Epidemiology and etiology of breast cancer
Encyclopedia
Risk factors of breast cancer may be divided into preventable and non preventable. Their study belongs in the field of epidemiology
. Breast cancer
, like other forms of cancer, is considered to result from multiple environmental and hereditary risk factors.
Although many epidemiological risk factors have been identified, the cause of any individual breast cancer is most often unknowable. Epidemiological research informs the patterns of breast cancer incidence across certain populations, but not in a given individual. Approximately 5% of new breast cancers are attributable to hereditary syndromes and well-established risk factors accounted for approximately 30% of cases.
The probability of breast cancer rises with age, but breast cancer tends to be more aggressive in younger people.
Men diagnosed with breast cancer tend to be older than women with breast cancer. They are more likely to be diagnosed with hormone-receptor positive tumors, with about six out of seven cases being estrogen-receptor positive. The overall prognosis is worse for men than for women.
being a member of the International Cancer Genome Consortium
is leading efforts to map breast cancer's complete genome
.
Two autosomal dominant gene
s, BRCA1
and BRCA2
, account for most of the cases of familial breast cancer. Women who carry a harmful BRCA mutation
have a 60% to 80% risk of developing breast cancer in their lifetimes. Other associated malignancies include ovarian cancer
and pancreatic cancer
. If a mother or a sister was diagnosed breast cancer, the risk of a hereditary BRCA1 or BRCA2 gene mutation is about 2-fold higher than those women without a familial history. Commercial testing for BRCA1 and BRCA2 gene mutations has been available in most developed countries since at least 2004.
In addition to the BRCA genes associated with breast cancer, the presence of NBR2
, near breast cancer gene 1, has been discovered, and research into its contribution to breast cancer pathogenesis is ongoing.
and non-BRCA2
breast tumors
(and even some sporadic
carcinomas) are believed to result from the expression of weakly penetrant but highly prevalent mutations in various genes. For instance, polymorphism has been identified in genes associated to the metabolism of estrogens and/or carcinogens (CYP1A1
, CYP1B1
, CYP17, CYP19, COMT, NAT2, GSTM1, GSTP1
, GSTT, . . . ), to estrogen, androgen and vitamin D action (ESR1, AR
, VDR), to co-activation of gene transcription (AIB1), to DNA damage response pathways (CHEK2
, HRAS1, XRCC1
, XRCC3
, XRCC5). Sequence variants of these genes that are relatively common in the population may be associated with a small to moderate increased relative risk for breast cancer. Combinations of such variants could lead to multiplicative effects. Sporadic cancers likely result from the complex interplay between the expression of low penetrance gene(s) (‘‘risk variants’’) and environmental factors. However, the suspected impact of most of these variants on breast cancer risk should, in most cases, be confirmed in large populations studies. Indeed, low penetrance genes cannot be easily tracked through families, as is true for dominant high-risk genes.
Part of the hereditary non-BRCA1
and non-BRCA2
breast tumors
may be associated to rare syndromes, of which breast cancer
is only one component. Such syndromes result notably from mutations in TP53 (Li-Fraumeni syndrome
), ATM (Ataxia Telangiectasia
), STK11
/LKB1(Peutz-Jeghers syndrome
), PTEN
(Cowden syndrome
).
RAB11FIP1, TP53, PTEN and rs4973768 are also associated with increased risk of breast cancer. rs6504950 is associated with lower risk of breast cancer.
Mutations in RAD51C confer an increased risk for breast and ovarian cancer.
A study of more than one million middle-aged British women concluded that each daily alcoholic beverage increases the incidence of breast cancer by 11 cases per 1000 women. This means that among a group of 1000 women who have one drink per day, they will have 11 extra cases of breast cancer when compared to a group of women who drink less than one alcoholic beverage per week; a group of 1000 women who have four drinks per day will have an extra 44 cases of breast cancer compared to non-drinkers. One or two drinks each day increases the relative risk
to 150% of normal, and six drinks per day increases the risk to 330% of normal. Approximately 6% of breast cancers reported in the UK are due to women drinking alcohol.
The primary mechanism through which alcohol causes breast cancer is increased estrogen levels.
Another study showed no contribution of dietary fat intake on the incidence of breast cancer in over 300,000 women. A randomized controlled study of the consequences of a low-fat diet, the Women's Health Initiative, failed to show a statistically significant
reduction in breast cancer incidence in the group assigned to a low-fat diet, although the authors did find evidence of a benefit in the subgoup of women who followed the low-fat diet in a strict manner. A prospective cohort study, the Nurses' Health Study II, found increased breast cancer incidence in premenopausal women only, with higher intake of animal fat, but not vegetable fat.
Taken as a whole, these results point to a possible association between dietary fat intake and breast cancer incidence, though these interactions are hard to measure in large groups of women.
A study published in 2001 found higher levels of monounsaturated fatty acids MUFAs (especially oleic acid) in the erythrocyte membranes of postmenopausal women who developed breast cancer.
That same study discussed that a diet high in MUFAs is not the major determinant of erythrocyte membrane MUFAs, where most oleic acid in mammalian tissue is derived from the saturated stearic acid
residue. Where key conversion is controlled by the Delta9-desaturase
, which also regulates the transformation of the other common saturated fatty acids (SFAs) (myristic and palmitic). The study discussed that fat content of the diet has an important effect on Delta9-d activity, while high levels of SFAs increase Delta9-d activity by twofold to threefold, whereas polyunsaturated fatty acids (PUFAs) decrease.
That conclusion was partially contradicted by a latter study, which showed a direct relation between very high consumption of omega-6 (PUFAs) and breast cancer in postmenopausal women.
have been extensively studied in animal and human in-vitro and epidemiological studies. Research failed to establish any noticeable benefit and some phytoestrogens may present a breast cancer risk.
The literature support the following conclusions:
A 2011 study done at the University of Rochester Medical Center
found that low vitamin D levels among women with breast cancer correlate with more aggressive tumors and poorer prognosis. The study associated sub-optimal vitamin D levels with poor scores on every major biological marker that helps physicians predict a patient’s breast cancer outcome. The lead researcher stated, “Based on these results, doctors should strongly consider monitoring vitamin D levels among breast cancer patients and correcting them as needed.”
. Women who consumed mushrooms and green tea
had a 90% lower incidence of breast cancer. A case control study of 362 Korean women also reported an association between mushroom consumption and decreased risk of breast cancer.
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. 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.
However, not only sex hormones, but also insulin
levels are positively associated with the risk of breast cancer.
around 0.7) have all been correlated to lowered breast cancer risk in large studies. Women who give birth and breast-feed by the age of 20 may have even greater protection. In contrast, for instance, having the first live birth after age 30 doubles the risk compared to having first live birth at age less than 25. Never having children triples the risk.
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. Some studies have suggested that women who began using hormonal contraceptives before the age of 20 or before their first full-term pregnancy are at increased risk for breast cancer, but it is not clear how much of the risk stems from early age at first use, and how much stems from use before the first full-term pregnancy.
(menopausal 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 (hazard ratio
= 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. A correlation was found between the use of hormonal contraceptives and subsequent reliance on hormone replacement therapy.
(removal of ovaries) and mastectomy in individuals with high-risk mutations of BRCA1 or BRCA2 genes reduces the risk of developing breast cancer as well as reducing the risk of developing ovarian cancer. Because of a complex balance of benefits and risks of a prophylactic surgery it is recommended only in very specific cases.
has been used for chemoprevention in individuals at high risk for breast cancer. Overall it is recommended only in very special circumstances. In 2002, a clinical practice guideline by the US Preventive Services Task Force (USPSTF) recommended that "clinicians discuss chemoprevention with women at high risk for breast cancer and at low risk for adverse effects of chemoprevention" with a grade B recommendation.
s from the MORE, BCPT P-1, and Italian trials. In the MORE trial, the relative risk reduction
for raloxifene was 76%. The P-1 preventative study demonstrated that tamoxifen can prevent breast cancer in high-risk individuals. The relative risk reduction was up to 50% of new breast cancers, though the cancers prevented were more likely estrogen-receptor positive (this is analogous to the effect of finasteride
on the prevention of prostate cancer
, in which only low-grade prostate cancers were prevented). The Italian trial showed benefit from tamoxifen.
Additional randomized controlled trials have been published since the guidelines. The IBIS trial found benefit from tamoxifen. In 2006, the NSABP STAR trial demonstrated that raloxifene had equal efficacy in preventing breast cancer compared with tamoxifen, but that there were fewer side effects with raloxifene. The RUTH Trial concluded that "benefits of raloxifene in reducing the risks of invasive breast cancer and vertebral fracture should be weighed against the increased risks of venous thromboembolism and fatal stroke". On September 14, 2007, the US Food and Drug Administration approved raloxifene
(Evista) to prevent invasive breast cancer in postmenopausal women.
s (industrially made estrogenic compounds) and other endocrine disruptor
s are potential risk factors of breast cancer.
