Breast Cancer

Breast cancer
Classification and external resources

Mammograms showing a normal breast (left) and a cancerous breast (right).
10 C50
9 174175,V10.3
OMIM 114480
DiseasesDB 1598
MedlinePlus 000913
eMedicine med/2808 med/3287 radio/115 plastic/521
MeSH D001943

Breast cancer is a type of [2]

The size, stage, rate of growth, and other characteristics of a breast cancer determine the kinds of treatment. Treatment may include progesterone, which makes it possible to treat them by blocking the effects of these hormones.

Worldwide, breast cancer accounts for 22.9% of all cancers (excluding non-melanoma [8]

Prognosis and survival rates for breast cancer vary greatly depending on the cancer type, stage, treatment, and geographical location of the patient. Survival rates in the [9] In developing countries, however, survival rates are much poorer.

Contents

[edit] Signs and symptoms

Early signs of breast cancer

Breast cancer showing an inverted nipple, lump and skin dimpling.

The first noticeable [10] 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.[13]

Inflammatory breast cancer 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;[10] the absence of a discernible lump delays detection dangerously.

Another reported symptom complex of breast cancer is Paget’s disease of the breast. This syndrome presents as eczematoid skin changes such as redness and mild flaking of the nipple skin. As Paget’s 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 also have a lump in the breast.[14]

In rare cases, what initially appears as a fibroadenoma (hard movable lump) could in fact be a phyllodes tumor. 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.[15]

Occasionally, breast cancer presents as [17]

Most symptoms of breast disorders, including most lumps, do not turn out to represent underlying breast cancer. Less than 20% of lumps for example are cancer[19]

[edit] Risk factors

The primary risk factors for breast cancer are female sex and older age.[23] diet and obesity.

[edit] Lifestyle

[25]

The association between [33]

There is a relationship between diet and breast cancer including an increased risk with a high fat diet,[37]

Other risk factors include [42]

[edit] Genetics

Some genetic susceptibility probably plays a role in most cases.[46]

In less than 5% of cases, genetics plays a more significant role.[47]

[edit] Medical conditions

Certain breast changes: citation needed]

[edit] Pathophysiology

Overview of signal transduction pathways involved in apoptosis. Mutations leading to loss of apoptosis can lead to tumorigenesis.

Breast cancer, like other cancers, occurs because of an interaction between the environment and a defective gene. 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 mutations destroy their ability to stop dividing, to attach to other cells and to stay where they belong.

Normal cells will commit cell suicide (apoptosis) 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 PI3K/AKT pathway; another is the RAS/MEK/ERK 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 PTEN protein turns off the PI3K/AKT pathway when the cell is ready for cell suicide. 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.[48]

Mutations that can lead to breast cancer have been experimentally linked to estrogen exposure.[49]

Failure of [53]

In the United States, 10 to 20 percent of patients with breast cancer and patients with ovarian cancer have a first- or second-degree relative with one of these diseases. The familial tendency to develop these cancers is called [59] About half of hereditary breast–ovarian cancer syndromes involve unknown genes.

[edit] Diagnosis

Most types of breast cancer are easy to diagnose by microscopic analysis of the biopsy. There are however, rarer types of breast cancer that require specialized lab exams.

While screening techniques are useful in determining the possibility of cancer, a further testing is necessary to confirm whether a lump detected on screening is cancer, as opposed to a benign alternative such as a simple cyst.

Very often the results of noninvasive examination, mammography and additional tests that are performed in special circumstances such as ultrasound or MR imaging are sufficient to warrant excisional biopsy as the definitive diagnostic and curative method.

Both mammography and clinical breast exam, also used for screening, can indicate an approximate likelihood that a lump is cancer, and may also detect some other lesions.[60] When the tests are inconclusive Fine Needle Aspiration and Cytology (FNAC) may be used which is a confirmatory test. FNAC may be done in a GP’s office using local anaesthetic if required, involves attempting to extract a small portion of fluid from the lump. 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, these three tools can be used to diagnose breast cancer with a good degree of accuracy.

Other options for biopsy include core biopsy, where a section of the breast lump is removed, and an excisional biopsy, where the entire lump is removed.

