Breast cancer

Breast cancer
Breast cancer in the right breast
Specialty	Oncology
Symptoms	A lump in a breast, a change in breast shape, dimpling of the skin, fluid from the nipple, a newly inverted nipple, a red scaly patch of skin on the breast[1]
Risk factors	Being female, obesity, lack of exercise, alcohol, hormone replacement therapy during menopause, ionizing radiation, early age at first menstruation, having children late in life or not at all, older age, prior breast cancer, family history of breast cancer, Klinefelter syndrome[1][2][3]
Diagnostic method	Tissue biopsy[1]
Treatment	Surgery, radiation therapy, chemotherapy, hormonal therapy, targeted therapy[1]
Prognosis	Five-year survival rate ≈85% (US, UK)[4][5]
Frequency	2.1 million affected as of 2018[6]
Deaths	627,000 (2018)[6]

Breast cancer is cancer that develops from breast tissue.^[7] Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, fluid coming from the nipple, a newly-inverted nipple, or a red or scaly patch of skin.^[1] In those with distant spread of the disease, there may be bone pain, swollen lymph nodes, shortness of breath, or yellow skin.^[8]

Risk factors for developing breast cancer include being female, obesity, a lack of physical exercise, alcoholism, hormone replacement therapy during menopause, ionizing radiation, an early age at first menstruation, having children late in life or not at all, older age, having a prior history of breast cancer, and a family history of breast cancer.^[1][2] About 5–10% of cases are the result of a genetic predisposition inherited from a person's parents, including BRCA1 and BRCA2 among others.^[1] Breast cancer most commonly develops in cells from the lining of milk ducts and the lobules that supply these ducts with milk.^[1] Cancers developing from the ducts are known as ductal carcinomas, while those developing from lobules are known as lobular carcinomas.^[1] There are more than 18 other sub-types of breast cancer.^[2] Some, such as ductal carcinoma in situ, develop from pre-invasive lesions.^[2] The diagnosis of breast cancer is confirmed by taking a biopsy of the concerning tissue.^[1] 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.^[1]

The balance of benefits versus harms of breast cancer screening is controversial. A 2009 review for the US Preventive Services Task Force found evidence of benefit in those 40 to 70 years of age,^[9] and recommends screening every two years in women 40 to 74 years of age as of 2023.^[10][11] A 2013 Cochrane review found that it was unclear if mammographic screening does more harm than good, in that a large proportion of women who test positive turn out not to have the disease.^[12] The medications tamoxifen or raloxifene may be used in an effort to prevent breast cancer in those who are at high risk of developing it.^[2] Surgical removal of both breasts is another preventative measure in some high risk women.^[2] In those who have been diagnosed with cancer, a number of treatments may be used, including surgery, radiation therapy, chemotherapy, hormonal therapy, and targeted therapy.^[1] Types of surgery vary from breast-conserving surgery to mastectomy.^[13][14] Breast reconstruction may take place at the time of surgery or at a later date.^[14] 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.^[14]

Outcomes for breast cancer vary depending on the cancer type, the extent of disease, and the person's age.^[14] The five-year survival rates in England and the United States are between 80 and 90%.^[4][5][15] In developing countries, five-year survival rates are lower.^[2] Worldwide, breast cancer is the leading type of cancer in women, accounting for 25% of all cases.^[16] In 2018 it resulted in 2 million new cases and 627,000 deaths.^[6] It is more common in developed countries^[2] and is more than 100 times more common in women than in men.^[15][17]

Signs and symptoms

Early signs of possible breast cancer

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

Breast cancer most commonly presents as a lump that feels different from the rest of the breast tissue. More than 80% of cases are discovered when a person detects such a lump with the fingertips.^[18] The earliest breast cancers, however, are detected by a mammogram.^[19][20] Lumps found in lymph nodes located in the armpits^[18] may 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.^[21] Pain ("mastodynia") is an unreliable tool in determining the presence or absence of breast cancer, but may be indicative of other breast health issues.^[18][19][22]

Another symptom complex of breast cancer is Paget's disease of the breast. This syndrome presents as skin changes resembling eczema; 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 the women diagnosed with Paget's disease of the breast also have a lump in the breast.^[23][24]

