Obesity and Breast Cancer

The assertion that obesity causes or increases the risk of breast cancer is not an accurate one.

There is little doubt that being overweight and obese has an adverse effect on overall health. Indeed, carrying extra weight places strain on the cardiovascular and metabolic systems. So, this extra strain may, in turn, reduce the effectiveness of the body’s maintenance systems.

However, when it comes to breast cancer diagnosis there are, in most cases, common biochemical or genetic factors that cause both obesity and an increase in breast cancer risk.

Obesity is therefore just an indirect indication that an underlying genetic or biochemical factor is creating an increase in the ‘risk-context’ for breast cancer development.

I just want to let you know that I have a new page with more up-to-date information on Breast Cancer Risks for Obesity.

The Chicken or the Egg: Obesity and Breast Cancer

Claiming that obesity causes breast cancer is like saying, “Black asphalt causes burning feet on a hot summer day.” So, black asphalt is not the cause of the burning feet the heat of the sun is.

So, when physicians and authors make statements like ‘obesity increases the risk for breast cancer’ it is really just an arbitrary connection between two observable factors. Thus, it is not a direct, rational cause-effect type of scenario.

To summarize, it is true that maintaining a healthy weight is sound health advice. Indeed, obesity can bring about an increase in risk for many other diseases (such as type II diabetes). However, there is little rational basis to associate obesity with ‘helping to bring on’ breast cancer. At most, obesity is a ‘co-facilitator‘ in an increase in tumor aggressiveness, but that too is a tenuous suggestion.

How do Medics define obesity?

Medics traditionally measure obesity and ‘being overweight’ in three ways:-

Body composition describes where the body carries fat. For example, the upper body, abdominal region, hips, buttocks or legs. This measurement may also consider tape measurements like the ‘hips to abdominal’ ratio.
Skinfold measurement is an actual measuring of the thickness of fat rolls around the abdomen and other areas.
Body Mass Index (BMI)

Body Mass Index (BMI) as a measure of obesity, and projected breast cancer risk?

The body-mass-index is also useful as a measure of overall fitness. Specifically, BMI is the ratio of weight (in kilograms) to height (in meters) squared. Specialists state that a Body Mass Index (BMI) between 18.5 and 24.9 kg/m2 is healthy for women. The definition of obesity is a BMI of greater than 30 kg/m2.

<18.5 underweight

18.5 to 24.9 healthy

25.0 to 29.9 overweight

>30.0 obese

Some studies suggest that the risk of breast cancer increases by 10% to 20% with each increase of body mass index category. However, if statistics show that 10%-20% more women have breast cancer in higher BMI categories, it is because this same percentage of women have a genetic predisposition to both obesity and to breast cancer. Thus, there is no cause-effect connection between the two statistics.

Body ‘type’ measurements: Can the location of fat increase risk?

In addition to simple obesity according to body mass index, the distribution of body fat may also be of importance. Some researchers feel that women with large amounts of the upper body and abdominal fat may have a greater risk of breast cancer. So, women who carry their fat in the hips, lower extremities, and buttocks have a lower risk.

According to the theory, women with a proportionately greater localization of fat in the upper body also tend to have lower levels of sex-hormone-binding globulin (SHBG) discussed below, which could possibly increase breast cancer risk.

There is no rational basis to associate a particular body type with breast cancer development. There may be no relation at all, or they may be the result of similar genetic predispositions, but there is no basis to conclude that one has caused the other.

Even within the obesity camp, studies on the effects of fat distribution are less consistent than those associated with BMI. One recent study concludes that if higher amounts of the upper body and abdominal fat increase the likelihood of breast cancer, it may also decrease the chance of lymph node metastasis.

Since lymph node involvement is almost always associated with a poorer prognosis, it is possible that women with proportionally greater upper body fat, in fact, have a more favorable outlook.

It is possible that a woman’s level of fat could exert a small influence on the prognosis, but not the original cause. All in all, we conclude that BMI and body composition measurements exert zero-to-minimal influence on breast cancer development. Furthermore, such claims are simply random connections between observable co-existent health issues.

Mammogram Accuracy: Do Obese women more commonly screen positive for breast cancer?

