Excess body weight is responsible for about 11% of cancers in women and 5% of men. Did you know that the risk for postmenopausal breast cancer is 1.5 times higher in overweight women and 2 times higher in women with obesity? Let’s understand more about how obesity contributes to breast cancer risk.
How Does Body Weight Affect Breast Cancer Risk?
Being overweight or obese increases the risk for breast cancer, especially in postmenopausal women. Your Body Mass Index (BMI) determines if you have a healthy weight, are overweight, or are obese.
A BMI between 18 and 24.9 is considered healthy. A BMI between 25 and 29.9 means that you are overweight. If your BMI is higher than 30, it could indicate obesity.
Women with a BMI over 25 are at an increased risk of developing breast cancer than those with a healthy weight. In addition, this risk is exceptionally high after menopause. Being overweight or obese also increases the risk of breast cancer recurrence.
The exact link between increased weight and breast cancer risk is complicated and multifactorial. The high risk appears to be connected to the estrogen production by the fat cells.
In premenopausal women, estrogen is mainly produced by the ovaries. However, in postmenopausal women, adipose tissues or fat tissues is the main source of estrogen production.
The number of fat cells is higher in overweight or obese women. This results in increased estrogen production, which is a risk factor for breast cancer development. This is especially of significance for Hormone-Receptive breast cancers that develop and grow on exposure to estrogen.
It has been found that women who are obese after menopause are at a 30% higher risk of developing breast cancer. Gaining more than 22 pounds after menopause can increase the risk of breast cancer by 18%.
Obesity And Breast Cancer Risk
Obesity and Breast Cancer Risk in Premenopausal Women
Studies report an association between obesity and a lower risk of Estrogen-Receptor Positive (ER-Positive) breast cancer but a higher risk of ER-negative and Triple-negative breast cancer in premenopausal obese women.
In addition, a study from the Breast Cancer Surveillance Consortium database showed that obesity is associated with an increased risk for Inflammatory Breast Cancer (IBC) in premenopausal women.
Obesity and Breast Cancer Risk in Postmenopausal Women
The Million Women Study followed 1.2 million UK women ages 50 to 64 years for a mean of 5.4 years. Out of these, 45,037 women had breast cancer. The study identified a nearly 30% higher risk of developing postmenopausal breast cancer with obesity.
A meta-analysis of 34 studies reported that the risk of postmenopausal breast cancer increases with every 5kg/m2 increase in BMI.
Risk Of Breast Cancer Mortality In Obese Patients
Obesity affects the prognosis and survival rate of breast cancer patients. A recent study found that obese women with breast cancer experienced an 11% decrease in overall survival rate, irrespective of their menopausal status.
Besides breast cancer, obesity is a risk factor for type 2 diabetes and heart diseases - the latter seems to be the leading cause of mortality in women with early-stage breast cancer.
It has also been observed that obese women with breast cancer are more likely to experience complications during surgery and radiation.
In addition, systemic chemotherapy and endocrine therapy for treating breast cancer are less effective in obese women, further reducing prognosis and survival rate.
Breast cancer-specific mortality among obese women is 1.3 times higher compared to women with a normal BMI.
The mortality rate in obese women is also dependent upon the type and characteristics of the tumor. For example, obese women with Luminal A and Luminal B breast cancer were 1.8 and 2.2 times more likely to die from cancer than normal-weight women.
However, obesity was not associated with breast cancer-specific mortality among women with HER2- and triple-negative tumors.
Genetic Factors That Influence The Relationship Between Obesity And Breast Cancer Risk
The BRIP1 Gene
BRCA1 Interacting Helicase 1 (BRIP1) is located on chromosome 17 and, along with the BRCA1 gene, helps repair any damage to the DNA. It is also responsible for maintaining chromosomal stability.
rs16945628 is a Single Nucleotide Polymorphism (SNP) in the BRIP1 gene. The TT genotype of this SNP is associated with an increased risk of breast cancer in women with a BMI of ≧25 kg/m2.