Diethylstilbestrol
(DES) is a synthetic form of estrogen
. It has been used between the early 1940s and 1971. Pregnant women took DES to prevent certain pregnancy complications. However, it also increased their risk of breast cancer. It also increased the risk of breast cancer in the prenatally exposed daughters after they have reached an age 40 years.
Furthermore, there is exposure to endocrine disruptors from the environment, in addition to phytoestrogens mentioned above in the diet section. See xenoestrogens in environmental factors below
s (PCBs). dioxins
and organic solvents, on the other hand, have only shown an association in sparse and methodologically limited studies, but are suggestive of an association. Overall, however, evidence is still based on a relatively small number of studies.
s (industrially made estrogenic compounds) are endocrine disruptor
s, and potential risk factors of breast cancer.
Endocrine disruption is the hypothesis that some chemicals in the body, such as Bisphenol A, are capable of interfering with the production, processing, and transmission of hormones.
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.
The increasing prevalence of these substances in the environment may explain the increasing incidence of breast cancer, though direct evidence is sparse.
(BPA) is a chemical compound used in the production of plastics found in numerous commercial products, including laptops, baby bottles, food containers, water main pipes, and laboratory and hospital equipment. BPA was first produced in 1891, but its estrogenic properties went undiscovered until the mid 1930s. Today it is considered a xenoestrogen, and it functions as an endocrine disruptor that interferes with hormones in the body and disrupts the normal functioning of the endocrine system. At very low levels the FDA has long considered BPA in food to be safe, but this has been challenged over the years as more information is discovered regarding the effects of the chemical.
Rats exposed prenatally to environmentally relevant doses of BPA show an increased number of intraductal hyperplasias (precancerious lesions) in mammary glands that appear during adulthood, while high doses induce the development of carcinomas in breast tissue. Animals exposed to BPA during fetal life develop palpable tumors, and all studies show an increased susceptibility to mammary gland neoplasia that manifests during adulthood. Exposure of mouse dams to environmentally relevant levels of BPA during organogenesis results in considerable alterations in the mammary gland. It was concluded that perinatal exposure to low doses of BPA results in altered mammary gland morphogenesis, induction of precancerous lesions, and carcinoma in situ.
A study sought to determine whether early exposure to BPA could accelerate mammary carcinogenesis in a dimethylbenzanthracene (DMBA) model of rodent mammary cancer. In the study, scientists exposed neonatal/prebubertal rats to BPA via lactation from nursing dams treated orally with 0, 25, and 250 µg BPA/kg body weight/day. For tumorigenesis studies, female offspring were exposed to 30 mg dimethylbenzanthracene (DMBA)/kg body weight at 50 days of age. DMBA induces mammary tumors and allows chemicals that predispose for mammary cancer to increase the number of mammary adenocarcinomas. The results of the study showed that female rats in the control, BPA 25, and BPA 250 groups administered DMBA exhibited a BPA dose-dependent increase in mammary tumors. The groups had 2.84, 3.82, and 5.00 mammary tumors per rat respectively. Treatment with BPA also reduced tumor latency, with the median tumor latency of 65, 53, and 56.5 days for 0, BPA 25, and BPA 250 groups respectively. Maternal exposure to BPA during lactation decreased time to first tumor latency and increased the number of DMBA-induced mammary tumors in female offspring. If these effects found in rodents carry over to humans, even minimal exposure to BPA could cause an increased risk for breast cancer.
The elevated incidence of breast cancer in women has been associated with prolonged exposure to high levels of estrogens. Xenoestrogens, such as BPA have the capacity to perturb normal hormonal actions. This study provides evidence of the estrogenic effects of BPA. In this study the human breast epithelial cells MCF-10F were treated with 10-3 M, 10-4 M, 10-5 M and 10-6 M BPA continuously for two weeks. The cells treated with 10-3 M BPA died on the second day of treatment. The concentration of 10-4 M BPA was also toxic for the breast epithelial cells, and they died on the fourth day of treatment. This data indicated that these concentrations of BPA are toxic for MCF-10F cells. After the two-week observation period it was seen that the cells formed a high percentage of duct like structures in collagen. MCF-10F cells treated with 10-5 M and 10-6 M BPA formed a high percentage of solid masses, 27% and 20% respectively. This data indicates that BPA is able to induce neoplastic transformation of human breast epithelial cells. Epigenetic changes are involved in the early stages of cancer initiation by altering ductulogenesis. BPA was able to induce transformation of human breast MCF-10F epithelial cells. After treatment with BPA, the cells produced fewer collagen tubules and more solid masses.
Consumer groups recommend that people wishing to lower their exposure to bisphenol A avoid canned food and polycarbonate plastic containers (which shares resin identification code
7 with many other plastics) unless the packaging indicates the plastic is bisphenol A-free. The National Toxicology Panel recommends avoiding microwaving food in plastic containers, putting plastics in the dishwasher, or using harsh detergents on plastics, to avoid leaching.
s are chemicals that are produced when products such as dyes, polyurethane products, and certain pesticides are made. They are also found in cigarette smoke, fuel exhaust, and in over cooked, burned meat. The three types of aromatic amines monocyclic, polycyclic, and heterocyclic have all been found in recent studies of breast health. Monocyclic amines have been found to cause mammary cancer in rats. Studies have shown that women who eat higher amounts of overcooked meat, meaning more exposure to heterocyclic amines, have also been diagnosed with more post-menopausal breast cancer. Heterocyclic amines also have the ability to copy estrogen and in laboratory studies have been found to encourage the growth of cancerous tumors on human tissue.
is a petrochemical solvent. Benzene exposure mostly originates from air pollution resulting from industrial burning, exhaust and gas fumes, as well as cigarette smoke. The International Agency for Research on Cancer and the National Toxicology Program have labeled benzene as a definite human carcinogen. Multiple studies point to a correlation between benzene exposure and breast cancer risk. Laboratory studies on mice have shown that a high level of benzene exposure can lead to mammary cancer.
is a chemical that can be found in some personal care products, mainly in the form of fragrance. It is also used for the sterilization of various medical objects. The National Toxicology Program has labeled ethylene oxide as a definite human and animal carcinogen. A study done by the National Institute for Occupational Safety and Health including 7,576 women found a direct correlation between breast cancer rates and exposure to ethylene oxide during medical sterilization processes. Also, human breast cells put into contact with small amounts of ethylene oxide in a laboratory can lead to DNA damage of the breast tissue.
is produced when PVC or polyvinly chloride is made. PVC is found in plastic packaging, outerwear, plastic toys and other plastic products. Vinyl chloride can be found in cigarette smoke and the air around garbage and land fills. It can also be found in the wastewater when PVC is made. The National Toxicology Program and the International Agency for Research on Cancer have both labeled vinyl chloride as a definite human carcinogen.
. Beginning in the mid-1990s, a number of studies suggested 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. By 2005 enough evidence had accumulated for the [California Environmental Protection Agency] to conclude that breathing secondhand smoke causes breast cancer in younger, primarily premenopausal women. The Agency concluded that the risk was increased by 70%, based on epidemiological studies and the fact that there are many mammary carcinogens in secondhand smoke. The following year (2006) the US Surgeon General
identified the same risk increase and concluded that the evidence is "suggestive," one step below causal. There is some evidence that exposure to tobacco smoke is most problematic between puberty and first childbirth. The reason is that breast tissue appears most sensitive to chemical carcinogens breast cells not fully differentiated until lactation. The likely reason that the older studies of active smoking did not detect risks associated with smoking was that they compared active smokers to all nonsmokers (which includes many passive smokers). The newer studies, which exclude passive smokers from the control group, generally show elevated risks associated with active as well as passive smoking.
has concluded that passive smoking
causes breast cancer and the US Surgeon General has concluded that the evidence is "suggestive," one step below causal. There is some evidence that exposure to tobacco smoke is most problematic between puberty and first childbirth. The reason that breast tissue appears most sensitive to chemical carcinogens in this phase is that breast cells are not fully differentiated until lactation.
to the chest (for example, as treatments for other cancers) have a relative risk of breast cancer between 2.1 to 4.0. The risk increases with increased dose. In addition, the risk is higher in women irradiated before age 30, when there is still breast development.
(most notably the polychlorinated dibenzodioxins) are chemicals that are produced when chlorinated products are burned, such as polyvinyl chloride (PVC). This occurs when chlorinated products are used in certain manufacturing industries. Dioxins are also added to the air when gasoline and diesel fuels break down. Dioxins are able to bioaccumulate, meaning that they settle and stay in human and animal fat for long periods of time. There are many different types of dioxins and only a few of them have been labeled by the Environmental Protection Agency as definite human carcinogens and endocrine hormone disruptors. Although dioxins are floating in the air, they eventually settle on plants and other vegetation surfaces. These plants and vegetation are them eaten by cows and other animals. Humans end up eating the produce, milk, eggs, and meat produced by these animals that have consumed dioxin covered vegetation. Dioxins are more harmful when ingested this way. Multiple studies have led to the idea that increased dioxin levels can increase one's risk for breast cancer. A study done in 1976 after a chemical plant explosion in Seveso, Italy concluded that high dioxin level exposure in a woman's body correlated with a more than double chance of developing breast cancer.