In addition vacuum-assisted breast biopsy (VAB) may help diagnose breast cancer among patients with a mammographically detected breast in women.[61]

[edit] Classification

Breast cancers are classified by several grading systems. Each of these influences the prognosis 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 [62]
  • Grade. Grading 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. lymph 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:

  • Receptor status. Breast cancer cells have receptors on their surface and in their cytoplasm and nucleus. Chemical messengers such as hormones bind to receptors, and this causes changes in the cell. Breast cancer cells may or may not have three important receptors: estrogen receptor (ER), progesterone receptor (PR), and HER2.
    ER+ cancer cells depend on estrogen for their growth, so they can be treated with drugs to block estrogen effects (e.g. prolactin receptor.

In cases of breast cancer with low risk for metastasis, the risks associated with [66] This is because these procedures expose the patient to a substantial amount of potentially dangerous ionizing radiation.

  • DNA assays. DNA testing of various types including DNA microarrays 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.

[edit] Prevention

The [68]

Prophylactic bilateral [70] Some carcinogens are known to take advantage of deficiencies in processes that depend on normal BRCA1 and BRCA2 function.

[edit] Screening

Breast cancer screening refers to testing otherwise-healthy women for breast cancer in an attempt to achieve an earlier diagnosis. The assumption is that early detection will improve outcomes. A number of screening test have been employed including: clinical and self mammography, genetic screening, ultrasound, and magnetic resonance imaging.

A clinical or self [73]

For the average woman, the U.S. Preventive Services Task Force recommends (2009) mammography every two years in women between the ages of 50 and 74.[78]

Molecular breast imaging is currently under study and may also be an alternative.[79]

[edit] Management

The management of breast cancer will be different pending various factors, including the stage of the cancer. Breast cancer is usually treated with surgery and then possibly with chemotherapy or radiation, or both. A multidisciplinary approach is preferable.[80] Hormone positive cancers are treated with long term hormone blocking therapy. Treatments are given with increasing aggressiveness according to the prognosis and risk of recurrence. The NPI Nottingham Prognostic Index is a useful tool in assessing the prognosis

  • Stage 1 cancers (and DCIS) have an excellent prognosis and are generally treated with lumpectomy and sometimes radiation.[82] Chemotherapy is uncommon for other types of stage 1 cancers.
  • 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 lymph node removal), chemotherapy (plus trastuzumab 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. 10-year survival rate is 5% without treatment and 10% with optimal treatment.[83]

[edit] Surgery

Chest after right breast mastectomy

Surgery involves the physical removal of the tumor, typically along with some of the surrounding tissue and frequently sentinel node biopsy.

Standard surgeries include:

If the patient desires, then breast prostheses to simulate a breast under clothing, or choose a flat chest.

[edit] Medication

Drugs used after and in addition to surgery are called neoadjuvant therapy.

There are currently three main groups of medications used for adjuvant breast cancer treatment: hormone blocking therapy, chemotherapy, and monoclonal antibodies.

Hormone blocking therapy
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. [85]
Chemotherapy
Predominately used for stage 2–4 disease, being particularly beneficial in estrogen receptor-negative (ER-) disease. They are given in combinations, usually for 3–6 months. One of the most common treatments is cyclophosphamide plus citation needed]
Monoclonal antibodies
[87] Other monoclonal antibodies are also undergoing clinical trials. Trastuzumab is only effective in patients with HER2 amplification/overexpression.

Between 25 and thirty percent of breast cancers have an amplification of the HER2 gene or overexpression of its protein product.[88] This receptor is normally stimulated by a growth factor which causes the cell to divide; in the absence of the growth factor, the cell will normally stop growing. Overexpression of this receptor in breast cancer is associated with increased disease recurrence and worse prognosis.

Aspirin may reduce mortality from breast cancer.[89]

[edit] Radiation

[94] and is considered essential when breast cancer is treated by removing only the lump (Lumpectomy or Wide local excision).

[edit] Prognosis

An example of recurrent breast cancer

A prognosis is a prediction of outcome and the probability of progression-free survival (PFS) or disease-free survival (DFS). These predictions are based on experience with breast cancer patients with similar classification. A prognosis is an estimate, as patients with the same classification will survive a different amount of time, and classifications are not always precise. Survival is usually calculated as an average number of months (or years) that 50% of patients survive, or the percentage of patients that are alive after 1, 5, 15, and 20 years. Prognosis is important for treatment decisions because patients with a good prognosis are usually offered less invasive treatments, such as lumpectomy and radiation or hormone therapy, while patients with poor prognosis are usually offered more aggressive treatment, such as more extensive mastectomy and one or more chemotherapy drugs.

