What Is Triple-Negative Breast Cancer?

As the second-most common cancer in the United States, breast cancer is the leading cause of cancer-related deaths in women in the country.¹ 

Every year, more than 250,000 women are diagnosed with breast cancer.²

The prognosis depends on: 

• The cancer’s stage

• The subtype of breast cancer

• Treatment

• Genetic, environmental, and socioeconomic factors

An aggressive, difficult-to-treat form of breast cancer is triple-negative breast cancer (TNBC). It often has a significantly worse prognosis than other types of breast cancer.  

What is triple-negative breast cancer?

Doctors classify types of breast cancer according to molecular markers found in breast cancer tissues. They can determine the subtype by looking for the following hormone receptors:³

• Estrogen receptor (ER)

• Progesterone receptor (PR) 

• Human epidermal growth factor receptor (HER2), more recently known as ERBB2

The majority of breast cancers (70–75%) are ER- or PR-positive or both. Most are either ER-positive or ER-PR-positive. ER-negative/PR positive currently represents less than 1% of this category.⁴

Approximately 20–25% of breast cancers rely on the growth pathways regulated by HER2. Therefore, these are HER2-positive.⁵

Identifying these subtypes is crucial to determine treatment: Doctors use drugs that target specific receptors. 

In the case of triple-negative breast cancer, the tumor cells don’t express any of these receptors. They are negative for estrogen, progesterone, and human epidermal growth factor receptors. 

Because the tumor cells don’t have the receptors that medications target, triple-negative breast cancer is difficult to treat. 

Triple-negative breast cancer symptoms are the same as other forms of breast cancer and may include:⁶

• A lump in the breast or underarm

• A change in the breast’s shape or size 

• Breast tissue thickening or swelling

• Breast or nipple pain

• Changes to the skin on the breast or nipple: Irritation, dimpling, redness, or flakiness

• Pulling in of the nipple

• Unusual nipple discharge

To determine the subtype of cancer, your doctor conducts a biopsy. If the biopsy reveals the cells lack these three receptors, the cancer is triple-negative breast cancer. 

How common is triple-negative breast cancer?

Triple-negative breast cancer accounts for approximately 15% of invasive breast cancer cases.⁷

Evidence suggests the condition is more common in: 

• Women of West African and Hispanic descent⁸

• Premenopausal women

• Women with lower socioeconomic status⁹

• Women who carry the breast cancer susceptibility gene (BRCA1/2) mutation

Studies suggest that women of West African descent in the United States are twice as likely as European women to be diagnosed with triple-negative breast cancer.¹⁰

In the United States, the prevalence of TNBC varies geographically, with higher rates in the southeastern part of the country.

Proportionally, the southeastern United States has more women of West African descent, which could explain the difference in rates around the country. 

From a sociological perspective, another explanation is that young women in low socioeconomic areas are more likely to start childbearing at a younger age. This is associated with a higher risk of TNBC.

Uncontrollable risk factors for triple-negative breast cancer

While triple-negative breast cancer can affect anyone, certain uncontrollable factors put you at higher risk, including:

• Sex: Women are far more likely than men to develop triple-negative breast cancer.

• Race/ethnicity: Women of West African and Hispanic descent are more likely to develop this form of breast cancer than women of European descent. 

• Age: Unlike other forms of breast cancer, premenopausal women under 40 are more likely to develop triple-negative breast cancer. 

• Age of first period: Having your first period early, possibly before the age of 13, is associated with a higher incidence of this cancer.¹¹

• Genetics: Research has linked certain gene mutations to an increased risk of developing TNBC, including:¹²

  • BRCA1

  • BRCA2

  • BARD1

  • PALB2

  • RAD51D

  • BRIP1

  • RAD51C

Potentially manageable risk factors for triple-negative breast cancer

While you can’t change your ethnicity, certain risk factors for triple-negative breast cancer are potentially modifiable. 

The most important among these is body mass index (BMI). Multiple studies have shown that obesity increases the risk of developing breast cancer or the rate at which it progresses. 