(NCI) and National Institute of Environmental Health Sciences
conducted a study in 2005 that suggests that artificial light during the night can be a factor for breast cancer by disrupting melatonin
levels.
In 2007, "shiftwork that involves circadian disruption" was listed as a probable carcinogen by the World Health Organization's International Agency for Research on Cancer. (IARC Press release No. 180). Multiple studies have documented a link between night shift work and the increased incidence of breast cancer. A review of current knowledge of the health consequences of exposure to artificial light at night including the increased incidence of breast cancer and an explanation of the causal mechanisms has been published in the Journal of Pineal Research in 2007.
Several studies have found that black women in the U.S. are more likely to die from breast cancer even though white women are more likely to be diagnosed with the disease. Even after diagnosis, black women are less likely to get treatment compared to white women. Scholars have advanced several theories for the disparities, including inadequate access to screening, reduced availability of the most advanced surgical and medical techniques, or some biological characteristic of the disease in the African American population. Some studies suggest that the racial disparity in breast cancer outcomes may reflect cultural biases more than biological disease differences. However, the lack of diversity in clinical trials for breast cancer treatment may contribute to these disparities, with recent research indicating that black women are more likely to have estrogen receptor negative breast cancers, which are not responsive to hormone treatments that are effective for most white women. Research is currently ongoing to define the contribution of both biological and cultural factors.
Part of the differences in incidence that is attributable to race and economic status may be explained by past use of hormone replacement therapy
Specifically about green tea
, one study has found significant inverse association between risk of breast cancer and green tea intake in Asian women who were low soy consumers.
is an environmental factor that can be found in air pollution and can be produced by combustion engines, as well as petroleum refineries. It is found in cigarette smoke and is also used in the making and processing of certain synthetic rubber products and fungicides. The National Toxicology Program has labeled 1,3-Butadiene as definite human carcinogen. The EPA has stated that people are mainly put in contact with this chemical through the means of simple inhalation.
of the breast. The radiodense area on a mammogram is white and is associated with ductal and lobular epithelium, connective tissue and fluid in the breast
. The radiolucent area is dark gray or black and is associated with fat in the breast. High mammographic density is associated with a higher risk of developing breast cancer
, but the reasons for this link are not certain and are being studied.
increases the risk of developing breast cancer; it is a controversial subject and the current scientific consensus
has concluded there is no significant association between first-trimester abortion and breast cancer risk.
s. In research published in the Journal of Applied Toxicology
, Dr. Philippa D. Darbre of the University of Reading
has shown that aluminum salts increase estrogen-related gene expression in human breast cancer cells grown in the laboratory.
Fortunately, this in-vitro association between aluminum salts and estrogen activity does not translate into an increased risk of breast cancer in humans. The lack of association between underarm deodorants and breast cancer has been the subject of a number of research articles.
. The human papilloma virus is well known for its capability to immortalize breast cancer cells which is used in research, however the role of this viruses in human breast cancer remains controversial.
Humans are not the only mammals susceptible 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. This finding is taken to mean that a viral origin of human breast cancer is at least possible, though there is no definitive evidence to support the claim that MMTV causes human breast cancer. For example, there may be critical differences between cancer pathogenesis in mice and people.
A human homologue of the mammary virus has been described in 1971 and linked to to human breast cancer in several small epidemiologic studies.
said that nuns developed breast cancer at a higher rate than married women because they did not engage in sexual intercourse
, and the "unnatural" lack of sexual activity caused instability of the breasts; others countered that the cause was frequently too much sexual activity. Other theories from the 18th century included various sorts of problems with the movement of body fluids, such as lymphatic blockages, curdled breast milk
or the transformation of pus left after an infection.
In modern times, women are more likely to blame themselves, perhaps deciding that their diet, childbearing history, decision not to breastfeed, or level of exercise is the cause.
Epidemiology
Epidemiology is the study of health-event, health-characteristic, or health-determinant patterns in a population. It is the cornerstone method of public health research, and helps inform policy decisions and evidence-based medicine by identifying risk factors for disease and targets for preventive...
. Breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
, like other forms of cancer, is considered to result from multiple environmental and hereditary risk factors.
Although many epidemiological risk factors have been identified, the cause of any individual breast cancer is most often unknowable. Epidemiological research informs the patterns of breast cancer incidence across certain populations, but not in a given individual. Approximately 5% of new breast cancers are attributable to hereditary syndromes and well-established risk factors accounted for approximately 30% of cases.
Age
The risk of getting breast cancer increases with age. A woman is more than 100 times more likely to develop breast cancer in her 60s than in her 20s. If all women lived to age 95, about one in eight would be diagnosed with breast cancer at some point during their lives. However, the actual lifetime risk is lower than that, because 90% of women die before age 95, most commonly from heart attacks, strokes, or other forms of cancer.The probability of breast cancer rises with age, but breast cancer tends to be more aggressive in younger people.
Sex
Men have a much lower risk of developing breast cancer than women. In developed countries, about 99% of breast cancer cases are diagnosed in women; in a few African countries, which represent the highest incidence of male breast cancer, men account for 5–15% of breast cancer cases. The rate of breast cancer in men appears to be rising somewhat.Men diagnosed with breast cancer tend to be older than women with breast cancer. They are more likely to be diagnosed with hormone-receptor positive tumors, with about six out of seven cases being estrogen-receptor positive. The overall prognosis is worse for men than for women.
Heredity
United KingdomUnited Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
being a member of the International Cancer Genome Consortium
International Cancer Genome Consortium
The International Cancer Genome Consortium is a voluntary scientific organization that provides a forum for collaboration among the world's leading cancer and genomic researchers....
is leading efforts to map breast cancer's complete genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
.
BRCA1 and BRCA2
In 5% of breast cancer cases, there is a strong inherited familial risk.Two autosomal dominant gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s, BRCA1
BRCA1
BRCA1 is a human caretaker gene that produces a protein called breast cancer type 1 susceptibility protein, responsible for repairing DNA. The first evidence for the existence of the gene was provided by the King laboratory at UC Berkeley in 1990...
and BRCA2
BRCA2
BRCA2 is a protein that in humans is encoded by the BRCA2 gene.BRCA2 orthologs have been identified in most mammals for which complete genome data are available....
, account for most of the cases of familial breast cancer. Women who carry a harmful BRCA mutation
BRCA mutation
A BRCA mutation is a mutation in either of the genes BRCA1 and BRCA2. Harmful mutations in these genes produce a hereditary breast-ovarian cancer syndrome in affected families...
have a 60% to 80% risk of developing breast cancer in their lifetimes. Other associated malignancies include ovarian cancer
Ovarian cancer
Ovarian cancer is a cancerous growth arising from the ovary. Symptoms are frequently very subtle early on and may include: bloating, pelvic pain, difficulty eating and frequent urination, and are easily confused with other illnesses....
and pancreatic cancer
Pancreatic cancer
Pancreatic cancer refers to a malignant neoplasm of the pancreas. The most common type of pancreatic cancer, accounting for 95% of these tumors is adenocarcinoma, which arises within the exocrine component of the pancreas. A minority arises from the islet cells and is classified as a...
. If a mother or a sister was diagnosed breast cancer, the risk of a hereditary BRCA1 or BRCA2 gene mutation is about 2-fold higher than those women without a familial history. Commercial testing for BRCA1 and BRCA2 gene mutations has been available in most developed countries since at least 2004.
In addition to the BRCA genes associated with breast cancer, the presence of NBR2
NBR2
NBR2 is a gene best known for its location near the breast cancer associated gene BRCA1. Like BRCA1, NBR2 has been a subject of research, but links to breast cancer are currently inconclusive....
, near breast cancer gene 1, has been discovered, and research into its contribution to breast cancer pathogenesis is ongoing.
Other genes
Hereditary non-BRCA1BRCA1
BRCA1 is a human caretaker gene that produces a protein called breast cancer type 1 susceptibility protein, responsible for repairing DNA. The first evidence for the existence of the gene was provided by the King laboratory at UC Berkeley in 1990...
and non-BRCA2
BRCA2
BRCA2 is a protein that in humans is encoded by the BRCA2 gene.BRCA2 orthologs have been identified in most mammals for which complete genome data are available....
breast tumors
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
(and even some sporadic
carcinomas) are believed to result from the expression of weakly penetrant but highly prevalent mutations in various genes. For instance, polymorphism has been identified in genes associated to the metabolism of estrogens and/or carcinogens (CYP1A1
CYP1A1
Cytochrome P450, family 1, subfamily A, polypeptide 1 is a protein that in humans is encoded by the CYP1A1 gene. The protein is a member of the cytochrome P450 superfamily of enzymes.-Function:...
, CYP1B1
CYP1B1
Cytochrome P450 1B1 is an enzyme that in humans is encoded by the CYP1B1 gene.- Function :CYP1B1 belongs to the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids...
