Breast cancer is that develops from tissue. Signs of breast cancer may include a in the breast, a change in breast shape, of the skin, fluid coming from the nipple, a newly inverted nipple, or a red or scaly patch of skin. In those with , there may be , swollen , , or .
Risk factors for developing breast cancer include being female, , lack of physical exercise, drinking , during , , early age at , having children late or not at all, older age, prior history of breast cancer, and family history. About 5–10% of cases are due to genes from a person's parents, including and among others.Breast cancer most commonly develops in cells from the lining of and the that supply the ducts with milk. Cancers developing from the ducts are known as , while those developing from lobules are known as . In addition, there are more than 18 other sub-types of breast cancer. Some cancers, such as , develop from . The diagnosis of breast cancer is confirmed by taking a of the concerning lump. Once the diagnosis is made, further tests are done to determine if the cancer has spread beyond the breast and which treatments are most likely to be effective.
The balance of benefits versus harms of is controversial. A 2013 stated that it is unclear if screening does more good or harm. A 2009 review for the found evidence of benefit in those 40 to 70 years of age, and the organization recommends screening every two years in women 50 to 74 years old. The medications or may be used in an effort to prevent breast cancer in those who are at high risk of developing it. is another preventative measure in some high risk women. In those who have been diagnosed with cancer, a number of treatments may be used, including , , , and . Types of surgery vary from to . may take place at the time of surgery or at a later date. In those in whom the cancer has spread to other parts of the body, treatments are mostly aimed at improving quality of life and comfort.
Outcomes for breast cancer vary depending on the cancer type, , and person's age. Survival rates in the are high, with between 80% and 90% of those in England and the United States . In developing countries survival rates are poorer. Worldwide, breast cancer is the leading type of cancer in women, accounting for 25% of all cases. In 2012 it resulted in 1.68 million new cases and 522,000 deaths. It is more common in developed countries and is more than 100 times more common in women than in men.
Signs and symptomsBreast cancer Breast cancer showing an inverted nipple, lump, and skin dimpling.
The first noticeable of breast cancer is typically a that feels different from the rest of the breast tissue. More than 80% of breast cancer cases are discovered when the woman feels a lump. The earliest breast cancers are detected by a . Lumps found in lymph nodes located in the armpits can also indicate breast cancer.
Indications of breast cancer other than a lump may include thickening different from the other breast tissue, one breast becoming larger or lower, a nipple changing position or shape or becoming inverted, skin puckering or dimpling, a rash on or around a nipple, discharge from nipple/s, constant pain in part of the breast or armpit, and swelling beneath the armpit or around the collarbone. Pain ("") is an unreliable tool in determining the presence or absence of breast cancer, but may be indicative of other issues.
is a particular type of breast cancer which can pose a substantial diagnostic challenge. Symptoms may resemble a breast inflammation and may include itching, pain, swelling, nipple inversion, warmth and redness throughout the breast, as well as an orange-peel texture to the skin referred to as peau d'orange. As inflammatory breast cancer does not present as a lump there can sometimes be a delay in diagnosis.
Another reported symptom complex of breast cancer is . This presents as skin changes resembling , such as redness, discoloration, or mild flaking of the nipple skin. As Paget's disease of the breast advances, symptoms may include tingling, itching, increased sensitivity, burning, and pain. There may also be discharge from the nipple. Approximately half of women diagnosed with Paget's disease of the breast also have a lump in the breast.
In rare cases, what initially appears as a (hard, movable non-cancerous lump) could in fact be a . Phyllodes tumors are formed within the stroma (connective tissue) of the breast and contain glandular as well as stromal tissue. Phyllodes tumors are not staged in the usual sense; they are classified on the basis of their appearance under the microscope as benign, borderline, or malignant.
Occasionally, breast cancer presents as disease—that is, cancer that has spread beyond the original organ. The symptoms caused by will depend on the location of metastasis. Common sites of metastasis include bone, liver, lung and brain. Unexplained weight loss can occasionally signal breast cancer, as can symptoms of fevers or chills. Bone or joint pains can sometimes be manifestations of metastatic breast cancer, as can jaundice or neurological symptoms. These symptoms are called , meaning they could be manifestations of many other illnesses.
Most symptoms of breast disorders, including most lumps, do not turn out to represent underlying breast cancer. Fewer than 20% of lumps, for example, are cancerous, and such as and of the breast are more common causes of breast disorder symptoms.
Risk factors can be divided into two categories:
- modifiable risk factors (things that people can change themselves, such as consumption of alcoholic beverages), and
- fixed risk factors (things that cannot be changed, such as age and biological sex).
The primary risk factors for breast cancer are being female and older age. Other potential risk factors include genetics, lack of childbearing or lack of breastfeeding, higher levels of certain hormones, certain dietary patterns, and obesity. One study indicates that exposure to light pollution is a risk factor for the development of breast cancer.
Obesity and drinking alcoholic beverages are among the most common modifiable risk factors.
appears to increase the risk of breast cancer, with the greater the amount smoked and the earlier in life that smoking began, the higher the risk. In those who are long-term smokers, the risk is increased 35% to 50%. A lack of physical activity has been linked to about 10% of cases. regularly for prolonged periods is associated with higher mortality from breast cancer. The risk is not negated by regular exercise, though it is lowered.
There is an association between use of and the development of breast cancer, but whether oral contraceptives use may actually premenopausal breast cancer is a matter of debate. If there is indeed a link, the absolute effect is small. Additionally, it is not clear if the association exists with newer hormonal birth controls. In those with mutations in the breast cancer susceptibility genes or , or who have a family history of breast cancer, use of modern oral contraceptives does not appear to affect the risk of breast cancer.
The association between and breast cancer has not been clearly determined; some studies have found support for an association while others have not. In the 1980s, the posited that increased the risk of developing breast cancer. This hypothesis was the subject of extensive scientific inquiry, which concluded that neither nor abortions are associated with a heightened risk for breast cancer.
A number of dietary factors have been linked to the risk for breast cancer. , even at relatively low (one to three drinks per week) and moderate levels. The risk is highest among heavy drinkers. Dietary factors which may increase risk include a high-fat diet and obesity-related levels. Dietary iodine deficiency may also play a role. Evidence for fiber is unclear. A 2015 review found that studies trying to link fiber intake with breast cancer produced mixed results. In 2016 a tentative association between low fiber intake during adolescence and breast cancer was observed.
Other risk factors include and . A number of chemicals have also been linked, including , , and Although the radiation from is a low dose, it is estimated that yearly screening from 40 to 80 years of age will cause approximately 225 cases of fatal breast cancer per million women screened.
Some genetic susceptibility may play a minor role in most cases. Overall, however, genetics is believed to be the primary cause of 5–10% of all cases. Women whose mother was diagnosed before 50 have an increased risk of 1.7 and those whose mother was diagnosed at age 50 or after has an increased risk of 1.4. In those with zero, one or two affected relatives, the risk of breast cancer before the age of 80 is 7.8%, 13.3%, and 21.1% with a subsequent mortality from the disease of 2.3%, 4.2%, and 7.6% respectively. In those with a first degree relative with the disease the risk of breast cancer between the age of 40 and 50 is double that of the general population.
In less than 5% of cases, genetics plays a more significant role by causing a . This includes those who carry the . These mutations account for up to 90% of the total genetic influence with a risk of breast cancer of 60–80% in those affected. Other significant mutations include p53 (), PTEN (), and STK11 (), CHEK2, ATM, BRIP1, and PALB2. In 2012, researchers said that there are four genetically distinct types of the breast cancer and that in each type, hallmark genetic changes lead to many cancers.
Breast changes like and , found in benign breast conditions such as , are correlated with an increased breast cancer risk.
might also increase the risk of breast cancer. Autoimmune diseases such as seem also to increase the risk for the acquisition of breast cancer.
Main article:Overview of signal transduction pathways involved in . Mutations leading to loss of this ability can lead to cancer formation.
Breast cancer, like other , occurs because of an interaction between an environmental (external) factor and a genetically susceptible host. Normal cells divide as many times as needed and stop. They attach to other cells and stay in place in tissues. Cells become cancerous when they lose their ability to stop dividing, to attach to other cells, to stay where they belong, and to die at the proper time.
Normal cells will commit cell suicide () when they are no longer needed. Until then, they are protected from cell suicide by several protein clusters and pathways. One of the protective pathways is the / pathway; another is the // pathway. Sometimes the genes along these protective pathways are mutated in a way that turns them permanently "on", rendering the cell incapable of committing suicide when it is no longer needed. This is one of the steps that causes cancer in combination with other mutations. Normally, the protein turns off the PI3K/AKT pathway when the cell is ready for programmed cell death. In some breast cancers, the gene for the PTEN protein is mutated, so the PI3K/AKT pathway is stuck in the "on" position, and the cancer cell does not commit suicide.
Mutations that can lead to breast cancer have been experimentally linked to estrogen exposure.
Abnormal signaling in the interaction between and can facilitate malignant cell growth. In breast adipose tissue, overexpression of leptin leads to increased cell proliferation and cancer.
