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 where the cancer cells do not have receptors for estrogen, progesterone, and HER2. This makes it difficult to treat because many of the drugs used for breast cancer treatment target these hormone receptors. Triple-negative breast cancer is more likely to grow and spread quicker than other forms of breast cancer. 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.
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Common Causes

The common risk factors for triple-negative breast cancer include:

  • Age: Most breast cancer diagnoses occur in women over the age of 60, but triple-negative breast cancer may appear earlier, in women 50 years old and younger.
  • Weight: Those who are overweight or obese have a higher risk.
  • Ethnicity: African Americans and Hispanics are more prone to developing triple-negative breast cancer than Caucasians or Asians.
  • Genetic mutations: Genetic changes such as the BRCA1 gene can increase the risk of this type of breast cancer.
  • Family history: A family history of breast cancer increases the risk of triple-negative breast cancer.
  • Oral birth control: One study found a 2.5-fold increase of triple-negative breast cancer among women under age 45 who used oral contraception for more than a year.

Genetics

One of the leading causes of triple-negative is genetic changes in the BRCA1 and BRCA2 genes. These genes normally help produce tumor suppressant proteins in the body.

It's been estimated that 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.

The BRCA1, BRCA2, BARD1, PALB2, RAD51D genes increase the risk of any type of breast cancer by 20% and also increase the chances that the breast cancer diagnosis will be triple-negative breast cancer.

Cardiovascular

Heart disease and breast cancer share some of the same risk factors, such as smoking and obesity. While cardiovascular disease doesn't cause breast cancer, people who have been diagnosed with breast cancer are at risk of dying from cardiovascular-related disease.

This proves true especially in the case of triple-negative breast cancer, as it's often treated with chemotherapy and certain chemotherapy drugs can contribute to heart disease.

In one study with 147 triple-negative breast cancer patients, only 31% of patients had 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 hormonal birth control or hormone replacement therapy
  • Smoking

Making sure to be active, 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, 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 your lifestyle and health. It's also worth noting that the increased risks linked to hormone-based medication decrease around 10 years after ceasing use of them.

A Word From Verywell

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—having one or more of them won’t necessarily cause you to get triple-negative breast cancer and not having any of the above risk factors doesn't 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 regularly, and make sure to stay on top of your breast health, through self-exams at home, having your healthcare provider give you a breast check during your annual exam, and with regularly scheduled mammograms as recommended for 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
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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