, CYP17, CYP19, COMT, NAT2, GSTM1, GSTP1
GSTP1
Glutathione S-transferase P is an enzyme that in humans is encoded by the GSTP1 gene.-Interactions:GSTP1 has been shown to interact with Fanconi anemia, complementation group C and MAPK8.-Further reading:...
, GSTT, . . . ), to estrogen, androgen and vitamin D action (ESR1, AR
Androgen receptor
The androgen receptor , also known as NR3C4 , is a type of nuclear receptor that is activated by binding of either of the androgenic hormones testosterone or dihydrotestosterone in the cytoplasm and then translocating into the nucleus...
, VDR), to co-activation of gene transcription (AIB1), to DNA damage response pathways (CHEK2
CHEK2
CHEK2 is the official symbol for the human gene CHK2 checkpoint homolog. It is located on the long arm of chromosome 22.-Function:The protein encoded by this gene, CHK2 a protein kinase that is activated in response to DNA damage and is involved in cell cycle arrest.In response to DNA damage and...
, HRAS1, XRCC1
XRCC1
XRCC1 is a DNA repair protein.It complexes with DNA ligase III.-Interactions:XRCC1 has been shown to interact with PARP2, DNA polymerase beta, Aprataxin, Oxoguanine glycosylase, PCNA, APEX1, PNKP and PARP1.-Further reading:-External links:...
, XRCC3
XRCC3
DNA repair protein XRCC3 is a protein that in humans is encoded by the XRCC3 gene.-Further reading:...
, XRCC5). Sequence variants of these genes that are relatively common in the population may be associated with a small to moderate increased relative risk for breast cancer. Combinations of such variants could lead to multiplicative effects. Sporadic cancers likely result from the complex interplay between the expression of low penetrance gene(s) (‘‘risk variants’’) and environmental factors. However, the suspected impact of most of these variants on breast cancer risk should, in most cases, be confirmed in large populations studies. Indeed, low penetrance genes cannot be easily tracked through families, as is true for dominant high-risk genes.
Part of the hereditary non-BRCA1
BRCA1
BRCA1 is a human caretaker gene that produces a protein called breast cancer type 1 susceptibility protein, responsible for repairing DNA. The first evidence for the existence of the gene was provided by the King laboratory at UC Berkeley in 1990...
and non-BRCA2
BRCA2
BRCA2 is a protein that in humans is encoded by the BRCA2 gene.BRCA2 orthologs have been identified in most mammals for which complete genome data are available....
breast tumors
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
may be associated to rare syndromes, of which breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
is only one component. Such syndromes result notably from mutations in TP53 (Li-Fraumeni syndrome
Li-Fraumeni syndrome
Li-Fraumeni syndrome is an extremely rare autosomal dominant hereditary disorder. It is named after Frederick Pei Li and Joseph F. Fraumeni, Jr., the American physicians who first recognized and described the syndrome. Li-Fraumeni syndrome greatly increases susceptibility to cancer...
), ATM (Ataxia Telangiectasia
Ataxia telangiectasia
Ataxia telangiectasia is a rare, neurodegenerative, inherited disease that affects many parts of the body and causes severe disability. Ataxia refers to poor coordination and telangiectasia to small dilated blood vessels, both of which are hallmarks of the disease...
), STK11
STK11
Serine/threonine kinase 11 also known as liver kinase B1 or renal carcinoma antigen NY-REN-19 is a protein kinase that in humans is encoded by the STK11 gene.-Expression:...
/LKB1(Peutz-Jeghers syndrome
Peutz-Jeghers syndrome
Peutz–Jeghers syndrome, also known as hereditary intestinal polyposis syndrome, is an autosomal dominant genetic disease characterized by the development of benign hamartomatous polyps in the gastrointestinal tract and hyperpigmented macules on the lips and oral mucosa...
), PTEN
PTEN (gene)
Phosphatase and tensin homolog is a protein that, in humans, is encoded by the PTEN gene. Mutations of this gene are a step in the development of many cancers....
(Cowden syndrome
Cowden syndrome
Cowden syndrome is a rare autosomal dominant inherited disorder characterized by multiple tumor-like growths called hamartomas and an increased risk of certain forms of cancer....
).
RAB11FIP1, TP53, PTEN and rs4973768 are also associated with increased risk of breast cancer. rs6504950 is associated with lower risk of breast cancer.
Mutations in RAD51C confer an increased risk for breast and ovarian cancer.
Prior cancers
People who have previously been diagnosed with breast, ovarian, uterine, or bowel cancer have a higher risk of developing breast cancer in the future. Mothers of children with soft-tissue sarcoma may have an increased risk of breast cancer. Men with prostate cancer may have an elevated risk of breast cancer, although the absolute risk remains low.Alcohol
Alcohol is a risk factor for breast cancer in women.A study of more than one million middle-aged British women concluded that each daily alcoholic beverage increases the incidence of breast cancer by 11 cases per 1000 women. This means that among a group of 1000 women who have one drink per day, they will have 11 extra cases of breast cancer when compared to a group of women who drink less than one alcoholic beverage per week; a group of 1000 women who have four drinks per day will have an extra 44 cases of breast cancer compared to non-drinkers. One or two drinks each day increases the relative risk
Relative risk
In statistics and mathematical epidemiology, relative risk is the risk of an event relative to exposure. Relative risk is a ratio of the probability of the event occurring in the exposed group versus a non-exposed group....
to 150% of normal, and six drinks per day increases the risk to 330% of normal. Approximately 6% of breast cancers reported in the UK are due to women drinking alcohol.
The primary mechanism through which alcohol causes breast cancer is increased estrogen levels.
Fat intake
Dietary influences have been examined since decades with conflicting results and so far failed to confirm any significant dependency. One recent study suggests that low-fat diets may significantly decrease the risk of breast cancer as well as the recurrence of breast cancer.Another study showed no contribution of dietary fat intake on the incidence of breast cancer in over 300,000 women. A randomized controlled study of the consequences of a low-fat diet, the Women's Health Initiative, failed to show a statistically significant
Statistical significance
In statistics, a result is called statistically significant if it is unlikely to have occurred by chance. The phrase test of significance was coined by Ronald Fisher....
reduction in breast cancer incidence in the group assigned to a low-fat diet, although the authors did find evidence of a benefit in the subgoup of women who followed the low-fat diet in a strict manner. A prospective cohort study, the Nurses' Health Study II, found increased breast cancer incidence in premenopausal women only, with higher intake of animal fat, but not vegetable fat.
Taken as a whole, these results point to a possible association between dietary fat intake and breast cancer incidence, though these interactions are hard to measure in large groups of women.
Specific dietary fatty acids
Although many claims have been made in popular literature there is no solid evidence linking specific fats to breast cancer.A study published in 2001 found higher levels of monounsaturated fatty acids MUFAs (especially oleic acid) in the erythrocyte membranes of postmenopausal women who developed breast cancer.
That same study discussed that a diet high in MUFAs is not the major determinant of erythrocyte membrane MUFAs, where most oleic acid in mammalian tissue is derived from the saturated stearic acid
Stearic acid
Stearic acid is the saturated fatty acid with an 18 carbon chain and has the IUPAC name octadecanoic acid. It is a waxy solid, and its chemical formula is CH316CO2H. Its name comes from the Greek word στέαρ "stéatos", which means tallow. The salts and esters of stearic acid are called stearates...
residue. Where key conversion is controlled by the Delta9-desaturase
Stearoyl-CoA 9-desaturase
In enzymology, a stearoyl-CoA 9-desaturase is an enzyme that catalyzes the chemical reactionThe 4 substrates of this enzyme are stearoyl-CoA, ferrocytochrome b5, O2, and H+, whereas its 3 products are oleoyl-CoA, ferricytochrome b5, and H2O....
, which also regulates the transformation of the other common saturated fatty acids (SFAs) (myristic and palmitic). The study discussed that fat content of the diet has an important effect on Delta9-d activity, while high levels of SFAs increase Delta9-d activity by twofold to threefold, whereas polyunsaturated fatty acids (PUFAs) decrease.
That conclusion was partially contradicted by a latter study, which showed a direct relation between very high consumption of omega-6 (PUFAs) and breast cancer in postmenopausal women.
Phytoestrogens
PhytoestrogensPhytoestrogens
Phytoestrogens are plant-derived xenoestrogens functioning as the primary female sex hormone not generated within the endocrine system but consumed by eating phytoestrogonic plants...
have been extensively studied in animal and human in-vitro and epidemiological studies. Research failed to establish any noticeable benefit and some phytoestrogens may present a breast cancer risk.
The literature support the following conclusions:
- Plant estrogen intake in early adolescence may protect against breast cancer later in life.
- The potential risks of isoflavones on breast tissue in women at high risk for breast cancer is still unclear.
