Identifying Tumor Markers

Technological advances are continually changing the way breast cancer is diagnosed.  Physicians classify breast cancer according to what is known as the molecular subtype. Tumor markers and genetic profiling tests discern a cancer's molecular subtype.  The molecular subtypes gives clues as to how quickly the disease progresses and chances of survival.  Physicians use this information to select the best combination of treatments.  Estrogen and progesterone receptors (ER and PR) and HER2 are the currently used subtypes for classification.  The different subtypes are:

 

*Estrogen receptor ER-positive, PR-positive, and HER2-negative

*HER2-positive

*ER-negative, PR-negative, HER2-negative (referred to as triple negative)

*Normal breast-like

 

Estrogen and Progesterone Receptors

How fast breast cancer grows may depend upon levels of estrogen and progesterone (ER and PR).  These female hormones signal special receptor cells, found in normal cells and possibly in breast cancer cells as well.  Breast cancers are maybe classified as ER positive or negative and PR positive or negative.  The ER or PR status is further defined using a scale of 1 to 3, indicating density of receptors.  Estrogen and progesterone may signal receptor cells to activate cell division and growth, therefore causing spread of cancer to other parts of the breast and possibly other parts of the body.

At least one of these receptors is found in two-thirds of breast cancer cases.  With ER and PR positive cases, anti-estrogen agents are used to suppress hormone production, helping to prevent recurrence of breast cancer.

Women should only receive hormone treatment when it will be effective, therefore ER and PR testing must be accurate.  American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN) recommends ER/PR testing for all invasive breast cancers.  However, the two organizations differ on recommendations regarding ducal carcinoma in situ (DCIS).  The NCCN recommends ER and PR testing for DCIS, but ASCO guidelines state there is insufficient evidence to recommend routine ER/PR testing.  Both agencies recommend testing only from accredited facilities.  Testing may also be repeated to verify accuracy.

 

HER2

The presence of a specialized protein, HER2, is associated with faster growing tumors and also an increased likelihood of recurrence.  This protein can be found on the surface breast cells and breast cancer cells.  The HER2/neu gene is the gene related to this protein.  Approximately 20% of breast cancers contained high levels of the HER2 protein or gene.

The NCCN suggests that HER2 testing should be done on all invasive breast cancers.  ASCO and the College of American Pathologists (CAP), who have established a joint clinical practice guideline, also agree with NCCN regarding HER2 testing for invasive cancers.   All three agencies recommend testing by approved methods at accredited facilities.  Physicians may also ask for testing to be repeated to verify accuracy.

 

Other Tumor Makers

 

While potential of other useful tumor markers are being investigated, only two others have been found to offer consistent information.  These tumor markers are urokinase-type plasminogen activator (uPa) and plasminogen activator inhibitor 1 (PAI-1).  The lower the level of uPA and PAI-1, the less likely the cancer will recur.  Therefore, additional prevention treatment may be unnecessary.  Although the ASCO guideline suggests these markers may be beneficial, routine use of these markers has not been recommended.  Further evidence is needed to add routine use to the guidelines.