Breast Cancer
Breast cancer is cancer of breast tissue. Worldwide, it is the most common form of cancer in females, affecting approximately one out of twelve to thirteen women who reach age ninety at some stage of their life in the Western world. It is (after lung cancer) the second most fatal cancer in women. Because the breast is composed of identical tissues in males and females, breast cancer can also occur in males, but here the incidence is very low, less than 1 percent.
History of breast cancer
Breast cancer is one of the oldest known forms of cancer tumors.
oldest description of cancer (although the term cancer was not used)
was discovered in Egypt and dates back to approximately 1600 B.C. The Edwin Smith Papyrus,
or writing, describes 8 cases of tumors or ulcers of the breast that
were treated by cauterization, with a tool called "the fire drill." The
writing says about the disease, "There is no treatment."
At least one of the described cases is male. This papyrus is 5 meters
long and is kept in the New York Historical Society. Scholars believe
that the actual document is a copy of an original document from the
30th century before Christ. In any case, for centuries, physicians
described similar cases in their practises, with the same sad
conclusion. It wasn't until greater understanding of the circulatory
system was added to the body of medical knowledge in the 17th century
that doctors made the link to the lymph glands in the armpit. The
French surgeon Jean Louis Petit (1674-1750) and later the Scottish surgeon Benjamin Bell
(1749-1806) were the first to remove the lymph nodes, breast tissue,
and breast muscle. Their successful work was carried on by William Stewart Halsted who started performing mastectomies in 1882. He became known for his Halsted radical mastectomy, a surgical procedure that remained popular up to the 1970's and was performed on Betty Ford.
Epidemiologic risk factors and etiology
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, given the underlying primary cause. 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 a woman who lives to the age of 90 the chances of getting breast cancer her entire lifetime is about 12.5% or one in eight. Men can also develop breast cancer, but their risk is less than one in 1000
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 women. One type
of breast cancer that is especially aggressive and disproportionately
occurs in younger women 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.
Genes
Two genes, BRCA1 and BRCA2, have been linked to the rare familial form of breast cancer .
Women in families expressing mutations in these genes have a much
higher risk of developing breast cancer than women who do not. Not all
people who inherit mutations in these genes will develop breast cancer.
Together with Li-Fraumeni syndrome (p53 mutations), these genetic aberrations determine around 5% of all breast cancer cases
suggesting that the remainder is sporadic. Recently it was found that
newly discovered gene called BARD1 if exists in combination with BRCA2 gene may increase the risk of breast cancer to as much as 80 percent 1. Genetic counseling and genetic testing should be considered for families who may carry a hereditary form of cancer.
Alcohol
Alcohol generally appears to increase the risk of breast cancer in women. The 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 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 U.K. 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 . 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.
Obesity
Gaining weight after the menopause can increase a woman's risk.
Putting on 9.9kg (22lbs) increased the risk of developing 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 cause of breast cancer.
Hormones
The International Agency for Research on Cancer
(IARC) in Lyon, France invited 21 scientists from eight countries in
June 2005, to evaluate the risk of cancer for humans of combined estrogen-progesterone contraceptives and combined estrogen-progesterone menopausal therapy. The working group
found that there is a small increase in the relative risk of breast
cancer in current and recent users of combined oral contraceptives
The risk decreases to that of those who have never used such
combined therapy ten years after cessation of use. The scientists
described combined oral estrogen-progesterone contraceptives as
"carcinogenic to humans."
They also found an increased risk of breast cancer in women under
treatment with combined menopausal therapy, which is confined mostly to
current or recent users, increases with duration of use and exceeds
that in women taking estrogen-only therapy .
Other
Other established risk factors include not having children, delaying first childbirth, not breastfeeding, early menarche (the first menstrual period), late menopause, obesity and taking hormone replacement therapy.
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. Darby of the University of Reading has shown that
aluminum salts increase estrogen-related gene expression in human
breast cancer cells grown in the laboratory.
Symptoms
Early
signs of Breast Cancer
Early breast cancer causes no symptoms and is not painful. Usually
breast cancer is discovered before any symptoms are present, either on
mammography or by feeling a breast lump. A lump under the arm or above
the collarbone that does not go away may be present. Other possible
symptoms include breast discharge, nipple inversion and changes in the
skin overlying the breast.
Screening
Due to the high incidence of breast cancer among older women,
screening is now recommended in many countries. Screening methods
suggested include breast self-examination and mammography.
Only mammography has been proved to reduce mortality from breast
cancer. In some countries routine (annual) mammography of older women
is encouraged as a screening method to diagnose early breast cancer.
Normal
(Left) versus cancerous (right) mammography image.
Mammography is still the modality of choice for screening of early breast cancer. Magnetic resonance imaging
(MRI) has been shown to detect cancers that are not visible on
mammograms, but it has several disadvantages. For example, although it
is more sensitive, it is less specific than mammography. As a result,
MRI studies will have more false positives,
which may have undesirable financial and psychological costs. It is
also a relatively expensive procedure, and one which requires the
intravenous injection of a chemical agent to be effective. It may be
valuable for younger women, whose breasts are denser with less fat and
more connective tissue, making it harder to spot cancers on mammograms.
Ultrasound
alone is not adequate as a screening tool but it is a useful additional
investigation, especially for the characterization of benign tumours.
The U.S. National Cancer Institute
recommends screening mammography with a baseline mammogram at age 35,
mammograms every two years beginning at age 40, and then annual
mammograms beginning at age 50. In the UK, women are invited to attend
for screening once every three years beginning at age 50. Women with
one or more first degree relatives (mother, sister, daughter) with
premenopausal breast cancer should begin screening at an earlier age.
It is usually suggested to start screening at an age that is 10 years
less than the age at which the relative was diagnosed with breast
cancer.
Breast cancers detected by mammography are usually smaller than
those detected clinically, and women who undergo mammography are more
likely to be eligible for breast-conserving therapy.
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Breast cancer in males
For years the medical profession assumed that male breast cancer was
significantly different from female breast cancer. Today they are
grouped together and receive the same treatment regimens. Since the
male breast tissue is confined to the area directly behind the nipple,
treatment for males has always been a mastectomy.
Since the psychological effects of this surgery are just as great for
males as for females, experimental surgery has been started to
introduce the lumpectomy for males.
The incidence
of breast cancer in males is very low, possibly due to the different
endocrine milieu or the small total amount of glandular tissue. Seminal
research in recognizing the incidence of male breast cancer was
performed by the U.S. military at Madigan Army Medical Center. Most swelling or development of the male breast is likely to be the more benign condition of gynecomastia.
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