Breast Cancer Risk Factors
by Hans R. Larsen, MSc ChE
Vitamin D and breast cancer
SAN DIEGO, CA. A report has just appeared in the Journal of Steroid Biochemistry & Molecular Biology by Garland et al that addresses the issue of vitamin D and breast cancer risk with a pooled analysis of studies that determined the vitamin D status from serum 25-hydroxyvitamin D (25(OH)D) levels. The list of authors includes both well-known vitamin D experts and nutritional epidemiologists. The authors were only able to find two studies that met their requirements for inclusion in their pooled analysis, but together they involved 1760 individuals. Both studies covered a wide range of 25(OH)D levels and exhibited a high level of inverse correlation between breast cancer risk and the serum level of this vitamin D marker. When pooled analysis was carried out, the odds ratios for the lowest to highest quintile of 25(OH)D levels were 1.00, 0.90, 0.70, 0.70 and 0.50, i.e. the highest vitamin D status provided a 50% reduction in risk. The authors present a graph of risk (odds ratio) against serum 25(OH)D levels with an amazing correlation coefficient of 0.94 (a statistical measure of the goodness of fit to the model, in this case a straight line, and 1.00 represents a perfect fit), a correlation coefficient that would please those trained in the physical sciences and in fact a correlation very rarely seen in plots presented in the medical literature.
The authors discuss the level of intake that would accomplish the 50% level of risk reduction. If a person were to start at a serum level of 24 nmol/L (10 ng/mL) it would require supplementation of 4000 IU/day to achieve the required level of 120 nmol/L. This exceeds the current upper limit of 2000 IU/day. However, as they point out, a proposal has been made to raise this limit to 4000 IU/day. Levels of 24 nmol/L are not uncommon among US women in the winter months. An alternative they explore is to take 2000 IU/day orally and make up the balance by judicious sun exposure. They estimate that 12 minutes of sun exposure for 50% of the skin would produce the missing 2000 IU. However, this would not happen in the northern latitudes in the winter months.
The authors hammer home their point regarding the importance of vitamin D by calculating that, based on their data, an intake of 4000 IU of vitamin D per day would, in the U.S., prevent over 100,000 cases of breast cancer per year. Intake of 2000 IU/day was estimated to prevent 66,000 cases. In this paper, vitamin D refers to vitamin D3.
Weight gain and breast cancer risk
For lifetime adult weight gain it was found that there was a 4% increase in risk of postmenopausal breast cancer for each 5 kg (11 lbs) increase in adult weight, In addition, there was a tendency for a stronger association for those with a higher waist circumference which suggested that fat accumulation around the waist was of greatest significance. Only those with estrogen/progesterone positive tumors exhibited weight-related increases in risk. Weight gain from age of first pregnancy to assessment was also associated with increased risk, but the trend with the amount of weight gain was not significant. However, weight change from age of first pregnancy to age of menopause was associated with increased risk with a significant trend associated with the amount of weight gain. Other than this, there were no significant associations with the time of life in which weight gain occurred. This study also confirmed what others have observed, i.e. there is a protective effect of higher
body weight at age 20, with women in the highest quartile having a significant reduced risk of 27% as compared to those in the lowest quartile. No association was found for weight gain during pregnancy and the risk of postmenopausal breast cancer.
Weight gain during adulthood increases breast cancer risk
Overall, the women who gained weight in adulthood faced a higher lifetime risk of all types of breast cancer after menopause. The greater the amount of weight gained, the greater the risk of breast cancer of all types, stages, and grades. Specifically, women who gained over 60 pounds had an 89 per cent higher risk of ductal type tumors than women who gained 20 pounds or less during adulthood, and 54 per cent higher risk of lobular type cancers. The likelihood of metastatic disease (cancer which spreads to other organs) was more than three times higher among women who gained over 60 pounds. When hormone receptors in the breast cancer cells were examined, it was found that weight gain was linked exclusively to tumors with estrogen receptors present (ER-positive). This is predicted by earlier findings that breast cancer risk is linked to increased lifetime levels of circulating estrogen. Fat tissue increases estrogen levels, contributing to the risk.
Obese women may have the chance of mitigating their breast cancer risk by taking hormone replacement therapy, the researchers explain. They add that current weight is not as important as weight gained since the age of 18. These data underline the importance of maintaining a healthy body weight throughout adulthood, they conclude.