Inflammatory Breast Cancer presents with similar effects. Inflammatory Breast Cancer is a rare (only seen in less than 5% of breast cancer diagnosis) yet aggressive form of breast cancer characterized by the swollen, red areas formed on the top of the Breast. The visual effects of Inflammatory Breast Cancer is a result of a blockage of lymph vessels by cancer cells. This type of breast cancer is seen in more commonly diagnosed in younger ages, obese women and African American women. As inflammatory breast cancer does not present as a lump there can sometimes be a delay in diagnosis.^[25]

In rare cases, what initially appears as a fibroadenoma (hard, movable non-cancerous 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.^[26]

Malignant tumors can result in metastatic tumors— secondary tumors (originating from the primary tumor) that spread beyond the site of origination. The symptoms caused by metastatic breast cancer will depend on the location of metastasis. Common sites of metastasis include bone, liver, lung, and brain.^[27] When cancer has reached such an invasive state, it is categorized as a stage 4 cancer, cancers of this state are oftentimes fatal.^[28] Common symptoms of stage 4 cancer include unexplained weight loss, bone and joint pain, jaundice and neurological symptoms. These symptoms are called non-specific symptoms because they could be manifestations of many other illnesses.^[29]

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 cancerous,^[30] and benign breast diseases such as mastitis and fibroadenoma of the breast are more common causes of breast disorder symptoms.^[31]

Risk factors

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).^[32]

The primary risk factors for breast cancer are being female and older age.^[33] Other potential risk factors include genetics,^[34] lack of childbearing or lack of breastfeeding,^[35] higher levels of certain hormones,^[36][37] certain dietary patterns, and obesity. One study indicates that exposure to light pollution is a risk factor for the development of breast cancer.^[38]

Pathophysiology

Ducts and lobules, the main locations of breast cancers.

Overview of signal transduction pathways involved in programmed cell death. Mutations leading to loss of this ability can lead to cancer formation.

Breast cancer, like other cancers, 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 (programmed cell death) 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 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.^[77]

Mutations that can lead to breast cancer have been experimentally linked to estrogen exposure.^[78] Additionally, G-protein coupled estrogen receptors have been associated with various cancers of the female reproductive system including breast cancer.^[79]

Abnormal growth factor signaling in the interaction between stromal cells and epithelial cells can facilitate malignant cell growth.^[80][81] In breast adipose tissue, overexpression of leptin leads to increased cell proliferation and cancer.^[82]

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 hereditary breast–ovarian cancer syndrome. The best known of these, the BRCA mutations, 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 p53, BRCA1 and BRCA2, 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.^[59][83] 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.^[84] 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).^[85] These carcinogens cause DNA damage such as DNA cross links and double strand breaks that often require repairs by pathways containing BRCA1 and BRCA2.^[86][87] However, mutations in BRCA genes account for only 2 to 3 percent of all breast cancers.^[88] Levin et al. say that cancer may not be inevitable for all carriers of BRCA1 and BRCA2 mutations.^[89] About half of hereditary breast–ovarian cancer syndromes involve unknown genes. Furthermore, certain latent viruses, may decrease the expression of the BRCA1 gene and increase the risk of breast tumors.^[90]

GATA-3 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.^[91]

Diagnosis

Mammograms showing a normal breast (left) and a breast with cancer (right)

Most types of breast cancer are easy to diagnose by microscopic analysis of a sample - or biopsy - 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 cyst.^[92] 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 fine needle aspiration, or fine needle aspiration and cytology, FNAC) to help establish the diagnosis. A needle aspiration can be performed in a healthcare provider's office or clinic. A local anesthetic may be used to numb the breast tissue to prevent pain during the procedure, but may not be necessary if the lump isn't beneath the skin. 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 core biopsy or vacuum-assisted breast biopsy,^[93] which are procedures in which a section of the breast lump is removed; or an excisional biopsy, 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 ultrasound or MRI) are sufficient to warrant excisional biopsy as the definitive diagnostic and primary treatment method.^[94]

• 
  MRI showing breast cancer
• 
  Excised human breast tissue, showing an irregular, dense, white stellate area of cancer 2 cm in diameter, within yellow fatty tissue.
• 
  High-grade invasive ductal carcinoma, with minimal tubule formation, marked pleomorphism, and prominent mitoses, 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.