In the United States, 10 to 20 percent of people with breast cancer and people with ovarian cancer have a first- or second-degree relative with one of these diseases. The familial tendency to develop these cancers is called . The best known of these, the , confer a lifetime risk of breast cancer of between 60 and 85 percent and a lifetime risk of ovarian cancer of between 15 and 40 percent. Some mutations associated with cancer, such as , and , occur in mechanisms to correct errors in DNA. These mutations are either inherited or acquired after birth. Presumably, they allow further mutations, which allow uncontrolled division, lack of attachment, and metastasis to distant organs. However, there is strong evidence of residual risk variation that goes well beyond hereditary BRCA gene mutations between carrier families. This is caused by unobserved risk factors. This implicates environmental and other causes as triggers for breast cancers. The inherited mutation in BRCA1 or BRCA2 genes can interfere with repair of DNA cross links and DNA double strand breaks (known functions of the encoded protein). These carcinogens cause DNA damage such as DNA cross links and double strand breaks that often require repairs by pathways containing BRCA1 and BRCA2. However, mutations in BRCA genes account for only 2 to 3 percent of all breast cancers. Levin et al. say that cancer may not be inevitable for all carriers of BRCA1 and BRCA2 mutations. About half of hereditary breast–ovarian cancer syndromes involve unknown genes.
directly controls the expression of estrogen receptor (ER) and other genes associated with epithelial differentiation, and the loss of GATA-3 leads to loss of differentiation and poor prognosis due to cancer cell invasion and metastasis.
DiagnosisEarly signs of possible breast cancer
Most types of breast cancer are easy to diagnose by microscopic analysis of a sample—or —of the affected area of the breast. Also, there are types of breast cancer that require specialized lab exams.
The two most commonly used screening methods, physical examination of the breasts by a healthcare provider and mammography, can offer an approximate likelihood that a lump is cancer, and may also detect some other lesions, such as a simple . When these examinations are inconclusive, a healthcare provider can remove a sample of the fluid in the lump for microscopic analysis (a procedure known as , or fine needle aspiration and cytology—FNAC) to help establish the diagnosis. The needle aspiration may be performed in a healthcare provider's office or clinic using local anaesthetic if required. A finding of clear fluid makes the lump highly unlikely to be cancerous, but bloody fluid may be sent off for inspection under a microscope for cancerous cells. Together, physical examination of the breasts, mammography, and FNAC can be used to diagnose breast cancer with a good degree of accuracy.
Other options for biopsy include a or , which are procedures in which a section of the breast lump is removed; or an , in which the entire lump is removed. Very often the results of physical examination by a healthcare provider, mammography, and additional tests that may be performed in special circumstances (such as imaging by or ) are sufficient to warrant excisional biopsy as the definitive diagnostic and primary treatment method.
MRI showing breast cancer
Excised human , showing an irregular, dense, white area of 2 cm in diameter, within yellow fatty tissue.
High-grade invasive ductal carcinoma, with minimal tubule formation, marked , and prominent , 40x field.
Micrograph showing a lymph node invaded by ductal breast carcinoma, with an extension of the tumor beyond the lymph node.
Neuropilin-2 expression in normal breast and breast carcinoma tissue.
F-18 FDG PET/CT: A breast cancer metastasis to the right scapula
Needle breast biopsy.
Elastography shows stiff cancer tissue on ultrasound imaging.
Ultrasound image shows irregularly shaped mass of breast cancer.
Infiltrating (Invasive) breast carcinoma.
Breast cancers are classified by several grading systems. Each of these influences the and can affect treatment response. Description of a breast cancer optimally includes all of these factors.
- Histopathology. Breast cancer is usually classified primarily by its appearance. Most breast cancers are derived from the epithelium lining the ducts or lobules, and these cancers are classified as or lobular carcinoma. Carcinoma in situ is growth of low-grade cancerous or precancerous cells within a particular tissue compartment such as the mammary duct without invasion of the surrounding tissue. In contrast, invasive carcinoma does not confine itself to the initial tissue compartment.
- Grade. compares the appearance of the breast cancer cells to the appearance of normal breast tissue. Normal cells in an organ like the breast become differentiated, meaning that they take on specific shapes and forms that reflect their function as part of that organ. Cancerous cells lose that differentiation. In cancer, the cells that would normally line up in an orderly way to make up the milk ducts become disorganized. Cell division becomes uncontrolled. Cell nuclei become less uniform. Pathologists describe cells as well differentiated (low grade), moderately differentiated (intermediate grade), and poorly differentiated (high grade) as the cells progressively lose the features seen in normal breast cells. Poorly differentiated cancers (the ones whose tissue is least like normal breast tissue) have a worse prognosis.
Stage. using the is based on the size of the tumor (T), whether or not the tumor has spread to the nodes (N) in the armpits, and whether the tumor has metastasized (M) (i.e. spread to a more distant part of the body). Larger size, nodal spread, and metastasis have a larger stage number and a worse prognosis.
The main stages are:
- Stage 0 is a pre-cancerous or marker condition, either (DCIS) or (LCIS).
- Stages 1–3 are within the breast or regional lymph nodes.
- Stage 4 is that has a less favorable prognosis since it has spread beyond the breast and regional lymph nodes.
Stage T1 breast cancer
Stage T2 breast cancer
Stage T3 breast cancer
Receptor status. Breast cancer cells have on their surface and in their and . Chemical messengers such as bind to , and this causes changes in the cell. Breast cancer cells may or may not have three important receptors: (ER), (PR), and .
ER+ cancer cells (that is, cancer cells that have estrogen receptors) depend on estrogen for their growth, so they can be treated with drugs to block estrogen effects (e.g. ), and generally have a better prognosis. Untreated, HER2+ breast cancers are generally more aggressive than HER2- breast cancers, but HER2+ cancer cells respond to drugs such as the monoclonal antibody (in combination with conventional chemotherapy), and this has improved the prognosis significantly. Cells that do not have any of these three receptor types (estrogen receptors, progesterone receptors, or HER2) are called , although they frequently do express receptors for other hormones, such as and .
- DNA assays. of various types including have compared normal cells to breast cancer cells. The specific changes in a particular breast cancer can be used to classify the cancer in several ways, and may assist in choosing the most effective treatment for that DNA type.
Stage 1A breast cancer
Stage 1B breast cancer
Stage 2A breast cancer
Stage 2A breast cancer
Stage 2B breast cancer
Stage 2B breast cancer
Stage 2B breast cancer
Stage 3A breast cancer
Stage 3A breast cancer
Stage 3A breast cancer
Stage 3B breast cancer
Stage 3B breast cancer
Stage 4 breast cancer
Women can reduce their risk of breast cancer by maintaining a healthy weight, reducing alcohol use, increasing physical activity, and breast-feeding. These modifications might prevent 38% of breast cancers in the US, 42% in the UK, 28% in Brazil and 20% in China. The benefits with moderate such as brisk walking are seen at all age groups including postmenopausal women. High levels of physical activity reduce the risk of breast cancer by about 14%. Strategies that encourage regular physical activity and reduce obesity could also have other benefits, such as reduced risks of cardiovascular disease and diabetes.
High intake of citrus fruit has been associated with a 10% reduction in the risk of breast cancer.
Marine appear to reduce the risk. High consumption of -based foods may reduce risk.
Removal of both breasts before any cancer has been diagnosed or any suspicious lump or other lesion has appeared (a procedure known as prophylactic bilateral ) may be considered in people with BRCA1 and BRCA2 mutations, which are associated with a substantially heightened risk for an eventual diagnosis of breast cancer. Evidence is not strong enough to support this procedure in anyone but those at the highest risk. BRCA testing is recommended in those with a high family risk after genetic counseling. It is not recommended routinely. This is because there are many forms of changes in BRCA genes, ranging from harmless to obviously dangerous . The effect of most of the identifiable changes in the genes is uncertain. Testing in an average-risk person is particularly likely to return one of these indeterminate, useless results. It is unclear if removing the second breast in those who have breast cancer in one is beneficial.
The (such as tamoxifen) reduce the risk of breast cancer but increase the risk of and . There is no overall change in the risk of death. They are thus not recommended for the prevention of breast cancer in women at average risk but may be offered for those at high risk. The benefit of breast cancer reduction continues for at least five years after stopping a course of treatment with these medications.
Main article:A mobile breast cancer screening unit in New Zealand
Breast cancer screening refers to testing otherwise-healthy women for breast cancer in an attempt to achieve an earlier diagnosis under the assumption that early detection will improve outcomes. A number of screening tests have been employed including clinical and self , , genetic screening, ultrasound, and magnetic resonance imaging.
A clinical or self involves feeling the breast for or other abnormalities. Clinical breast exams are performed by health care providers, while self-breast exams are performed by the person themselves. Evidence does not support the effectiveness of either type of breast exam, as by the time a lump is large enough to be found it is likely to have been growing for several years and thus soon be large enough to be found without an exam. Mammographic screening for breast cancer uses to examine the breast for any uncharacteristic masses or lumps. During a screening, the breast is compressed and a technician takes photos from multiple angles. A general mammogram takes photos of the entire breast, while a diagnostic mammogram focuses on a specific lump or area of concern.
A number of national bodies recommend breast cancer screening. For the average woman, the recommends mammography every two years in women between the ages of 50 and 74, the recommends mammography between 50 and 69 with most programs using a 2-year frequency, and in Canada screening is recommended between the ages of 50 and 74 at a frequency of 2 to 3 years. These task force reports point out that in addition to unnecessary surgery and anxiety, the risks of more frequent mammograms include a small but significant increase in breast cancer induced by radiation.
