Breast cancer is the most common cancer for women in India as well as around the world. It is multifactorial in origin and various risk factors have been identified.
A ‘risk factor ‘is anything that increases risk of developing breast cancer. Many of the risk factors for breast cancer are beyond our control. However, obesity is an important risk factor which can be controlled.
Obesity is associated with an increased risk of breast cancer in postmenopausal women and a worse prognosis for all major breast cancer subtypes regardless of menopausal status.
Understanding Obesity
Obesity is a condition in which a person has an unhealthy amount or distribution of body fat.
Being overweight and obese is defined as having a BMI (body mass index) over 25. Body Mass Index (BMI) is a measure used to know whether a person has a healthy weight and is calculated by dividing a persons weight in kgs by the square of height in meters. Studies show that obese women have a higher risk of developing breast cancer compared to women who maintain a healthy weight.
BMI estimates the body weight status, but it is not without its limitations. For example, it doesn’t include measurements of fat and muscle in the body. So, a person with lot of muscle and little fat can have same BMI as a person with lot of fat and little muscle. Body composition study is important measure to know the amount of fat verses the amount of muscle in a person’s body.
Being overweight can also increase the risk of the breast cancer coming back (recurrence) in women who had the disease. There is evidence that weight gain post breast cancer diagnosis is associated with worse prognosis and lower overall survival. Being overweight at the time of breast cancer diagnosis and weight gain after diagnosis are also linked to poor survival.
Gaining weight in adulthood increases the risk of breast cancer before and after the menopause. One large study found that, women who gained about 10 kgs after the of age 18 yrs had 15% higher risk of breast cancer compared to women who gained little or no weight. Women who gained 25 kgs or more had 45% higher risk.
While the epidemiological link between obesity and breast cancer incidence and outcome is well established, the molecular mechanism explaining how obesity promotes breast cancer development and progression is less clear. Various mechanisms have been proposed to explain the correlation between obesity and breast cancer. These proposed mechanisms share some common themes; primarily, the role of fat cells in breast cancer and obesity-associated chronic inflammation.
Apart from its role as a depot for energy storage, fatty tissue also called as adipose tissue acts as a secretory organ, producing metabolic substrates (such as free fatty acids and cholesterol), growth factors, hormones, and certain chemicals referred to as adipokines. Studies have shown that these factors secreted by fat cells can promote breast cancer initiation, growth, and migration. The co-culture of breast cancer cells with fat cells (adipocytes) increases the proliferation, migration, and invasiveness.
Factors Relating Obesity with Breast Cancer
Estrogen Levels
The term, "obese" specifically points towards an increased fat tissue percentage which is associated with higher estrogen levels.The biosynthesis of estrogens differs between premenopausal and postmenopausal women. Premenopausal women mainly synthesize estrogens in the ovaries. However, in postmenopausal women ovarian biosynthesis is replaced by peripheral site synthesis, and in obese postmenopausal women, fatty tissue is the main source of estrogen biosynthesis.
Fatty tissues contain certain enzyme which facilitates them to make more estrogen. This mechanism of estrogen production can lead to local estrogen levels in breast tumour that are as much as 10-fold higher compared with the circulation, although this is something that cannot routinely be measured.
Circulating estrogens, the estradiol, are known to stimulate the proliferation of breast epithelial cells and potentially exert a mutagenic effect. Higher levels of circulating estradiol as a result of increased obesity and increased enzymes in fat tissue are thought to contribute, in part, to the greater risk of breast cancer in obese postmenopausal women.
Weight loss through either caloric restriction, exercise or gastric bypass surgery has been shown to lead to a reduction in circulating estrogen, although the relationship of the amount of weight lost to reductions in serum estrogens was not always proportional. Weight reduction in obese person reduces estrogen levels.
Inflammation
Obesity is associated with inflammation characterised by elevated levels of circulating chemicals which promote tumorigenesis and growth. Obesity causes both, in-breast and systemic inflammation, which contribute to increased risk of development and progression of breast cancer.
Additionally, increased circulating levels of these chemical mediators in obese breast cancer patients correlate with poor prognosis. It has been seen that malignant cells may co-opt the inflammatory mechanism, leading to increased growth, invasion, and metastasis.
Insulin
Obesity also instigates insulin resistance, a condition in which cells do not respond properly to insulin, causing the body to produce more insulin in order to control blood sugar levels. However, insulin is an inflammatory agent that can result in abdominal weight gain, creating a snowball effect of inflammation and enlarged fat cells. And since increased fat cells results in obesity and insulin resistance, which can result in an overproduction of estrogen raising the risk of breast cancer.
Insulin resistance, characterized by elevated plasma insulin levels, occurs in association with obesity-related inflammation and plays an important role in breast cancer progression. Insulin promotes cell proliferation and inhibition of cell death.
Additionally, insulin, to a lesser degree, interacts with estrogen signaling pathways to promote hormone sensitive breast cancers. Increased estrogen is responsible for stimulating growth of Estrogen receptor positive breast tumors. Together, these findings suggest that obesity-associated insulin resistance has multiple local and systemic consequences that help to explain the link between obesity and breast cancer.
Leptin
Fat tissue is recognised as an active endocrine organ secreting Leptin and Adiponectin which regulate appetite, insulin insensitivity & resistance, inflammation, immunity, blood vessels formation.
Elevated leptin levels are found in obese individuals. It has stimulatory role in cancers like breast cancer. Leptin is a promoter of cell proliferation.
Tumor tissues requires oxygen and nutrients for rapid growth, so in order to supply nutrient, new blood vessel formation (major factor of cancer spread) is stimulated. Leptin act as an inducer that ultimately promotes the growth of the breast cancer.
Adiponectin
Adiponectin is reduced in obese individuals. It is an inhibitor of cell proliferation and promoter of apoptosis (programmed cell death) in breast cancer cells. It has been observed that cancer patient has lower adiponectin levels.
Controlling Obesity
Whether you're at risk of obesity, currently overweight or at a healthy weight, you can take steps to prevent unhealthy weight gain and related health problems. Not surprisingly, the steps to prevent weight gain are the same as the steps to lose weight: daily exercise, a healthy diet, and a long-term commitment to watch what you eat and drink.
Exercise regularly. 150 mins of moderate aerobic activity or 75 mins vigorous aerobic activity per week. Incorporate weight training regimen at least 3 times per week.
Focus on low-calorie, low carbohydrate & nutrient-dense foods.
Consume less “bad” fat and more “good “fat.
Consume less processed and sugary foods.
Eat plenty of dietary fibre.
Focus on eating low- glycemic index foods. The glycemic index (GI) is a scale used to measure how quickly a food item will raise blood sugar.
Focus on reducing daily stress. Stress may trigger a brain response that changes eating patterns and leads to cravings for high-calorie foods.
Healthy sleep pattern. Sleep deprivation is associated with obesity.
Restrict alcohol intake.
IT’S NEVER TOO LATE TO ADOPT A HEALTHY LIFESTYLE
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