Classification

Main article: Breast cancer 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.

Histopathologic types of breast cancer, with relative incidences and prognoses.

• Histopathology. Breast cancer is usually classified primarily by its histological appearance. Most breast cancers are derived from the epithelium lining the ducts or lobules, and these cancers are classified as ductal 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.^[95]
• 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. Breast cancer staging using the TNM system is based on the size of the tumor (T), whether or not the tumor has spread to the 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:
  • Stage 0 is a pre-cancerous or marker condition, either ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS).
  • Stages 1–3 are within the breast or regional lymph nodes.
  • Stage 4 is 'metastatic' cancer 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
• 
  Metastatic or stage 4 breast cancer

Where available, imaging studies may be employed as part of the staging process in select cases to look for signs of metastatic cancer. However, in cases of breast cancer with low risk for metastasis, the risks associated with PET scans, CT scans, or bone scans outweigh the possible benefits, as these procedures expose the person to a substantial amount of potentially dangerous ionizing radiation.^[96][97]

• 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 (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. tamoxifen), and generally have a better prognosis. Untreated, HER2+ breast cancers are generally more aggressive than HER2- breast cancers,^[98][99] but HER2+ cancer cells respond to drugs such as the monoclonal antibody trastuzumab (in combination with conventional chemotherapy), and this has improved the prognosis significantly.^[100] Cells that do not have any of these three receptor types (estrogen receptors, progesterone receptors, or HER2) are called triple-negative, although they frequently do express receptors for other hormones, such as androgen receptor and prolactin receptor.
• 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.

• 
  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

Screening

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 breast exams, mammography, genetic screening, ultrasound, and magnetic resonance imaging.

A clinical or self breast exam involves feeling the breast for lumps or other abnormalities. Clinical breast exams are performed by health care providers, while self-breast exams are performed by the person themselves.^[101] 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.^[102][103] Mammographic screening for breast cancer uses X-rays 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.^[104]

A number of national bodies recommend breast cancer screening. For the average woman, the U.S. Preventive Services Task Force recommends mammography every two years in women between the ages of 40 and 74,^[10], the American College of Physicians recommended starting at 50 in 2019,^[105] the Council of Europe recommends mammography between 50 and 69 with most programs using a 2-year frequency,^[106] while the European Commission recommends mammography from 45 to 75 every 2 to 3 years,^[107] and in Canada screening is recommended between the ages of 50 and 74 at a frequency of 2 to 3 years.^[108] 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.^[109]

The Cochrane collaboration (2013) states that the best quality evidence neither demonstrates a reduction in cancer specific, nor a reduction in all cause mortality from screening mammography.^[12] 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).^[12] 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.^[12][110] This has resulted in the view that it is not clear whether mammography screening does more good or harm.^[12] 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.^[111] Whether MRI as a screening method has greater harms or benefits when compared to standard mammography is not known.^[112][113]

Prevention

Management

The management of breast cancer depends on various factors, including the stage of the cancer and the person's age. Treatments are more aggressive when the cancer is more advanced or there is a higher risk of recurrence of the cancer following treatment.

Breast cancer is usually treated with surgery, which may be followed by chemotherapy or radiation therapy, or both. A multidisciplinary approach is preferable.^[130] 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. Although this range of treatment is still being studied.^[131]

Surgery

Chest after right breast mastectomy

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 sentinel lymph node biopsy.

Standard surgeries include:

• Mastectomy: Removal of the whole breast.
• Quadrantectomy: Removal of one-quarter of the breast.
• Lumpectomy: Removal of a small part of the breast.

Once the tumor has been removed, if the person desires, breast reconstruction surgery, a type of plastic surgery, may then be performed to improve the aesthetic appearance of the treated site. Alternatively, women use breast prostheses to simulate a breast under clothing, or choose a flat chest. Nipple prosthesis can be used at any time following the mastectomy.

