Main Tumor Markers in Human Breast Cancer

Human Breast Cancer

Breast cancer is a heterogeneous disease with distinct pathological and molecular properties, as well as clinical manifestations. Breast cancer can be categorized into five main intrinsic molecular subtypes based on molecular features: Luminal A, Luminal B, HER2-enriched, Basal-like, and Claudin-low. Invasive ductal carcinoma is the most prevalent malignant breast tumor, accounting for 75% of cancer cases and having a high lymphatic metastatic risk. Initial breast cancers can spread through lymphatic or blood vessels, resulting in distant metastasis, particularly to bones, which can cause discomfort, mobility difficulties, neurogenic disorders, hypercalcemia, and pathological fractures. The later the diagnosis, the more likely metastasis, which can occur in the brain, bone marrow, liver, lymph nodes, and lung.

Among women, breast cancer is the most common malignancy, accounting for approximately 25% of newly diagnosed cancer cases worldwide. In the United States, about 13% of women develop breast cancer. The incidence of breast cancer varies globally, with the highest rates in Australia, New Zealand, most parts of Europe, and North America, intermediate rates in South America and Eastern Europe, and the lowest rates in most parts of Asia and Africa. The etiology of breast cancer is complex and multifaceted, involving genetic, environmental, and lifestyle factors. The incidence is associated with multiple factors, including gender, age, estrogen levels, family history, gene mutations (such as BRCA1 and BRCA2 mutations), and unhealthy lifestyle choices, among others. Despite the increasing incidence of breast cancer globally, mortality rates have declined due to improved screening and treatment methods over recent decades.

Breast cancer treatment is multidisciplinary, including local treatments (surgery and radiotherapy) and systemic therapies. Systemic treatments include endocrine therapy for hormone receptor-positive disease, chemotherapy, anti-HER2 therapy for HER2-positive disease, bone-stabilizing agents, poly (ADP-ribose) polymerase inhibitors for BRCA mutation carriers, and recent immunotherapies. Despite significant advances in breast cancer treatment, local and distant recurrences remain major threats. About 20-30% of early-stage breast cancer patients eventually develop distant metastatic disease recurrence. Moreover, achieving equitable access to treatment advancements globally remains a future challenge in breast cancer care.

Figure 1. Anatomy of the Breast and Pathological Classification of Breast Cancer Tissues
(Source: Nolan E, et al. 2023)

Cancer Antigen 15-3 (CA 15-3)

CA 15-3 is a protein with a high molecular weight (300-450 KDa) that belongs to the transmembrane receptor MUC-1 and possesses cell adhesion properties. MUC-1 can be found on the apical plasma membrane of normal secretory epithelial cells. However, following malignant transformation, MUC-1 may be overexpressed on both the membrane surface and the cytoplasm. CA 15-3 identifies a soluble version of MUC-1 protein and is the most often utilized blood marker in breast cancer patients. In breast cancer patients, CA 15-3 expression in tumor cells triggers the production of antibodies (anti-CA 15-3) as part of the immune response. Approximately 80% of patients with metastatic breast cancer have CA 15-3 leakage from cancer cell surfaces into the blood. Thus, this glycoprotein antigen is the most widely used serum tumor marker in breast cancer. The reference range for serum CA 15-3 is less than 30 U/mL.

Figure 2. CA 15-3 Levels Comparison in Healthy Individuals and Breast Cancer Patients
(Source: Siddiqua J, et al. 2010)

CA 15-3 is essential for detecting and monitoring breast cancer. It contributes to determining the amount of breast cancer dissemination, particularly bone metastases. Elevated CA 15-3 levels indicate metastases, particularly bone metastasis. CA 15-3 can be considered a useful predictor of bone metastase prognosis in relevant patients.

To detect CA 15-3, several analytical techniques can be utilized, including enzyme-linked immunosorbent assay (ELISA), fluorescence immunoassay, electrochemiluminescence, and radioimmunoassay. However, these techniques have certain disadvantages, including expensive costs, the requirement for experienced personnel, lengthy analysis periods, and sophisticated labor-intensive testing procedures.

CA15-3 ELISA Kits

CA15-3 Antibodies

CA15-3 Antigens

CEA Antibodies

CEA Antigens

CEA ELISA Kits