Study: Weight may affect breast cancer risk in women with an inherited BRCA mutation

Relevance: Medium

Strength of Science: Medium

Research Timeline: Animal Studies

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What is this study about?

This study looked at the links between a higher body weight and DNA damage in normal breast cells from women with an inherited BRCA mutation. Because DNA damage can increase cancer risk, researchers also studied ways to decrease DNA damage in both human and mouse breast cells that had a mutation in BRCA1 or BRCA2. Note that when we use "men" and "women" we refer to the sex assigned at birth.

Why is this study important?

Obesity after menopause increases breast cancer risk in the general population. Some research has suggested that obesity also increases breast cancer risk for women with an inherited BRCA mutation. This study adds more evidence on the health benefits of staying fit.

Study findings

The researchers looked at normal breast tissue from people and mice with BRCA mutations to see if there is a link between obesity and breast cancer risk.

Healthy breast tissue in women with BRCA1 or BRCA2 mutations
The researchers looked at healthy breast tissue from women with an inherited BRCA mutation who had mastectomies to lower their risk for cancer. The researchers separated the women into two groups based on their body mass index (BMI) - a fitness score that takes into account height and weight. 

• women who were overweight had a body mass index (BMI) of 25 or above.
• women who were not overweight had a body mass index of less than 25.

Researchers found that:

• Breast cells from women with a high BMI had more DNA damage than cells from those with a lower BMI.
  • This is important because DNA damage that the body cannot repair can lead to breast cancer.
• Researchers tested whether drugs could reduce DNA damage of normal breast cells grown in the lab:
  • Normal breast cells treated with the hormone therapy drug fulvestrant, had less DNA damage than cells that were not treated with fulvestrant.
  • Normal breast cells that were treated with the diabetes drug metformin had less DNA damage than cells that were not treated with metformin.

While the results from this study suggests that taking metformin to decrease DNA damage may be a way to reduce breast cancer risk, clinical trials of metformin to prevent breast cancer have had mixed results.

High-fat diet and risk findings in mice
The research team also compared high-fat and low-fat diets in mice that had a BRCA mutation. They found that:

• Mice with a BRCA mutation that were fed a high-fat diet had more DNA damage than those that were fed a low-fat diet.
• After exposure to cancer-causing chemicals, mice with high-fat diets developed tumors more frequently than mice on low-fat diets.

Risk of ovarian cancer
The most common type of ovarian cancer often begins in the fallopian tubes. The study team tested tissue from the ovaries and fallopian tubes of women with an inherited BRCA mutation. They found that:

• A higher BMI was associated with more DNA damage in the cells around the fallopian tubes but not in cells around the ovaries. This finding supports the idea that many ovarian cancers begin in the fallopian tubes.

Conclusions

This study links being overweight to increased DNA damage in women with an inherited mutation in a BRCA gene. Increased DNA damage may increase breast cancer risk. Findings in mice suggest the benefit of a low-fat diet. Importantly, the results of this study may form the basis for future clinical trials of a drug to decrease breast cancer risk in people with an inherited BRCA mutation.

What does this mean for me?

A lot of research has shown that additional body weight increases the risk for breast cancer. If you have an inherited BRCA mutation, being overweight or obese may further increase your risk of breast cancer. 

Much of this research was done on cells in the lab or in mice, not in people. The results of this study may form the basis for future clinical trials of a drug to decrease breast cancer risk in people with an inherited BRCA mutation. These findings suggest that eating a low-fat diet and maintaining a healthy body weight can help lower their risk for breast cancer. However, more research is needed to prove this is true. 

Talk with your doctor if you would like to lose weight. They can refer you to a nutritionist and other experts who can help you to healthily lose weight. There are many health benefits to maintaining a healthy diet and weight.

Reference

Bhardwaj P, Iyengar NM, Zahid H, et al., Obesity promotes breast epithelium DNA damage in women carrying a germline mutation in BRCA1 or BRCA2. Science Translational Medicine; 2023; 15. Published online February 22, 2023.

Disclosure: FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity

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posted 3/30/23