Triple-negative breast cancer (TNBC), a subtype of breast cancer, is a rare, malignant breast disease that lacks receptors for the hormones estrogen and progesterone and the human epidermal growth factor (HER2) protein usually found in other breast cancers. An aggressive cancer, triple-negative breast cancer grows and spreads more quickly than other types of invasive breast cancer. Triple-negative breast cancer is also more likely to reoccur and has a worse outcome (prognosis) than other breast cancers. Triple-negative breast cancer accounts for 10-15% of all breast cancers and is more common in women under the age of 40 who are African American or Hispanic, and who carry the BRCA1 gene mutation. Seventy percent of breast cancers in individuals with a BRCA gene mutation are triple-negative. Triple-negative breast cancer is classified in the following stages: Stage 0 – Ductal cancer in situ (DCIS), which is a non-invasive breast cancer. The cancer cells are still located in a breast duct and have not spread. Stage 1A – The breast cancer tumor is 2 centimeters or smaller and has not spread. Stage 1B – The tumor is 2 centimeters or smaller (or undetectable) with microscopic spread (micrometastases) into one-to-three axillary (underarm) lymph nodes. The metastasis is more than .2 millimeters but less than 2 millimeters and has not spread to other parts of the body. Stage IIA – One of the following has occurred, and the cancer has not spread beyond the lymph nodes: 1) The tumor is 2 centimeters (or undetectable) and has spread to one-to-three axillary (underarm) lymph nodes, with the cancer in the lymph nodes greater than 2 millimeters; 2) the tumor is 2 centimeters or smaller (or undetectable) and microscopic cancer is found in the internal mammary (breast) lymph nodes; 3) the tumor is 2 centimeters or smaller (or undetectable) and has spread to one-to-three axillary (underarm) lymph nodes and the internal mammary (breast) lymph nodes; or 4) the tumor is greater than 2 centimeters but less than 5 centimeters, but has not spread to lymph nodes. Stage IIB – One of the following has occurred, and the cancer has not spread beyond the lymph nodes: 1) the tumor is larger than 2 centimeters but less than 5 centimeters and has spread to one-to-three axillary (underarm) lymph nodes, and microscopic cancer is found in the internal mammary (breast) lymph nodes; or 2) the tumor is larger than 5 centimeters but has not invaded the chest wall or skin. Stage IIIA – One of the following has occurred, and the cancer has not spread beyond the lymph nodes: 1) the tumor is less than 5 centimeters (or undetectable) and has spread to four-to-nine axillary (underarm) lymph nodes; or 2) the tumor is greater than 5 centimeters, has not invaded the chest wall or skin, but has spread to one-to-nine axillary (underarm) lymph nodes or internal mammary (breast) nodes. Stage IIIB – The tumor has invaded the chest wall or skin, but hasn’t spread to other parts of the body, and one of the following has occurred: 1) the tumor has not spread to the lymph nodes; 2) the tumor has spread to one-to-three axillary (underarm) lymph nodes, and microscopic cancer has spread to the internal mammary (breast) nodes; or 3) the tumor has spread to four-to-nine axillary (underarm) lymph nodes, or it has caused swelling in the internal mammary (breast) nodes. Stage IIIC – The tumor is any size (or undetectable), had not spread beyond the lymph nodes, and one of the following has occurred: 1) the cancer has spread to 10 or more axillary (underarm) nodes; 2) the cancer has spread to the lymph nodes under the clavicle (collar bone); the cancer has spread to the lymph nodes above the collarbone; 3) the cancer has spread to axillary (underarm) lymph nodes; or 4) the cancer has spread to four or more axillary (underarm) lymph nodes, and microscopic cancer is found in internal mammary (breast) lymph nodes. Stage IV – The cancer is any size and may or may not have spread to close lymph nodes, but it has spread to organs such as the liver, lung, brain, or bones, or other distant lymph nodes.

Alternative names for triple-negative breast cancer include ductal cancer in situ (DCIS), HER-negative breast cancer, invasive breast cancer, metastatic breast cancer, and PD-L1 protein breast cancer.

The cause of triple-negative breast cancer has been linked to a mutation in the BRCA1 gene, as most breast cancers caused by a BRCA1 gene mutation are triple-negative (thus lacking the three receptors for estrogen, progesterone, and the human epidermal growth factor (HER2) protein). When BRCA1 genes are normal, they may prevent the development of cancer. However, a mutation in the BRCA1 gene can make cells more susceptible to further mutations that can lead to different types of breast and ovarian cancer.

Symptoms of triple-negative breast cancer are the same as for other types of breast cancers, for which the most common initial symptom is the discovery of a painless, hard mass with uneven edges, although some breast cancer lumps can also be tender, or even painful, soft, and round. Additional symptoms of breast cancer may include breast swelling; breast or nipple pain; nipple discharge; nipple or breast skin that is reddened, dry, flaking, or thickened; nipple retraction, orange peel skin (dimpling), and swollen lymph nodes (usually under the arm or around the collarbone).

