Breast Cancer Classification and external resources |
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Mammogram showing breast cancer (indicated by arrow) | |
ICD-10 | C50. |
ICD-9 | 174-175 |
OMIM | 114480 |
DiseasesDB | 1598 |
MedlinePlus | 000913 |
eMedicine | med/2808 med/3287 radio/115 plastic/521 |
MeSH | D001943 |
Breast cancer is a cancer that starts in the cells of the breast in women and men. Worldwide, breast cancer is the second most common type of cancer after lung cancer (10.4% of all cancer incidence, both sexes counted)[1] and the fifth most common cause of cancer death.[2] In 2005, breast cancer caused 502,000 deaths worldwide (7% of cancer deaths; almost 1% of all deaths).[2]
Because the breast is composed of identical tissues in males and females, breast cancer also occurs in males.[3][4] Incidences of breast cancer in men are approximately 100 times less common than in women, but men with breast cancer are considered to have the same statistical survival rates as women.[5]
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Breast cancers are described along four different classification schemes, or groups, each based on different criteria and serving a different purpose:
Breast cancer is usually, but not always, primarily classified by its histological appearance. Rare variants are defined on the basis of physical exam findings. For example, Inflammatory breast cancer (IBC), a form of ductal carcinoma or malignant cancer in the ducts, is distinguished from other carcinomas by the inflamed appearance of the affected breast.[6] In the future, some pathologic classifications may be changed. For example, a subset of ductal carcinomas may be re-named basal-like carcinoma (part of the "triple-negative" tumors).
The first symptom, or subjective sign, of breast cancer is typically a lump that feels different than the surrounding breast tissue. According to the Merck Manual, more than 80% of breast cancer cases are discovered when the woman feels a lump.[7] According to the American Cancer Society (ACS), the first medical sign, or objective indication of breast cancer as detected by a physician, is discovered by mammogram.[8] Lumps found in lymph nodes located in the armpits[7] and/or collarbone can also indicate breast cancer.
Indications of breast cancer other than a lump may include changes in breast size or shape, skin dimpling, nipple inversion, or spontaneous single-nipple discharge. Pain is an unreliable tool in determining the presence or absence of breast cancer, but may be indicative of other breast-related health issues such as mastodynia.[8][7][9]
When breast cancer cells invade the dermal lymphatics, small lymph vessels in the skin of the breast, its presentation can resemble skin inflammation and thus is known as inflammatory breast cancer (IBC). Symptoms of inflammatory breast cancer include pain, swelling, warmth and redness throughout the breast, as well as an orange peel texture to the skin referred to as peau d'orange.[7]
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.[10]
Occasionally, breast cancer presents as metastatic disease, that is, cancer that has spread beyond the original organ. Metastatic breast cancer will cause symptoms that depend on the location of metastasis. More common sites of metastasis include bone, liver, lung and brain. Unexplained weight loss can occasionally herald an occult 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 "non-specific," meaning they can also be manifestations of many other illnesses.[11]
Most symptoms of breast disorder do not turn out to represent underlying breast cancer. Benign breast diseases such as mastitis and fibroadenoma of the breast are more common causes of breast disorder symptoms. The appearance of a new symptom should be taken seriously by both patients and their doctors, because of the possibility of an underlying breast cancer at almost any age.[12]
Epidemiological risk factors for a disease can provide important clues as to the etiology, or cause, of a disease. 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.[13][14]
Today, breast cancer, like other forms of cancer, is considered to be the final outcome of multiple environmental and hereditary factors. Some of these factors include:
Although many epidemiological risk factors have been identified, the cause of any individual breast cancer is often unknowable. In other words, epidemiological research informs the patterns of breast cancer incidence across certain populations, but not in a given individual. Due to breast cancer is vary in different racial and ethnic group. The primary risk factors that have been identified are sex,[18] age,[19] childbearing, hormones,[20] a high-fat diet,[21] alcohol intake,[22][23] obesity,[24] and environmental factors such as tobacco use, radiation[17] and shiftwork.[25]
No etiology is known for 95% of breast cancer cases, while approximately 5% of new breast cancers are attributable to hereditary syndromes.[26] In particular, carriers of the breast cancer susceptibility genes, BRCA1 and BRCA2, are at a 30-40% increased risk for breast and ovarian cancer, depending on in which portion of the protein the mutation occurs.[27]
Worldwide, breast cancer is by far the most common cancer amongst women, with an incidence rate more than twice that of colorectal cancer and cervical cancer and about three times that of lung cancer. However breast cancer mortality worldwide is just 25% greater than that of lung cancer in women.[1] In 2005, breast cancer caused 502,000 deaths worldwide (7% of cancer deaths; almost 1% of all deaths).[2] The number of cases worldwide has significantly increased since the 1970s, a phenomenon partly blamed on modern lifestyles in the Western world.[28][29]
The incidence of breast cancer varies greatly around the world, being lower 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.[30]