Vitamin D
Vitamin D is related to reduced risk of breast cancer and disease prognosis.A 2011 study done at the University of Rochester Medical Center
University of Rochester Medical Center
The University of Rochester Medical Center , located in Rochester, New York, is one of the main campuses of the University of Rochester and comprises the university's primary medical education, research and patient care facilities....
found that low vitamin D levels among women with breast cancer correlate with more aggressive tumors and poorer prognosis. The study associated sub-optimal vitamin D levels with poor scores on every major biological marker that helps physicians predict a patient’s breast cancer outcome. The lead researcher stated, “Based on these results, doctors should strongly consider monitoring vitamin D levels among breast cancer patients and correcting them as needed.”
Brassica vegetables
In a study published in the Journal of the American Medical Association, biomedical investigators found that Brassicas vegetable intake (broccoli, cauliflower, cabbage, kale and Brussels sprouts) was inversely related to breast cancer development. The relative risk among women in the highest decile of Brassica vegetable consumption (median, 1.5 servings per day) compared to the lowest decile (virtually no consumption) was 0.58. That is, women who consumed around 1.5 servings of Brassica vegetables per day had 42% less risk of developing breast cancer than those who consumed virtually none.Country diet
A significant environmental effect is likely responsible for the different rates of breast cancer incidence between countries with different dietary customs. Researchers have long measured that breast cancer rates in an immigrant population soon come to resemble the rates of the host country after a few generations. The reason for this is speculated to be immigrant uptake of the host country diet. The prototypical example of this phenomenon is the changing rate of breast cancer after the arrival of Japanese immigrants to America.Mushrooms
In 2009, a case-control study of the eating habits of 2,018 women suggested that women who consumed mushrooms had an approximately 50% lower incidence of breast cancerBreast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
. Women who consumed mushrooms and green tea
Green tea
Green tea is made solely from the leaves of Camellia sinensis that have undergone minimal oxidation during processing. Green tea originates from China and has become associated with many cultures throughout Asia. It has recently become more widespread in the West, where black tea is traditionally...
had a 90% lower incidence of breast cancer. A case control study of 362 Korean women also reported an association between mushroom consumption and decreased risk of breast cancer.
Iodine deficiency
The protective effects of iodine on breast cancer have been postulated from epidemiologic evidence and described in animal models.Obesity
Gaining weight after menopause can increase a woman's risk. A recent study found that putting on 9.9 kg (22 lbs) after menopause increased the risk of developing breast cancer by 18%.Hormones
Persistently increased blood levels of estrogenEstrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
are associated with an increased risk of breast cancer, as are increased levels of the androgens androstenedione
Androstenedione
Androstenedione is a 19-carbon steroid hormone produced in the adrenal glands and the gonads as an intermediate step in the biochemical pathway that produces the androgen testosterone and the estrogens estrone and estradiol.-Synthesis:Androstenedione is the common precursor of male and female sex...
and testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
(which can be directly converted by aromatase
Aromatase
Aromatase is an enzyme responsible for a key step in the biosynthesis of estrogens. It is a member of the cytochrome P450 superfamily , which are monooxygenases that catalyze many reactions involved in steroidogenesis. In particular, aromatase is responsible for the aromatization of androgens into...
to the estrogens estrone
Estrone
Estrone is an estrogenic hormone secreted by the ovary as well as adipose tissue.Estrone is one of several natural estrogens, which also include estriol and estradiol...
and estradiol
Estradiol
Estradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...
, respectively). Increased blood levels of progesterone
Progesterone
Progesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
are associated with a decreased risk of breast cancer in premenopausal women. A number of circumstances which increase exposure to endogenous estrogens including not having children, delaying first childbirth, not breastfeeding, early menarche
Menarche
Menarche is the first menstrual cycle, or first menstrual bleeding, in female human beings. From both social and medical perspectives it is often considered the central event of female puberty, as it signals the possibility of fertility....
(the first menstrual period) and late menopause
Menopause
Menopause is a term used to describe the permanent cessation of the primary functions of the human ovaries: the ripening and release of ova and the release of hormones that cause both the creation of the uterine lining and the subsequent shedding of the uterine lining...
are suspected of increasing lifetime risk for developing breast cancer.
However, not only sex hormones, but also insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
levels are positively associated with the risk of breast cancer.
Pregnancy, childbearing and breastfeeding
Lower age of first childbirth, compared to the average age of 24, having more children (about 7% lowered risk per child), and breastfeeding (4.3% per breastfeeding year, with an average relative riskRelative risk
In statistics and mathematical epidemiology, relative risk is the risk of an event relative to exposure. Relative risk is a ratio of the probability of the event occurring in the exposed group versus a non-exposed group....
around 0.7) have all been correlated to lowered breast cancer risk in large studies. Women who give birth and breast-feed by the age of 20 may have even greater protection. In contrast, for instance, having the first live birth after age 30 doubles the risk compared to having first live birth at age less than 25. Never having children triples the risk.
Hormonal contraception
Hormonal contraceptivesHormonal contraception
Hormonal contraception refers to birth control methods that act on the endocrine system. Almost all methods are composed of steroid hormones, although in India one selective estrogen receptor modulator is marketed as a contraceptive. The original hormonal method—the combined oral contraceptive...
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
Relative risk
In statistics and mathematical epidemiology, relative risk is the risk of an event relative to exposure. Relative risk is a ratio of the probability of the event occurring in the exposed group versus a non-exposed group....
(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. Some studies have suggested that women who began using hormonal contraceptives before the age of 20 or before their first full-term pregnancy are at increased risk for breast cancer, but it is not clear how much of the risk stems from early age at first use, and how much stems from use before the first full-term pregnancy.
Hormone replacement therapy
Data exist from both observational and randomized clinical trials regarding the association between menopausal hormone replacement therapyHormone replacement therapy (menopause)
Hormone replacement therapy is a system of medical treatment for surgically menopausal, perimenopausal and to a lesser extent postmenopausal women...
(menopausal 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
Progestin
A progestin is a synthetic progestogen that has progestinic effects similar to progesterone. The two most common uses of progestins are for hormonal contraception , and to prevent endometrial hyperplasia from unopposed estrogen in hormone replacement therapy...
arm of the Women's Health Initiative
Women's Health Initiative
The Women's Health Initiative was initiated by the U.S. National Institutes of Health in 1991. The objective of this women's health research initiative was to conduct medical research into some of the major health problems of older women...
(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 (hazard ratio
Hazard ratio
In survival analysis, the hazard ratio is the ratio of the hazard rates corresponding to the conditions described by two sets of explanatory variables. For example, in a drug study, the treated population may die at twice the rate per unit time as the control population. The hazard ratio would be...
= 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. A correlation was found between the use of hormonal contraceptives and subsequent reliance on hormone replacement therapy.
Oophorectomy and mastectomy
Prophylactic oophorectomyOophorectomy
Oophorectomy is the surgical removal of an ovary or ovaries. The surgery is also called ovariectomy, but this term has been traditionally used in basic science research describing the surgical removal of ovaries in laboratory animals...
(removal of ovaries) and mastectomy in individuals with high-risk mutations of BRCA1 or BRCA2 genes reduces the risk of developing breast cancer as well as reducing the risk of developing ovarian cancer. Because of a complex balance of benefits and risks of a prophylactic surgery it is recommended only in very specific cases.
Hormonal therapy
Hormonal therapyHormonal therapy (oncology)
Hormonal therapy is one of the major modalities of medical treatment for cancer, others being cytotoxic chemotherapy and targeted therapy . It involves the manipulation of the endocrine system through exogenous administration of specific hormones, particularly steroid hormones, or drugs which...
has been used for chemoprevention in individuals at high risk for breast cancer. Overall it is recommended only in very special circumstances. In 2002, a clinical practice guideline by the US Preventive Services Task Force (USPSTF) recommended that "clinicians discuss chemoprevention with women at high risk for breast cancer and at low risk for adverse effects of chemoprevention" with a grade B recommendation.
Selective estrogen receptor modulators (SERMs)
The guidelines were based on studies of SERMSelective estrogen receptor modulator
Selective Estrogen Receptor Modulators are a class of compounds that act on the estrogen receptor. A characteristic that distinguishes these substances from pure receptor agonists and antagonists is that their action is different in various tissues, thereby granting the possibility to selectively...
s from the MORE, BCPT P-1, and Italian trials. In the MORE trial, the relative risk reduction
Relative risk reduction
In epidemiology, the relative risk reduction is a measure calculated by dividing the absolute risk reduction by the control event rate.The relative risk reduction can be more useful than the absolute risk reduction in determining an appropriate treatment plan, because it accounts not only for the...
for raloxifene was 76%. The P-1 preventative study demonstrated that tamoxifen can prevent breast cancer in high-risk individuals. The relative risk reduction was up to 50% of new breast cancers, though the cancers prevented were more likely estrogen-receptor positive (this is analogous to the effect of finasteride
Finasteride
Finasteride is a synthetic antiandrogen that inhibits type II 5-alpha reductase, the enzyme that converts testosterone to dihydrotestosterone...
on the prevention of prostate cancer
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
, in which only low-grade prostate cancers were prevented). The Italian trial showed benefit from tamoxifen.
