Carrying excess weight can have a profound effect on many areas of personal health, including the development and progression of triple-negative breast cancer (TNBC).

Triple-negative breast cancer is a rare type of breast cancer. It lacks estrogen, progesterone, or human epidermal growth factor (HER2) receptors, the three common types of receptors found on other breast cancer cells.

The absence of these receptors means triple-negative breast cancer (TNBC) will test negative on all three types of breast cancer receptor tests, earning it the name “triple-negative.”

The lack of receptors alone makes TNBC challenging to treat, but other factors, such as obesity, may speed up this cancer’s progression, adding new levels of complexity.

This article explores how obesity affects TNBC and breast cancer.

What are breast cancer receptors?

Breast cancer receptors are proteins on or in the cell that allow in certain signals. They are an important part of diagnosis and reveal pathways of treatment. Without any receptors, fewer therapeutic options become available to treat TNBC.

The World Health Organization (WHO) defines obesity as excessive or abnormal fat accumulation that presents a risk to health.

On the body mass index (BMI), a common tool used in the clinical setting, body fat assessment divides a person’s weight in kilograms (kg) by height in square meters (m2). Thirty points or higher is considered obese for adults.

  • Underweight: BMI of less than 18.5
  • Healthy weight: BMI of 18.5 to 24.9
  • Overweight: BMI of 25 to 29.9
  • Obesity: BMI of 30 or higher

However, there is more to obesity than BMI. Not all weight gain can be due to fat, particularly in certain niche formats, such as bodybuilding.

Fat distribution may be a more telling factor when it comes to health. For example, an average BMI with a large waist circumference can indicate a potentially unhealthy accumulation of body fat around the abdomen.

Obesity is associated with an overall increased risk for breast cancer, as well as 12 other types of cancer.

It can impact disease progression, recurrence, and prognosis.

A 2021 study published in The American Surgeon found that out of more than 400 patients, there was an association between obesity and larger breast cancer tumors and more node-positive disease at initial presentation.

Node-positive breast cancer is cancer that has spread into nearby lymph nodes. Node involvement is associated with an increased risk of recurrence in cancer and can directly affect the mortality rate.

Obesity has the same range of effects in TNBC. According to a 2022 study published in the Journal of Clinical Oncology, there was a link between obesity and higher cases of node involvement with TNBC. It was also associated with the earlier development of distant metastatic disease.

Triple-negative breast cancer disproportionately affects women with the genetic BRCA1 variant as well as premenopausal African American women.

High rates of obesity and insulin resistance may account for some of this disparity among African American women, according to a 2018 review published in The American Journal of Pathology.

The exact relationship between breast cancer and obesity is still under exploration, but inflammation, metabolism, and how fat tissue changes biology appear to be intricately linked.

Excess fat tissue in obesity may influence breast cancer by:

  • producing excess amounts of estrogen, promoting cellular growth and spread
  • increasing levels of leptin, encouraging an abnormal amount of cell growth
  • impairing tumor immunity by altering tissue structure
  • creating oxidative stress and chronic inflammation
  • disrupting cellular growth and metabolic regulators in the body

Certain factors may have more prominent roles when it comes to triple-negative breast cancer.

A 2022 study in the journal BMC Cancer found that insulin-resistant fat cells in obesity secreted specific cytokines — proteins that regulate cell growth and activity — that helped TNBC grow quickly and spread throughout the body.

As in other cancers, leptin appears to play a role in TNBC. A 2019 study in Breast Cancer Research linked leptin to the aggressive progression of TNBC but didn’t find that it contributed to the spread of the disease.

Obesity can significantly impact disease-free survival (survival with no cancer recurrence) and overall survival.

A 2022 review in Cancer and Metastasis Reviews notes that obesity can be associated with lower rates of disease-free survival and overall survival across all breast cancer subtypes.

The same review indicates that women living with breast cancer and obesity are 46% more likely to develop cancers distant from the original site 10 years after initial diagnosis.

The way obesity impacts TNBC prognosis directly is less clear, with some research suggesting opposing views.

A 2018 review in Medicine found that obesity had no statistically significant impact on disease-free survival or overall survival.

In a 2022 review in the Journal of the National Cancer Institute, researchers found that obesity appeared to impact disease-free survival but not overall survival.

It is unclear if post-diagnosis weight loss can improve TNBC or other breast cancer outcomes.

However, a 2021 study in the Journal of the National Cancer Institute found that survivors of breast cancer who were overweight or obese had a significantly increased risk of a second cancer diagnosis. In fact, for every 5 kg/m2 increase in BMI, the risk of a second cancer diagnosis increased by 7%.

Weight loss, then, could possibly lower the risk of a recurrence of breast cancer and secondary cancers.

The National Cancer Institute (NCI) cautions that current research cannot clearly establish that obesity causes cancer. People who lose weight may have other varying factors that influence improved outcomes.

Research into obesity and triple-negative breast cancer is ongoing, with new approaches targeting TNBC-specific mechanisms to aid in risk negation and improved outlook.

A 2020 study published in the Journal of Cellular and Molecular Medicine looked at the role of apelin in rodent models for TNBC. By controlling increased obesity-related apelin levels with the apelinergic antagonist F13A, TNBC growth was significantly inhibited.

Other work is underway to explore how obesity may hinder emerging immunotherapy treatments for TNBC.

A 2019 review in Frontiers in Immunology suggests that obesity may dampen the antitumor immune response and increase the risk of immunotherapy-induced immune-related adverse events (irAEs).

For this reason, experts encourage more inclusive TNBC immunotherapy clinical trials to fully understand how obesity may impact emerging treatments.

Obesity can increase the chances of developing breast cancer. In triple-negative breast cancer (TNBC), obesity is associated with more advanced disease, higher recurrence rates, and an earlier spread of cancer to distant locations.

While TNBC is challenging to treat because traditional hormone therapy options are not useful, surgery, chemotherapy, and immunotherapy are all available options.

Information about TNBC is available via the Triple Negative Breast Cancer Foundation and the American Cancer Society.

Support groups, counseling, and financial assistance are also available through the CancerCare organization.