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Page: Epidemiologic Risk Factors and Etiology
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It is important to have a model of causation of a disease in order to distinguish epidemiological risk factors or associations with disease, from the biological etiology and primary cause, secondary co-factors, and simple promoters of the disease. The first work on breast cancer epidemiology was done by Janet Lane-Claypon, who published a comparative study in 1926 of 500 breast cancer cases and 500 control patients of the same background and lifestyle for the British Ministry of Health.
Today, breast cancer, like other forms of cancer, is considered to be a result of damage to DNA. How this mechanism may occur comes from several known or hypothesized factors (such as exposure to ionizing radiation, or viral mutagenesis). Some factors lead to an increased rate of mutation (exposure to estrogens) and decreased repair (the BRCA1, BRCA2 and p53) genes. Although many epidemiological risk factors, and biological co-factors and promoters have been identified, the majority of breast cancer incidence remains unattributable, and the primary cause is unknown.
Dietary influences have been proposed and examined, and recent research suggests that low fat diets may significantly decrease the risk of breast cancer as well as the recurrence of breast cancer. A significant environmental effect was revealed by the large difference in breast cancer incidence between countries and continents, and a migration effect which slowly increases the risk of breast cancer even across generations after migration from a country of lower incidence to a country of higher incidence, such as moving from China or Japan to the United States. Humans are not the only mammal prone to breast cancer. Some strains of mice, namely the house mouse (Mus domesticus) are prone to breast cancer which is caused by infection with the mouse mammary tumour virus (MMTV or "Bittner virus" for its discoverer Hans Bittner), by random insertional mutagenesis. Suspicion of MMTV or other viruses in human breast cancer is controversial, and the idea is not generally accepted for lack of direct and definitive evidence. There is much more research in diagnosis and treatment of breast cancer than in its cause.
Age
The risk of getting breast cancer increases with age. For someone who lives to the age of 90, the chances of getting breast cancer is about 14.3% or one in seven during their lifetime. Men can also develop breast cancer, but their risk is less than one in 1000 (see sex and illness).[citation needed] This risk is modified by many different factors. In 5% of breast cancer cases, there is a strong inherited familial risk.
The probability of breast cancer rises with age but breast cancer tends to be more aggressive when it occurs in younger people. One type of breast cancer that is especially aggressive and disproportionately occurs in younger people is inflammatory breast cancer. It is initially staged as Stage IIIb or Stage IV. It also is unique because it often does not present with a lump so that it often is not detected by mammography or ultrasound. It presents with the signs and symptoms of a breast infection like mastitis.
Alcohol
Alcohol generally appears to increase the risk of breast cancer. The UK's Review of Alcohol: Association with Breast Cancer concludes that "studies confirm previous observations that there appears to be an association between alcohol intake and increased risk of breast cancer in women. On balance, there was a weak association between the amount of alcohol consumed and the relative risk."
The National Institute on Alcohol Abuse and Alcoholism (NIAAA) concludes that "Chronic alcohol consumption has been associated with a small (averaging 10 percent) increase in a woman's risk of breast cancer. According to these studies, the risk appears to increase as the quantity and duration of alcohol consumption increases. Other studies, however, have found no evidence of such a link.
The Committee on Carcinogenicity of Chemicals in Food, Consumer Products Non-Technical Summary concludes, "the new research estimates that a woman drinking an average of two units of alcohol per day has a lifetime risk of developing breast cancer 8% higher than a woman who drinks an average of one unit of alcohol per day. The risk of breast cancer further increases with each additional drink consumed per day. The research also concludes that approximately 6% (between 3.2% and 8.8%) of breast cancers reported in the UK each year could be prevented if drinking was reduced to a very low level (i.e. less than 1 unit/week)."
It has been reported that "two drinks daily increase the risk of getting breast cancer by about 25 percent" (NCI), but the evidence is inconsistent. The Framingham study has carefully tracked individuals since the 1940s. Data from that research found that drinking alcohol moderately did not increase breast cancer risk (Wellness Facts). Similarly, research by the Danish National Institute for Public Health found that moderate drinking had virtually no effect on breast cancer risk.
Breast cancer constitutes about 7.3% of all cancers. Among women, breast cancer comprises 60% of alcohol-attributable cancers. One study suggests that women who frequently drink red wine may have an increased risk of developing breast cancer.
"Folate intake counteracts breast cancer risk associated with alcohol consumption" and "women who drink alcohol and have a high folate intake are not at increased risk of cancer." Those who have a high (200 micrograms or more per day) level of folate (folic acid or Vitamin B9) in their diet are not at increased risk of breast cancer compared to those who abstain from alcohol.[27] Foods rich in folate include citrus fruits, citrus juices, dark green leafy vegetables (such as spinach), dried beans, and peas. Vitamin B9 can also be taken in a multivitamin pill.