One study compared women with TNBC to those with more common forms of breast cancer. It found that 50% of the women with triple-negative breast cancer were obese compared to 36% of women with other subtypes of breast cancer.

Another modifiable risk factor that seems to play a role in triple-negative breast cancer development is using oral contraceptives. 

Various studies have confirmed that the prolonged use of oral contraceptives is significantly associated with the development of triple-negative breast cancer.

As with other forms of breast cancer, certain lifestyle changes can decrease your risk of developing TNBC, including:

• Regular physical activity

• Minimal alcohol consumption

• A healthy diet rich in fruits and vegetables

• Quitting smoking

• Limiting exposure to certain chemicals

Modern treatment for triple-negative breast cancer

Triple-negative breast cancer is a more aggressive form, and it’s harder to treat. 

Because the tumor cells are negative for ER, PR, and HER2, hormone therapy and drugs that target HER2 are not effective treatments for TNBC.

Until recently, standard treatments for this form of cancer were limited to surgery, chemotherapy, and radiation therapy. 

Surgery

If the tumor is caught early enough while it’s small, the first treatment option might be surgery. The surgeon may remove the lump (a lumpectomy) or the whole breast (a mastectomy.) The specific treatment depends on how large the lump is. 

After surgery, radiation or chemotherapy might reduce the chances of the lump returning. 

If the tumor is large, your doctor may use chemotherapy to shrink the tumor before surgery.

Radiation therapy

Doctors use localized radiation therapy after surgery in many cases, particularly if the cancer was large or spread to the lymph nodes. 

Radiation therapy uses targeted high-energy rays, such as x-rays or gamma rays, to destroy any remaining cancer cells that surgery may not have removed. 

Chemotherapy

If the cancer has spread to other parts of your body (metastasized), chemotherapy is often the treatment of choice. It’s a systemic treatment, so it travels throughout your body to kill cancer cells wherever they might be. 

In some situations, your doctor may recommend surgery and radiation as well.

Sometimes, doctors treat cancer with a single drug but often combine several drugs. This is known as combination chemotherapy. 

If you carry the BRCA mutation and traditional chemotherapy hasn’t been effective, platinum chemotherapy drugs or targeted drugs (PARP inhibitors) may be viable treatment options. 

New treatment options

The US Food and Drug Administration (FDA) has recently approved new drugs for treating metastatic triple-negative breast cancer that has not responded to other treatments. 

Trodelvy

A type of targeted therapy known as an antibody-drug conjugate, Trodelvy delivers a chemotherapy drug directly to the cancer cell, preventing it from growing and spreading.¹³

Tecentriq 

Research has shown the effectiveness of this immunotherapy treatment for women with triple-negative breast cancer who test positive for a protein known as PD-L1.¹⁴

PD-L1 stops the immune system from attacking the cancer cells, and Tecentriq blocks this protein. Doctors use it in combination with a chemotherapy drug called Abraxane. 

Triple-negative breast cancer is a heterogeneous (varied) cancer, and research has revealed clusters of tumor subtypes within this form of breast cancer. 

Moving forward, the characteristics of these clusters may play an important role in developing targeted therapies to address particular subtypes of triple-negative breast cancer.¹⁵

Stages and survival rate for triple-negative breast cancer

The American Joint Committee on Cancer oversees a cancer staging system called the TNM System. This system ensures some uniformity in how doctors and researchers talk about and treat breast cancer.

The TNM System

This classification system uses letters and numbers to describe the clinical characteristics of cancer tumors. 

• T: This describes the size of the original tumor and whether it has spread to nearby tissue. 

• N: This provides information about whether cancer is present in the lymph nodes.

• M: This identifies whether the cancer has spread to other parts of the body.

The letters T, N, and M are followed by an X, 0, 1, 2, 3, or 4. 

If the category can’t be properly assessed, it’s followed by an X. For example, MX means that metastasis can’t be assessed. 

