Triple-negative breast cancer (TNBC) is a specific and aggressive form of breast cancer characterized by the absence of three key receptors: estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2). This means that the cancer cells do not have these receptors, which are commonly targeted in other breast cancer treatments. Because of this, TNBC does not respond to hormonal therapies or drugs that target HER2, making it more challenging to treat.
The causes of triple-negative breast cancer are complex and not fully understood, but they involve a combination of genetic, biological, and environmental factors. Unlike some other breast cancers, TNBC tends to be more common in younger women, African American women, and those with a family history of breast cancer, especially if they carry mutations in certain genes.
One of the most significant genetic contributors to TNBC is mutations in the BRCA1 gene. BRCA1 is a tumor suppressor gene that helps repair damaged DNA. When this gene is mutated, the repair process is impaired, leading to increased risk of cancer development. Women with BRCA1 mutations are more likely to develop triple-negative breast cancer compared to other breast cancer types. BRCA2 mutations can also increase risk but are less specifically linked to TNBC.
Beyond BRCA mutations, other genetic alterations and molecular changes in the cancer cells contribute to the development of TNBC. These include abnormalities in genes involved in cell growth, division, and death, which lead to uncontrolled proliferation of abnormal breast cells. The lack of hormone receptors means these cancer cells grow independently of estrogen and progesterone signals, which normally regulate breast tissue growth.
Hormonal factors also play a role in breast cancer risk in general, but their relationship with TNBC is less direct. Early menstruation, late menopause, and hormone replacement therapy increase breast cancer risk overall but are not strongly linked to triple-negative cases. This suggests that TNBC may arise through different biological pathways than hormone receptor-positive breast cancers.
Lifestyle and environmental factors contribute as well. Obesity, alcohol consumption, smoking, and lack of physical activity are known to increase breast cancer risk and may influence TNBC development. However, these factors alone do not cause TNBC but can interact with genetic predispositions to increase risk.
Inflammation and immune system factors are also being studied in relation to TNBC. Chronic inflammation in breast tissue may create an environment that supports cancer growth. Additionally, TNBC often shows higher levels of immune cell infiltration, which is a focus of new treatment approaches.
TNBC tends to be more aggressive and fast-growing compared to other breast cancer types. It often presents as a lump or thickening in the breast and may be diagnosed at a more advanced stage. Because it lacks the receptors that many targeted therapies use, treatment options are typically limited to chemotherapy, radiation, and surgery.
In summary, triple-negative breast cancer arises from a complex interplay of genetic mutations—most notably BRCA1—biological factors that drive rapid cell growth without hormone receptor involvement, and lifestyle or environmental influences that may increase risk. Its aggressive nature and lack of targeted treatment options make understanding its causes critical for developing better prevention and therapies.