Prognostic factors are reflected in the Nottingham Prognostic Index is a commonly used prognostic tool.

The [95]

discussion of breast cancer grade.

The presence of estrogen and progesterone receptors in the cancer cell is important in guiding treatment. Those who do not test positive for these specific receptors will not be able to respond to hormone therapy, and this can affect their chance of survival depending upon what treatment options remain, the exact type of the cancer, and how advanced the disease is.

In addition to hormone receptors, there are other cell surface proteins that may affect prognosis and treatment. HER2 status directs the course of treatment. Patients whose cancer cells are positive for HER2 have more aggressive disease and may be treated with the ‘targeted therapy’, trastuzumab (Herceptin), a monoclonal antibody that targets this protein and improves the prognosis significantly.

Younger women tend to have a poorer prognosis than post-menopausal women due to several factors. Their breasts are active with their cycles, they may be nursing infants, and 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.[97]

Since breast cancer in males is usually detected at later stages outcome are typically worse.[98]

[edit] Psychological aspects

The emotional impact of cancer diagnosis, symptoms, treatment, and related issues can be severe. Most larger hospitals are associated with cancer support groups which provide a supportive environment to help patients cope and gain perspective from cancer survivors. Online cancer support groups are also very beneficial to cancer patients, especially in dealing with uncertainty and body-image problems inherent in cancer treatment.

Not all breast cancer patients experience their illness in the same manner. Factors such as age can have a significant impact on the way a patient copes with a breast cancer diagnosis. Premenopausal women with estrogen-receptor positive breast cancer must confront the issues of early menopause induced by many of the chemotherapy regimens used to treat their breast cancer, especially those that use hormones to counteract ovarian function.[99]

On the other hand, a small 2007 study conducted by researchers at the College of Public Health of the University of Georgia suggested a need for greater attention to promoting functioning and psychological well-being among older cancer survivors, even when they may not have obvious cancer-related medical complications.[100]

[edit] Epidemiology

[101]

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Worldwide, breast cancer is the most common invasive cancer in women. (The most common form of cancer is non-invasive [102]

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).[6]

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 incidence rates 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.[103]

The number of cases worldwide has significantly increased since the 1970s, a phenomenon partly attributed to the modern lifestyles.[106]

[edit] History

Breast cancer surgery in 18th century

Because of its visibility, breast cancer was the form of cancer most often described in ancient documents.[107]

The oldest description of cancer was discovered in Egypt and dates back to approximately 1600 BC. The [111]

Although breast cancer was known in ancient times, it was uncommon until the 19th century, when improvements in sanitation and control of deadly [111]

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 arsenic, were relatively common.

Mastectomy for breast cancer was performed at least as early as AD 548, when it was proposed by the court physician [112]

Their successful work was carried on by [113]

Radical mastectomies remained the standard of care in America until the 1970s, but in Europe, breast-sparing procedures, often followed radiation therapy, were generally adopted in the 1950s.[113]

Breast cancer staging systems were developed in the 1920s and 1930s.[113]

During the 1970s, a new understanding of metastasis 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 chemotherapy developed after World War II.[115]

The French surgeon Bernard Peyrilhe (1737–1804) realized the first experimental transmission of cancer by injecting extracts of breast cancer into an animal.

Prominent women who died of breast cancer include Anne of Austria, the mother of Louis XIV of France; Mary Washington, mother of George, and Rachel Carson, the environmentalist.[116]

The first case-controlled study on breast cancer epidemiology was done by Janet Lane-Claypon, who published a comparative study in 1926 of 500 breast cancer cases and 500 control patients of the same background and lifestyle for the British Ministry of Health.[117]

In the 1980s and 1990s, thousands of women who had successfully completed standard treatment then demanded and received high-dose bone marrow transplants, 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.[118]

The 1995 reports from the Nurses’ Health Study and the 2002 conclusions of the Women’s Health Initiative trial conclusively proved that hormone replacement therapy significantly increased the incidence of breast cancer.[118]

[edit] Society and culture

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 raising awareness 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 American Cancer Society) during the 1930s and 1940s was one of the first organized campaigns. In 1952, the first peer-to-peer support group, called “Reach to Recovery”, began providing post-mastectomy, in-hospital visits from women who had survived breast cancer.[119]

The [121]

[edit] Pink ribbon

The pink ribbon is a symbol to show support for breast cancer awareness

A pink ribbon is the most prominent symbol of breast cancer awareness. Pink ribbons, which can be made inexpensively, are sometimes sold as fundraisers, much like poppies on Remembrance Day. 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—usually white, middle-aged, middle-class and upper-class, educated women.[122]

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.[123]

Wearing or displaying a pink ribbon has been criticized by the opponents of this practice as a kind of [128]

[edit] Breast cancer culture

Breast cancer culture, or 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. Appearing to have suffered bravely is the passport into the culture.