The (2013) states that the best quality evidence neither demonstrates a reduction in cancer specific, nor a reduction in all cause mortality from screening mammography. When less rigorous trials are added to the analysis there is a reduction in mortality due to breast cancer of 0.05% (a decrease of 1 in 2000 deaths from breast cancer over 10 years or a relative decrease of 15% from breast cancer). Screening over 10 years results in a 30% increase in rates of over-diagnosis and over-treatment (3 to 14 per 1000) and more than half will have at least one falsely positive test. This has resulted in the view that it is not clear whether mammography screening does more good or harm. Cochrane states that, due to recent improvements in breast cancer treatment, and the risks of false positives from breast cancer screening leading to unnecessary treatment, "it therefore no longer seems beneficial to attend for breast cancer screening" at any age. Whether MRI as a screening method has greater harms or benefits when compared to standard mammography is not known.
The management of breast cancer depends on various factors, including the of the cancer and the person's age. Treatments are more aggressive when the prognosis is worse or there is a higher risk of recurrence of the cancer following treatment.
Breast cancer is usually treated with , which may be followed by chemotherapy or radiation therapy, or both. A multidisciplinary approach is preferable. Hormone receptor-positive cancers are often treated with hormone-blocking therapy over courses of several years. Monoclonal antibodies, or other immune-modulating treatments, may be administered in certain cases of metastatic and other advanced stages of breast cancer.
Surgery involves the physical removal of the tumor, typically along with some of the surrounding tissue. One or more lymph nodes may be biopsied during the surgery; increasingly the lymph node sampling is performed by a biopsy.
Standard surgeries include:
- : Removal of the whole breast.
- : Removal of one-quarter of the breast.
- : Removal of a small part of the breast.
Once the tumor has been removed, if the person desires, , a type of , may then be performed to improve the aesthetic appearance of the treated site. Alternatively, women use to simulate a breast under clothing, or choose a flat chest. can be used at any time following the mastectomy.
Drugs used after and in addition to surgery are called . Chemotherapy or other types of therapy prior to surgery are called . may reduce mortality from breast cancer.
There are currently three main groups of medications used for adjuvant breast cancer treatment: hormone-blocking agents, chemotherapy, and monoclonal antibodies.Some breast cancers require estrogen to continue growing. They can be identified by the presence of estrogen receptors (ER+) and progesterone receptors (PR+) on their surface (sometimes referred to together as hormone receptors). These ER+ cancers can be treated with drugs that either block the receptors, e.g. , or alternatively block the production of estrogen with an , e.g. or . The use of tamoxifen is recommended for 10 years. Letrozole is recommended for 5 years. Aromatase inhibitors are only suitable for women after menopause; however, in this group, they appear better than tamoxifen. This is because the active aromatase in postmenopausal women is different from the prevalent form in premenopausal women, and therefore these agents are ineffective in inhibiting the predominant aromatase of premenopausal women. Aromatase inhibitors should not be given to premenopausal women with intact ovarian function (unless they are also on treatment to stop their ovaries from working). Chemotherapy is predominantly used for cases of breast cancer in stages 2–4, and is particularly beneficial in estrogen receptor-negative (ER-) disease. The chemotherapy medications are administered in combinations, usually for periods of 3–6 months. One of the most common regimens, known as "AC", combines with . Sometimes a drug, such as , is added, and the regime is then known as "CAT". Another common treatment is cyclophosphamide, , and (or "CMF"). Most chemotherapy medications work by destroying fast-growing and/or fast-replicating cancer cells, either by causing DNA damage upon replication or by other mechanisms. However, the medications also damage fast-growing normal cells, which may cause serious side effects. Damage to the heart muscle is the most dangerous complication of doxorubicin, for example. , a monoclonal antibody to HER2 (a cell receptor that is especially active in some breast cancer cells), has improved the 5-year disease free survival of stage 1–3 HER2-positive breast cancers to about 87% (overall survival 95%). When stimulated by certain growth factors, HER2 causes cellular growth and division; in the absence of stimulation by the growth factor, the cell will normally stop growing. Between 25% and 30% of breast cancers the HER2 gene or its protein product, and overexpression of HER2 in breast cancer is associated with increased disease recurrence and worse prognosis. When trastuzumab binds to the HER2 in breast cancer cells that overexpress the receptor, trastuzumab prevents growth factors from being able to bind to and stimulate the receptors, effectively blocking the growth of the cancer cells. Trastuzumab, however, is very expensive, and its use may cause serious side effects (approximately 2% of people who receive it suffer significant heart damage).
RadiationInternal radiotherapy for breast cancer
is given after surgery to the region of the tumor bed and regional lymph nodes, to destroy microscopic tumor cells that may have escaped surgery. It may also have a beneficial effect on tumor microenvironment.Radiation therapy can be delivered as or as (internal radiotherapy). Conventionally radiotherapy is given after the operation for breast cancer. Radiation can also be given at the time of operation on the breast cancer. Radiation can reduce the risk of recurrence by 50–66% (1/2 – 2/3 reduction of risk) when delivered in the correct dose and is considered essential when breast cancer is treated by removing only the lump (Lumpectomy or Wide local excision).
PrognosisBreasts after double mastectomy followed by nipple-sparing reconstruction with implants An example of an advanced recurrent breast cancer with an ulcerating axillary mass
The of the breast cancer is the most important component of traditional classification methods of breast cancer, because it has a greater effect on the prognosis than the other considerations. Staging takes into consideration size, local involvement, lymph node status and whether metastatic disease is present. The higher the stage at diagnosis, the poorer the prognosis. The stage is raised by the invasiveness of disease to lymph nodes, chest wall, skin or beyond, and the aggressiveness of the cancer cells. The stage is lowered by the presence of cancer-free zones and close-to-normal cell behaviour (grading). Size is not a factor in staging unless the cancer is invasive. For example, Ductal Carcinoma In Situ (DCIS) involving the entire breast will still be stage zero and consequently an excellent prognosis with a 10-year disease free survival of about 98%.
- Stage 1 cancers (and DCIS, LCIS) have an excellent prognosis and are generally treated with lumpectomy and sometimes radiation.
- Stage 2 and 3 cancers with a progressively poorer prognosis and greater risk of recurrence are generally treated with surgery (lumpectomy or mastectomy with or without ), chemotherapy (plus for HER2+ cancers) and sometimes radiation (particularly following large cancers, multiple positive nodes or lumpectomy).
- Stage 4, metastatic cancer, (i.e. spread to distant sites) has poor prognosis and is managed by various combination of all treatments from surgery, radiation, chemotherapy and targeted therapies. Ten-year survival rate is 5% without treatment and 10% with optimal treatment.
is assessed by comparison of the breast cancer cells to normal breast cells. The closer to normal the cancer cells are, the slower their growth and the better the prognosis. If cells are not well differentiated, they will appear immature, will divide more rapidly, and will tend to spread. Well differentiated is given a grade of 1, moderate is grade 2, while poor or undifferentiated is given a higher grade of 3 or 4 (depending upon the scale used). The most widely used grading system is the Nottingham scheme.
Younger women with an age of less than 40 years or women over 80 years tend to have a poorer prognosis than post-menopausal women due to several factors. Their breasts may change with their menstrual cycles, they may be nursing infants, and they may be unaware of changes in their breasts. Therefore, younger women are usually at a more advanced stage when diagnosed. There may also be biologic factors contributing to a higher risk of disease recurrence for younger women with breast cancer.
Not all people with breast cancer experience their illness in the same manner. Factors such as age can have a significant impact on the way a person copes with a breast cancer diagnosis. Premenopausal women with estrogen-receptor positive breast cancer must confront the issues of early induced by many of the chemotherapy regimens used to treat their breast cancer, especially those that use hormones to counteract ovarian function.
Main article:death from breast cancer per 100,000 inhabitants in 2004.
Worldwide, breast cancer is the most common invasive cancer in women. It affects about 12% of women worldwide. (The most common form of cancer is non-invasive ; non-invasive cancers are generally easily cured, cause very few deaths, and are routinely excluded from cancer statistics.) Breast cancer comprises 22.9% of invasive cancers in women and 16% of all female cancers. In 2012, it comprised 25.2% of cancers diagnosed in women, making it the most common female cancer.
In 2008, breast cancer caused 458,503 deaths worldwide (13.7% of cancer deaths in women and 6.0% of all cancer deaths for men and women together)., the second most common cause of cancer-related death in women, caused 12.8% of cancer deaths in women (18.2% of all cancer deaths for men and women together).
The incidence of breast cancer varies greatly around the world: it is lowest in less-developed countries and greatest in the more-developed countries. In the twelve world regions, the annual age-standardized per 100,000 women are as follows: in Eastern Asia, 18; South Central Asia, 22; sub-Saharan Africa, 22; South-Eastern Asia, 26; North Africa and Western Asia, 28; South and Central America, 42; Eastern Europe, 49; Southern Europe, 56; Northern Europe, 73; Oceania, 74; Western Europe, 78; and in North America, 90.