Breast cancer information sources sometimes imply that mammograms are more difficult to read for obese women, and this leads to missed diagnosis and untreated tumors. This assertion is completely false. Radiographers find cancers more easily on mammograms of obese women because they are easier to interpret. Thus, this leads to higher detection rates of smaller curable cancers. Interpreting those statistics out of context can make it seem like obese women have “more cancer“.

Another suggestion is that obese women, on breast cancer screening, are up to three times more likely to have breast cancers at a more advanced stage of the disease. This is a misleading statement. It can be more difficult for an obese woman to check for lumps in the breast. Thus, by the time the lump shows and she goes for a mammogram, the tumor is at a larger, more advanced stage.

Obesity can influence hormone levels

There is no question that fluctuations in hormonal levels directly influence the rate and extent of cancer development. Hormones essentially give signals for cells either to grow, to stop growing, or to maintain their present status and function.

The most significant hormonal changes a women goes through in her life are at the time of

puberty
pregnancy
childbirth
menopause

Obesity can, to a very small extent, amplify negative or ‘risk-increasing’ aspects of these natural hormonal changes. Thus, it may be safe to say that obesity is a secondary factor to increase the risk for breast cancer. However, we still maintain that the ‘causal’ effect of obesity on breast cancer risk is minimal.

Estrogen and other hormones; partly influenced by excess fat tissue

The hormonal system is a vast, dynamic network of checks and balances that medical science does not fully understand. There are many different hormones associated with breast cancer, but estrogen is perhaps the most prominent. Post-menopausal women will naturally experience decreased estrogen levels. Fat cells very slightly increase estrogen levels, which might influence the balance of estrogen and other hormones associated with a lesion site. There is a considerable debate, however, as to the authenticity of this influence.

Increased risk due to a higher concentration of estrogen?

Recent studies have suggested that average concentrations of estrogen in obese women are considerably higher than for thin women. After menopause, the primary source of estrogen in a woman’s body is fat tissue. Researchers who suggest a connection between obesity and breast cancer risk believe that higher than average levels of estrogen can stimulate certain types of breast cancer, (tumors located in estrogen-sensitive tissues) causing them to grow faster. However, other physicians maintain that the influence of estrogen from fat-tissues is negligible. A connection between obesity and estrogen levels is viable, but conclusions have to be based on a very large sample pool controlled for age and menopausal status, and any connections to breast cancer would have to follow from this, at the exclusion of all other possible factors.

A few cancer researchers have suggested the main connection between obesity and breast cancer was elevated levels of xenoestrogens in fat cells. Xenoestrogen is a man-made toxin found in environmental pollution, and it has been suggested these xenoestrogens are stored fat cells, and subsequently release high volumes of estrogen-like compounds into the system. While not entirely discounted, far more likely sources of higher estrogen levels are natural genetic interactions involving estradiol and leptin. Dismissing the notion of ‘obesity causing breast cancer‘ for the moment, there is some validity to the idea that once a malignant lesion has developed, fat levels can, via hormone levels, exert a very minor influence on cancer aggressiveness.

Leptin and estradiol: decreased tumor suppression in obese women

Leptin has been shown to be present in over 85% of primary breast tumors. Furthermore, Leptin is an adipocyte-derived hormone, (a hormone found in fat cells). The main purpose of Leptin is to signal to the body that no more food is necessary. Indeed, in some cases, lack of this hormone can, in fact, be a cause of obesity. But leptin is also involved in sexual reproduction, lactation, and cell differentiation and proliferation. Leptin is activated by signals received from a leptin receptor, “ObR“, and the leptin-ObR connection has for many years been associated with breast cancer development. Some cancer studies now suggest that factors associated with obesity may indirectly alter the delicate balance in the ‘leptin signalling‘ process.

Estradiol is another female sex hormone, and levels of both ‘free‘ and ‘bound‘ estradiol (bound to serum albumin) have been shown to increase after menopause. Women with breast cancer tend to have higher levels of both types of estradiol but lower levels of sex-hormone-binding globulin (SHBG). As with many hormones, there is often a delicate balance between ‘increasing‘ and ‘inhibiting‘ functions. The increase of estradiol and decrease in sex-hormone-binding globulin, common in both obese and post-menopausal women, can throw off this balance. When breast carcinoma is present, this could possibly result in undesired stimulation of tumor growth.