The woman with breast cancer is given a cultural template that constrains her emotional and social responses into a socially acceptable discourse: She is to use the emotional trauma of being diagnosed with breast cancer and the suffering of extended treatment to transform herself into a stronger, happier and more sensitive person who is grateful for the opportunity to become a better person. Breast cancer thereby becomes a [129]

As with most cultural models, people who conform to the model are given social status, in this case as cancer survivors. Women who reject the model are shunned, punished and shamed.[129]

The culture is criticized for treating adult women like little girls, as evidenced by “baby” toys such as pink teddy bears given to adult women.[129]

The primary purposes or goals of breast cancer culture are to maintain breast cancer’s dominance as the preëminent 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.[130]

[edit] Overemphasis

Compared to other diseases or other cancers, breast cancer receives a disproportionate share of resources and attention. In 2001 MP cancer-related fatigue, have been studied in little except 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.[134]

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.[135]

[edit] In pregnancy

Cancers found during or shortly after pregnancy appear at approximately the same rate as other cancers in women of a similar age. As a result, breast cancer is one of the more common cancers found during pregnancy, although it is still rare, because only about 1 in 1,000 pregnant women experience any sort of cancer.[136]

Diagnosing a new cancer in a pregnant woman is difficult, in part because any symptoms are commonly assumed to be a normal discomfort associated with pregnancy.[136]

Treatment is generally the same as for non-pregnant women.[136]

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 mastitis. Also, when chemotherapy is being given after birth, many of the drugs pass through breast milk to the baby, which could harm the baby.[136]

[edit] Research

A considerable part of the current knowledge on breast carcinomas is based on in vivo and in vitro studies performed with breast cancer cell (BCC) lines. These provide an unlimited source of homogenous self-replicating material, free of contaminating stromal cells, and often easily cultured in simple standard media. The first line described, BT-20, 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 BCC 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 BCC lines issued from metastatic tumors, mainly from Medline-based survey.

Treatments are constantly evaluated in randomized, controlled trials, to evaluate and compare individual drugs, combinations of drugs, and surgical and radiation techniques. The latest research is reported annually at scientific meetings such as that of the [138] These studies are reviewed by professional societies and other organizations, and formulated into guidelines for specific treatment groups and risk category.

List of cell lines

Mainly based on Lacroix and Leclercq (2004).[140]

Cell line Primary tumor Origin of cells Estrogen receptors Progesterone receptors ERBB2 amplification Mutated TP53 Tumorigenic in mice Reference
600MPE Invasive ductal carcinoma + [141]
AU565 Adenocarcinoma + [141]
BT-20 Invasive ductal carcinoma Primary No No No Yes Yes [142]
BT-474 Invasive ductal carcinoma Primary Yes Yes Yes Yes Yes [143]
BT-483 Invasive ductal carcinoma + + [141]
BT-549 Invasive ductal carcinoma + [141]
Evsa-T Invasive ductal carcinoma, mucin-producing, signet-ring type ascites) No Yes  ? Yes  ? [144]
Hs578T Carcinosarcoma Primary No No No Yes No [145]
MCF-7 Invasive ductal carcinoma pleural effusion) Yes Yes No No (wild-type) Yes (with estrogen supplementation) [146]
MDA-MB-231 Invasive ductal carcinoma pleural effusion) No No No Yes Yes [147]
SkBr3 Invasive ductal carcinoma pleural effusion) No No Yes Yes No [148]
T-47D Invasive ductal carcinoma pleural effusion) Yes Yes No Yes Yes (with estrogen supplementation) [149]

[edit] In other animals

[edit] References

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This article uses material from the Wikipedia article Breast Cancer, which is released under the Creative Commons Attribution-Share-Alike License 3.0.

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