The IGFBP3 Gene
Insulin-like Growth Factor Binding Protein 3 or IGFBP3 gene is located on chromosome 7 and participates in cell growth, multiplication, and differentiation, and cancer development in the breast tissue.
rs2854744 is an SNP in the IGFBP3 gene linked to the risk of breast cancer. The CC genotype of this gene significantly increases the risk of breast cancer compared to the AA genotype. This increase was found to be more pronounced in older women.
Studies also showed that women carrying the AC+CC genotypes of the IGFBP3 gene had a larger tumor size in the breast.
Non-Genetic Factors That Influence The Relationship Between Obesity And Breast Cancer Risk
Obesity is a critical non-genetic risk factor for breast cancer.
- Studies show that women who gained weight as adults have a greater risk of developing breast cancer than those who were overweight since childhood.
- Having excess fat around the waist area may increase breast cancer risk more than having extra fat in the hips and thighs in women.
Other factors that increase breast cancer risk in obese women are:
- Lack of physical activity
- Taking hormones like oral contraceptives or Hormone Replacement Therapy (HRT) during menopause
- Reproductive history: Women who have given birth after 30 years of age, have not had a full-term pregnancy, and have not breastfed have an increased risk of breast cancer.
- Drinking alcohol and smoking
Does Weight Loss Reduce Breast Cancer Risk?
According to a 2019 study, sustained weight loss is associated with lower breast cancer risk for women aged 50 years and older.
The researchers looked at 180,885 women from 10 studies. The women's weights were recorded 3 times over a period of 10 years; once when they enrolled and once every 5 years.
Weight changes of 2 kilograms or less (about 4.4 lbs) were counted as stable.
The study reported the following*:
- Women who lost 2 to 4.5 kg (about 4.4 to 10 lbs.) had a 13% lower risk.
- Women who lost 4.5 to 9 kg (10- 20 lbs.) had a 16% lower risk.
- Women who lost 9 kg or more (20+ lbs.) had a 26% lower risk.
- Women who lost 9 kg or more and gained some (but not all) of the weight back had a lower risk.
*Compared with those whose weight was stable.
The study did not include women on postmenopausal hormone therapy, and the results were more prominent in obese or overweight women.
Despite this, the study suggests that even a modest amount of sustained weight loss can lower your breast cancer risk and improve survival rate, if diagnosed with breast cancer.
Recommendations to Reduce Breast Cancer Risk
- Maintain a healthy weight by eating a balanced diet, cutting out excess carbohydrates and processed foods, exercising regularly, and avoiding alcohol.
- Have a healthy eating pattern that is rich in fiber, proteins, vitamins, and minerals.
- If you have been advised to take hormone replacement therapy and oral contraceptives, discuss with your doctor the risk involved.
- Breastfeeding can lower breast cancer risk, especially if a woman breastfeeds for longer than one year.
- If you have a family history of breast cancer, genetic testing is recommended to detect abnormal changes in the BRCA1 and BRCA2 genes. Talk to your doctor to know more about this.
Summary
- Being overweight or obese increases the risk of developing breast cancer. This risk is exceptionally high in postmenopausal women.
- An increase in weight increases fat cells in the body and a subsequent rise in estrogen levels. Exposure to estrogen increases the risk of breast cancer development.
- Women with BMI over 25 have a higher risk for breast cancer.
- Obese premenopausal women have a lower risk for ER-Positive breast cancer but an increased risk for ER-negative and triple-negative breast cancer.
- Breast-cancer-specific mortality among obese women is 1.3 times higher than in women with normal BMI.
- Few genes like BRIP1 and IGFBP3 are associated with breast cancer risk in obese women.
- Other factors like lack of physical activity, hormone replacement therapy, reproductive history, alcohol consumption, and smoking increase breast cancer risk in obese women.
- According to a study, sustained weight loss in women over 50 can help reduce breast cancer risk compared with women whose weight was stable.
References:
- https://www.genecards.org/cgi-bin/carddisp.pl?gene=IGFBP3
- https://www.breastcancer.org/risk/factors/weight
- https://www.cancer.org/latest-news/how-your-weight-affects-your-risk-of-breast-cancer.html
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5591063/
- https://www.hindawi.com/journals/jo/2013/906495/