Vitamin D, breast and ovarian cancer
Breast cancer risk from magnetic fields investigated
Breast cancer linked to depression
The researchers confirmed that early age at first menstruation (menarche) and a family history of breast
cancer are potent risk factors for breast cancer. However, they also found a strong association between
depression, anxiety, a feeling of hopelessness, and loss of interest and pleasures and the risk of breast
cancer. Women who were depressed and hopeless had almost twice the risk of developing breast cancer
than did more cheerful and upbeat women even after allowing for other known risk factors.
Breast cancer linked to stress
Breast cancer linked to use of antibiotics
Researchers from the University of Washington and the Fred Hutchinson Cancer Research Center recently reported a clear association between the risk of breast cancer and exposure to antibiotics. Their study involved 2266 women with primary, invasive breast cancer and 7953 randomly selected age- matched controls. The researchers found that women who had been exposed to antibiotics for 1-50 days had a 45% greater relative risk of developing breast cancer and dying from breast cancer than did women who had never used antibiotics. Women who had used antibiotics for more than 1,000 days in their lifetime had double the risk.
The researchers point out that it is not clear whether the observed association is due to the fact that
antibiotics actually promote breast cancer or whether the increased risk stems from the underlying
condition (infection, inflammation) that is being treated with the antibiotic. Antibiotics are known to disturb
the intestinal microflora and interfere with the metabolism of phytochemicals that may help prevent
cancer. The antibiotic tetracycline may be associated with an increased production of inflammatory
prostaglandins. The researchers found no difference in association between breast cancer and antibiotic-
use among premenopausal versus postmenopausal women and the type of antibiotic used did not alter
the strength of the association either. They conclude that their findings lend further support to oft-
repeated warnings to limit the prescription of antibiotics as much as possible and not prescribe them for
Editor's comment: It seems to me that the observed association could well involve candida overgrowth. Frequent and prolonged use of antibiotics will almost certainly lead to an overgrowth of candida (yeast infection). Candida, like alcohol, is a potent generator of aldehyde and both alcohol itself and its metabolite, acetaldehyde, have been linked to an increased risk of breast cancer. I have seen no medical evidence of a possible candida connection, but to be on the safe side it is a good idea to take probiotics (acidophilus) when taking antibiotics unless there is a specific reason not to.
Electric blankets linked to breast cancer.
Cancer trends in the USA
Cancer of the colon and rectum
The report concludes that overall cancer incidence and death rates began to stabilize in the mid to late
1990s, but have lately shown signs of increasing again.
No benefits of hormone therapy
There was a slight, but statistically non-significant increase in cancer incidence among HRT users.
Breast cancer rates were 27 per cent higher in the HRT group and lung cancer incidence was 39 per cent
higher. Women who used HRT also tended to have more hip fractures. The researchers conclude that
HRT does not reduce cardiovascular events in women with heart disease and increases the risk of blood
clots, gallstones, and hip fractures.
Sun avoidance increases cancer risk
NEWPORT NEWS, VIRGINIA. There is ample evidence that lack of sun exposure increases the risk of many types of cancer. The mortality rates for breast cancer, prostate cancer, colon cancer, ovarian cancer, and non-Hodgkin lymphoma are twice as high in the northeastern part of the US as in the southwest. Dr. William Grant, PhD, an independent American researcher, now reports additional evidence indicating the eight more cancers are associated with lack of exposure to UV-B radiation (sunshine!). Dr. Grant found a clear inverse correlation between UV-B exposure and mortality from bladder, kidney, lung, pancreatic, stomach, rectal, esophageal cancers and cancer of the corpus uteri. He estimates that over 21,000 white Americans, 1400 African Americans, and 500 people from Asian and other minorities die prematurely every year from cancer because they don't get enough sunshine.
Dr. Grant and most other researchers in the field believe that the lack of sun exposure leads to a vitamin- D deficiency, which is known to be implicated in the progression of many cancers. Vitamin D is formed in the skin when it is exposed to sunlight. Vitamin D formation is totally inhibited by sunscreens and most clothing. Dr. Grant points out that winter time UV-B levels in Boston are insufficient to promote vitamin D synthesis in the skin. He advocates prudent sun exposure when it is available and vitamin D supplementation when it is not. Editor's Note: If lack of sun exposure is a problem in northern USA then it is obviously even more of a problem in Canada. Researchers at the University of Toronto recently concluded that Canadians need to supplement with 4000 IU/day of vitamin D when they are not exposed to sunshine.
