Individuals with BRCA1 and BRCA2 gene mutations put people at a higher risk of developing breast and ovarian cancer. A recent research article by Bhardwaj et al., sheds light on the impact of Body Mass Index (BMI) on breast cancer risk for BRCA mutation carriers.
Obesity, (having a BMI of 30 or higher), is a known risk factor for breast cancer among women in the general population after menopause. However, for women with a BRCA1 or BRCA2 mutation, the relationship between BMI and breast cancer risk has been unclear due to conflicting findings in previous studies.
In the study, researchers investigated the impact of BMI on the breast tissue of BRCA mutation carriers. They found a positive correlation between BMI and DNA damage in normal breast epithelial cells in high BMI individuals. In other words, a higher BMI increases DNA damage, potentially also increases the risk of breast cancer.
The researchers further explored the mechanisms behind this link. They discovered that obesity-associated factors, such as estrogen biosynthesis, are activated in the breast adipose microenvironment of BRCA mutation carriers. These alterations affected neighboring breast epithelial cells, contributing to increased DNA damage.
Estrogen, a hormone known to play a significant role in breast cancer development, is influenced by obesity-associated factors. In breast tissue explants cultured from BRCA mutation carriers, blocking estrogen biosynthesis or estrogen receptor activity reduced DNA damage. This suggests that targeting estrogen may have a protective effect against breast cancer in this higher-risk population.
The study also explored the impact of other obesity-associated factors, such as leptin and insulin. These factors increase DNA damage in BRCA heterozygous epithelial cells. However, inhibiting the signaling of these factors with specific interventions decreased DNA damage. This opens up potential avenues for reducing breast cancer risk in BRCA mutation carriers through targeted therapies.
To strengthen their findings, the researchers conducted experiments on mice. They found that increased adiposity (body fat) was associated with mammary gland DNA damage and increased tumor development, further supporting the connection between BMI and breast cancer risk.
The results of this study support the link between elevated BMI and breast cancer development in BRCA mutation carriers. Therefore, maintaining a healthy body weight is particularly important for reducing breast cancer risk in this population. Additionally, pharmacologically targeting estrogen or metabolic dysfunction may offer possible preventive strategies.
This study brings us valuable insights into reducing breast cancer risk for individuals with BRCA mutations. By maintaining a healthy weight, avoiding processed foods, and exploring targeted interventions, BRCA mutation carriers can take proactive steps towards better breast health.