Additional randomized controlled trials have been published since the guidelines. The IBIS trial found benefit from tamoxifen. In 2006, the NSABP STAR trial demonstrated that raloxifene had equal efficacy in preventing breast cancer compared with tamoxifen, but that there were fewer side effects with raloxifene. The RUTH Trial concluded that "benefits of raloxifene in reducing the risks of invasive breast cancer and vertebral fracture should be weighed against the increased risks of venous thromboembolism and fatal stroke". On September 14, 2007, the US Food and Drug Administration approved raloxifene
Raloxifene
Raloxifene is an oral selective estrogen receptor modulator that has estrogenic actions on bone and anti-estrogenic actions on the uterus and breast...
(Evista) to prevent invasive breast cancer in postmenopausal women.
Endocrine disruptors
Many xenoestrogenXenoestrogen
Xenoestrogens are a type of xenohormone that imitates estrogen. They are widely used industrial compounds such as PCB, BPA and Phthalates, that have estrogenic effects on a living organism even though they differ chemically from the naturally occurring estrogenic substances internally produced by...
s (industrially made estrogenic compounds) and other endocrine disruptor
Endocrine disruptor
Endocrine disruptors are chemicals that interfere with endocrine in animals, including humans. These disruptions can cause cancerous tumors, birth defects, and other developmental disorders...
s are potential risk factors of breast cancer.
Diethylstilbestrol
Diethylstilbestrol
Diethylstilbestrol is a synthetic nonsteroidal estrogen that was first synthesized in 1938. Human exposure to DES occurred through diverse sources, such as dietary ingestion from supplemented cattle feed and medical treatment for certain conditions, including breast and prostate cancers...
(DES) is a synthetic form of estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
. It has been used between the early 1940s and 1971. Pregnant women took DES to prevent certain pregnancy complications. However, it also increased their risk of breast cancer. It also increased the risk of breast cancer in the prenatally exposed daughters after they have reached an age 40 years.
Furthermore, there is exposure to endocrine disruptors from the environment, in addition to phytoestrogens mentioned above in the diet section. See xenoestrogens in environmental factors below
Environmental factors
According to a review, the main mechanisms by which environmental compounds increase breast cancer risk are acting like hormones, especially estrogen, or affecting susceptibility to carcinogenesis. The evidence to date generally supports an association between breast cancer and polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenylPolychlorinated biphenyl
Polychlorinated biphenyls are a class of organic compounds with 2 to 10 chlorine atoms attached to biphenyl, which is a molecule composed of two benzene rings. The chemical formula for PCBs is C12H10-xClx...
s (PCBs). dioxins
Dioxins and dioxin-like compounds
Dioxins and dioxin-like compounds are by-products of various industrial processes, and are commonly regarded as highly toxic compounds that are environmental pollutants and persistent organic pollutants . They include:...
and organic solvents, on the other hand, have only shown an association in sparse and methodologically limited studies, but are suggestive of an association. Overall, however, evidence is still based on a relatively small number of studies.
Xenoestrogens
Many xenoestrogenXenoestrogen
Xenoestrogens are a type of xenohormone that imitates estrogen. They are widely used industrial compounds such as PCB, BPA and Phthalates, that have estrogenic effects on a living organism even though they differ chemically from the naturally occurring estrogenic substances internally produced by...
s (industrially made estrogenic compounds) are endocrine disruptor
Endocrine disruptor
Endocrine disruptors are chemicals that interfere with endocrine in animals, including humans. These disruptions can cause cancerous tumors, birth defects, and other developmental disorders...
s, and potential risk factors of breast cancer.
Endocrine disruption is the hypothesis that some chemicals in the body, such as Bisphenol A, are capable of interfering with the production, processing, and transmission of hormones.
A substantial and growing body of evidence indicates that exposures to certain toxic chemicals and hormone-mimicking compounds including chemicals used in pesticides, cosmetics
Cosmetics
Cosmetics are substances used to enhance the appearance or odor of the human body. Cosmetics include skin-care creams, lotions, powders, perfumes, lipsticks, fingernail and toe nail polish, eye and facial makeup, towelettes, permanent waves, colored contact lenses, hair colors, hair sprays and...
and cleaning products contribute to the development of breast cancer.
The increasing prevalence of these substances in the environment may explain the increasing incidence of breast cancer, though direct evidence is sparse.
Bisphenol A
Bisphenol ABisphenol A
Bisphenol A is an organic compound with two phenol functional groups. It is used to make polycarbonate plastic and epoxy resins, along with other applications....
(BPA) is a chemical compound used in the production of plastics found in numerous commercial products, including laptops, baby bottles, food containers, water main pipes, and laboratory and hospital equipment. BPA was first produced in 1891, but its estrogenic properties went undiscovered until the mid 1930s. Today it is considered a xenoestrogen, and it functions as an endocrine disruptor that interferes with hormones in the body and disrupts the normal functioning of the endocrine system. At very low levels the FDA has long considered BPA in food to be safe, but this has been challenged over the years as more information is discovered regarding the effects of the chemical.
Rats exposed prenatally to environmentally relevant doses of BPA show an increased number of intraductal hyperplasias (precancerious lesions) in mammary glands that appear during adulthood, while high doses induce the development of carcinomas in breast tissue. Animals exposed to BPA during fetal life develop palpable tumors, and all studies show an increased susceptibility to mammary gland neoplasia that manifests during adulthood. Exposure of mouse dams to environmentally relevant levels of BPA during organogenesis results in considerable alterations in the mammary gland. It was concluded that perinatal exposure to low doses of BPA results in altered mammary gland morphogenesis, induction of precancerous lesions, and carcinoma in situ.
A study sought to determine whether early exposure to BPA could accelerate mammary carcinogenesis in a dimethylbenzanthracene (DMBA) model of rodent mammary cancer. In the study, scientists exposed neonatal/prebubertal rats to BPA via lactation from nursing dams treated orally with 0, 25, and 250 µg BPA/kg body weight/day. For tumorigenesis studies, female offspring were exposed to 30 mg dimethylbenzanthracene (DMBA)/kg body weight at 50 days of age. DMBA induces mammary tumors and allows chemicals that predispose for mammary cancer to increase the number of mammary adenocarcinomas. The results of the study showed that female rats in the control, BPA 25, and BPA 250 groups administered DMBA exhibited a BPA dose-dependent increase in mammary tumors. The groups had 2.84, 3.82, and 5.00 mammary tumors per rat respectively. Treatment with BPA also reduced tumor latency, with the median tumor latency of 65, 53, and 56.5 days for 0, BPA 25, and BPA 250 groups respectively. Maternal exposure to BPA during lactation decreased time to first tumor latency and increased the number of DMBA-induced mammary tumors in female offspring. If these effects found in rodents carry over to humans, even minimal exposure to BPA could cause an increased risk for breast cancer.
The elevated incidence of breast cancer in women has been associated with prolonged exposure to high levels of estrogens. Xenoestrogens, such as BPA have the capacity to perturb normal hormonal actions. This study provides evidence of the estrogenic effects of BPA. In this study the human breast epithelial cells MCF-10F were treated with 10-3 M, 10-4 M, 10-5 M and 10-6 M BPA continuously for two weeks. The cells treated with 10-3 M BPA died on the second day of treatment. The concentration of 10-4 M BPA was also toxic for the breast epithelial cells, and they died on the fourth day of treatment. This data indicated that these concentrations of BPA are toxic for MCF-10F cells. After the two-week observation period it was seen that the cells formed a high percentage of duct like structures in collagen. MCF-10F cells treated with 10-5 M and 10-6 M BPA formed a high percentage of solid masses, 27% and 20% respectively. This data indicates that BPA is able to induce neoplastic transformation of human breast epithelial cells. Epigenetic changes are involved in the early stages of cancer initiation by altering ductulogenesis. BPA was able to induce transformation of human breast MCF-10F epithelial cells. After treatment with BPA, the cells produced fewer collagen tubules and more solid masses.
Consumer groups recommend that people wishing to lower their exposure to bisphenol A avoid canned food and polycarbonate plastic containers (which shares resin identification code
Resin identification code
The SPI resin identification coding system is a set of symbols placed on plastics to identify the polymer type. It was developed by the Society of the Plastics Industry in 1988, and is used internationally....
7 with many other plastics) unless the packaging indicates the plastic is bisphenol A-free. The National Toxicology Panel recommends avoiding microwaving food in plastic containers, putting plastics in the dishwasher, or using harsh detergents on plastics, to avoid leaching.
Aromatic Amines
Aromatic amineAromatic amine
An aromatic amine is an amine with an aromatic substituent - that is -NH2, -NH- or nitrogen group attached to an aromatic hydrocarbon, whose structure usually contains one or more benzene rings. Aniline is the simplest example....
s are chemicals that are produced when products such as dyes, polyurethane products, and certain pesticides are made. They are also found in cigarette smoke, fuel exhaust, and in over cooked, burned meat. The three types of aromatic amines monocyclic, polycyclic, and heterocyclic have all been found in recent studies of breast health. Monocyclic amines have been found to cause mammary cancer in rats. Studies have shown that women who eat higher amounts of overcooked meat, meaning more exposure to heterocyclic amines, have also been diagnosed with more post-menopausal breast cancer. Heterocyclic amines also have the ability to copy estrogen and in laboratory studies have been found to encourage the growth of cancerous tumors on human tissue.
