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893 Histo-molecular classifications and practical challenges in the management of triple-negative breast carcinoma
  1. Nouha Bouayed and
  2. Balkiss Abdelmoula
  1. Medical University of Sfax, Genomics of Signalopathies at the service of Precision Medicine LR23ES07, Sfax, Tunisia


Introduction/Background The 8th edition of the American Joint Committee on Cancer (AJCC) Staging System Manual (2017), the 5th edition WHO Classification of Breast Tumors (2019) and the multiple recommendations of the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) (2020 to 2023) have indicated that the stratification of breast cancer (BC) has greatly benefited from a dynamic comprehensive integration of molecular biomarkers. This integration enhances the accuracy of prognostic assessments and improves the therapeutic management of BC patients.

Methodology A literature review about the biological and molecular specificities of BC was conducted to highlight the recent guidelines for molecular diagnostics in the management of triple-negative breast carcinoma (TNBC).

Results Our review showcased the evolution of BC staging from histological to immunohistochemical and genomic analysis. Immunohistochemistry has facilitated the histo-molecular classification of BC into four classes: luminal A, luminal B, HER2-positive, and triple-negative. The 2023 HER2 Breast Testing Guideline Update reaffirmed criteria for identifying HER2-positive BC, requiring over 10% strong membrane marking or a HER2 CEP17 ratio ≥2. Constituting 10–20% of BC cases, TNBC predominantly affects younger women. This aggressive form lacks estrogen/progesterone receptors and HER2 amplification, leading to poor prognoses and limited targeted treatment options. KEYNOTE-355 Clinical Trials demonstrated the efficacy of PD1/PD-L1 monoclonal antibodies for TNBC expressing PD-L1 with a CPS of 10 or higher. Although PD-L1 analysis guides immunotherapy eligibility, there’s limited data on pathologists’ agreement in assessing PD-L1. Ongoing therapeutic cancer mRNA vaccination for BC, particularly TNBC, explores personalized vaccines targeting specific antigens, promising potential advancements in treatment.

Conclusion TNBC is molecularly heterogeneous and its treatment remains a great clinical challenge. The development of novel biomarkers, such as epigenetic ones, may endorse the stratification of TNBC into more subtypes. TNBC high immunogenicity also validates their advantage for therapeutic management using cancer immunotherapy, particularly mRNA vaccines.

Disclosures None

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