Metaplastic breast cancer (MBC) is an uncommon and distinct form of invasive breast cancer, representing less than 1% of all cases. It originates in the milk ducts but is defined by its unique cellular composition. Unlike more common breast cancers, metaplastic tumors contain a mixture of different cell types. This blend arises from a process where glandular cells transform into other varieties, creating a complex tumor that can appear as a combination of breast cells and cells resembling skin, bone, or other tissues.
Defining Characteristics and Subtypes
The term “metaplasia” describes a biological process where one mature cell type converts into another. In MBC, this results in a tumor that is a composite of both carcinoma elements (cancerous cells of epithelial origin) and sarcoma-like elements (cancerous cells of connective tissue origin). This dual composition is the fundamental characteristic of metaplastic breast cancer.
The World Health Organization (WHO) categorizes MBC into several subtypes based on the appearance of these transformed cells.
- Spindle cell carcinoma, where cells are elongated.
- Squamous cell carcinoma, which involves cells similar to those on the surface of the skin.
- Metaplastic carcinoma with mesenchymal differentiation, where tumors may contain elements that look like cartilage or bone.
- Low-grade adenosquamous carcinoma.
- Fibromatosis-like metaplastic carcinoma.
A primary feature of metaplastic breast cancer is its receptor status. The vast majority of these tumors are classified as triple-negative breast cancer (TNBC). This means the cancer cells test negative for estrogen receptors (ER), progesterone receptors (PR), and a protein called human epidermal growth factor receptor 2 (HER2), which has direct implications for management.
The Diagnostic Process
The diagnostic process for metaplastic breast cancer often begins with the detection of a lump in the breast. These lumps are frequently palpable, feeling firm to the touch, and may be noticed because of their rapid growth. The initial symptoms are indistinguishable from other types of breast cancer and can include changes in breast shape or size, skin dimpling, or nipple inversion.
Following the discovery of a breast abnormality, imaging tests are the next step. A mammogram can identify a suspicious mass, and an ultrasound is used to gather more detail about its characteristics. While these imaging tools are effective at locating a tumor, they cannot definitively distinguish MBC from other forms of invasive ductal carcinoma based on appearance alone.
The only way to confirm a diagnosis of metaplastic breast cancer is through a biopsy. A core needle biopsy is a common procedure where a small sample of the suspicious tissue is removed for laboratory analysis. A pathologist then examines this tissue under a microscope to identify the mixture of cell types that are the hallmark of MBC.
As part of this pathological workup, the tissue sample undergoes immunohistochemistry (IHC) tests. These tests are performed to determine the tumor’s hormone receptor status (ER and PR) and its HER2 status. This step confirms whether the cancer is triple-negative, a common finding with MBC that provides information for treatment planning.
Treatment Protocols for Metaplastic Tumors
Surgery is the primary and initial treatment for nearly all patients with metaplastic breast cancer. The specific surgical approach depends on factors like tumor size and location. A lumpectomy, which is a breast-conserving surgery that removes only the tumor and a small margin of surrounding tissue, may be an option. In other cases, a mastectomy, the complete removal of the breast, is recommended. Surgeons will also check the lymph nodes for cancer spread through a sentinel lymph node biopsy or an axillary lymph node dissection.
Following surgery, systemic therapies are considered to address cancer cells that may have traveled beyond the breast. Because the majority of metaplastic tumors are triple-negative, they do not respond to treatments that target hormone receptors or HER2-targeted therapies. This makes chemotherapy the principal systemic treatment used for MBC. Regimens often include taxane-based or anthracycline-based drugs, which are administered to kill cancer cells throughout the body and reduce the risk of the cancer returning.
Radiation therapy is another component of the treatment plan for MBC. It is recommended for patients who undergo a lumpectomy to destroy any remaining cancer cells and lower the chance of a local recurrence. Radiation may also be advised after a mastectomy, particularly if the tumor was large or if cancer cells were found in the lymph nodes.
Given the challenges in treating MBC, researchers are exploring new therapeutic avenues. Immunotherapy, specifically a class of drugs called checkpoint inhibitors, has shown promise in treating triple-negative breast cancers. These drugs work by helping the body’s own immune system recognize and attack cancer cells. Patients are often encouraged to consider participating in clinical trials, which provide access to these and other emerging treatments.
Prognosis and Factors Influencing Outlook
Metaplastic breast cancer is considered more aggressive than more common types of breast cancer and has historically been associated with a more challenging prognosis. The outlook for an individual is influenced by several specific factors related to their diagnosis.
The single most significant factor in determining prognosis is the stage of the cancer at the time of diagnosis. Staging incorporates the size of the tumor and whether the cancer has spread to nearby lymph nodes or to distant parts of the body. Cancers detected at an earlier stage, before they have had a chance to spread, are associated with better outcomes.
The grade of the tumor also plays a role in the long-term outlook. Tumor grade is a measure of how abnormal the cancer cells appear under a microscope compared to healthy cells. Higher-grade tumors, which look more disorganized and are dividing more rapidly, tend to be more aggressive. The specific subtype of metaplastic cells and the effectiveness of chemotherapy can also influence the prognosis.
Compared to other breast cancer types, MBC has a higher likelihood of recurrence. This recurrence can be local, returning in the treated breast or chest wall, or distant. Distant recurrence, or metastasis, occurs when the cancer spreads to other organs, with the lungs being a common site for MBC.