Benzene
BenzeneBenzene
Benzene is an organic chemical compound. It is composed of 6 carbon atoms in a ring, with 1 hydrogen atom attached to each carbon atom, with the molecular formula C6H6....
is a petrochemical solvent. Benzene exposure mostly originates from air pollution resulting from industrial burning, exhaust and gas fumes, as well as cigarette smoke. The International Agency for Research on Cancer and the National Toxicology Program have labeled benzene as a definite human carcinogen. Multiple studies point to a correlation between benzene exposure and breast cancer risk. Laboratory studies on mice have shown that a high level of benzene exposure can lead to mammary cancer.
DDT
Although the pesticide DDT was banned over 20 years ago, studies have shown that there are still trace amounts found in certain agricultural products, as well as in human and animal milk. While individual studies have come to conflicting conclusions, the most recent reviews of all the evidence conclude that exposure to DDT before puberty increases the risk of breast cancer later in life.Ethylene oxide
Ethylene oxideEthylene oxide
Ethylene oxide, also called oxirane, is the organic compound with the formula . It is a cyclic ether. This means that it is composed of two alkyl groups attached to an oxygen atom in a cyclic shape . This colorless flammable gas with a faintly sweet odor is the simplest epoxide, a three-membered...
is a chemical that can be found in some personal care products, mainly in the form of fragrance. It is also used for the sterilization of various medical objects. The National Toxicology Program has labeled ethylene oxide as a definite human and animal carcinogen. A study done by the National Institute for Occupational Safety and Health including 7,576 women found a direct correlation between breast cancer rates and exposure to ethylene oxide during medical sterilization processes. Also, human breast cells put into contact with small amounts of ethylene oxide in a laboratory can lead to DNA damage of the breast tissue.
Polycyclic aromatic hydrocarbons
Polycyclic aromatic hydrocarbons are chemical products of combustion from coal burners, fuel, cigarette smoke, and various other sources. PAH's are often found in the air and are breathed into the body. PAH's bioaccumulate easily and can copy the estrogen hormone. PAH's can also be genotoxic, meaning they have the ability to harm DNA.Vinyl chloride
Vinyl chlorideVinyl chloride
Vinyl chloride is the organochloride with the formula H2C:CHCl. It is also called vinyl chloride monomer, VCM or chloroethene. This colorless compound is an important industrial chemical chiefly used to produce the polymer polyvinyl chloride . At ambient pressure and temperature, vinyl chloride...
is produced when PVC or polyvinly chloride is made. PVC is found in plastic packaging, outerwear, plastic toys and other plastic products. Vinyl chloride can be found in cigarette smoke and the air around garbage and land fills. It can also be found in the wastewater when PVC is made. The National Toxicology Program and the International Agency for Research on Cancer have both labeled vinyl chloride as a definite human carcinogen.
Tobacco
Until recently, most studies had not found an increased risk of breast cancer from active tobacco smokingTobacco smoking
Tobacco smoking is the practice where tobacco is burned and the resulting smoke is inhaled. The practice may have begun as early as 5000–3000 BCE. Tobacco was introduced to Eurasia in the late 16th century where it followed common trade routes...
. Beginning in the mid-1990s, a number of studies suggested an increased risk of breast cancer in both active smokers and those exposed to secondhand smoke
Passive smoking
Passive smoking is the inhalation of smoke, called secondhand smoke or environmental tobacco smoke , from tobacco products used by others. It occurs when tobacco smoke permeates any environment, causing its inhalation by people within that environment. Exposure to secondhand tobacco smoke causes...
compared to women who reported no exposure to secondhand smoke. By 2005 enough evidence had accumulated for the [California Environmental Protection Agency] to conclude that breathing secondhand smoke causes breast cancer in younger, primarily premenopausal women. The Agency concluded that the risk was increased by 70%, based on epidemiological studies and the fact that there are many mammary carcinogens in secondhand smoke. The following year (2006) the US Surgeon General
Surgeon General of the United States
The Surgeon General of the United States is the operational head of the Public Health Service Commissioned Corps and thus the leading spokesperson on matters of public health in the federal government...
identified the same risk increase and concluded that the evidence is "suggestive," one step below causal. There is some evidence that exposure to tobacco smoke is most problematic between puberty and first childbirth. The reason is that breast tissue appears most sensitive to chemical carcinogens breast cells not fully differentiated until lactation. The likely reason that the older studies of active smoking did not detect risks associated with smoking was that they compared active smokers to all nonsmokers (which includes many passive smokers). The newer studies, which exclude passive smokers from the control group, generally show elevated risks associated with active as well as passive smoking.
Passive smoking
Breathing secondhand smoke increases breast cancer risk by 70% in younger, primarily pre-menopausal women. The California Environmental Protection AgencyCalifornia Environmental Protection Agency
The California Environmental Protection Agency is a state cabinet-level agency within the government of California. Cal/EPA is composed of six departments, boards and offices responsible for environmental research, regulating and administering the state's environmental protection programs, and...
has concluded that passive smoking
Passive smoking
Passive smoking is the inhalation of smoke, called secondhand smoke or environmental tobacco smoke , from tobacco products used by others. It occurs when tobacco smoke permeates any environment, causing its inhalation by people within that environment. Exposure to secondhand tobacco smoke causes...
causes breast cancer and the US Surgeon General has concluded that the evidence is "suggestive," one step below causal. There is some evidence that exposure to tobacco smoke is most problematic between puberty and first childbirth. The reason that breast tissue appears most sensitive to chemical carcinogens in this phase is that breast cells are not fully differentiated until lactation.
Radiation
Women who have received high-dose ionizing radiationIonizing radiation
Ionizing radiation is radiation composed of particles that individually have sufficient energy to remove an electron from an atom or molecule. This ionization produces free radicals, which are atoms or molecules containing unpaired electrons...
to the chest (for example, as treatments for other cancers) have a relative risk of breast cancer between 2.1 to 4.0. The risk increases with increased dose. In addition, the risk is higher in women irradiated before age 30, when there is still breast development.
Dioxins
DioxinsDioxins and dioxin-like compounds
Dioxins and dioxin-like compounds are by-products of various industrial processes, and are commonly regarded as highly toxic compounds that are environmental pollutants and persistent organic pollutants . They include:...
(most notably the polychlorinated dibenzodioxins) are chemicals that are produced when chlorinated products are burned, such as polyvinyl chloride (PVC). This occurs when chlorinated products are used in certain manufacturing industries. Dioxins are also added to the air when gasoline and diesel fuels break down. Dioxins are able to bioaccumulate, meaning that they settle and stay in human and animal fat for long periods of time. There are many different types of dioxins and only a few of them have been labeled by the Environmental Protection Agency as definite human carcinogens and endocrine hormone disruptors. Although dioxins are floating in the air, they eventually settle on plants and other vegetation surfaces. These plants and vegetation are them eaten by cows and other animals. Humans end up eating the produce, milk, eggs, and meat produced by these animals that have consumed dioxin covered vegetation. Dioxins are more harmful when ingested this way. Multiple studies have led to the idea that increased dioxin levels can increase one's risk for breast cancer. A study done in 1976 after a chemical plant explosion in Seveso, Italy concluded that high dioxin level exposure in a woman's body correlated with a more than double chance of developing breast cancer.
Light at night and disturbance of circadian rhythm
In 1978 Cohen et al. proposed that reduced production of the hormone melatonin might increase the risk of breast cancer and citing "environmental lighting" as a possible causal factor. Researchers at the National Cancer InstituteNational Cancer Institute
The National Cancer Institute is part of the National Institutes of Health , which is one of 11 agencies that are part of the U.S. Department of Health and Human Services. The NCI coordinates the U.S...
(NCI) and National Institute of Environmental Health Sciences
National Institute of Environmental Health Sciences
The National Institute of Environmental Health Sciences is a part of the National Institutes of Health , which is in turn a part of the Department of Health and Human Services ....
conducted a study in 2005 that suggests that artificial light during the night can be a factor for breast cancer by disrupting melatonin
Melatonin
Melatonin , also known chemically as N-acetyl-5-methoxytryptamine, is a naturally occurring compound found in animals, plants, and microbes...
levels.
In 2007, "shiftwork that involves circadian disruption" was listed as a probable carcinogen by the World Health Organization's International Agency for Research on Cancer. (IARC Press release No. 180). Multiple studies have documented a link between night shift work and the increased incidence of breast cancer. A review of current knowledge of the health consequences of exposure to artificial light at night including the increased incidence of breast cancer and an explanation of the causal mechanisms has been published in the Journal of Pineal Research in 2007.