Women in the United States have the highest incidence rates of breast cancer in the world; 141 among white women and 122 among African American women.[31][32] Among women in the US, breast cancer is the most common cancer and the second-most common cause of cancer death (after lung cancer).[32] Women in the US have a 1 in 8 (12.5%) lifetime chance of developing invasive breast cancer and a 1 in 35 (3%) chance of breast cancer causing their death.[32] In 2007, breast cancer was expected to cause 40,910 deaths in the US (7% of cancer deaths; almost 2% of all deaths).[8]
In the US, both incidence and death rates for breast cancer have been declining in the last few years in Native Americans and Alaskan Natives.[33][8] Nevertheless, a US study conducted in 2005 by the Society for Women's Health Research indicated that breast cancer remains the most feared disease,[34] even though heart disease is a much more common cause of death among women.[35] Many doctors say that women exaggerate their risk of breast cancer.[36]
45,000 cases diagnosed and 12,500 deaths per annum. 60% of cases are treated with Tamoxifen, of these the drug becomes ineffective in 35%.[37]
Lower age of first childbirth (less than 24 years maternal age), having more children (about 7% lowered risk per child), and breastfeeding (4% per breastfeeding year, with an average relative risk around 0.7[38][39]) have all been correlated to lowered breast cancer risk in large studies.[40]
A high consumption of omega-6 polyunsaturated fatty acids (PUFAs), which are found in most types of vegetable oil [e.g. soybean oil, corn oil - the most consumed oil in USA, sunflower oil, etc.], may indeed increase the likelihood that postmenopausal women will develop breast cancer[41]. The analysis suggested an inverse association between total polyunsaturated fatty acids [omega-6] and breast cancer risk, but individual polyunsaturated fatty acids behaved differently [from each other]. [...] a derivative of linoleic acid [...] was inversely associated with the risk of breast cancer[42]
Phytoestrogens such as found in soybeans have been extensively studied in animal and human in-vitro and epidemiological studies. The literature support the following conclusions:
Studies have found that "folate intake counteracts breast cancer risk associated with alcohol consumption"[45] and "women who drink alcohol and have a high folate intake are not at increased risk of cancer."[46][47][48] A prospective study of over 17,000 women found that those who consume 40 grams of alcohol (about 3-4 drinks) per day have a higher risk of breast cancer. However, in women who take 200 micrograms of folate (folic acid or Vitamin B9) every day, the risk of breast cancer drops below that of alcohol abstainers.[49]
Folate is involved in the synthesis, repair, and functioning of DNA, the body’s genetic map, and a deficiency of folate may result in damage to DNA that may lead to cancer.[50] In addition to breast cancer, studies have also associated diets low in folate with increased risk of pancreatic, and colon cancer.[51][52]
Foods rich in folate include citrus fruits, citrus juices, dark green leafy vegetables (such as spinach), dried beans, and peas.
Breathing secondhand smoke increases breast cancer risk by 70% in younger, primarily pre-menopausal women. The California Environmental Protection Agency has concluded that passive smoking causes breast cancer[53] and the US Surgeon General[54] has concluded that the evidence is "suggestive," one step below causal. There is some evidence that exposure to tobacco smoke is most problematic between puberty and first childbirth. The reason that breast tissue appears most sensitive to chemical carcinogens in this phase is that breast cells are not fully differentiated until lactation.[55]
Prophylactic oophorectomy (removal of ovaries), in high-risk individuals, when child-bearing is complete, reduces the risk of developing breast cancer by 60%, as well as reducing the risk of developing ovarian cancer by 96%.[56]
Hormonal therapy has been used for chemoprevention in individuals at high risk for breast cancer. In 2002, a clinical practice guideline by the US Preventive Services Task Force (USPSTF) recommended that "clinicians discuss chemoprevention with women at high risk for breast cancer and at low risk for adverse effects of chemoprevention" with a grade B recommendation.[57][58][59]
The guidelines were based on studies of SERMs from the MORE, BCPT P-1, and Italian trials. In the MORE trial, the relative risk reduction for raloxifene was 76%.[60] The P-1 preventative study demonstrated that tamoxifen can prevent breast cancer in high-risk individuals. The relative risk reduction was up to 50% of new breast cancers, though the cancers prevented were more likely estrogen-receptor positive (this is analogous to the effect of finasteride on the prevention of prostate cancer, in which only low-grade prostate cancers were prevented).[61][62] The Italian trial showed benefit from tamoxifen.[63]
Additional randomized controlled trials have been published since the guidelines. The IBIS trial found benefit from tamoxifen.[64] In 2006, the NSABP STAR trial demonstrated that raloxifene had equal efficacy in preventing breast cancer compared with tamoxifen, but that there were fewer side effects with raloxifene.[65] The RUTH Trial concluded that "benefits of raloxifene in reducing the risks of invasive breast cancer and vertebral fracture should be weighed against the increased risks of venous thromboembolism and fatal stroke".[66] On September 14, 2007, the US Food and Drug Administration approved raloxifene (Evista) to prevent invasive breast cancer in postmenopausal women.[67]
Breast cancer screening is an attempt to find unsuspected cancers. The most common screening methods are self and clinical breast exams, x-ray mammography, and breast Magnetic Resonance Imaging (MRI). Genetic testing may also be used.