Radiation

Internal radiotherapy for breast cancer

Radiotherapy 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.^[145][146] Radiation therapy can be delivered as external beam radiotherapy or as brachytherapy (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^[147] and is considered essential when breast cancer is treated by removing only the lump (Lumpectomy or Wide local excision). In early breast cancer, partial breast irradiation does not give the same cancer control in the breast as treating the whole breast and may cause worse side effects.^[148]

Prognosis

Breasts after double mastectomy followed by nipple-sparing reconstruction with implants

An extreme example of an advanced recurrent breast cancer with an ulcerating axillary mass

Epidemiology

Age-standardized death from breast cancer per 100,000 inhabitants in 2004.^[159]

no data   <2   2–4   4–6   6–8   8–10   10–12

12–14   14–16   16–18   18–20   20–22   >22

Worldwide, breast cancer is the most-common invasive cancer in women.^[160] Along with lung cancer, breast cancer is the most commonly diagnosed cancer, with 2.09 million cases each in 2018.^[161] Breast cancer affects 1 in 7 (14%) of women worldwide.^[162] (The most common form of cancer is non-invasive non-melanoma skin cancer; 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^[163] and 16% of all female cancers.^[164] In 2012, it comprised 25.2% of cancers diagnosed in women, making it the most-common female cancer.^[165]

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).^[163] Lung cancer, the second most-common cause of cancer-related deaths in women, caused 12.8% of cancer deaths in women (18.2% of all cancer deaths for men and women together).^[163]

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: 18 in Eastern Asia, 22 in South Central Asia and sub-Saharan Africa, 26 in South-Eastern Asia, 26, 28 in North Africa and Western Asia, 42 in South and Central America, 42, 49 in Eastern Europe, 56 in Southern Europe, 73 in Northern Europe, 74 in Oceania, 78 in Western Europe, and 90 in North America.^[166] Metastatic breast cancer affects between 19% (United States) and 50% (parts of Africa) of women with breast cancer.^[167]

The number of cases worldwide has significantly increased since the 1970s, a phenomenon partly attributed to the modern lifestyles.^[168][169] Breast cancer is strongly related to age with only 5% of all breast cancers occurring in women under 40 years old.^[170] 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.^[171] Based on U.S. statistics in 2015 there were 2.8 million women affected by breast cancer.^[160] In the United States, the age-adjusted incidence 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.^[172]

History

Breast cancer surgery in 18th century

Because of its visibility, breast cancer was the form of cancer most often described in ancient documents.^[173] 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 fungating lesions: the tumor would become necrotic (die from the inside, causing the tumor to appear to break up) and ulcerate through the skin, weeping fetid, dark fluid.^[173]

The oldest discovered evidence of breast cancer is from Egypt and dates back 4200 years, to the Sixth Dynasty.^[174] The study of a woman's remains from the necropolis of Qubbet el-Hawa showed the typical destructive damage due to metastatic spread.^[174] The Edwin Smith Papyrus describes 8 cases of tumors or ulcers of the breast that were treated by cauterization. The writing says about the disease, "There is no treatment."^[175] 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 humoralism, and thus believed that breast cancer was generally caused by imbalances in the fundamental fluids that controlled the body, especially an excess of black bile.^[176] Alternatively it was seen as divine punishment.^[177] 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.^[176][178] 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.^[178]

Although breast cancer was known in ancient times, it was uncommon until the 19th century, when improvements in sanitation and control of deadly infectious diseases resulted in dramatic increases in lifespan. Previously, most women had died too young to have developed breast cancer.^[178] Additionally, early and frequent childbearing and breastfeeding probably reduced the rate of breast cancer development in those women who did survive to middle age.^[178]

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 Aetios of Amida to Theodora.^[173] 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 lymph nodes in the armpit. The French surgeon Jean Louis Petit (1674–1750) performed total mastectomies that included removing the axillary lymph nodes, as he recognized that this reduced recurrence.^[179] Petit's work was built on by another French surgeon, Bernard Peyrilhe (1737–1804), who additionally removed the pectoral muscle underlying the breast, as he judged that this greatly improved the prognosis.^[180] The Scottish surgeon Benjamin Bell (1749–1806) advocated removal of the entire breast, even when only a portion was affected.^[181]

