Ciencia

Serum Tumor Markers in Breast Cancer: Are They of Clinical Value?
1. Michael J. Duffy
+Author Affiliations
1. 1Department of Nuclear Medicine, St. Vincent’s University Hospital; UCD School of Medicine and Medical Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin; and Dublin Molecular Medicine Institute, Dublin, Ireland.-------------------------------------------------
Abstract
Background: Although multiple serum-based tumor markers have been described for breast cancer, such as CA 15-3, BR 27.29 (CA27.29), carcinoembryonic antigen (CEA), tissue polypeptide antigen, tissue polypeptide specific antigen, and HER-2 (the extracellular domain), the most widely used are CA 15-3 and CEA.
Methods: The literature relevant to serum tumormarkers in breast cancer was reviewed. Particular attention was given to systematic reviews, prospective randomized trials, and guidelines issued by expert panels.
Results: Because of a lack of sensitivity for early disease and lack of specificity, none of the available markers is of value for the detection of early breast cancer. High preoperative concentrations of CA 15-3 are, however, associatedwith adverse patient outcome. Although serial determinations of tumor markers after primary treatment for breast cancer can preclinically detect recurrent/metastatic disease with lead times of ∼2–9 months, the clinical value of this lead time remains to be determined. Serum markers, however, are the only validated approach for monitoring treatment in patients with advanced disease that cannot beevaluated by use of conventional criteria.
Conclusions: CA 15-3 is one of the first circulating prognostic factors for breast cancer. Preoperative concentrations thus might be combined with existing prognostic factors for predicting outcome in patients with newly diagnosed breast cancer. At present, the most important clinical application of CA 15-3 is in monitoring therapy in patients withadvanced breast cancer that is not assessable by existing clinical or radiologic procedures.
For many malignancies, serum tumor markers play an important role in patient management (1)(2)(3)(4)(5) (Table 1⇓ ). In breast cancer, however, the role of serum markers is less well established. The most widely used serum markers in breast cancer are CA 15-3 and carcinoembryonic antigen (CEA). 1 Less widelyused markers include BR 27.29 (also known as CA27.29), tissue polypeptide antigen (TPA), tissue polypeptide specific antigen (TPS) and the shed form of HER-2 [Table 2⇓ ; for a review, see Refs. (6)(7)(8)]. The potential uses of serum markers in breast cancer include aiding early diagnosis, determining prognosis, prospectively predicting response or resistance to specific therapies, surveillanceafter primary surgery, and monitoring therapy in patients with advanced disease. The aim of this review is to examine the role of serum tumor markers in the detection and management of patients with breast cancer. As CA 15-3 is the most widely used serum marker in breast cancer, most of the review will focus on it.
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Aiding Early Diagnosis
Lack ofsensitivity for early-stage disease combined with a lack of specificity precludes the use of all existing serum markers for the early diagnosis of breast cancer. For example, CA 15-3 concentrations are increased in ∼10% of patients with stage I disease, 20% with stage II disease, 40% with stage III disease, and 75% with stage IV disease (9). According to an American Society of Clinical Oncology(ASCO) Expert Panel, a CA 15-3 concentration 5- to 10-fold above the upper limit of the reference interval could alert a physician to the presence of metastatic disease (9). However, a low concentration does not exclude metastasis (9).
As well as lacking sensitivity for early disease, CA 15-3 also lacks specificity for breast cancer. Increased concentrations of the marker can be found in a small...