The number of cases worldwide has significantly increased since the 1970s, a phenomenon partly attributed to the modern lifestyles.Breast cancer is strongly related to age with only 5% of all breast cancers occurring in women under 40 years old. There were more than 41,000 newly diagnosed cases of breast cancer registered in England in 2011, around 80% of these cases were in women age 50 or older Based on U.S. statistics in 2015 there were 2.8 million women affected by breast cancer. In the United States, the of breast cancer per 100,000 women rose from around 102 cases per year in the 1970s to around 141 in the late 1990s, and has since fallen, holding steady around 125 since 2003. However age-adjusted deaths from breast cancer per 100,000 women only rose slightly from 31.4 in 1975 to 33.2 in 1989 and have since declined steadily to 20.5 in 2014.
HistoryBreast cancer surgery in 18th century
Because of its visibility, breast cancer was the form of cancer most often described in ancient documents. Because autopsies were rare, cancers of the internal organs were essentially invisible to ancient medicine. Breast cancer, however, could be felt through the skin, and in its advanced state often developed into : the tumor would become (die from the inside, causing the tumor to appear to break up) and through the skin, weeping fetid, dark fluid.
The oldest discovered evidence of breast cancer is from Egypt and dates back 4200 years, to the . The study of a woman's remains from the necropolis of showed the typical destructive damage due to spread. The describes 8 cases of tumors or ulcers of the breast that were treated by . The writing says about the disease, "There is no treatment." For centuries, physicians described similar cases in their practices, with the same conclusion. Ancient medicine, from the time of the Greeks through the 17th century, was based on , and thus believed that breast cancer was generally caused by imbalances in the fundamental fluids that controlled the body, especially an excess of . Alternatively it was seen as . In the 18th century, a wide variety of medical explanations were proposed, including a lack of sexual activity, too much sexual activity, physical injuries to the breast, curdled breast milk, and various forms of lymphatic blockages, either internal or due to restrictive clothing. In the 19th century, the Scottish surgeon John Rodman said that fear of cancer caused cancer, and that this anxiety, learned by example from the mother, accounted for breast cancer's tendency to run in families.
Although breast cancer was known in ancient times, it was uncommon until the 19th century, when improvements in sanitation and control of deadly resulted in dramatic increases in lifespan. Previously, most women had died too young to have developed breast cancer. Additionally, early and frequent childbearing and breastfeeding probably reduced the rate of breast cancer development in those women who did survive to middle age.
Because ancient medicine believed that the cause was systemic, rather than local, and because surgery carried a high mortality rate, the preferred treatments tended to be pharmacological rather than surgical. Herbal and mineral preparations, especially involving the poison , were relatively common.
Mastectomy for breast cancer was performed at least as early as AD 548, when it was proposed by the court physician to Theodora. It was not until doctors achieved greater understanding of the circulatory system in the 17th century that they could link breast cancer's spread to the in the armpit. The French surgeon (1674–1750) performed total mastectomies which included removing the , as he recognized that this reduced recurrence. Petit's work was built on by another French surgeon, (1737–1804), who additionally removed the underlying the breast, as he judged that this greatly improved the prognosis. The Scottish surgeon (1749–1806) advocated removal of the entire breast, even when only a portion was affected.
Their successful work was carried on by who started performing in 1882, helped greatly by advances in general surgical technology, such as and . The Halsted radical mastectomy often involved removing both breasts, associated lymph nodes, and the underlying chest muscles. This often led to long-term pain and disability, but was seen as necessary in order to prevent the cancer from recurring. Before the advent of the Halsted radical mastectomy, 20-year survival rates were only 10%; Halsted's surgery raised that rate to 50%. Extending Halsted's work, promoted superradical mastectomies, taking even more tissue, until 1963, when the ten-year survival rates proved equal to the less-damaging radical mastectomy.
Radical mastectomies remained the standard of care in America until the 1970s, but in Europe, breast-sparing procedures, often followed by radiation therapy, were generally adopted in the 1950s. One reason for this striking difference in approach may be the structure of the medical professions: European surgeons, descended from the , were held in less esteem than ; in America, the surgeon was the king of the medical profession. Additionally, there were far more European women surgeons: Less than one percent of American surgical oncologists were female, but some European breast cancer wards boasted a medical staff that was half female. American health insurance companies also paid surgeons more to perform radical mastectomies than they did to perform more intricate breast-sparing surgeries.
Breast cancer staging systems were developed in the 1920s and 1930s.
During the 1970s, a new understanding of led to perceiving cancer as a systemic illness as well as a localized one, and more sparing procedures were developed that proved equally effective. Modern developed after .
Prominent women who died of breast cancer include , the mother of Louis XIV of France; , mother of George, and , the environmentalist.
The first study on breast cancer epidemiology was done by , who published a comparative study in 1926 of 500 breast cancer cases and 500 controls of the same background and lifestyle for the British Ministry of Health.
In the 1980s and 1990s, thousands of women who had successfully completed standard treatment then demanded and received high-dose , thinking this would lead to better long-term survival. However, it proved completely ineffective, and 15–20% of women died because of the brutal treatment.
The 1995 reports from the and the 2002 conclusions of the trial conclusively proved that significantly increased the incidence of breast cancer.
Society and culture
See also: and
Before the 20th century, breast cancer was feared and discussed in hushed tones, as if it were shameful. As little could be safely done with primitive surgical techniques, women tended to suffer silently rather than seeking care. When surgery advanced, and long-term survival rates improved, women began of the disease and the possibility of successful treatment. The "Women's Field Army", run by the American Society for the Control of Cancer (later the ) during the 1930s and 1940s was one of the first organized campaigns. In 1952, the first peer-to-peer , called "Reach to Recovery", began providing post-mastectomy, in-hospital visits from women who had survived breast cancer.
The of the 1980s and 1990s developed out of the larger and women's health movement of the 20th century. This series of political and educational campaigns, partly inspired by the politically and socially effective awareness campaigns, resulted in the widespread acceptance of second opinions before surgery, less invasive surgical procedures, support groups, and other advances in care.
Main article:The is a symbol to show support for breast cancer awareness
A is the most prominent symbol of breast cancer awareness. Pink ribbons, which can be made inexpensively, are sometimes sold as fundraisers, much like . They may be worn to honor those who have been diagnosed with breast cancer, or to identify products that the manufacturer would like to sell to consumers that are interested in breast cancer.
The pink ribbon is associated with individual generosity, faith in scientific progress, and a "can-do" attitude. It encourages consumers to focus on the emotionally appealing ultimate vision of a cure for breast cancer, rather than on the fraught path between current knowledge and any future cures.
Wearing or displaying a pink ribbon has been criticized by the opponents of this practice as a kind of , because it has no practical positive effect. It has also been criticized as , because some people wear the pink ribbon to show good will towards women with breast cancer, but then oppose these women's practical goals, like and anti-pollution legislation. Critics say that the feel-good nature of pink ribbons and pink consumption distracts society from the lack of progress on preventing and curing breast cancer. It is also criticized for reinforcing gender stereotypes and women and their breasts. launched the "Think Before You Pink" campaign, and said that businesses have co-opted the pink campaign to promote products that cause breast cancer, such as alcoholic beverages.
Breast cancer culture
Breast cancer culture, also known as pink ribbon culture, is the set of activities, attitudes, and values that surround and shape breast cancer in public. The dominant values are selflessness, cheerfulness, unity, and optimism.
In breast cancer culture, breast cancer therapy is viewed as a rather than a disease. To fit into this mold, the woman with breast cancer needs to normalize and feminize her appearance, and minimize the disruption that her health issues cause anyone else. Anger, sadness, and negativity must be silenced.
As with most cultural models, people who conform to the model are given social status, in this case as . Women who reject the model are shunned, punished and shamed.
The culture is criticized for treating adult women like little girls, as evidenced by "baby" toys such as pink given to adult women.
The primary purposes or goals of breast cancer culture are to maintain breast cancer's dominance as the pre-eminent women's health issue, to promote the appearance that society is doing something effective about breast cancer, and to sustain and expand the social, political, and financial power of breast cancer activists.
Compared to other diseases or other cancers, breast cancer receives a proportionately greater share of resources and attention. In 2001 MP , chairman of the all party group on cancer stated "The treatment has been skewed by the , there is no doubt about that. Breast cancer sufferers get better treatment in terms of bed spaces, facilities and doctors and nurses."Breast cancer also receives significantly more media coverage than other, equally prevalent cancers, with a study by Prostate Coalition showing 2.6 breast cancer stories for each one covering . Ultimately there is a concern that favoring sufferers of breast cancer with disproportionate funding and research on their behalf may well be costing lives elsewhere. Partly because of its relatively high prevalence and long-term survival rates, research is biased towards breast cancer. Some subjects, such as , have been studied little except in women with breast cancer.
One result of breast cancer's high visibility is that statistical results can sometimes be misinterpreted, such as the claim that one in eight women will be diagnosed with breast cancer during their lives—a claim that depends on the unrealistic assumption that no woman will die of any other disease before the age of 95. This obscures the reality, which is that about ten times as many women will die from or than from breast cancer.
The emphasis on breast cancer screening may be harming women by subjecting them to unnecessary radiation, biopsies, and surgery. One-third of diagnosed breast cancers might recede on their own. Screening mammography efficiently finds non-life-threatening, asymptomatic breast cancers and pre-cancers, even while overlooking serious cancers. According to H. Gilbert Welch of the , research on screening mammography has taken the "brain-dead approach that says the best test is the one that finds the most cancers" rather than the one that finds dangerous cancers.
