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How do molecular assessments help in the management of breast cancer?
Several molecular methods assist in the management of breast cancer. These include:
Assessment of sentinel lymph node involvement. In the absence of the demonstration of metastatic cells the requirement for wide axillary resection is obviated. For intraoperative assessment cytokeratin 19 mRNA is demonstrated using the One Step Nucleic acid Amplification (OSNA) assay. Post-operatively, ICC is used in FFPE sections to demonstrate cytokeratin in any metastatic cells that may be present.
ICC to assist diagnosis and prognosis. Various antibodies can be applied to FFPE sections. Smooth muscle actin demonstration can assist in distinguishing between DCIS, where the basement membrane visualized by the antibody remains intact, in contrast to a broken or absent basement membrane that is indicative of the presence of invasive cancer. E-cadherin demonstration and assessment of proliferation index using an antibody such as Ki67 can assist in distinguishing between Luminal A and Luminal B invasive cancers that have different prognoses.
Hormone and HER2 receptor status. It is mandatory to assess the status of these receptors. This is used to guide targeted hormonal or HER2 therapy and provide prognostic indicators. ICC is used to establish the ER and PR and HER2 status in FFPE sections and interpretation uses semi-quantitative methods. In the case of borderline ICC results for HER2, ISH is used as to establish if the copy number change for the gene. All of these assessments are undertaken in accordance with internationally agreed guidelines.
Gene expression profiling. Commercially available gene expression profiling can be undertaken for early stage invasive breast cancers with the objective of determining if a patient is likely to benefit from chemotherapy in addition to targeted therapy. The Oncotype DX test is of these commercially available assays and screens for the expression of 21 genes.
Considerable advances are being made in understanding the molecular profiles of breast cancer and it is likely that this will lead to new markers for the management of this disease being identified.