Racial and socioeconomic factors
Incidence and mortality vary with race and social status. Incidence rises with improving economic situation, while mortality is tied to low economic status. In the US incidence is significantly lower and mortality higher among black women and this difference appears to persist even after adjustment for economic status. It is currently unclear if significant racial differences in incidence and mortality persist after adjustment for economic status between women of white, Hispanic and asian origin in the US.Several studies have found that black women in the U.S. are more likely to die from breast cancer even though white women are more likely to be diagnosed with the disease. Even after diagnosis, black women are less likely to get treatment compared to white women. Scholars have advanced several theories for the disparities, including inadequate access to screening, reduced availability of the most advanced surgical and medical techniques, or some biological characteristic of the disease in the African American population. Some studies suggest that the racial disparity in breast cancer outcomes may reflect cultural biases more than biological disease differences. However, the lack of diversity in clinical trials for breast cancer treatment may contribute to these disparities, with recent research indicating that black women are more likely to have estrogen receptor negative breast cancers, which are not responsive to hormone treatments that are effective for most white women. Research is currently ongoing to define the contribution of both biological and cultural factors.
Part of the differences in incidence that is attributable to race and economic status may be explained by past use of hormone replacement therapy
Hormone replacement therapy (menopause)
Hormone replacement therapy is a system of medical treatment for surgically menopausal, perimenopausal and to a lesser extent postmenopausal women...
Tea
One research published in 2009 has show that moderate green or black tea consumption (three or more cups per day) can reduce breast cancer risk by 37% in women younger than 50 years old, comparing with women who drank no tea at all. But no association was found for overall women. However that study has been criticized for inaccuracy and another study found no substantial association between and tea consumption in the overall, but found a weak inverse association between caffeine-containing beverages and risk of postmenopausal breast cancer.Specifically about green tea
Green tea
Green tea is made solely from the leaves of Camellia sinensis that have undergone minimal oxidation during processing. Green tea originates from China and has become associated with many cultures throughout Asia. It has recently become more widespread in the West, where black tea is traditionally...
, one study has found significant inverse association between risk of breast cancer and green tea intake in Asian women who were low soy consumers.
1,3-Butadiene
1,3-Butadiene1,3-Butadiene
1,3-Butadiene is a simple conjugated diene with the formula C4H6. It is an important industrial chemical used as a monomer in the production of synthetic rubber. When the word butadiene is used, most of the time it refers to 1,3-butadiene....
is an environmental factor that can be found in air pollution and can be produced by combustion engines, as well as petroleum refineries. It is found in cigarette smoke and is also used in the making and processing of certain synthetic rubber products and fungicides. The National Toxicology Program has labeled 1,3-Butadiene as definite human carcinogen. The EPA has stated that people are mainly put in contact with this chemical through the means of simple inhalation.
Mammographic density
Mammographic density refers to the relative proportions of radiodense area compared to the radiolucent area on a mammogram, which is basically an x-rayX-ray
X-radiation is a form of electromagnetic radiation. X-rays have a wavelength in the range of 0.01 to 10 nanometers, corresponding to frequencies in the range 30 petahertz to 30 exahertz and energies in the range 120 eV to 120 keV. They are shorter in wavelength than UV rays and longer than gamma...
of the breast. The radiodense area on a mammogram is white and is associated with ductal and lobular epithelium, connective tissue and fluid in the breast
Breast
The breast is the upper ventral region of the torso of a primate, in left and right sides, which in a female contains the mammary gland that secretes milk used to feed infants.Both men and women develop breasts from the same embryological tissues...
. The radiolucent area is dark gray or black and is associated with fat in the breast. High mammographic density is associated with a higher risk of developing breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
, but the reasons for this link are not certain and are being studied.
Red No. 3
Red No. 3 is a coloring agent used in some foods. In laboratory tests human breast cell DNA was found positive for damage when put into contact with Red No. 3, which means that it is genotoxic.Abortion
The abortion-breast cancer (ABC) hypothesis (supporters call it the abortion-breast cancer link) posits induced abortionAbortion
Abortion is defined as the termination of pregnancy by the removal or expulsion from the uterus of a fetus or embryo prior to viability. An abortion can occur spontaneously, in which case it is usually called a miscarriage, or it can be purposely induced...
increases the risk of developing breast cancer; it is a controversial subject and the current scientific consensus
Scientific consensus
Scientific consensus is the collective judgment, position, and opinion of the community of scientists in a particular field of study. Consensus implies general agreement, though not necessarily unanimity. Scientific consensus is not by itself a scientific argument, and it is not part of the...
has concluded there is no significant association between first-trimester abortion and breast cancer risk.
Deodorants
Much has been made of the possible contribution of aluminum-containing underarm antiperspirants to the incidence of breast cancer, since the most common location of a breast cancer is the upper outer quadrant of the breast. Aluminum salts, such as those used in anti-perspirants, have recently been classified as metalloestrogenMetalloestrogen
Metalloestrogens are a class of inorganic xenoestrogens which can affect the gene expression of human cells responding to estrogen. Effects are related to the physiologic function of estrogen because metalloestrogens have shown affinity for estrogen receptors...
s. In research published in the Journal of Applied Toxicology
Journal of Applied Toxicology
The Journal of Applied Toxicology is a bimonthly peer-reviewed scientific journal published since 1981 by John Wiley & Sons. It covers all aspects of toxicology and publishes reviews and research articles on mechanistic, fundamental, and applied research relating to the toxicity of drugs and...
, Dr. Philippa D. Darbre of the University of Reading
University of Reading
The University of Reading is a university in the English town of Reading, Berkshire. The University was established in 1892 as University College, Reading and received its Royal Charter in 1926. It is based on several campuses in, and around, the town of Reading.The University has a long tradition...
has shown that aluminum salts increase estrogen-related gene expression in human breast cancer cells grown in the laboratory.
Fortunately, this in-vitro association between aluminum salts and estrogen activity does not translate into an increased risk of breast cancer in humans. The lack of association between underarm deodorants and breast cancer has been the subject of a number of research articles.
Fertility treatments
There is no persuasive connection between fertility medications and breast cancer.Folic acid (folate)
The results of the studies about the influence of dietary folic acid on breast cancer have been contradictory.Viruses
Several kind of viruses are suspected to play a role or cause breast cancer, among them human papilloma virus, human cytomegalovirus and the Epstein-Barr virusEpstein-Barr virus
The Epstein–Barr virus , also called human herpesvirus 4 , is a virus of the herpes family and is one of the most common viruses in humans. It is best known as the cause of infectious mononucleosis...
. The human papilloma virus is well known for its capability to immortalize breast cancer cells which is used in research, however the role of this viruses in human breast cancer remains controversial.
Humans are not the only mammals susceptible 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. This finding is taken to mean that a viral origin of human breast cancer is at least possible, though there is no definitive evidence to support the claim that MMTV causes human breast cancer. For example, there may be critical differences between cancer pathogenesis in mice and people.
A human homologue of the mammary virus has been described in 1971 and linked to to human breast cancer in several small epidemiologic studies.
History
In past centuries, the development of breast cancer was most commonly seen as divine punishment or a trial. From ancient Greek medicine until the end of the 17th century, the dominant medical explanation was an imbalance of the four humors. By the start of the 18th century, humoralism had generally been rejected. Many other theories were put forward, often related to sexual activity: In 1713, Bernardino RamazziniBernardino Ramazzini
Bernardino Ramazzini was an Italian physician.Ramazzini was an early proponent of the use of cinchona bark in the treatment of Malaria...
said that nuns developed breast cancer at a higher rate than married women because they did not engage in sexual intercourse
Sexual intercourse
Sexual intercourse, also known as copulation or coitus, commonly refers to the act in which a male's penis enters a female's vagina for the purposes of sexual pleasure or reproduction. The entities may be of opposite sexes, or they may be hermaphroditic, as is the case with snails...
, and the "unnatural" lack of sexual activity caused instability of the breasts; others countered that the cause was frequently too much sexual activity. Other theories from the 18th century included various sorts of problems with the movement of body fluids, such as lymphatic blockages, curdled breast milk
Breast milk
Breast milk, more specifically human milk, is the milk produced by the breasts of a human female for her infant offspring...
or the transformation of pus left after an infection.
In modern times, women are more likely to blame themselves, perhaps deciding that their diet, childbearing history, decision not to breastfeed, or level of exercise is the cause.
See also
- Carcinogen#IARC classification of carcinogens
- XenoestrogenXenoestrogenXenoestrogens are a type of xenohormone that imitates estrogen. They are widely used industrial compounds such as PCB, BPA and Phthalates, that have estrogenic effects on a living organism even though they differ chemically from the naturally occurring estrogenic substances internally produced by...
- Your Disease RiskYour Disease RiskYour Disease Risk is a publicly available health risk assessment tool on the Internet. Launched in early 2000 and continually updated, the site offers risk assessments for twelve different cancers and four other important chronic diseases: heart disease, stroke, diabetes, and osteoporosis.The site...
External links
- GeneReviews/NCBI/NIH/UW entry on BRCA1 and BRCA2 Hereditary Breast/Ovarian Cancer
- Breast cancer database at Silent Spring Institute