page_title: Breast cancer classification
section_title: Background
hierarchical_section_title: Breast cancer classification / DNA classification / DNA microarrays / Background
caption_attribution_description: English: Molecular classification of breast cancer from mRNA expression profiles
context_page_description: Breast cancer classification divides breast cancer into categories according to different schemes criteria and serving a different purpose. The major categories are the histopathological type, the grade of the tumor, the stage of the tumor, and the expression of proteins and genes. As knowledge of cancer cell biology develops these classifications are updated.
  The purpose of classification is to select the best treatment. The effectiveness of a specific treatment is demonstrated for a specific breast cancer. That treatment may not be effective in a different breast cancer. Some breast cancers are aggressive and life-threatening, and must be treated with aggressive treatments that have major adverse effects. Other breast cancers are less aggressive and can be treated with less aggressive treatments, such as lumpectomy.
  Treatment algorithms rely on breast cancer classification to define specific subgroups that are each treated according to the best evidence available.
context_section_description: DNA microarrays have compared normal cells to breast cancer cells and found differences in the expression of hundreds of genes.  Although the significance of many of those genetic differences is unknown, independent analyses by different research groups has found that certain groups of genes have a tendency to co-express.  These co-expressing clusters have included hormone receptor-related genes, HER2-related genes, a group of basal-like genes, and proliferation genes. As might therefore be anticipated, there is considerable similarity between the receptor and microarray classifications, but assignment of individual tumors is by no means identical. By way of illustration, some analyses have suggested that approximately 75% of receptor classified triple-negative breast cancers (TNBC) basal-like tumors have the expected DNA expression profile, and a similar 75% of tumors with a typical basal-like DNA expression profile are receptor TNBC as well. To say this in a different way to emphasize things, this means that 25% of triple-negative breast cancer (TNBC) basal-like tumors as defined by one or other classification are excluded from the alternative classification's results. Which classification scheme (receptor IHC or DNA expression profile) more reliably assorts particular cancers to effective therapies is under investigation.
  Several commercially marketed DNA microarray tests analyze clusters of genes and may help decide which possible treatment is most effective for a particular cancer.  The use of these assays in breast cancers is supported by Level II evidence or Level III evidence. No tests have been verified by Level I evidence, which is rigorously defined as being derived from a prospective, randomized controlled trial where patients who used the test had a better outcome than those who did not.  Acquiring extensive Level I evidence would be clinically and ethically challenging. However, several validation approaches  are being actively pursued.
  Numerous genetic profiles have been developed. The most heavily marketed are:
  Oncotype DX is supported by Level II evidence, and was originally designed for use in estrogen receptor (ER) positive tumors, and has been endorsed by the American Society of Clinical Oncology (ASCO) and the NCCN.
  MammaPrint is supported only by Level III evidence, can be performed on estrogen receptor (ER) positive and negative tumors, and has FDA approval.
  Two other tests also only have Level III evidence: Theros and MapQuant Dx.
  These multigene assays, some partially and some completely commercialized, have been scientifically reviewed to compare them with other standard breast cancer classification methods such as grade and receptor status. Although these gene-expression profiles look at different individual genes, they seem to classify a given tumor into similar risk groups and thus provide concordant predictions of outcome.
  Although there is considerable evidence that these tests can refine the treatment decisions in a meaningful proportion of breast cancers they are fairly expensive; proposed selection criteria for which particular tumors may benefit by being interrogated by these assays remain controversial, particularly with lymph node positive cancers. One review characterized these genetic tests collectively as adding "modest prognostic information for patients with HER2-positive and triple-negative tumors, but when measures of clinical risk are equivocal (e.g., intermediate expression of ER and intermediate histologic grade), these assays could guide clinical decisions".
caption: Molecular classification of breast cancer from mRNA expression profiles
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