Breast cancers occur during pregnancy at the same rate as breast cancers in non-pregnant women of the same age. Breast cancer then becomes more common in the 5 or 10 years following pregnancy but then becomes less common than among the general population. These cancers are known as postpartum breast cancer and have worse outcomes including an increased risk of distant spread of disease and mortality. Other cancers found during or shortly after pregnancy appear at approximately the same rate as other cancers in women of a similar age.
Diagnosing new cancer in a pregnant woman is difficult, in part because any symptoms are commonly assumed to be a normal discomfort associated with pregnancy. As a result, cancer is typically discovered at a somewhat later stage than average in many pregnant or recently pregnant women. Some imaging procedures, such as (magnetic resonance imaging), , ultrasounds, and with fetal shielding are considered safe during pregnancy; some others, such as are not.
Treatment is generally the same as for non-pregnant women. However, radiation is normally avoided during pregnancy, especially if the fetal dose might exceed 100 cGy. In some cases, some or all treatments are postponed until after birth if the cancer is diagnosed late in the pregnancy. Early deliveries to speed the start of treatment are not uncommon. Surgery is generally considered safe during pregnancy, but some other treatments, especially certain chemotherapy drugs given during the , increase the risk of and pregnancy loss (spontaneous abortions and stillbirths). Elective are not required and do not improve the likelihood of the mother surviving or being cured.
Radiation treatments may interfere with the mother's ability to breastfeed her baby because it reduces the ability of that breast to produce milk and increases the risk of . Also, when chemotherapy is being given after birth, many of the drugs pass through breast milk to the baby, which could harm the baby.
Regarding future pregnancy among breast , there is often fear of . On the other hand, many still regard pregnancy and parenthood to represent normalcy, happiness and life fulfillment.
In breast cancer survivors, non-hormonal methods should be used as first-line options. -based methods such as , or have a poorly investigated but possible increased risk of cancer recurrence, but may be used if positive effects outweigh this possible risk.
Menopausal hormone replacement
In breast cancer survivors, it is recommended to first consider non-hormonal options for effects, such as or (SERMs) for osteoporosis, and for local symptoms. Observational studies of systemic after breast cancer are generally reassuring. If hormone replacement is necessary after breast cancer, estrogen-only therapy or estrogen therapy with an may be safer options than combined systemic therapy.
Treatments are being evaluated in trials. This includes individual drugs, combinations of drugs, and surgical and radiation techniques Investigations include new types of ,, oncolytic virotherapy, and immunotherapy.
The latest research is reported annually at scientific meetings such as that of the , San Antonio Breast Cancer Symposium, and the St. Gallen Oncology Conference in St. Gallen, Switzerland. These studies are reviewed by professional societies and other organizations, and formulated into guidelines for specific treatment groups and risk category.
, a retinoid, is also being studied as a way to reduce the risk of breast cancer (retinoids are medications related to ).
As of 2014 is being studied to see if it could be a substitute for a lumpectomy in small cancers. There is tentative evidence in those with tumors less than 2 centimeters. It may also be used in those in who surgery is not possible. Another review states that cryoablation looks promising for early breast cancer of small size.
Breast cancer cell lines
A considerable part of the current knowledge on breast carcinomas is based on and studies performed with derived from breast cancers. These provide an unlimited source of homogenous self-replicating material, free of contaminating cells, and often easily cultured in simple standard . The first breast cancer cell line described, , was established in 1958. Since then, and despite sustained work in this area, the number of permanent lines obtained has been strikingly low (about 100). Indeed, attempts to culture breast cancer cell lines from primary tumors have been largely unsuccessful. This poor efficiency was often due to technical difficulties associated with the extraction of viable tumor cells from their surrounding stroma. Most of the available breast cancer cell lines issued from metastatic tumors, mainly from . Effusions provided generally large numbers of dissociated, viable tumor cells with little or no contamination by and other tumor stroma cells. Many of the currently used BCC lines were established in the late 1970s. A very few of them, namely , , and , account for more than two-thirds of all abstracts reporting studies on mentioned breast cancer cell lines, as concluded from a -based survey.
transcription factors are implicated in breast cancer, more specifically in the process of cell motility at the basis of metastasis formation. Indeed, NFAT1 (NFATC2) and NFAT5 are pro-invasive and pro-migratory in breast carcinoma and NFAT3 (NFATc4) is an inhibitor of cell motility. NFAT1 regulates the expression of the TWEAKR and its ligand TWEAK with the Lipocalin 2 to increase breast cancer cell invasion and NFAT3 inhibits Lipocalin 2 expression to blunt the cell invasion.
Clinically, the most useful metabolic markers in breast cancer are the estrogen and progesterone receptors that are used to predict response to hormone therapy. New or potentially new markers for breast cancer include BRCA1 and BRCA2 to identify people at high risk of developing breast cancer, , and , for predicting response to therapeutic regimens, and , PA1-1 and for assessing prognosis.
- ^ . NCI. 23 May 2014. from the original on 5 July 2014. Retrieved 29 June 2014.
- ^ World Cancer Report 2014. World Health Organization. 2014. pp. Chapter 5.2. .
- . . 24 May 2007. Archived from on 27 November 2012.
- ^ . NCI. from the original on 3 July 2014. Retrieved 18 June 2014.
- ^ (PDF). Office for National Statistics. 29 October 2013. (PDF) from the original on 29 November 2014. Retrieved 29 June 2014.
- GBD 2015 Disease and Injury Incidence and Prevalence, Collaborators. (8 October 2016). . Lancet. 388 (10053): 1545–1602. :. . .
- GBD 2015 Mortality and Causes of Death, Collaborators. (8 October 2016). . Lancet. 388 (10053): 1459–1544. :. . .
- . NCI. from the original on 25 June 2014. Retrieved 29 June 2014.
- Saunders, Christobel; Jassal, Sunil (2009). (1. ed.). Oxford: Oxford University Press. p. Chapter 13. . from the original on 25 October 2015.
- ^ Gøtzsche PC, Jørgensen KJ (4 June 2013). "Screening for breast cancer with mammography". The Cochrane Database of Systematic Reviews. 6 (6): CD001877. :. .
- Nelson, HD; Tyne, K; Naik, A; Bougatsos, C; Chan, B; Nygren, P; Humphrey, L (November 2009). "Screening for Breast Cancer: Systematic Evidence Review Update for the US Preventive Services Task Force [Internet]". .
- ^ Siu, Albert L. (12 January 2016). "Screening for Breast Cancer: U.S. Preventive Services Task Force Recommendation Statement". Annals of Internal Medicine. 164 (4): 279–96. :. .
- (September 2013), , : an initiative of the , American College of Surgeons, from the original on 27 October 2013, retrieved 2 January 2013
- ^ . NCI. 26 June 2014. from the original on 5 July 2014. Retrieved 29 June 2014.
- ^ (PDF). . 2008. (PDF) from the original on 20 July 2011. Retrieved 26 February 2011.
- ^ World Cancer Report 2014. World Health Organization. 2014. pp. Chapter 1.1. .
- . . 2014. from the original on 4 July 2014. Retrieved 29 June 2014.
- ^ (February 2003). . from the original on 2 October 2011. Retrieved 5 February 2008.
- ^ American Cancer Society (2007). (PDF). Archived from (PDF) on 10 April 2007. Retrieved 26 April 2007.
- Watson M (2008). "Assessment of suspected cancer". InnoAiT. 1 (2): 94–107. :.
- (23 August 2006). . from the original on 12 February 2008. Retrieved 5 February 2008.
- (27 June 2005). . from the original on 10 April 2008. Retrieved 6 February 2008.
- answers.com. . from the original on 8 September 2010. Retrieved 10 August 2010.
- Lacroix M (December 2006). "Significance, detection and markers of disseminated breast cancer cells". . . 13 (4): 1033–67. :. .
- . Lippincott Williams & Wilkins. 2007. pp. 99–. .
- (February 2003). . from the original on 3 October 2011. Retrieved 5 February 2008.
- ^ Hayes,, James; Ricahrdson, Ann; Frampton, Chris (15 November 2013). "Population attributable risks for modifiable lifestyle factors and breast cancer in New Zealand women". IMJ. 43 (11): 1198–1204. :. .
- Reeder JG, Vogel VG (2008). "Breast cancer prevention". Cancer treatment and research. Cancer Treatment and Research. 141: 149–64. :. . .
- . Breast Cancer Care. from the original on 25 October 2013. Retrieved 22 October 2013.
- Collaborative Group on Hormonal Factors in Breast Cancer (August 2002). "Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries, including 50302 women with breast cancer and 96973 women without the disease". Lancet. 360 (9328): 187–95. :. .
- Yager JD, Davidson NE (2006). "Estrogen carcinogenesis in breast cancer". N Engl J Med. 354 (3): 270–82. :. .
- Mazzucco A, Santoro E, DeSoto, M, Hong Lee J (February 2009). . National Research Center for Women & Families.
- Light Pollution as new risk factor for human Breast and Prostate Cancers- Haim, Abraham; Portnov, Biris P., 2013,
- ^ Johnson KC, Miller AB, Collishaw NE, Palmer JR, Hammond SK, Salmon AG, Cantor KP, Miller MD, Boyd NF, Millar J, Turcotte F (Jan 2011). "Active smoking and secondhand smoke increase breast cancer risk: the report of the Canadian Expert Panel on Tobacco Smoke and Breast Cancer Risk (2009)". Tobacco control. 20 (1): e2. :. .
