Causes of Triple-Negative Breast Cancer

BRCA1 and BRCA2 gene defects are leading risk factors

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Triple-negative breast cancer is a type of breast cancer that is missing estrogen, progesterone, and HER2 receptors. This makes it difficult to treat with hormone medication as many of the drugs used for breast cancer treatment target these receptors. As a result, triple-negative breast cancer more likely to grow and spread quicker than other forms of breast cancer. It also can make treatment more difficult, leaving the patient to undergo chemotherapy or clinical trials. Approximately 10% to 15% of breast cancer diagnoses are triple-negative breast cancer. There are several risk factors and genetic causes that may increase a woman’s chance of having triple-negative breast cancer compared to other types of breast cancer.

Unrecognizable female gynecologist looking at a mammogram checking for breast cancer at the hospital.
ChooChin / Getty Images

Common Causes

The common causes and risk factors for triple-negative breast cancer are similar to the risk factors of all types of breast cancer, including:

  • Age: Most breast cancer diagnoses occur in women over the age of 60, but with triple-negative breast cancer this may appear earlier, in women 50 years old and younger.
  • Weight: Those who are overweight or obese have a higher risk.
  • Ethnicity: While more research is needed to pinpoint exactly why, African Americans and Hispanics are more prone to developing triple-negative breast cancer than Caucasians or Asians.
  • Evidence of genetic mutations, such as the BRCA1 gene.
  • Family history of breast cancer.
  • Age at first pregnancy: Those who have had children after the age of 30 or have never had children are at a higher risk.
  • Benign breast conditions like atypical ductal hyperplasia.
  • Use of hormone replacement therapy as you begin menopause.
  • Using oral birth control. One study found a 2.7-fold increase in oral contraception use for more than a year in women under 45.
  • Previous radiation exposure, particularly before the age of 30.


One of the leading causes of triple-negative is a woman’s genetic makeup, specifically the BRCA1 and BRCA2 genes, which are genes that are supposed to produce tumor suppressant proteins in the body. In the case of triple-negative breast cancer, 10% to 15% of Caucasians with triple-negative breast cancer have a BRCA1 gene mutation, while 35% of African Americans with triple-negative breast cancer have a BRCA1 gene mutation.

For a long time the BRCA1 gene was the only gene known for increasing the risk of triple-negative breast cancer, but with new research published in the Journal of the National Cancer Institute discovered five genes—BRCA1, BRCA2, BARD1, PALB2, RAD51D– that if defected can increase their risk of getting any type of breast cancer by 20% as well as elevating the chances that their breast cancer diagnosis be triple-negative breast cancer.


Heart disease and breast cancer share many of the same risk factors, such as diet, lifestyle choices, and obesity. While existing cardiovascular issues may not cause triple-negative breast cancer directly (or any other type of breast cancer, for that matter), there is a growing body of evidence that more cancer patients dying from cardiovascular-related disease. This proves true especially in the case of triple-negative breast cancer, as limited treatment options often lead to chemotherapy and certain chemotherapy drugs make the heart weaker and unable to pump and circulate blood throughout the body as efficiently as it once used to.

In one study with 147 triple-negative breast cancer patients, only 31% of patients had a normal electrocardiography (ECG) after each chemotherapy cycle, while others had reports of increased heart rate and a decreased left ventricular ejection fraction (how efficiently the left side out your heart pumps blood out).

Lifestyle Risk Factors

While you can’t change your genetic makeup or your age, there are a number of lifestyle factors you can change when it comes to decreasing your risk for triple-negative (and all) breast cancers. The most common lifestyle risk factors are:

  • A lack of physical activity.
  • Your weight after menopause.
  • Drinking excess amounts of alcohol.
  • Taking hormones—whether it be in the form of birth control or hormone replacement therapy.
  • Smoking

Making sure to move more, eat well, and drink in moderation are all simple steps you can take to decrease your risk and stay healthy. If you're concerned about your use of oral contraception, make sure to discuss it with your healthcare provider, who can outline the risks and benefits of each method so that together you can find the best fit for both your lifestyle and health. It's also worth noting that the increased risks linked to hormone-based medication like birth control or hormone replacement therapy linked to menopause disappeared around 10 years after ceasing use of them.

A Word From Verywell

There’s still much to learn about the causes of triple-negative breast cancer, along with the risk factors that increase those chances of a diagnosis. It can be scary to have the risk factors that may lead to a triple-negative cancer diagnosis down the road, particularly because treatment options are much more limited than in other types of breast cancer. That's why it’s important to keep in mind that these risk factors only increase your chances, meaning that having one or more of them won’t necessarily cause you to get triple-negative breast cancer nor does not having any of the above risk factors mean it’s impossible to get triple-negative breast cancer. The best thing you can do to protect yourself is to follow a healthy diet, exercise daily, and make sure to stay on top of your breast health, whether it be through self-exams at home, having your healthcare provider give you a breast check during your annual exam, or with regularly scheduled mammograms depending on your age. 

Frequently Asked Questions

  • Can stress make triple-negative breast cancer worse?

    It appears so, and animal studies are beginning to shed light on possible reasons why. For example, social stress, specifically prolonged isolation from others, reprograms certain fat cells in mammary glands to secrete a substance that causes nearby cancer cells to proliferate faster than they ordinarily might.Other research has found that stress can interfere with the effectiveness of certain cancer drugs.

  • What is the prognosis for triple-negative breast cancer?

    The five-year relative survival rates for triple-negative breast cancer depend on the stage of the cancer:

    • Localized (cancer has not spread beyond the original site): 91%
    • Regional (cancer has spread to nearby tissue or lymph nodes): 65%
    • Distant (cancer has spread to the lungs, liver, bones, or other distant areas): 12%
    • All three stages combined: 77%
  • Can triple-negative breast cancer be prevented?

    No. However, for women found to have mutations of either the BRCA1 gene or the BRCA2 gene, which significantly increases the risk of triple-negative breast cancer, a bilateral prophylactic mastectomy—surgical removal of both breasts—may reduce that risk by 95%.

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7 Sources
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