Grant, William B. An estimate of premature cancer mortality in the U.S. due to inadequate doses of solar ultraviolet-B radiation. Cancer, Vol. 94, March 15, 2002, pp. 1867-75
Breast cancer and hormone replacement therapy
Breast cancer and electromagnetic radiation
Physical activity and breast cancer risk
Glucarate and breast cancer prevention
Fats and breast cancer
Night work increases breast cancer risk
Breast cancer in women under 40 years
More on breast cancer and paroxetine
Antidepressants and breast cancer
Antibiotics linked to breast cancer
The researchers found that women under 50 years of age (at the start of the
study) who had used antibiotics to treat urinary tract infections had a 93 per
cent excess risk of developing breast cancer when followed-up for more than 10
years. The risk was greatest among younger women and lowest among women aged
60 years or more at entry to the study. It was also clear that urinary tract
infections as such were not associated with an excess breast cancer risk; it
was only when treated with antibiotics that a strong correlation showed up.
The study also confirmed already known risk factors for breast cancer such as
age, higher level of education, alcohol consumption, none or only a few
childbirths, living in an urban or industrial area, and being lean and tall.
The correlation between antibiotics treatment and breast cancer held true even
when adjusted for these factors. The researchers conclude that there may be a
correlation between breast cancer and the use of antibiotics to treat urinary
tract infections at a premenopausal age. They suggest that this conclusion is
biologically plausible, but recommend further large-scale studies to confirm
Breast cancer risk linked to fatty acid profile
The study found no significant correlation between omega-3 fatty acid levels
and breast cancer incidence, but did find a trend to increasing incidence with
increasing levels of omega-6 fatty acids in the adipose tissue samples. The
researchers also found a significant association between the ratio of EPA and
DHA to LA levels and breast cancer incidence in 4 out of 5 of the medical
centers involved in the study. Pooling all results showed that women with the
highest ratio had a 35% lower breast cancer incidence than women with the
lowest ratio. In other words, women with a relatively high adipose tissue
level of EPA and DHA (the main components of fish oils) and a relatively low
level of LA and its metabolites had a lower breast cancer risk. The
researchers note that LA (linoleic acid) is the precursor of certain
eicosanoids which may promote tumour growth. EPA and DHA inhibit the
production of these harmful compounds and may also, on their own, inhibit
tumour growth. The researchers also point out that several epidemiological
studies have found an inverse correlation between fish consumption and breast
cancer incidence and urge further studies to determine the relationship
between the dietary intake of specific fatty acids and breast cancer
Mammography: A risky procedure?
ABERDEEN, SCOTLAND. Researchers at the University of Aberdeen warn that the compressive force used in order to obtain usable mammograms may be a contributing factor to breast cancer. The British standard for the force used to squeeze the breast as flat as possible corresponds to placing twenty 1 kilogram bags of sugar on each breast. The researchers fear that this force may be excessive and enough to dislocate and spread any existing cancer cells. Animal experiments have shown that the number of cancer sites can increase by as much as 80% when tumors are manipulated mechanically. A recent study in Malmo, Sweden found that the death rate from breast cancer among women under 55 was 29% higher in a group which had been screened with mammography than in the unscreened control group. The screening procedure used "as much compression force as the women could tolerate".
The Lancet, July 11, 1992, p. 122
Estrogen treatment increases risk of breast cancer
Breast cancer rates related to fat intake
DDT implicated in breast cancer
Hereditary nature of breast cancer exaggerated
Induced abortion may increase breast cancer risk
Estrogen therapy may promote metastatic breast cancer
Hormone replacement therapy increases risk of breast cancer
Smoking increases risk of breast cancer
Insulin-like growth factors linked to cancer
Free radicals implicated in spread of breast cancer
Survival rate better for breast cancer victims if mother had it too
Fat intake and risk of breast cancer
IGF-1 linked to breast cancer
Hormone replacement therapy linked to breast cancer
Breast cancer and meat consumption
Cigarette smoking and breast cancer
Vitamin B12 deficiency and breast cancer
In a subsequent review of the findings Dr. Sang-Woon Choi, MD of Tufts
University points out that serum levels of folate are a poor indicator of
levels in tissues and that it may well be that there is a correlation between
folate levels in breast tissue and breast cancer risk. Dr. Choi speculates
that a vitamin B12 deficiency may lead to breast cancer because it could
result in less folate being available to ensure proper DNA replication and
Epstein-Barr virus implicated in breast cancer