- Lee IM, Shiroma EJ, Lobelo F, Puska P, Blair SN, Katzmarzyk PT (1 July 2012). . The Lancet. 380 (9838): 219–29. :. . .
- Biswas A, Oh PI, Faulkner GE, Bajaj RR, Silver MA, Mitchell MS, Alter DA (2015). "Sedentary Time and Its Association With Risk for Disease Incidence, Mortality, and Hospitalization in Adults: A Systematic Review and Meta-analysis". Annals of Internal Medicine. 162 (2): 123–32. :. .
- Kahlenborn C, Modugno F, Potter DM, Severs WB (Oct 2006). "Oral contraceptive use as a risk factor for premenopausal breast cancer: a meta-analysis". Mayo Clinic Proceedings. 81 (10): 1290–302. :. .
- ^ Veljković M, Veljković S (Sep 2010). "[The risk of breast cervical, endometrial and ovarian cancer in oral contraceptive users]". Medicinski pregled. 63 (9–10): 657–61. :. .
- ^ Casey PM, Cerhan JR, Pruthi S (January 2008). . Mayo Clinic Proceedings. 83 (1): 86–90; quiz 90–1. :. .
- Iodice S, Barile M, Rotmensz N, Feroce I, Bonanni B, Radice P, Bernard L, Maisonneuve P, Gandini S (August 2010). "Oral contraceptive use and breast or ovarian cancer risk in BRCA1/2 carriers: a meta-analysis". European Journal of Cancer. 46 (12): 2275–84. :. .
- Gaffield ME, Culwell KR, Ravi A (October 2009). "Oral contraceptives and family history of breast cancer". Contraception. 80 (4): 372–80. :. .
- Yang L, Jacobsen KH (December 2008). . . 17 (10): 1635–45. :. .
- Russo J, Russo IH (1980). . Am J Pathol. 100 (2): 505–506. . . In contrast, abortion is associated with increased risk of carcinomas of the breast. The explanation for these epidemiologic findings is not known, but the parallelism between the DMBA-induced rat mammary carcinoma model and the human situation is striking. ... Abortion would interrupt this process, leaving in the gland undifferentiated structures like those observed in the rat mammary gland, which could render the gland again susceptible to carcinogenesis.
- Beral V, Bull D, Doll R, Peto R, Reeves G (27 March 2004). "Breast cancer and abortion: collaborative reanalysis of data from 53 epidemiological studies, including 83?000 women with breast cancer from 16 countries". Lancet. 363 (9414): 1007–16. :. .
- ^ Shield, Kevin D.; Soerjomataram, Isabelle; Rehm, Jürgen (June 2016). "Alcohol Use and Breast Cancer: A Critical Review". Alcoholism, Clinical and Experimental Research. 40 (6): 1166–1181. :. . . All levels of evidence showed a risk relationship between alcohol consumption and the risk of breast cancer, even at low levels of consumption.
- Blackburn GL, Wang KA (September 2007). "Dietary fat reduction and breast cancer outcome: results from the Women's Intervention Nutrition Study (WINS)". The American Journal of Clinical Nutrition. 86 (3): s878–81. .
- BBC report 13 March 2007 at the .
- Kaiser J (29 November 2013). "Cancer. Cholesterol forges link between obesity and breast cancer". Science. 342 (6162): 1028. :. .
- Aceves C, Anguiano B, Delgado G (April 2005). "Is iodine a gatekeeper of the integrity of the mammary gland?". Journal of Mammary Gland Biology and Neoplasia. 10 (2): 189–96. :. .
- Mourouti, N; Kontogianni, MD; Papavagelis, C; Panagiotakos, DB (February 2015). "Diet and breast cancer: a systematic review". International journal of food sciences and nutrition. 66 (1): 1–42. :. .
- Aubrey, Allison (1 February 2016). . . from the original on 1 February 2016. Retrieved 1 February 2016.
- ^ American Cancer Society (2005). (PDF). Archived from (PDF) on 13 June 2007. Retrieved 26 April 2007.
- Wang XS, Armstrong ME, Cairns BJ, Key TJ, Travis RC (March 2011). . Occupational Medicine. 61 (2): 78–89. :. . .
- Brody JG, Rudel RA, Michels KB, Moysich KB, Bernstein L, Attfield KR, Gray S (June 2007). "Environmental pollutants, diet, physical activity, body size, and breast cancer: where do we stand in research to identify opportunities for prevention?". Cancer. 109 (12 Suppl): 2627–34. :. .
- Hendrick RE (October 2010). "Radiation doses and cancer risks from breast imaging studies". Radiology. 257 (1): 246–53. :. .
- ^ Boris Pasche (2010). Cancer Genetics (Cancer Treatment and Research). Berlin: Springer. pp. 19–20. .
- ^ Gage M, Wattendorf D, Henry LR (1 April 2012). "Translational advances regarding hereditary breast cancer syndromes". Journal of surgical oncology. 105 (5): 444–51. :. .
- Colditz, Graham A.; Kaphingst, Kimberly A.; Hankinson, Susan E.; Rosner, Bernard (19 February 2012). . Breast Cancer Research and Treatment. 133 (3): 1097–1104. :. . . .
- Collaborative Group on Hormonal Factors in Breast Cancer (27 October 2001). "Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58,209 women with breast cancer and 101,986 women without the disease". Lancet. 358 (9291): 1389–99. :. .
- Nelson HD, Zakher B, Cantor A, Fu R, Griffin J, O'Meara ES, Buist DS, Kerlikowske K, van Ravesteyn NT, Trentham-Dietz A, Mandelblatt JS, Miglioretti DL (1 May 2012). . Annals of Internal Medicine. 156 (9): 635–48. :. . .
- Kolata, Gina (23 September 2012). . The New York Times. from the original on 24 September 2012. Retrieved 23 September 2012.
- . Archived from on 27 May 2010.
- . National Cancer Institute. from the original on 25 April 2015.
- Afonso N, Bouwman D (August 2008). . Eur. J. Cancer Prev. 17 (4): 312–6. :. .
- Anothaisintawee T, Wiratkapun C, Lerdsitthichai P, Kasamesup V, Wongwaisayawan S, Srinakarin J, Hirunpat S, Woodtichartpreecha P, Boonlikit S, Teerawattananon Y, Thakkinstian A (2013). "Risk factors of breast cancer: a systematic review and meta-analysis". Asian Pacific Journal of Public Health. 25 (5): 368–387. :. .
- Böhm I (2011). "Breast cancer in lupus". Breast. 20 (3): 288–90. :. .
- Adrian Lee; Carlos Arteaga (14 December 2009). (PDF). Sunday Morning Year-End Review. Archived from (PDF) on 13 August 2013.
- Cavalieri E, Chakravarti D, Guttenplan J, Hart E, Ingle J, Jankowiak R, Muti P, Rogan E, Russo J, Santen R, Sutter T (August 2006). "Catechol estrogen quinones as initiators of breast and other human cancers: implications for biomarkers of susceptibility and cancer prevention". Biochimica et Biophysica Acta. 1766 (1): 63–78. :. .
- Haslam SZ, Woodward TL (June 2003). . Breast Cancer Res. 5 (4): 208–15. :. . .
- Wiseman BS, Werb Z (May 2002). . Science. 296 (5570): 1046–9. :. . .
- Jardé T, Perrier S, Vasson MP, Caldefie-Chézet F (January 2011). "Molecular mechanisms of leptin and adiponectin in breast cancer". Eur. J. Cancer. 47 (1): 33–43. :. .
- Dunning AM, Healey CS, Pharoah PD, Teare MD, Ponder BA, Easton DF (October 1999). . Cancer Epidemiology, Biomarkers & Prevention. 8 (10): 843–54. .
- Begg CB, Haile RW, Borg A, Malone KE, Concannon P, Thomas DC, Langholz B, Bernstein L, Olsen JH, Lynch CF, Anton-Culver H, Capanu M, Liang X, Hummer AJ, Sima C, Bernstein JL (January 2008). . JAMA. 299 (2): 194–201. :. . .
- Patel KJ, Yu VP, Lee H, Corcoran A, Thistlethwaite FC, Evans MJ, Colledge WH, Friedman LS, Ponder BA, Venkitaraman AR (February 1998). "Involvement of Brca2 in DNA repair". Mol. Cell. 1 (3): 347–57. :. .
- Marietta C, Thompson LH, Lamerdin JE, Brooks PJ (May 2009). . Mutat. Res. 664 (1–2): 77–83. :. . .
- Theruvathu JA, Jaruga P, Nath RG, Dizdaroglu M, Brooks PJ (2005). . Nucleic Acids Res. 33 (11): 3513–20. :. . .
- Wooster R, Weber BL (June 2003). "Breast and ovarian cancer". N. Engl. J. Med. 348 (23): 2339–47. :. .
- Levin B, Lech D, Friedenson B (2012). . Mol. Med. 18 (9): 1327–37. :. . .
- Kouros-Mehr H, Kim JW, Bechis SK, Werb Z (Apr 2008). . Current Opinion in Cell Biology. 20 (2): 164–70. :. . .
