Breast Tumor Markers – Are They Useful?

Breast cancer is the most common form of cancer in women and the second leading cause of cancer deaths in American women. In 2009, approximately 194,280 patients are estimated to be diagnosed with invasive breast cancer, and 62,280 with carcinoma in situ. An estimated 40,610 will die of this disease. For a woman of average risk, the lifetime incidence of breast cancer is one in eight.

Serum tumor markers for breast cancer used in the clinic include CA 15-3, CEA (carcinoembyonic antigen), and CA 27-29. All have low sensitivity and specificity, and thus not helpful in detecting early breast cancer. CA 15-3 levels are increased in approximately 5-30% of patients with stage 1 disease, 15-50% with stage 2, 60-70% with stage 3, and 65-90% with stage 4. CA 15-3 measurements are also elevated in 15-20% of women with benign breast conditions, 50-60% with liver disease, 20-70% pulmonary malignancies, 15-60% of gastrointestinal/colonic malignancies, and 40-60% of ovarian cancer cases. CEA is more prevalent in colorectal cancer, whereas CA 27-29 is more specific for breast cancer. These three tumor markers have, however, been validated for monitoring treatment in patients with advanced disease, particularly if the cancer cannot be evaluated with conventional imaging. The American Society of Clinical Oncology recommends the use of CEA, CA 15-3 and CA 27-29 only in metastatic settings, whereas the European Group on Tumor Markers recommends their use in disease surveillance in general.

With the current technology, circulating tumor cells have been found in very few cases of early stage breast cancer. Circulating tumor cells detected in both localized and metastatic breast cancer patients have been associated with worse outcome. Circulating tumor cells may also predict response to therapy.

There is much ongoing research to investigate new biomarkers for early detection of breast cancer. Blood-based markers include cells, DNA, RNA, peptides, sugars, and autoantibodies. Breast-based markers such as nipple/ductal fluid and breast fine needle aspiration (FNA) also include cells, DNA, RNA, proteins, sugars, and autoantibodies.

In the future, it is likely that a combination approach to measure simultaneously multiple markers would be most successful in detecting early breast cancer. Ideally, such a biomarker panel should be able to detect breast cancer in asymptomatic patients, and improve the accuracy of screening mammograms. A reliable biomarker signature may also signify new breast cancer, even in the setting of normal mammogram and physical examination, and would indicate further more intensive diagnostic workup and/or preventive treatment.

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