Basal-like breast cancer is a form of breast cancer identified by its molecular makeup. The cancer cells resemble the basal cells that form the lowest layer of the breast ducts, and the subtype is defined by the specific genes and proteins they express. This biological signature determines how the cancer behaves and how it is managed.
Characteristics of Basal-Like Tumors
The term “basal-like” originates from the cancer cells’ similarity to basal epithelial cells in the breast’s milk ducts. Gene expression analysis creates a “molecular portrait” of a tumor, allowing for this classification. Basal-like tumors are characterized by the expression of genes active in basal cells, such as those producing cytokeratins 5/6 and 17.
While often used interchangeably, basal-like breast cancer and triple-negative breast cancer (TNBC) are not identical. TNBC is defined by the absence of estrogen (ER), progesterone (PR), and HER2 receptors. While about 80% of basal-like cancers are triple-negative, a basal-like diagnosis is determined by a broader gene pattern, and some tumors may express ER or HER2.
This unique profile means basal-like cancers do not respond to therapies that target hormones. They are often aggressive, high-grade tumors that tend to grow and spread quickly. This contrasts with other molecular subtypes, such as Luminal A or Luminal B, which are hormone-receptor-positive.
Risk Factors and Genetic Links
Basal-like breast cancer is more frequently diagnosed in younger, premenopausal women under 40. There is also a higher incidence among women of African ancestry compared to other ethnicities.
The most significant genetic link is an inherited mutation in the BRCA1 gene, a tumor suppressor that helps repair damaged DNA. A mutation disrupts this repair mechanism, and an estimated 75% of breast cancers in women with a BRCA1 mutation have a basal-like or triple-negative profile.
The loss of normal BRCA1 function is thought to contribute to the development of these tumors. Even when the BRCA1 gene itself is not mutated, its pathway may be dysfunctional in some nonhereditary tumors. This strong hereditary link has direct implications for genetic counseling and testing for patients and their families.
Diagnosis and Staging
The diagnostic process begins with imaging like a mammogram or ultrasound, which may reveal a suspicious mass, often described as a hard or rubbery lump that feels immovable. If an abnormality is detected, a biopsy is performed to obtain a tissue sample for laboratory analysis.
Confirmation of the basal-like subtype involves a test called immunohistochemistry (IHC). Pathologists use IHC to test for the absence of ER, PR, and HER2 receptors. They also look for the presence of markers characteristic of basal cells, such as cytokeratins 5/6 (CK5/6) and epidermal growth factor receptor (EGFR).
Once the diagnosis is confirmed, the cancer is staged to determine its extent. Staging describes the tumor’s size and whether it has spread to lymph nodes or metastasized to distant parts of the body. This information is necessary for planning the most effective treatment.
Treatment Protocols
The primary systemic treatment for basal-like breast cancer is chemotherapy. Because the cells lack hormone and HER2 receptors, they are unresponsive to targeted treatments like hormone therapy. Chemotherapy is effective because it attacks the rapidly dividing cells characteristic of this cancer.
Surgical options depend on the tumor’s size and other factors. Common procedures include a lumpectomy, which removes the tumor, or a mastectomy, which removes the entire breast. Radiation therapy is often administered after surgery to destroy remaining cancer cells and reduce the risk of local recurrence.
An advancement in treating this subtype is the use of PARP inhibitors, such as olaparib and talazoparib. These drugs are effective for patients with an inherited BRCA1 or BRCA2 mutation. PARP is an enzyme that helps repair DNA; by blocking it, these inhibitors cause the cancer cells, which already have a faulty DNA repair system, to be destroyed. This targeted approach exploits a specific vulnerability in the cancer cells.
Prognosis and Recurrence Patterns
Due to its aggressive nature, basal-like breast cancer is associated with a poorer prognosis compared to other subtypes, particularly in the first few years following diagnosis. The risk is linked to a higher likelihood of early metastatic relapse.
This cancer has a unique recurrence pattern known as the “5-year paradox.” The risk of recurrence is highest in the first one to three years after treatment and then drops sharply. If the cancer does not return within five years, the long-term prognosis improves, with a lower risk of late recurrence than hormone-receptor-positive cancers.
When basal-like breast cancer recurs, it tends to spread to distant sites rather than returning locally. The most common sites for metastasis are visceral organs, such as the lungs and brain, instead of the bones. This distinct pattern of spread is a consideration in follow-up care.