- Saslow D, Hannan J, Osuch J, Alciati MH, Baines C, Barton M, Bobo JK, Coleman C, Dolan M, Gaumer G, Kopans D, Kutner S, Lane DS, Lawson H, Meissner H, Moorman C, Pennypacker H, Pierce P, Sciandra E, Smith R, Coates R (2004). "Clinical breast examination: practical recommendations for optimizing performance and reporting". CA: A Cancer Journal for Clinicians. 54 (6): 327–344. :. .
- Yu YH, Liang C, Yuan XZ (2010). "Diagnostic value of vacuum-assisted breast biopsy for breast carcinoma: a meta-analysis and systematic review". Breast cancer research and treatment. 120 (2): 469–79. :. .
- 10 November 2011 at the ., Ch. 253, Breast Cancer.
- , (PDF), Choosing Wisely: an initiative of the , , archived from (PDF) on 31 July 2012, retrieved 14 August 2012
- Carlson RW, Allred DC, Anderson BO, Burstein HJ, Carter WB, Edge SB, Erban JK, Farrar WB, Goldstein LJ, Gradishar WJ, Hayes DF, Hudis CA, Jahanzeb M, Kiel K, Ljung BM, Marcom PK, Mayer IA, McCormick B, Nabell LM, Pierce LJ, Reed EC, Smith ML, Somlo G, Theriault RL, Topham NS, Ward JH, Winer EP, Wolff AC (2009). "Breast cancer. Clinical practice guidelines in oncology". Journal of the National Comprehensive Cancer Network : JNCCN. 7 (2): 122–192. .
- Kumar, Vinay; Abul Abbas (2010). Robbins and Cotran Pathologic Basis of Disease. Philadelphia: Saunders, an imprint of Elsevier inc. p. 1090. .
- Sotiriou C, Pusztai L (February 2009). "Gene-expression signatures in breast cancer". N. Engl. J. Med. 360 (8): 790–800. :. .
- Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N (October 2005). "Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer". N. Engl. J. Med. 353 (16): 1673–84. :. .
- ^ . www.cancer.org. Retrieved 2018-04-18.
- Eliassen AH, Hankinson SE, Rosner B, Holmes MD, Willett WC (October 2010). . Arch. Intern. Med. 170 (19): 1758–64. :. . .
- Kyu, Hmwe H; Bachman, Victoria F; Alexander, Lily T; Mumford, John Everett; Afshin, Ashkan; Estep, Kara; Veerman, J Lennert; Delwiche, Kristen; Iannarone, Marissa L; Moyer, Madeline L; Cercy, Kelly; Vos, Theo; Murray, Christopher J L; Forouzanfar, Mohammad H (9 August 2016). . BMJ. 354: i3857. :. . .
- Song, Jung-Kook; Bae, Jong-Myon (1 March 2013). . Journal of Breast Cancer. 16 (1): 72–76. :. . . .
- Zheng JS, Hu XJ, Zhao YM, Yang J, Li D (2013). "Intake of fish and marine n-3 polyunsaturated fatty acids and risk of breast cancer: meta-analysis of data from 21 independent prospective cohort studies". BMJ. 346: f3706. :. .
- Wu, AH; Yu, MC; Tseng, CC; Pike, MC (15 January 2008). . British Journal of Cancer. 98 (1): 9–14. :. . .
- Hartmann LC, Schaid DJ, Woods JE, Crotty TP, Myers JL, Arnold PG, Petty PM, Sellers TA, Johnson JL, McDonnell SK, Frost MH, Jenkins RB (1999). "Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer". N Engl J Med. 340 (2): 77–84. :. .
- Meijers-Heijboer H, van Geel B, van Putten WL, Henzen-Logmans SC, Seynaeve C, Menke-Pluymers MB, Bartels CC, Verhoog LC, van den Ouweland AM, Niermeijer MF, Brekelmans CT, Klijn JG (2001). "Breast cancer after prophylactic bilateral mastectomy in women with BRCA1 and BRCA2 mutations". N Engl J Med. 345 (3): 159–164. :. .
- ^ Lostumbo, L; Carbine, NE; Wallace, J (10 November 2010). "Prophylactic mastectomy for the prevention of breast cancer". The Cochrane Database of Systematic Reviews (11): CD002748. :. .
- Moyer, Virginia A (24 December 2013). "Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer in Women: U.S. Preventive Services Task Force Recommendation Statement". Annals of Internal Medicine. 160 (4): 271–281. :.
- ^ Nelson HD, Smith ME, Griffin JC, Fu R (16 April 2013). "Use of medications to reduce risk for primary breast cancer: a systematic review for the U.S. Preventive Services Task Force.". Annals of Internal Medicine. 158 (8): 604–14. :. .
- Cuzick J, Sestak I, Bonanni B, Costantino JP, Cummings S, DeCensi A, Dowsett M, Forbes JF, Ford L, LaCroix AZ, Mershon J, Mitlak BH, Powles T, Veronesi U, Vogel V, Wickerham DL (25 May 2013). . Lancet. 381 (9880): 1827–34. :. . .
- Moyer VA (24 September 2013). "Medications for Risk Reduction of Primary Breast Cancer in Women: U.S. Preventive Services Task Force Recommendation Statement". Annals of Internal Medicine. 159 (10): 698–708. :. .
- Cuzick J, Sestak I, Bonanni B, Costantino JP, Cummings S, DeCensi A, Dowsett M, Forbes JF, Ford L, LaCroix AZ, Mershon J, Mitlak BH, Powles T, Veronesi U, Vogel V, Wickerham DL (31 March 2013). . The Lancet. 381 (9880): 1827–34. :. . .
- . Centers for Disease Control and Prevention. from the original on 18 November 2015. Retrieved 17 November 2015.
- . US Preventative Services Task Force. December 2009. from the original on 2 January 2013. Retrieved 24 December 2012.
- Kösters JP, Gøtzsche PC (2003). "Cochrane Database of Systematic Reviews". Cochrane Database Syst Rev (2): CD003373. :. .
- . WebMD. from the original on 28 December 2012. Retrieved 24 December 2012.
- Biesheuvel C, Weigel S, Heindel W (2011). . Breast care (Basel, Switzerland). 6 (2): 104–109. :. . .
- Tonelli M, Connor Gorber S, Joffres M, Dickinson J, Singh H, Lewin G, Birtwhistle R, Fitzpatrick-Lewis D, Hodgson N, Ciliska D, Gauld M, Liu YY (22 November 2011). . Canadian Medical Association Journal. 183 (17): 1991–2001. :. . .
- . United States Preventive Services Task Force. Archived from on 16 June 2013.
- Welch HG, Passow HJ (30 December 2013). "Quantifying the Benefits and Harms of Screening Mammography". JAMA Internal Medicine. 174 (3): 448–54. :. .
- . Cochrane Nordic. 27 August 2015. from the original on 29 October 2015. Retrieved 15 October 2015.
- US Preventive Services Task Force (17 November 2009). . Annals of Internal Medicine. 151 (10): 716–26, W–236. :. . from the original on 2 January 2013.
- Saini KS, Taylor C, Ramirez AJ, Palmieri C, Gunnarsson U, Schmoll HJ, Dolci SM, Ghenne C, Metzger-Filho O, Skrzypski M, Paesmans M, Ameye L, Piccart-Gebhart MJ, de Azambuja E (August 2011). "Role of the multidisciplinary team in breast cancer management: results from a large international survey involving 39 countries". Annals of Oncology. 23 (4): 853–9. :. .
- Holmes MD, Chen WY, Li L, Hertzmark E, Spiegelman D, Hankinson SE (2010). . Journal of Clinical Oncology. 28 (9): 1467–72. :. . .
- Ting Bao; Michelle A Rudek (2011). . European Oncology & Haematology. 7 (2): 106–8. from the original on 19 April 2012.
- Burstein, HJ; Temin, S; Anderson, H; Buchholz, TA; Davidson, NE; Gelmon, KE; Giordano, SH; Hudis, CA; Rowden, D; Solky, AJ; Stearns, V; Winer, EP; Griggs, JJ (27 May 2014). . Journal of Clinical Oncology. 32 (21): 2255–69. :. . .
- Early Breast Cancer Trialists' Collaborative Group (23 July 2015). "Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials". The Lancet. 386 (10001): 1341–1352. :. .
- Petit T, Dufour P, Tannock I (June 2011). "A critical evaluation of the role of aromatase inhibitors as adjuvant therapy for postmenopausal women with breast cancer". Endocr. Relat. Cancer. 18 (3): R79–89. :. .
- . www.uptodate.com. from the original on 4 September 2017. Retrieved 4 September 2017.
- Jahanzeb M (August 2008). "Adjuvant trastuzumab therapy for HER2-positive breast cancer". Clin. Breast Cancer. 8 (4): 324–33. :. .
- . from the original on 26 October 2009. Retrieved 17 November 2015.
- . Herceptin.com. from the original on 6 April 2010. Retrieved 8 May 2010.
- Massarut S, Baldassare G, Belleti B, Reccanello S, D'Andrea S, Ezio C, Perin T, Roncadin M, Vaidya JS (2006). . J Clin Oncol. 24 (18S): 10611. from the original on 12 January 2012.
