Advancing the PD-L1 CPS test in metastatic TNBC: Insights from pathologists and findings from a nationwide survey

Fusco, Nicola; Ivanova, Mariia; Frascarelli, Chiara; Criscitiello, Carmen; Cerbelli, Bruna; Pignataro, Maria Gemma; Pernazza, Angelina; Sajjadi, Elham; Venetis, Konstantinos; Cursano, Giulia; Pagni, Fabio; Di Bella, Camillo; Accardo, Marina; Amato, Michelina; Amico, Paolo; Bartoli, Caterina; Bogina, Giuseppe; Bortesi, Laura; Boldorini, Renzo; Bruno, Sara; Cabibi, Daniela; Caruana, Pietro; Dainese, Emanuele; De Camilli, Elisa; Dell’Anna, Vladimiro; Duda, Loren; Emmanuele, Carmela; Fanelli, Giuseppe Nicolò; Fernandes, Bethania; Ferrara, Gerardo; Gnetti, Letizia; Gurrera, Alessandra; Leone, Giorgia; Lucci, Raffaella; Mancini, Cristina; Marangi, Grazia; Mastropasqua, Mauro G.; Nibid, Lorenzo; Orrù, Sandra; Pastena, Maria; Peresi, Monica; Perracchio, Letizia; Santoro, Angela; Vezzosi, Vania; Zambelli, Claudia; Zuccalà, Valeria; Rizzo, Antonio; Costarelli, Leopoldo; Pietribiasi, Francesca; Santinelli, Alfredo; Scatena, Cristian; Curigliano, Giuseppe; Guerini-Rocco, Elena; Martini, Maurizio; Graziano, Paolo; Castellano, Isabella; d'Amati, Giulia

doi:10.1016/j.critrevonc.2023.104103

Cited by 5 publications

(1 citation statement)

References 60 publications

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“…HER2 is naturally expressed in normal breast epithelium, exhibiting variations in receptor quantities between cases with amplification of the HER2 gene and those without [ 32 ]. However, the capacity of IHC to detect subtle differences in receptor levels remains uncertain due to inherent limitations and technical nuances, much like other intricate IHC-based biomarkers [ 25 , 44 ]. Presently, a definitive quantitative threshold to distinguish between HER2-zero and HER2-low cases is yet to be defined [ 20 ].…”

Section: Improving the Detection And Reporting Of Her2-low Breast Can...mentioning

confidence: 99%

Standardized pathology report for HER2 testing in compliance with 2023 ASCO/CAP updates and 2023 ESMO consensus statements on HER2-low breast cancer

Ivanova,

Porta,

D’Ercole

et al. 2023

Virchows Arch

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Since the release of the DESTINY-Breast04 (DB-04) trial findings in June 2022, the field of pathology has seen a renaissance of HER2 as a predictive biomarker in breast cancer. The trial focused on patients with metastatic breast cancer who were classified as “HER2-low,” i.e., those with immunohistochemistry (IHC) HER2 1 + or 2 + and negative in situ hybridization (ISH) results. The study revealed that treating these patients with trastuzumab deruxtecan (T-DXd) instead of the oncologist’s chosen chemotherapy led to outstanding improvements in survival. This has challenged the existing binary HER2 pathological classification system, which categorized tumors as either positive (overexpression/amplification) or negative, as per the ASCO/CAP 2018 guideline reaffirmed by ASCO/CAP 2023 guideline update. Given that DB-04 excluded patients with HER2 IHC score 0 status, the results of the ongoing DB-06 trial may shed further light on the potential benefits of T-DXd therapy for these patients. Roughly half of all breast cancers are estimated to belong to the HER2-low category, which does not represent a distinct or specific subtype of cancer. Instead, it encompasses a diverse group of tumors that exhibit clinical, morphological, immunohistochemical, and molecular variations. However, HER2-low offers a distinctive biomarker status that identifies a specific therapeutic regimen (i.e., T-DXd) linked to a favorable prognosis in breast cancer. This unique association emphasizes the importance of accurately identifying these tumors. Differentiating between a HER2 IHC score 0 and score 1 + has not been clinically significant until now. To ensure accurate classification and avoid misdiagnosis, it is necessary to adopt standardized procedures, guidelines, and specialized training for pathologists in interpreting HER2 expression in the lower spectrum. Additionally, the utilization of artificial intelligence holds promise in supporting this endeavor. Here, we address the current state of the art and unresolved issues in assessing HER2-low status, with a particular emphasis on the score 0. We explore the dilemma surrounding the exclusion of HER2-zero patients from potentially beneficial therapy based on traditional HER2 testing. Additionally, we examine the clinical context, considering that DB-04 primarily involved heavily pretreated late-stage metastatic breast cancers. We also delve into emerging evidence suggesting that extrapolating HER2-low status from the original diagnosis may lead to misleading results. Finally, we provide recommendations for conducting high-quality testing and propose a standardized pathology report in compliance with 2023 ASCO/CAP updates and 2023 ESMO consensus statements on HER2-low breast cancer.

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Section: Improving the Detection And Reporting Of Her2-low Breast Can...mentioning

confidence: 99%