Explaining this aggressive breast cancer subtype: what it is, how it's treated, and how research is improving outcomes

To talk about triple-negative breast cancer (often shortened to TNBC), we must first understand how breast cancer is classified. The most basic classification of breast cancer is based on the presence of three common markers: estrogen receptor (called ER-positive), progesterone receptor (PR-positive), and human epidermal growth factor receptor 2 (HER2-positive).

More than 70 percent of breast cancers are ER-/PR-positive and rely on estrogen to grow, while about 20–25 percent of breast cancers are HER2-positive and depend on growth pathways regulated by that protein. These markers not only determine a tumor’s biology but also a person’s treatment plan, as there are targeted therapies for these subtypes.

Triple-negative breast cancer is so-named for the simple reason that its tumor cells do not express any of these three receptors. TNBC accounts for approximately 15 percent of invasive breast cancers.

Triple-negative breast cancers: tend to be more advanced when diagnosed and more aggressive than ER-/PR-positive cancers; disproportionately affect Black and Hispanic women as well as younger women; and are the most commonly diagnosed breast cancer in women with inherited mutations in the BRCA1 gene.

RELATED: Dr. Funmi Olopade Discusses Triple-Negative Breast Cancer in Black Women

Read on to learn about triple-negative breast cancer symptoms, treatments, and how BCRF-supported researchers are working to understand and better treat this subtype.

Triple-Negative Breast Cancer Symptoms

Most breast cancers are detected before a woman shows any symptoms through regular breast cancer screening such as mammography. However, triple-negative breast cancer is more likely to occur in younger women (less than 40 years old) before they reach screening age. That’s why it’s important for women of any age to be familiar with their breasts so they can spot any changes, such as a hard lump.

Other less common symptoms include swelling, skin dimpling, pain, nipple retraction, discharge, redness, or swollen lymph nodes under the arm. If you experience any of these symptoms and they persist beyond one menstrual cycle, consult your doctor, who may recommend imaging tests or a biopsy.

A triple-negative breast cancer diagnosis is not based on any specific symptoms, but on an assessment of cells from a biopsy, which are checked for estrogen, progesterone, and HER2 receptors to determine a person’s breast cancer subtype. Cells that lack these three receptors may then be definitively classified as triple-negative breast cancer. Using gene expression profiles, TNBC can be further classified as basal-like or as having specific mutations in genetic susceptibility genes such as BRCA1/2.

RELATED: Dr. Charles Perou on the Molecular Subtypes of Triple-Negative Breast Cancer

Triple-Negative Breast Cancer Survival Rate

Survival rates are estimates based on the outcomes of large numbers of people with a specific cancer—they cannot predict what will happen in every case. A relative survival rate compares women with the same subtype and stage of breast cancer to women in the overall population. Studies have analyzed data to determine the five-year relative survival rate for specific subtypes and stages of breast cancer, including triple-negative breast cancer.

A triple-negative breast cancer prognosis, like prognoses for other types of breast cancer, is influenced by several factors, including the stage at diagnosis and whether the disease has spread to lymph nodes or other locations in the body (triple-negative breast cancer metastasis). Because TNBC tends to be a more aggressive form of breast cancer for which there are fewer targeted treatment options, it often has a worse prognosis than more common types of breast cancer.

According to the SEER (Surveillance, Epidemiology, and End Results) database, the estimated five-year triple-negative breast cancer survival rate is:

  • 91.2 percent for those with localized breast cancer (cancer that is only within the breast)
  • 65.4 percent for those with regional breast cancer (cancer that has spread to nearby areas such as the lymph nodes)
  • 12.2 percent for those with distant/metastatic breast cancer (cancer that has spread to other areas in the body such as the bones, liver, or lungs)

It is important to keep in mind that these are estimates and do not indicate any given individual’s survival rate. While these data points give us a better understanding of the likelihood that treatment will be successful, our understanding of TNBC is evolving and helping to personalize risk prediction and prognosis so that each patient can receive the most appropriate treatment for their cancer and reduce the risk of triple-negative breast cancer recurrence.

Triple-Negative Breast Cancer Treatment

In contrast to hormone receptor (ER/PR)-positive and HER2-positive breast cancers, there are few FDA-approved targeted therapies for triple-negative breast cancer—making this an urgent priority.

Triple-negative breast cancer treatment is particularly complicated because there is no obvious drug target, as there is for ER/PR-positive or HER2-positive breast cancer. Currently, the standard treatments for TNBC are surgery, chemotherapy, and radiation.

But that is changing. As we learn more about the biology of this particularly complex form of breast cancer, it is clear that TNBC is not a single disease but a group of breast cancers with distinct molecular and clinicopathological characteristics. In fact, TNBC can be classified into several distinct molecular subtypes based on gene expression profiles. This has important implications for prognosis and triple-negative breast cancer treatments.

The stage at which a triple-negative breast cancer is diagnosed can dictate the treatment plan patients and their doctors choose.

Stages 1-3 triple-negative breast cancer:

  • If the tumor is small, breast-conserving surgery (lumpectomy) may be recommended.
  • If there is lymph node involvement, a mastectomy and lymph node removal may be performed.
  • If the tumor is large or if the cancer has spread to the lymph nodes, radiation may follow surgery.
  • In early-stage disease, chemotherapy may be given before surgery (neoadjuvant chemotherapy) to shrink a large tumor or after surgery (adjuvant chemotherapy) to reduce the chances of triple-negative breast cancer recurrence.

Stage 4 triple-negative breast cancer/triple-negative breast cancer metastasis:

  • Chemotherapy may be the initial treatment when the disease has spread to other parts of the body.
  • For patients with triple-negative breast cancer and a BRCA mutation who are no longer responding to common chemotherapy agents, other platinum-based chemotherapy drugs (cisplatin or carboplatin) may be used.
  • For patients with triple-negative breast cancer and a BRCA mutation, targeted drugs called PARP inhibitors (such as olaparib/Lynparza® or talazoparib/Talzenna®) may be used to target an important enzyme in DNA repair.
  • Immunotherapy agents (such as atezolizumab/Tecentriq® or pembrolizumab/Keytruda®) in combination with chemotherapy may be the first-line treatment for patients whose advanced triple-negative breast cancer cells have the PD-L1 protein. One out of five triple-negative breast cancers express this protein.
  • For patients who have already undergone two other drug treatments, the antibody-drug conjugate sacituzumab/Trodlevy® govitecan-hziy might be an option.

RELATED: Emerging Therapies for Triple-Negative Breast Cancer

BCRF’s Investment in Triple-Negative Breast Cancer Research

BCRF is the largest private funder of breast cancer research in the world and currently dedicates 35 percent of its total investment to triple-negative breast cancer. BCRF investigators have been involved in every major advancement in our understanding of this disease: determining its molecular and clinicopathological characteristics; discovering its association with BRCA mutations and how PARP inhibitors can treat these patients; and developing and testing drugs that are currently FDA-approved for triple-negative breast cancer treatment.

BCRF continues to fund research into all aspects of triple-negative breast cancer including:

  • Probing the basic biology of the disease
  • Improving the efficacy of current treatments
  • Determining ways to overcome resistance to treatments
  • Developing novel treatments
  • Investigating the disparate impact of this subtype in Black and Hispanic women

Through these investigations, BCRF researchers are looking for potential targets for triple-negative breast cancer treatment and are providing new insights into the molecular complexity of the disease. BCRF is deeply committed to addressing the lack of critical precision therapies for these patients. Only through research will we advance our understanding of triple-negative breast cancer to ultimately improve outcomes and save lives.

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