- Belletti B, Vaidya JS, D'Andrea S, Entschladen F, Roncadin M, Lovat F, Berton S, Perin T, Candiani E, Reccanello S, Veronesi A, Canzonieri V, Trovò MG, Zaenker KS, Colombatti A, Baldassarre G, Massarut S (March 2008). "Targeted intraoperative radiotherapy impairs the stimulation of breast cancer cell proliferation and invasion caused by surgical wounding". Clin. Cancer Res. 14 (5): 1325–32. :. .
- . Breastcancer.org. from the original on 17 November 2015. Retrieved 17 November 2015.
- . Merck.com. from the original on 10 November 2011. Retrieved 8 May 2010.
- (PDF). National Cancer Institute and the National Research Center for Women & Families. August 2004. Archived from (PDF) on 13 August 2013.
- . Merck.com. from the original on 10 November 2011. Retrieved 14 November 2010.
- Elston CW, Ellis IO (November 1991). "Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up". Histopathology. 19 (5): 403–10. :. .
- Peppercorn J (2009). . Oncology. 23 (6). from the original on 16 June 2009.
- Pritchard KI (2009). . Oncology. 23 (1). from the original on 5 July 2009.
- . World Health Organization. 2009. from the original on 11 November 2009. Retrieved 11 November 2009.
- ^ McGuire, A; Brown, JA; Malone, C; McLaughlin, R; Kerin, MJ (22 May 2015). . Cancers. 7 (2): 908–29. :. . .
- ^ . . 2008. from the original on 31 December 2011. Retrieved 26 February 2011. (cancer statistics often exclude non-melanoma skin cancers such as , which are common but rarely fatal)
- . World Health Organization. Archived from on 6 September 2015.
- World Cancer Report 2014. International Agency for Research on Cancer, World Health Organization. 2014. .
- 20 October 2008 at the .
- Laurance, Jeremy (29 September 2006). . . London. Archived from on 25 April 2008. Retrieved 9 October 2006.
- . Imaginis Corporation. 2006. from the original on 24 October 2006. Retrieved 9 October 2006.
- 10 September 2009 at the . WebMD. Retrieved 9 September 2009
- 5 November 2013 at the . Office for National Statistics, 2013
- , U.S. National Cancer Institute, accessed February 16, 2018
- ^ Olson, James Stuart (2002). Bathsheba's breast: women, cancer & history. Baltimore: The Johns Hopkins University Press. pp. 9–13. .
- ^ . Reuters. 24 March 2015. from the original on 27 March 2015. Retrieved 25 March 2015.
- . American Cancer Society. 25 March 2002. Archived from on 9 October 2006. Retrieved 9 October 2006.
- ^ , pp. 32–33
- Yalom, Marilyn (1997). A history of the breast. New York: Alfred A. Knopf. p. 234. .
- ^ Aronowitz, Robert A. (2007). Unnatural history: breast cancer and American society. Cambridge, UK: Cambridge University Press. pp. 22–24. .
- Faguet, Guy (2015). "Chapter 2: An Historical Overview: From Prehistory to WWII. From Medieval Europe to World War II". The Conquest of Cancer: A Distant Goal. p. 24. .
- Kaartinen, Marjo (2013). "Chapter 2: "But Sad Resources": Treating Cancer in the Eighteenth Century". Breast cancer in the eighteenth century. London: Pickering & Chatto. p. 53. .
- Macintyre, IM (June 2011). "Scientific surgeon of the Enlightenment or 'plagiarist in everything': a reappraisal of Benjamin Bell (1749-1806)". The journal of the Royal College of Physicians of Edinburgh. 41 (2): 174–81. :. .
- ^ , pp. 102–6
- , p. 1
- Marc Lacroix (2011). A Concise History of Breast Cancer. USA: Nova Science Publishers. pp. 59–68. .
- , pp. 26,28,229
- Alfredo Morabia (2004). . Boston: Birkhauser. pp. 301–302. . Retrieved 31 December 2007.
- ^ Sulik, Gayle A. (2010). Pink Ribbon Blues: How Breast Cancer Culture Undermines Women's Health. USA: Oxford University Press. pp. 200–3. . .
- , pp. 37–38
- , p. 4
- Bob Riter. . Cancer Resource Center of the Finger Lakes. Archived from on 23 June 2013. Retrieved 29 June 2013.
- , pp. 27–72
- , pp. 359–361
- , pp. 366–8
- Landeman, Anne (11 June 2008). . . from the original on 5 June 2011.
- , pp. 365–6
- , pp. 372–4
- 12 October 2010 at the . 9 October 2010, Angela Mulholland, CTV.ca News
- ^ Ehrenreich, Barbara (November 2001). . . Archived from on 20 November 2010.
- , p. 57
- ^ (7 October 2001). . . London. from the original on 26 December 2016.
- Arnst, Catherine (13 June 2007). . . . from the original on 6 August 2011.
- , pp. 199–200
- Ave, Melanie (10 October 2006). . . from the original on 24 August 2009.
- ^ Aschwanden, Christie (17 August 2009). . . from the original on 4 December 2010.
- Azim HA, Jr; Santoro, L; Russell-Edu, W; Pentheroudakis, G; Pavlidis, N; Peccatori, FA (November 2012). "Prognosis of pregnancy-associated breast cancer: a meta-analysis of 30 studies". Cancer treatment reviews. 38 (7): 834–42. :. .
- Schedin, P (April 2006). "Pregnancy-associated breast cancer and metastasis". Nature Reviews. Cancer. 6 (4): 281–91. :. .
- ^ Connie Henke Yarbro; Debra Wujcik; Barbara Holmes Gobel, eds. (2011). Cancer nursing: principles and practice (7 ed.). Jones & Bartlett Publishers. pp. 901–905. .
- ^ Gonçalves V, Sehovic I, Quinn G (2013). . Human Reproduction Update. 20 (2): 279–92. :. . .
- McNaught J, Reid RL, Provencher DM, et al. (July 2006). "Progesterone-only and non-hormonal contraception in the breast cancer survivor: Joint Review and Committee Opinion of the Society of Obstetricians and Gynaecologists of Canada and the Society of Gynecologic Oncologists of Canada". J Obstet Gynaecol Can. 28 (7): 616–39. :. .
- , from the . College Statement C-Gyn 15. 1st Endorsed: February 2003. Current: November 2011. Review: November 2014
- Venur, Vyshak Alva; Leone, José Pablo (13 September 2016). . International Journal of Molecular Sciences. 17 (9): 1543. :. . . from the original on 7 March 2017.
- Suryawanshi, Yogesh R.; Zhang, Tiantian; Essani, Karim (9 February 2017). . Medical Oncology. 34 (3): 43. :. . .
- Yu, Lin-Yu; Tang, Jie; Zhang, Cong-Min; Zeng, Wen-Jing; Yan, Han; Li, Mu-Peng; Chen, Xiao-Ping (12 January 2017). . International Journal of Environmental Research and Public Health. 14 (1): 68. :. . . from the original on 7 March 2017.
- 16 May 2010 at the . Abstracts, newsletters, and other reports of the meeting.
- Goldhirsch A, Ingle JN, Gelber RD, Coates AS, Thürlimann B, Senn HJ (August 2009). . Annals of Oncology. 20 (8): 1319–29. :. . .
- . Cancer. from the original on 12 November 2015. Retrieved 17 November 2015.
- . hindawi. from the original on 17 November 2015. Retrieved 17 November 2015.
- Sabel, MS (July 2014). "Nonsurgical ablation of breast cancer: future options for small breast tumors". Surgical oncology clinics of North America. 23 (3): 593–608. :. .
- ^ Roubidoux, MA; Yang, W; Stafford, RJ (March 2014). "Image-guided ablation in breast cancer treatment". Techniques in vascular and interventional radiology. 17 (1): 49–54. :. .
- Fornage, Bruno D; Hwang, Rosa F (August 2014). "Current Status of Imaging-Guided Percutaneous Ablation of Breast Cancer". American Journal of Roentgenology. 203 (2): 442–448. :.
- Jauliac S, López-Rodriguez C, Shaw LM, Brown LF, Rao A, Toker A (July 2002). "The role of NFAT transcription factors in integrin-mediated carcinoma invasion". Nature Cell Biology. 4 (7): 540–4. :. .
- Yoeli-Lerner M, Yiu GK, Rabinovitz I, Erhardt P, Jauliac S, Toker A (23 November 2005). "Akt blocks breast cancer cell motility and invasion through the transcription factor NFAT". Molecular Cell. 20 (4): 539–50. :. .
- ^ Fougère M, Gaudineau B, Barbier J, Guaddachi F, Feugeas JP, Auboeuf D, Jauliac S (15 April 2010). "NFAT3 transcription factor inhibits breast cancer cell motility by targeting the Lipocalin 2 gene". Oncogene. 29 (15): 2292–301. :. .
- Gaudineau B, Fougère M, Guaddachi F, Lemoine F, de la Grange P, Jauliac S (1 October 2012). "Lipocalin 2 (LCN2), the TNF-like receptor TWEAKR and its ligand TWEAK act downstream of NFAT1 to regulate breast cancer cell invasion". Journal of Cell Science. 125 (19): 4475–4486. :. .
- Duffy MJ (2001). "Biochemical markers in breast cancer: which ones are clinically useful?". Clin Biochem. 34 (5): 347–52. :. .
Hot actress indian photos
Debbie clemens sports illustrated photo
Tia and tamera mowry parents photos
Change cover photo facebook album
Foto hot mayang sari