Environmental causes
Women who have received high-dose ionizing radiation to the chest have a relative risk of breast cancer between 2.1 to 4.0. Most studies have not found an increased risk of breast cancer from active tobacco smoking, although a number of studies suggest an increased risk of breast cancer in both active smokers and those exposed to secondhand smoke compared to women who reported no exposure to secondhand smoke.
Although environmental exposures are not generally cited as risk factors for the disease (except for diet, pharmaceuticals and radiation), a substantial and growing body of evidence indicates that exposures to certain toxic chemicals and hormone-mimicking compounds including chemicals used in pesticides, cosmetics and cleaning products contribute to the development of breast cancer.
A recent Canadian study concluded that female farm workers are three times more likely to have breast cancer.
Genes
Two autosomal dominant genes, BRCA1 and BRCA2, have been linked to the rare familial form of breast cancer. People in families expressing mutations in these genes have a 60% to 80% risk of developing breast cancer according to Robbins Pathological Basis of Disease. If a mother or a sister was diagnosed breast cancer, the risk is about 2-fold higher than those women without a familial history.
Hormones
Persistently increased blood levels of estrogen are associated with an increased risk of breast cancer, as are increased levels of the androgens androstenedione and testosterone (which can be directly converted by aromatase to the estrogens estrone and estradiol, respectively). Increased blood levels of progesterone are associated with a decreased risk of breast cancer in premenopausal women.[30] A number of circumstances which increase exposure to endogenous estrogens including not having children, delaying first childbirth, not breastfeeding, early menarche (the first menstrual period) and late menopause are suspected of increasing lifetime risk for developing breast cancer.
Hormonal contraceptives may produce a slight increase in the risk of breast cancer diagnosis among current and recent users, but this appears to be a short-term effect. In 1996 the largest collaborative reanalysis of individual data on over 150,000 women in 54 studies of breast cancer found a relative risk (RR) of 1.24 of breast cancer diagnosis among current combined oral contraceptive pill users; 10 or more years after stopping, no difference was seen. Further, the cancers diagnosed in women who had ever used hormonal contraceptives were less advanced than those in nonusers, raising the possibility that the small excess among users was due to increased detection. The relative risk of breast cancer diagnosis associated with current and recent use of hormonal contraceptives did not appear to vary with family history of breast cancer.
Data exist from both observational and randomized clinical trials regarding the association between postmenopausal hormone replacement therapy (HRT) and breast cancer. The largest meta-analysis (1997) of data from 51 observational studies, indicated a relative risk of breast cancer of 1.35 for women who had used HRT for 5 or more years after menopause. The estrogen-plus-progestin arm of the Women's Health Initiative (WHI), a randomized controlled trial, which randomized more than 16,000 postmenopausal women to receive combined hormone therapy or placebo, was halted early (2002) because health risks exceeded benefits. One of the adverse outcomes prompting closure was a significant increase in both total and invasive breast cancers (RR = 1.24) in women randomized to receive estrogen and progestin for an average of 5 years. HRT-related breast cancers had adverse prognostic characteristics (more advanced stages and larger tumors) compared with cancers occurring in the placebo group, and HRT was also associated with a substantial increase in abnormal mammograms. Short-term use of hormones for treatment of menopausal symptoms appears to confer little or no breast cancer risk.
Light levels
Researchers at the National Cancer Institute and National Institute of Environmental Health Sciences have concluded a study that suggests that artificial light during the night can be a factor for breast cancer.
Obesity
Gaining weight after the menopause can increase a woman's risk. A recent study found that putting on 9.9kg (22lbs) after menopause increased the risk of developing breast cancer by 18%.
Unproven
* It has been hypothesized that abortion may increase the risk of breast cancer because of hormones in early pregnancy. Recent large studies do not support this association. The most recent study, whose results were published in April 2007, followed more than 100,000 women, ranging in age from 29 to 46 at the study's outset, for 10 years.
* Although not well-quantified, there has long been a concern about risk associated with environmental estrogenic compounds, such as dioxins, or phytoestrogens such as found in soybeans.
* Aluminum salts, such as those used in anti-perspirants, have recently been classified as metalloestrogens. In research published in the Journal of Applied Toxicology, Dr. Philippa D. Darbre of the University of Reading has shown that aluminium salts increase estrogen-related gene expression in human breast cancer cells grown in the laboratory.
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Important notice:
The content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other
qualified health provider with any questions you may have regarding a medical condition.
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