However, one must always bear in mind that it is likely genetic predisposition which has led to the development of both obesity and breast cancer. Moving forward, fat-influenced hormone levels may affect the progression of cancer but did not cause it.

Relationship between Leptin and E-cadherin: Tumor Suppression

Those who feel that obesity either increases the risk and severity of breast cancer often point to changes surrounding the ‘E-cadherin‘ molecule. E-cadherin is important for the maintenance of healthy epithelial tissues and functions to increase intercellular adhesion. With respect to breast cancer it is generally viewed as a positive agent; a kind of ‘tumor suppressor‘. However, in the presence of increased amounts of leptin and estradiol, the ‘uptake‘ of pro-androgenic (new blood vessels and blood supply) and pro-proliferative (allowing cells to grow more freely) factors is increased and the leptin and estradiol begin to function as ‘tumor enhancers‘ instead.

To put it another way, as a wound heals, the body welcomes pro-angiogenic and pro-proliferative cells and proteins, but these same agents can work against the body when fighting breast cancer as they may improve the tumors ability to grow and spread. The E-cadherin molecule helps the aggregations of cells and enhances the transformation of normal cells to cancerous ones, which increases tumor mass.

So, it is possible that the hormonal interactions surrounding leptin, estradiol, and E-cadherin could increase the risk of cancer growth and spread, and new treatments geared to ‘inhibiting‘ leptin receptivity in obese women with breast cancer are being tested. However, there is nothing to suggest that being obese or overweight is in any way a precursor to the original breast carcinoma.

Hormone replacement therapy: inconclusive risk indicator in obese women

Hormone replacement therapy is a controversial topic. The evidence clearly supports an increased risk of breast cancer for post-menopausal women who receive these supplemental hormones. When combined with the obesity-factor, however, women who take menopausal hormones appear to be at no more increased risk than women of average weight. On the contrary, some studies have shown that obese women who have had NOT had hormone replacement therapy are the ones with increased breast cancer risk.

It is difficult to make any useful generalizations here. Hormonal balance is not clearly understood, even within the medical profession, increased risk or severity due to hormone levels, altered via excess fat tissue, has not been broadly confirmed. It would be completely medically unsound for obese women, in particular, to take menopausal hormones with an intent to lower their breast cancer risk.

Effects of Tamoxifen for obese women with breast cancer

Tamoxifen is most frequently used as chemical therapy for inhibiting growth and recurrence of breast cancer. This drug is oriented towards a woman’s hormonal system and is a highly effective treatment for HER2 positive patients. For obese women, there is no difference in success rates or recurrence compared to women of normal weight, but, there is a suggestion of an increased risk of breast cancer development in the opposite breast. There may also be an increased risk for obese women of developing other cancers. However, these developments cannot be conclusively traced to the tamoxifen and are far more likely to be caused by pre-existing genetic factors associated with both cancer development and obesity, to begin with.

General conclusions on obesity and breast cancer risk

Obesity neither causes nor increases the risk of breast cancer. Connecting the two conditions is logically flawed; when you observe two health effects (breast cancer and obesity) you cannot logically conclude that one causes the other. Both are the most likely the result of pre-existing genetic causes, and both tend to affect women in the latter half of their lives. Most BMI related studies are done in comparison to a population of normal weight BMI people, with an average age in their early 20s. (Younger people tend to be thinner). Large breast cancer studies, however, tend to focus on women in their 40’s and 50’s.., by which time many more women have become overweight, and some have developed breast cancer.

A recent study estimated that in the United States, up to 18 000 deaths per year due to breast cancer for women over 50 may not have occurred had the women been able to maintain a BMI under 25 during their adult lives. This conclusion is highly dubious. A more likely observation would be that a certain percentage of women who died of breast cancer, also happened to be obese. It is possible that breast cancer severity is affected by altered hormonal levels influenced by extra fat tissues, but this effect is very small.

For further reading, you may want to visit a cool and handy tool called The Gail Model, which is specifically meant for estimating breast cancer risk. Know your risk now!

References

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… and a few more References

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Ando, Sebastiano.Obesity-breast Cancer Link May Be Due To Fat Tissue- Federation of American Societies for Experimental Biology (2007, May 2)

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