Grade 3 breast cancer
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Summary
10 papers analyzed
These studies suggest grade 3 breast cancer is aggressive with poor prognosis, but treatment can be tailored using genetic markers, recurrence scores, and radiotherapy options.
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Understanding Grade 3 Breast Cancer: Molecular Features, Prognosis, and Treatment Implications
Molecular Biological Features of Grade 3 Breast Cancer
Grade 3 breast cancers are characterized by aggressive molecular profiles. These tumors are often estrogen receptor (ER)-negative and associated with advanced stages of the disease. They are frequently linked to human epidermal growth factor receptor 2 (HER2) and basal subtypes, as well as increased MKI67 expression, indicating high cell proliferation rates. Gene set enrichment analysis has shown that grade 3 tumors are enriched with gene sets related to cell proliferation, cell cycle, and immune activity. These tumors also exhibit significant infiltration by immune cells such as macrophage M1, follicular helper T cells, and activated natural killer cells, along with elevated T-cell exhaustion markers.
Prognostic Value of the 21-Gene Recurrence Score in Grade 3 Breast Cancer
The 21-gene recurrence score (RS) is a valuable tool for stratifying patients with grade 3 breast cancer, particularly those with hormone receptor-positive, HER2-negative tumors. This score helps identify patients who may benefit from chemotherapy in addition to endocrine therapy. Studies have shown that patients with high RS benefit significantly from chemotherapy, whereas those with low RS do not derive the same benefit, highlighting the importance of RS in tailoring treatment recommendations.
RNA-Sequencing and Genetic Reclassification
RNA-sequencing has proven effective in differentiating between high and low transcriptomic grades (TG) of breast cancer. This method has shown high accuracy in classifying grade 1 and grade 3 tumors and has the potential to reclassify grade 2 tumors into high and low TG, thereby improving the precision of treatment strategies and reducing the risk of over- or under-treatment. Additionally, genetic reclassification of histologic grades has identified new clinical subtypes, providing a more objective measure of grade and enhancing prognostic accuracy.
Molecular Heterogeneity and Prognosis
Grade 3 breast cancers exhibit significant molecular heterogeneity, which impacts prognosis and treatment outcomes. Copy number alterations (CNA) in grade 3 tumors have been linked to poor prognosis, and these genetic markers can help tailor adjuvant treatments for better clinical outcomes. Furthermore, the basal phenotype, identified by specific cytokeratin expressions, is associated with poor survival, particularly in grade 3 tumors, underscoring the need for routine identification and targeted treatment strategies.
Impact of Radiotherapy on Local Relapse
Hypofractionated radiotherapy has been shown to be as effective as conventional fractionation in controlling local disease in patients with grade 3 early breast cancer. Long-term studies have demonstrated no significant difference in local relapse rates between the two radiotherapy schedules, suggesting that hypofractionation is a viable option for breast-conserving therapy in these patients.
Clinical Significance in Triple-Negative Breast Cancer
In triple-negative breast cancer (TNBC), grade 3 tumors have been associated with better outcomes compared to grade 2 tumors. Studies have shown that grade 3 TNBC patients have a lower risk of relapse and death compared to those with grade 2 tumors, highlighting the importance of tumor grade in predicting patient outcomes and guiding treatment decisions.
Diagnostic and Prognostic Biomarkers
Grade-specific biomarkers, such as UBE2C, CCNB2, CDK1, KIF2C, and NDC80, have been identified as potential diagnostic and prognostic tools for breast cancer. These genes are significantly expressed in grade 3 tumors and are associated with cancer-specific processes and poor patient survival. Their expression profiles can help in the early detection and prognosis of high-grade breast cancers.
Protein Signatures and Histological Grade
Protein expression profiling has revealed that certain immunoregulatory proteins can serve as biomarkers for histological grading of breast cancer. These protein signatures can classify grade 1 versus grade 3 tumors and help reclassify grade 2 tumors, potentially leading to improved prognosis and tailored treatment plans.
Conclusion
Grade 3 breast cancers are aggressive and exhibit distinct molecular and immunological features. The use of genetic and protein biomarkers, along with tools like the 21-gene recurrence score, can significantly enhance the accuracy of prognosis and treatment strategies. Understanding the molecular heterogeneity and leveraging advanced diagnostic tools are crucial for improving patient outcomes in grade 3 breast cancer.
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