Oncology

Triple-Negative Breast Cancer: Causes, Risks and Treatment

admin Mar 04, 2025

Breast cancer is primarily categorised by three main markers, namely oestrogen receptor (ER-positive), progesterone receptor (PR-positive) and human epidermal growth factor receptor 2 (HER2-positive). Over 70% of breast cancers are ER-/PR-positive, meaning they grow in response to oestrogen. Around 20-25% of breast cancers are HER2-positive, depending on growth pathways activated by this protein. These markers affect the tumour’s biology and influence treatment plans, as specific targeted therapies exist for these types.

Triple negative breast cancer is named because its tumour cells lack these three specific receptors. This type makes up about 15 per cent of invasive breast cancer cases. Breast cancer is considered triple positive breast cancer when it contains these three receptors, namely oestrogen receptors (oestrogen receptor-positive), progesterone receptors (progesterone receptor-positive) and elevated HER2 proteins that serve as receptors (HER2-positive).

Causes

While the exact cause remains unclear, researchers associate it with mutations in the breast cancer (BRCA) genes. When the BRCA gene is altered or damaged, it can result in the unchecked growth of tumours, such as those found in breast cancer.

Symptoms

Symptoms of triple negative breast cancer are similar to those of other types of breast cancer, which are more common. TNBC symptoms may include:

New lump or mass.
Localised or general swelling in the breast.
Having dimples in the skin texture.
Pain in the breast or nipple.
The nipple retracts backwards.
Dry, scaly, thickened or red skin on the nipple or breast
Nipple discharge other than breast milk.
Swollen lymph nodes, which may happen when breast cancer spreads to the lymph nodes beneath the arm or above the collarbone.
Many breast cancer symptoms can also be attributable to less serious conditions, so as you think about your situation, please remember that. That said, not having some of the symptoms does not mean you are free of breast cancer.

Risk factors

Traditional risk factors for all types of breast cancer, including lifestyle and environmental influences, also affect triple-negative breast cancer. However, additional genetic factors have been specifically linked to TNBC.

Age: Women who are premenopausal or under 50 years old face a higher risk of developing TNBC.
Ethnicity: The incidence of TNBC is notably higher among Black women compared to white women, with Black women being diagnosed with TNBC at twice the rate of their white counterparts.
BRCA1 gene mutation: Approximately 10-15% of white women with TNBC test positive for a BRCA1 gene mutation, while around 35% of Black women with TNBC have this mutation.
Other gene mutations: Mutations in the BRCA2 gene and other genetic mutations also contribute to the risk of TNBC, although they are less significant than BRCA1 mutations.
Family history: A strong family history of any type of breast cancer, along with other prognostic factors, can elevate the risk of developing TNBC and other forms of breast cancer.
Personal history: Having a personal history of any type of breast cancer increases the likelihood of developing TNBC.

Stages

Healthcare providers use the TNM cancer staging system to determine treatment plans. In this system, T indicates tumour size, N refers to cancer in lymph nodes and M denotes metastasis, meaning cancer has spread. The stages of breast cancer include:

Stage 0: The disease is non-invasive, meaning it has not spread beyond your breast ducts.
Stage I: The cancer cells have begun to spread to the nearby breast tissue.
Stage II: The tumour is either smaller than 2 cm across and spreads to underarm lymph nodes or larger than 5 cm across but has not affected the underarm lymph nodes. Tumours at this stage can range from 2 to 5 cm in size and may or may not involve nearby lymph nodes.
Stage III: At stage three, breast cancer has spread beyond its original site. It may have invaded nearby tissues and lymph nodes, but it has not reached distant organs. Healthcare providers often refer to Stage III breast cancer as locally advanced breast cancer. Here, a common question that arises is ‘Is third stage breast cancer curable?’. Healthcare providers regard stage three breast cancer as a locally advanced cancer that is potentially curable.
Stage IV: The cancer has spread to areas outside of your breast, such as the bones, liver, lungs or brain. Stage IV breast cancer is also referred to as metastatic breast cancer.

Diagnosis

The triple test for breast cancer is considered the most dependable method for diagnosis. These triple tests are:

Medical and personal history and clinical breast exam: Your healthcare provider will check your breasts for any indications of cancer and discuss your medical and personal history with you.
Imaging: To diagnose breast cancer, mammograms, ultrasounds and occasionally MRIs are utilised.
Biopsy: A biopsy involves taking a tissue sample, which is then sent to a lab for analysis. This step is essential for an accurate breast cancer diagnosis.

Triple negative breast cancer treatment

New types of treatment for TNBC are being investigated by healthcare providers and researchers. New drug combinations and novel approaches to current therapies are being tested in recent clinical trials. Other current therapies specific to these include:

Chemotherapy: For stage nul tri breast cancer (TNBC), healthcare providers may use a combo of chemotherapy and surgery.
Immunotherapy: A combination of immunotherapy and chemotherapy may be used by healthcare providers to shrink the size of the tumour before surgery. You can also receive immunotherapy. You may continue that for up to a year after your surgery and radiation post-surgery.
Surgery: This can be a lumpectomy to remove a particular lump or a mastectomy to remove the entire breast. Then, your healthcare provider generally performs a sentinel node biopsy or axillary node surgery to see if there are signs that your breast cancer has spread to lymph nodes.
Targeted therapy: This is a combination of chemotherapy and immunotherapy with cancer (cell) targeted treatments. An example of this is the usage of inhibitors of poly ADP ribose polymerase (PARP). This enzyme has an important role to play in repairing cells from DNA damage.
Radiotherapy: Following surgery, radiotherapy decreases the possibility of cancer returning.

Is there a cure for triple-negative breast cancer?

Currently, there is no cure, but treatments exist that can help individuals live longer with the disease, including cases where it recurs or spreads. For instance, the U.S. Food and Drug Administration (FDA) has recently approved a new treatment for metastatic TNBC. Antibody-drug conjugates enable cancer therapies to specifically target tumors by homing in on cancer-specific antibodies.

Conclusion

TNBC is a type of breast cancer that is known for being aggressive and challenging to treat. It tends to spread and come back more often than other forms of breast cancer. However, there are effective treatment options available, and researchers are actively developing therapies that specifically target TNBC. If you have been diagnosed with TNBC, it is essential to have an in-depth discussion with your healthcare provider or oncologist about your treatment choices and what you can expect moving forward.