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

Summary

A study that looked at normal breast cells from women with an inherited BRCA mutation found more DNA damage among women who were overweight (based on a measurement known as body mass index) than those who were not overweight. The results suggest that maintaining a lower weight may reduce breast cancer among this high-risk population. (Posted 3/30/23)

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

Most relevant for: People with an inherited mutation in BRCA1 or BRCA2 concerned about their breast cancer risk.
It may also be relevant for:

  • previvors
  • people with a genetic mutation linked to cancer risk
  • people with a family history of cancer

Relevance: Medium

Strength of Science: Medium

Research Timeline: Animal Studies

Relevance Rating Details


What is this study about?

This study looked at the links between a higher body weight and damage in normal breast cells from women with an inherited mutation. Because damage can increase cancer risk, researchers also studied ways to decrease damage in both human and mouse breast cells that had a mutation in or . 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 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 mutations to see if there is a link between obesity and breast cancer risk.

Healthy breast tissue in women with or mutations
The researchers looked at healthy breast tissue from women with an inherited 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 damage than cells from those with a lower BMI.
    • This is important because damage that the body cannot repair can lead to breast cancer.
  • Researchers tested whether drugs could reduce damage of normal breast cells grown in the lab:
    • Normal breast cells treated with the hormone therapy drug fulvestrant, had less damage than cells that were not treated with fulvestrant.
    • Normal breast cells that were treated with the diabetes drug metformin had less damage than cells that were not treated with metformin.

While the results from this study suggests that taking metformin to decrease 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 mutation. They found that:

  • Mice with a  mutation that were fed a high-fat diet had more 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 . The study team tested tissue from the ovaries and of women with an inherited mutation. They found that:

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

Conclusions

This study links being overweight to increased damage in women with an in a gene. Increased 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 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 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 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 damage in women carrying a in or . 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

Questions To Ask Your Doctor
Questions To Ask Your Doctor

  • Does my body mass index increase my risk of developing cancer?
  • What can I do to lower my risk of cancer?
  • Do you know of cancer prevention clinical trials that might be right for me?

Guidelines
Guidelines

The American Cancer Society (ACS) guidelines on exercise, nutrition and weight for cancer prevention recommend the following: 

Diet and nutrition

  • Follow a healthy eating pattern, including:
    • foods that are high in nutrients in amounts that help you acheive and maintain a healthy body weight.
    • a variety of vegetables, fiber-rich legumes (beans and peas) and whole fruits in a variety of colors. Consume at least 2½ to 3 cups of vegetables and 1½ to 2 cups of fruit each day, depending on your calorie requirements. 
    • whole grains rather than refined grains. At least half of the grains you eat should be whole grains. 
  • A healthy eating pattern that limits or does not include:
    • red and processed meats.
    • sugar-sweetened beverages. 
    • highly processed foods and refined grain products.
  • It is best not to drink alcohol. People who choose to drink alcohol should:
    • have no more than 1 drink per day (women) or 2 drinks per day (men).

Exercise

  • Exercise regularly.
    • Adults should get at least 150 minutes of moderate-intensity activity (equal to a brisk walk) or 75 minutes of vigorous activity (heart rate is increased, breathing is faster and you are sweating) each week, preferably spread throughout the week.
    • Physical activity has been shown to lower the risk of several types of cancer, including breast, endometrial, and colon. It also reduces the risk of other serious diseases including diabetes and heart disease.

Weight

  • Achieve and keep a healthy weight.
    • Being overweight or obese is a risk factor for many cancers, including breast, colon, endometrial and pancreatic. You can control your weight through regular exercise and healthy eating.

Other experts, including the following, also provide guidelines for exercise, nutrition and health: 

Updated: 07/19/2022

Open clinical trials
Open clinical trials

The following are studies focused on nutrition and cancer prevention. 

Multiple cancers

Breast cancer

Colorectal cancer

Visit our Featured Research Page and Research Search and Enroll Tool to find additional studies enrolling people with or at high risk for cancer.

Updated: 05/28/2023

Strengths and limitations

This study had strengths and limitations. 

Strengths

  • The study addresses a topic of high interest to people with mutations: how to reduce their cancer risk.
  • The study has multiple parts and aims to lay the groundwork for future clinical trials.

Limitations

  • The high-BMI group included significantly more women who were older and premenopausal compared to the low-BMI group. This means that factors other than BMI that occur in women who are older or menopausal may account for these results.
  • The sample was too small to look at and separately.
  • This study only involved tissue that was removed from women and grown in the lab. It is not clear whether these results also apply to men with mutations. Nor is it clear whether results from cells in a person would respond similarly to cells grown in a lab dish.
  • Some of these results are preliminary findings and still need to be tested in clinical trials.
  • The majority of participants (93%) were white or did not provide racial or ethnic information, so whether these findings are generalizable to other populations is unclear.

Peer Support
Peer Support

The following organizations offer peer support services for people with, or at high risk for breast cancer:

Updated: 05/07/2024

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