Since triple-negative breast cancer lacks receptors for the hormones estrogen, progesterone, and the human epidermal growth factor (HER2) protein that are present in other breast cancers, this cancer cannot be treated with hormone therapies and HER2 protein receptors administered for other breast cancers. Therefore, other therapies such as lumpectomy (breast conserving surgery), mastectomy, breast reconstruction, radiation therapy, chemotherapy, and immunotherapy are used to treat triple-negative breast cancer. Treatment decisions are based on the stages of the triple-negative breast cancer: Stages I-III triple-negative breast cancers are usually treated with lumpectomy (breast conserving surgery) or mastectomy, followed by radiation if the cancer has spread to nearby lymph nodes. Chemotherapy may be administered before surgery (neoadjuvant) to reduce the size of a large tumor before resection. For residual cancer after neoadjuvant chemotherapy, the oral chemotherapy drug, capecitabine, may be prescribed for 18-24 weeks. Chemotherapy may also be administered after surgery (adjuvant) to lower the chances of the cancer reoccurring. Stage IV triple-negative breast cancer is usually treated first with chemotherapy, as the cancer has spread to other areas of the body. Chemotherapy medications for Stage IV include anthracyclines, capecitabine, eribulin, gemcitabine, and others. Women with triple-negative breast cancer who carry the BRCA gene mutation, and for who chemotherapy medications are no longer working, other medications, such as carboplatin or cisplatin (platinum medications) or targeted PARP inhibitors, Olaparib (Lynparza) and talazoparib (Talzenna), may be administered. A form of advanced triple-negative breast cancer that produces a PD-L1 protein (20% of triple-negative breast cancers) may initially be treated with the immunotherapy medication of atezolizumab combined with Abraxane (nab-paclitaxel). Lumpectomy (Breast-Conserving Surgery) is a surgical procedure where the breast lump is removed, along with a few lymph nodes to determine whether the cancer has spread. This surgery is usually done for early stage breast cancer for a small breast lump, on an outpatient basis, and may be followed with radiation therapy. Mastectomy is a surgical procedure where the affected breast is removed, along with nearby lymph nodes to determine whether the cancer has spread. Patients may elect to have a Breast Reconstruction procedure performed directly following mastectomy during the same surgical session. Radiation therapy usually follows lumpectomy (breast-conserving surgery) where high levels of radiation are directed at the affected breast to kill any residual cancer. Radiation therapy for breast cancer is usually administered four-to-five days a week for six weeks. Chemotherapy is the primary systemic treatment option for triple-negative breast cancer and is administered to kill any cancers cells that may have spread elsewhere in the body, as well as to lower the chances of the cancer reoccurring. While triple-negative breast cancer usually demonstrates a good response to initial chemotherapy, the cancer tends to reoccur. Immunotherapy is a newer approach to cancer treatment that helps the patient’s own immune system to kill cancer cells, often by targeting certain proteins (immune checkpoint inhibitors) that help cancers avoid the immune system response, such the PD-L1 protein. Tecentriq (atezolizumab), an immune checkpoint inhibitor administered in combination with the chemotherapy, Abraxane (nab-paclitaxel), is the first immunotherapy treatment approved for locally advanced or metastatic (spreading) triple-negative, PD-L1-positive breast cancer. Patients with triple-negative breast cancer may also consider participating in clinical trials for new treatments because these may allow for access to medications not otherwise available for treatment. Patients undergoing treatment for triple-negative breast cancer may experience treatment-related side effects, which depend on the treatment, and more commonly include swelling in the arm (lymphedema), nausea and vomiting, skin and nail changes, and loss of hair. Treatment for these and other side effects is an essential part of breast cancer care.

There are a variety of support groups for triple-negative breast cancer: Breast Cancer.org - https://www.breastcancer.org/community/acknowledging/triple-negative Triple Negative Breast Cancer Foundation - https://tnbcfoundation.org/

While in the past, most triple negative breast cancers have usually spread rapidly or relapsed and have had a generally poor outcome with patients quickly dying, today women diagnosed with this cancer have better outcomes as treatments have improved. However, survival rates for triple-negative breast cancer are based on many factors such as a patient’s age, overall health, the cancer stage, how and where the cancer has spread, response to treatment, and other factors.

Complications of triple-negative breast cancer are related to the cancer itself and/or the side effects of treatment. Advanced breast cancer-related complications include pain and cancer spread (metastasis) to organs such as the liver, lung, brain, and bones. Breast cancer treatment-related complications can include breast swelling and tenderness, scar tissue, wound infection, or bleeding, and swelling of the arm (lymphedema) due to removal of the lymph nodes.

Any changes in the breast, breast skin, or nipple, the appearance of a mass or lump in the breast, pain in the breast, swollen axillary (underarm) lymph nodes, or swollen lymph nodes above or below the collarbone (clavicle) should be evaluated by a medical professional.

Regular screening for breast cancer (mammograms) are recommended. Performing regular breast self-exams and noticing any changes, while being aware of the signs and symptoms of breast cancer, is important for early detection of breast cancer. Individuals with a family history of breast cancer should be undergo genetic screening for the BRCA1 or BRCA2 gene mutations. Early detection of breast cancer can provide a better chance for successful treatment.