If the category is followed by a zero, it means no evidence exists. For example, N0 means that nearby lymph nodes do not contain cancer. 

T0 means that the tumor has not started growing into healthy breast tissue, and M0 means no spread to distant organs.

• T1, T2, T3, T4: The higher the number, the larger the tumor and the more extensively it has grown into healthy breast tissue

• N1, N2, N3: The higher the number, the greater the extent of lymph node involvement

• M1: This means that the cancer has metastasized

Doctors sometimes use other terms to describe breast cancer stages. 

These include: 

• Local (confined to the breast)

• Regional (involves the lymph nodes)

• Distant (has spread to other parts of the body)

Stages 0 to IV

A classification system describes the progress of breast cancer. This system allocates symptoms to different stages depending on how advanced the cancer is. 

Stage 0 describes non-invasive breast cancer, and stage IV describes cancer that has spread to other parts of the body. Stage 0 or stage I cancer is easier to treat than stage IV. 

Each case is different. The type of cancer also affects the allocation of stages, so classifying them is a complex task, and we can’t provide a comprehensive overview here.

Very simplistically, we can understand the stages as follows:

Stage 0

Non-invasive cancer that has not spread into surrounding healthy breast tissue.

Stage I

Very early-stage invasive breast cancer. The cancerous cells have begun to invade surrounding breast tissue but are still very small (<2cm). It often corresponds to T1 on the TNM system.

Stage II

The cancer has become larger or spread to the lymph nodes.

Stage III

This cancer is larger, has spread to the breast wall or skin, and involves more lymph nodes (4–9). There’s no spread to other organs. 

It’s the stage doctors classify all types of inflammatory breast cancer as. 

Inflammatory breast cancer is an aggressive, very invasive form of breast cancer that varies in symptoms and prognosis. It often doesn't involve a lump and involves swelling and extensive skin changes. Some cases of triple-negative breast cancer fall under this type.

Stage IV

The cancer has spread to other organs in the body. 

Survival rates for triple-negative breast cancer

Because triple-negative breast cancer tends to affect younger women who are not yet part of nationwide screening programs, it’s often only detected in more advanced stages. 

Late detection, combined with it being an aggressive, hard-to-treat form of cancer, affects the prognosis. Women diagnosed with triple-negative breast cancer often have a worse prognosis than those with more common forms of breast cancer.

Survival rates are based on data collected from other women who had the same form of breast cancer. These rates don’t determine the outcome of individual cases. 

However, they can indicate the likelihood of successful treatment at a given point in the cancer’s progression. 

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

• 91.2% for cancer that’s restricted to the breast

• 65.4% for cancer that’s spread to the lymph nodes

• 12.2% for cancer that’s spread to other parts of the body

Unfortunately, triple-negative breast cancer has a higher rate of recurrence than other forms of breast cancer, particularly in the first five years after diagnosis.¹⁶

The role of race in the development and progression of triple-negative breast cancer

Race appears to play a role in the risk of developing triple-negative breast cancer and the prognosis. Current literature suggests the relative risk of death for women with breast cancer is 71% higher for Black women and 14% higher for Hispanic women compared to non-Hispanic white women.¹⁷

In the United States, race also appears to be an independent predictor of five-year survival for triple-negative breast cancer. Black and Hispanic women have lower survival rates than their non-Hispanic white counterparts.  

Researchers carried out a retrospective study of 26,963 women with a primary diagnosis of triple-negative breast cancer (based on data from the 2010-2016 SEER database). 

They found that higher proportions of Hispanic and Black women under 40 were diagnosed with triple-negative breast cancer than non-Hispanic white women. 

Compared to women in the non-Hispanic white group, higher proportions of women in the Hispanic and Black groups were diagnosed with high-grade tumors (grades III-IV). 

Hispanic women had the highest risk of death, and Black women had a lower probability of survival than non-Hispanic white women.

In the case of Black and Hispanic women, earlier disease onset, more advanced stage at diagnosis, and aggressive tumor phenotype make triple-negative breast cancer harder to treat. 

