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BREAST CANCER Epidemiologic
risk factors and etiology
Age, Alcohol, Environmental causes,
Genes, Hormones,
Light levels, Obesity, Unproven
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).
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, but these are small
effects, and do not distinguish differences in risk within populations, as
well as they do between populations.
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 a
very small (~ 5%) proportion 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 [5] 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 (Friedenreich et al.; Longnecker; Nasca). 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 (Chu et al. ; Schatzkin et al.; Webser et
al)."
The Committee on Carcinogenicity of Chemicals in Food, Consumer Products
Non-Technical Summary [8] concludes, "[t]he new research estimates that a
woman drinking an average of two units of alcohol per day has a lifetime
risk of developing breast cancer 19% 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 "[t]wo 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 (Petri, et al).
Breast cancer constitutes about 7.3% of all cancers.[9] 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. 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
All women and men are at risk for breast cancer, regardless of
hereditary factors. In fact, 85 to 90 percent of breast cancer incidences
cannot be explained by inherited genetic predisposition. Other known risk
factors and personal characteristics include personal or family history of
breast cancer, high breast tissue density, earlier onset of menstruation
(8 years or younger), later menopause (55 years or older), late first-term
pregnancy (25 years or older), no children or no breast-feeding, early or
recent use of oral contraceptives, more than four years use of hormone
replacement therapy, postmenopausal obesity, alcohol consumption,
exposures to secondhand cigarette smoke and exposure to ionizing
radiation.
When all known risk factors and
characteristics are added together including genetics and family history,
as much as 50 percent of breast cancer cases remain unexplained.
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.[18] 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.[19]
Combined oral contraceptive pills may produce a slight increase in breast
cancer risk among long-term users, but this appears to be a short-term
effect. The largest meta-analysis (1996) of data from 54 studies
identified a relative risk (RR) of 1.24 for current 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. Breast cancer risk
associated with hormonal contraceptive use did not appear to vary with
family history of breast cancer.[20]
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 can be a factor for breast cancer.[21]
Obesity
Gaining weight after the menopause can increase a woman's or man's
risk. Putting on 9.9kg (22lbs) 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.
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 soy beans.
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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History of breast cancer
Types of breast cancer
Risk factors and etiology
Age
Alcohol
Environmental causes
Genes
Hormones
Light levels
Obesity
Unproven
Prevention in high-risk
individuals
Prevention of
Environmental Causes
Symptoms
Screening
Diagnosis
Treatment
Surgery
Radiation therapy
Indications for radiation
Types of radiotherapy
Side effects of
radiation
Systemic therapy
Chemotherapy
Hormonal treatment
Targeted therapy
Preclinical
Flax seeds
Alternative medicine
Prognosis
Breast cancer in males
Spreading elsewhere
Breast cancer awareness
References |