Their successful work was carried on by William Stewart Halsted who started performing radical mastectomies in 1882, helped greatly by advances in general surgical technology, such as aseptic technique and anesthesia. 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.^[182] Before the advent of the Halsted radical mastectomy, 20-year survival rates were only 10%; Halsted's surgery raised that rate to 50%.^[183] Extending Halsted's work, Jerome Urban promoted superradical mastectomies, taking even more tissue, until 1963, when the ten-year survival rates proved equal to the less-damaging radical mastectomy.^[182]

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.^[182] One reason for this striking difference in approach may be the structure of the medical professions: European surgeons, descended from the barber surgeon, were held in less esteem than physicians; in America, the surgeon was the king of the medical profession.^[182] 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.^[182] American health insurance companies also paid surgeons more to perform radical mastectomies than they did to perform more intricate breast-sparing surgeries.^[182]

Breast cancer staging systems were developed in the 1920s and 1930s.^[182]

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.^[184]

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.^[185]

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 controls of the same background and lifestyle for the British Ministry of Health.^[186]

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.^[187]

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.^[187]

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.^[188]

The breast cancer movement of the 1980s and 1990s developed out of the larger feminist movements and women's health movement of the 20th century.^[189] This series of political and educational campaigns, partly inspired by the politically and socially effective AIDS awareness campaigns, resulted in the widespread acceptance of second opinions before surgery, less invasive surgical procedures, support groups, and other advances in care.^[190]

Pink ribbon

Main article: 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.^[191]

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.^[192]

Wearing or displaying a pink ribbon has been criticized by the opponents of this practice as a kind of slacktivism, because it has no practical positive effect. It has also been criticized as hypocrisy, 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 patient rights and anti-pollution legislation.^[193][194] 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.^[195] It is also criticized for reinforcing gender stereotypes and objectifying women and their breasts.^[196] Breast Cancer Action 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.^[197]

Pregnancy

Pregnancy at an early age decreases the risk of developing breast cancer later in life.^[205] The risk of breast cancer also declines with the number of children a woman has.^[205] Breast cancer then becomes more common in the 5 or 10 years following pregnancy but then becomes less common than among the general population.^[206] These cancers are known as postpartum breast cancer and have worse outcomes including an increased risk of distant spread of disease and mortality.^[207] Other cancers found during or shortly after pregnancy appear at approximately the same rate as other cancers in women of a similar age.^[208]

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.^[208] 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 MRIs (magnetic resonance imaging), CT scans, ultrasounds, and mammograms with fetal shielding are considered safe during pregnancy; some others, such as PET scans are not.^[208]

Treatment is generally the same as for non-pregnant women.^[208] 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 first trimester, increase the risk of birth defects and pregnancy loss (spontaneous abortions and stillbirths).^[208] Elective abortions are not required and do not improve the likelihood of the mother surviving or being cured.^[208]

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.^[208]

Regarding future pregnancy among breast cancer survivors, there is often fear of cancer recurrence.^[209] On the other hand, many still regard pregnancy and parenthood to represent normalcy, happiness and life fulfillment.^[209]

Hormones

Research

Treatments are being evaluated in trials. This includes individual drugs, combinations of drugs, and surgical and radiation techniques Investigations include new types of targeted therapy,^[213] cancer vaccines, oncolytic virotherapy,^[214] gene therapy^[215][216] and immunotherapy.^[217]

The latest research is reported annually at scientific meetings such as that of the American Society of Clinical Oncology, San Antonio Breast Cancer Symposium,^[218] and the St. Gallen Oncology Conference in St. Gallen, Switzerland.^[219] These studies are reviewed by professional societies and other organizations, and formulated into guidelines for specific treatment groups and risk category.

Fenretinide, a retinoid, is also being studied as a way to reduce the risk of breast cancer (retinoids are medications related to vitamin A).^[220][221] In particular, combinations of ribociclib plus endocrine therapy have been the subject of clinical trials.^[222]

A 2019 review found moderate certainty evidence that giving people antibiotics before breast cancer surgery helped to prevent surgical site infection (SSI). Further study is required to determine the most effective antibiotic protocol and use in women undergoing immediate breast reconstruction.^[223]

Other animals

• Mammary tumor for breast cancer in other animals
• Mouse models of breast cancer metastasis

References

External links

• Breast cancer at Curlie