However, these are not the only factors contributing to racial disparity in the incidence and prognosis of triple-negative breast cancer.

Socioeconomic factors also play an important role in who is likely to develop triple-negative breast cancer and who is more likely to survive. 

Socioeconomic status determines: 

• Where you live

• What you eat

• Your level of education and health education

• Your work

• Exposure to hazards

• Your social support system

• Your healthcare access

Black and Hispanic women in the United States tend to have lower socioeconomic status than non-Hispanic white women. This results from biases and discrimination that also significantly impact their health. 

Access to health-promoting neighborhoods

A 2022 study of racial disparities in triple negative breast cancer examined neighborhood effects.

Neighborhoods with unsafe streets, unhealthy food options, and many alcohol stores are less likely to be good for your health than those with healthy food options and safe green spaces. 

This study found that compared to predominantly white neighborhoods, predominantly Black neighborhoods differed in ways that impact the risk of triple-negative breast cancer.¹⁸

Notably, these neighborhoods had more alcohol retailers and fast-food outlets and higher rates of obesity. Research has linked metabolic syndrome (hypertension, high blood sugar, obesity, and high cholesterol) and binge drinking to an increased risk of breast cancer. 

Obesity disproportionately affects Black women, whether due to eating habits or genetic predisposition. It directly impacts biological processes that promote tumor growth, making the progression of triple-negative breast cancer more aggressive. 

Additional comorbidities such as diabetes and hypertension also contribute to higher morbidity rates among Black women. 

Access to healthcare

Socioeconomic status impacts access to healthcare. Reduced healthcare access or lack of insurance may result in delayed screening and diagnosis, with a bigger tumor burden at diagnosis. 

A 2021 study found that Black women are potentially more likely to die from triple-negative breast cancer than their non-Hispanic white counterparts due to the lower likelihood that they would receive adequate treatment with surgery and chemotherapy.¹⁹

Being able to afford quick access to high-quality care or living in an area with available healthcare providers may pose significant challenges for many. This can impact early diagnosis by their primary health care physician or their referral to a specialist. 

According to a five-year retrospective study (2015–2018) 73.3% of women diagnosed with breast cancer in a San Bernardino emergency department were Hispanic or Black.²⁰

The study also reported a significant delay (a median of 461 days) between the preliminary emergency room diagnosis to the definitive diagnosis in a primary care clinic in the follow-up appointment. 

This suggests that women seen in a safety net hospital with Medicaid funding may suffer from significant delays before the final diagnosis, impacting their prognosis and final outcome. 

The lowdown

Triple-negative breast cancer (TNBC) is a particularly aggressive form that disproportionately affects women of West African and Hispanic descent. Black women are more likely to develop triple-negative breast cancer and less likely to survive. 

TNBC is harder to treat than other more common forms because of the lack of ER/PR/HER2 receptors and targeted drug treatments. 

Certain modifiable risk factors can play a significant role in the disease’s progression, such as body mass index, alcohol consumption, poor diet, and use of oral contraceptives. 

In addition to ongoing genetic research, better access to healthcare, health education, and screening programs might improve outcomes for Black and Hispanic women with triple-negative breast cancer. 

Frequently asked questions

Is triple-negative breast cancer genetic?

While anyone can develop triple-negative breast cancer, certain genetic factors such as ethnicity can put you at greater risk of developing the disease. Women of African and Hispanic descent are more likely to develop triple-negative breast cancer than those of other ethnicities. In addition, women who carry certain gene mutations (BRCA1/2, BARD1, PALB2, and RAD51D) are more likely to develop triple-negative breast cancer than those who don’t. 

Can men get triple-negative breast cancer?

While men can develop triple-negative breast cancer, it’s very uncommon. Triple-negative breast cancer cases make up a very small percentage of all male breast cancer cases.²¹

What fuels triple-negative breast cancer?

Obesity can fuel the rate at which triple-negative breast cancer progresses. This is because obesity directly impacts biological processes that promote tumor growth.