‘What Does Triple-Negative Breast Cancer Mean?’ and Other Common Questions

If you or someone you care about is diagnosed with triple-negative breast cancer (TNBC), it can be a frightening and confusing time. Your heart and mind are racing and you have so many questions. How is triple-negative breast cancer different from other types of breast cancer? What types of treatment are available and how effective are they?

To help break it all down, we asked experts in the Breast Program at the Ann B. Barshinger Cancer Institute, to answer the questions patients most often ask. 

What Does Triple-Negative Breast Cancer Mean?

There are many types of breast cancer. The type is determined by the specific changes (mutations) in the breast cells that become cancer. Triple-negative breast cancer is an aggressive type of invasive breast cancer that accounts for about 10-20% of all breast cancers. It is also sometimes referred to as infiltrating breast cancer, or when it originates in a milk duct, invasive ductal carcinoma or infiltrating ductal carcinoma. Like other invasive breast cancers, TNBC is more likely to spread beyond the breast (metastasize) and recur after treatment.

When a sample of breast tissue (biopsy) is examined to determine if it is cancerous, the cells are also tested to determine the cancer type. This helps oncologists recommend the most effective treatment.

Some tumors test positive for receptors, or proteins known to fuel breast cancer growth:

• Estrogen (ER) hormone receptor
• Progesterone (PR) hormone receptor
• Human epidermal growth factor receptor 2 (HER2) 

If the cancer cells test negative for all three of these receptors, the diagnosis is triple-negative breast cancer. The cause of its growth is unclear. 

Penn Medicine Lancaster General Health tests all invasive breast cancers to see if the tumor qualifies as triple negative. We offer comprehensive care and innovative treatment for every stage of TNBC.

What are the Symptoms of TNBC?

Triple-negative breast cancer may be discovered as a mass or suspicious finding on a mammogram before showing any symptoms. However, some people may experience:

• Changes in the breast shape
• Breast or nipple pain
• Discharge from the nipple
• Nipple inversion
• Swelling of the breast
• A lump
• Thickening of the nipple skin
• New crease in the breast

How is TNBC Diagnosed?

Triple-negative breast cancer and invasive ductal carcinoma (IDC) are most commonly seen on a mammogram or through other tests ordered when symptoms are present. TNBC and IDC may also be found on breast examination.

If cancer is suspected on a mammogram, your doctor may order other imaging studies and/or a biopsy. After tissue from the biopsy is removed, it is examined and tested in the lab to determine its HER2 and hormone receptor status. Once the genetic and hormonal make-up of the tumor are determined, your cancer team will recommend the best and most effective treatments.

How is Triple-Negative Breast Cancer Treated?

Without receptors, common breast cancer treatments like hormone therapy are typically ineffective against TNBC. However, recent developments in research have led to several new options for some patients with TNBC including immunotherapy, which activates the immune system to fight the cancer. Your breast cancer treatment for TNBC may include:

• Surgery, which can involve a lumpectomy (removing cancerous breast tissue) or mastectomy (removing the entire breast) and breast reconstruction to recreate the shape and appearance of your breast.
• Chemotherapy, using oral or intravenous (IV) drugs to attack cancer cells.
• Radiation therapy, may be recommended following surgery or chemotherapy to kill any cancer cells that may remain.
• Targeted therapy, uses drugs to block the growth of cancer cells by focusing on the mutated, or changed, genes or proteins that make cancer cells multiply quickly. For select patients with advanced-stage HER2-negative breast cancer and a BRCA1 or BRCA2 mutation, targeted therapies called PARP inhibitors stop PARP proteins from repairing damaged DNA in cells. Cancer cells are destroyed when they are not repaired.
  
  For some people with TNBC, we may recommend targeted therapy used in combination with chemotherapy. We use a drug that binds to a specific protein on the cancer cells and guides chemotherapy directly to those cells.

• Immunotherapy, which triggers a patient’s own immune system to recognize and destroy cancer cells. The immune system relies on proteins located on cells (checkpoints) to know whether or not to attack a cell. Breast cancer cells sometimes alter these checkpoints to avoid an attack from the immune system. Drugs called immune checkpoint inhibitors target checkpoint proteins in a way that allows immune cells to recognize and destroy cancer cells.
  
  In 2019, the FDA approved the first checkpoint inhibitor for the treatment of breast cancer, a drug called atezolizumab (Tecentriq®), that works in combination with chemotherapy to treat metastatic TNBC in patients whose tumors express the PD-L1 protein.
• Clinical trials, offer access to promising breast cancer treatments for TNBC, including a study involving CAR-T cell therapy, an advanced form of cancer immunotherapy that was developed at Penn Medicine. 

Are There Risk Factors for TNBC and Can I Reduce Them?

Your chance of developing triple-negative breast cancer is greater if you have the following risk factors:

• Your age: Women age 50 and younger and premenopausal women have a greater risk of TNBC.
• You have the BRCA1 gene mutation: Approximately 70% of breast cancers diagnosed in women with an inherited BRCA1 gene mutation are TNBC.
• Your ethnicity: Black and Hispanic women have a higher rate of TNBC. 

While there is no absolute way to prevent breast cancer, it is recommended that everyone: 

• Receive age-appropriate screenings
• Eat a balanced diet 
• Limit alcohol intake
• Get regular exercise
• Maintain a healthy body weight

It is important for women to know the symptoms and warning signs and be aware of any family history of breast cancer.

If you are at high risk for TNBC, the Cancer Risk Evaluation Program at Penn Medicine Lancaster General Health offers education, counseling and support. The Basser Center for BRCA in Philadelphia offers resources just for people with a BRCA gene mutation.