Advantages and limitations of molecular genetic prognostic tests for breast cancer. A systematic literature review
AuthorDelgado, André Berli
Background: Breast cancer is the most commonly diagnosed cancer in women internationally, and the most common cause of cancer related death among women. There are many ways to classify breast cancer, and breast cancer can be divided into several subgroups depending on which classification system is used. Pathological reports of breast carcinoma not only depend on one of these systems but include histopathological classification, grade of the tumor, and immunohistochemical (IHC) parameters like estrogen receptor (ER), progesterone receptor (PR), HER2- and Ki67-status. With the development of microarrays, it is now possible to analyze the genes of the cells, and with gene expression profiling (GEP) we have been able to evaluate breast cancer prognosis based on the gene expression of the cancer cells. Different genetic signatures of breast cancer have been obtained through DNA microarray technology, RNA sequencing and bioinformatic models. Some of these signatures have been validated through clinical studies and been translated into commercial prognostic assays. Four such commercial prognostic assays are Oncotype DX, MammaPrint, EndoPredict and PAM5-ROR. Methods: A literature search were conducted on the databases Medline and Embase. The inclusion criteria of the search were based on the Population, Intervention, Comparison and Outcome (PICO) framework. The search included terms to identify studies assessing the prognostic or economic aspects of Oncotype DX, MammaPrint, EndoPredict or Prosigna. Out of a total of 290 identified studies, 5 were included in this thesis. Results: Through the systematic literature search only studies focusing on Oncotype DX were included. The litterateur search disclosed that the Oncotype DX recurrence score (RS) is significantly associated with worse prognosis. The Oncotype DX RS were associated with both overall survival, disease free survival and local recurrence. The literature search also disclosed that Oncotype DX may be cost effective, especially in the high-risk RS group, were chemotherapy seemed to be clearly cost-effective because of the gain of additional quality- adjusted life-years (QUALY) at a low cost. Conclusion: The findings of this thesis suggest that Oncotype DX have an independent prognostic significance and is significantly associated with survival and risk of recurrence and may be helpful to guide treatment. Studies also show that Oncotype DX may be a cost effective alternative when used to guide adjuvant chemotherapy treatment.
PublisherUiT Norges arktiske universitet
UiT The Arctic University of Norway
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