

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Immunotherapy in Breast Cancer Patients: A Focus on the Use of the Currently Available Biomarkers in Oncology

Cited by 28 publications

References 154 publications

Atlas of PD-L1 for Pathologists: Indications, Scores, Diagnostic Platforms and Reporting Systems

Atlas of PD-L1 for Pathologists: Indications, Scores, Diagnostic Platforms and Reporting Systems

Association of Molecular Biomarker Heterogeneity With Treatment Pattern and Disease Outcomes in Multifocal or Multicentric Breast Cancer

Breast Cancer during Pregnancy as a Special Type of Early-Onset Breast Cancer: Analysis of the Tumor Immune Microenvironment and Risk Profiles

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