Breast self-examination involves examining one's own breasts using a specific palpation technique to detect any lumps in the breast tissue, which may be cancerous. Clinical exams are similar, except they are performed by a clinician or doctor.
X-ray mammography uses x-rays to examine the breast for any uncharacteristic masses or lumps. Regular mammograms -- the process of getting breast mammography -- is often recommended as a preventative measure, particularly for older women and at-risk individuals. A recent study involving 160,921 women recruited at age 39-41 showed that annual screening mammograms up to age 48 did decrease breast cancer mortality over an average of 10.7 years. This reduction, however, was not statistically significant. The results may be due to chance. According to these findings, about 2,500 women would need to be screened to prevent one breast cancer death during this time period.[68]
Breast MRIs are another imaging technique that can be used to spot potentially cancerous masses.
The most recent technology for breast cancer screening is ultrasound computed tomography, which uses sound waves to create a three-dimensional image and detect breast cancer without the use of dangerous radiation used in x-ray mammography. This method was discovered at Los Alamos National Laboratory.[69]
Genetic testing for breast cancer typically involves testing for mutations in the BRCA genes. This is not generally a recommended technique except for those at elevated risk for breast cancer.
While screening techniques discussed above are useful in determining the presence of cancer, they are not in and of themselves diagnostic of cancer. Pathology is the study and diagnosis of disease; only microscopic evaluation of a biopsy specimen can yield a cancer diagnosis. A number of procedures can obtain tissue or cells for histological or cytological examination. Such procedures include fine-needle aspiration, nipple aspirates, ductal lavage, core needle biopsy, and local surgical excision. Occasionally, pre-surgical procedures such as fine needle aspirate may not yield enough tissue to make a diagnosis, or may miss the cancer entirely.
Breast cancer is staged according to the TNM system, updated in the AJCC Staging Manual, now on its sixth edition. Prognosis is closely linked to results of staging, and staging is also used to allocate patients to treatments both in clinical trials and clinical practice. The information for staging is as follows:
TX: Primary tumor cannot be assessed. T0: No evidence of tumor. Tis: Carcinoma in situ, no invasion T1: Tumor is 2 cm or less T2: Tumor is more than 2 cm but not more than 5 cm T3: Tumor is more than 5 cm T4: Tumor of any size growing into the chest wall or skin, or inflammatory breast cancer
NX: Nearby lymph nodes cannot be assessed N0: Cancer has not spread to regional lymph nodes. N1: Cancer has spread to 1 to 3 axillary or one internal mammary lymph node N2: Cancer has spread to 4 to 9 axillary lymph nodes or multiple internal mammary lymph nodes N3: One of the following applies:
Cancer has spread to 10 or more axillary lymph nodes, or Cancer has spread to the lymph nodes under the clavicle (collar bone), or Cancer has spread to the lymph nodes above the clavicle, or Cancer involves axillary lymph nodes and has enlarged the internal mammary lymph nodes, or Cancer involves 4 or more axillary lymph nodes, and tiny amounts of cancer are found in internal mammary lymph nodes on sentinel lymph node biopsy.
MX: Presence of distant spread (metastasis) cannot be assessed. M0: No distant spread. M1: Spread to distant organs, not including the supraclavicular lymph node, has occurred
Summary of stages:
Approximately 90% of new breast cancer cases in the US will be classified as "early-stage" cases (DCIS, Stage I,IIA, IIB or IIIA), due to early detection and prevention techniques. Early-stage treatment options are different from late-stage options.[70]
Breast lesions are examined for certain markers, notably sex steroid hormone receptors. About two thirds of postmenopausal breast cancers are estrogen receptor positive (ER+) and progesterone receptor positive (PR+).[71] Receptor status modifies the treatment as, for instance, only ER-positive tumors, not ER-negative tumors, are sensitive to hormonal therapy.
The breast cancer is also usually tested for the presence of human epidermal growth factor receptor 2, a protein also known as HER2, neu or erbB2. HER2 is a cell-surface protein involved in cell development. In normal cells, HER2 controls aspects of cell growth and division. When activated in cancer cells, HER2 accelerates tumor formation. About 20-30% of breast cancers overexpress HER2. Those patients may be candidates for the drug trastuzumab, both in the postsurgical setting (so-called "adjuvant" therapy), and in the metastatic setting.[72]
The mainstay of breast cancer treatment is surgery when the tumor is localized, with possible adjuvant hormonal therapy (with tamoxifen or an aromatase inhibitor), chemotherapy, and/or radiotherapy. At present, the treatment recommendations after surgery (adjuvant therapy) follow a pattern. This pattern is subject to change, as every two years, a worldwide conference takes place in St. Gallen, Switzerland, to discuss the actual results of worldwide multi-center studies. Depending on clinical criteria (age, type of cancer, size, metastasis) patients are roughly divided to high risk and low risk cases, with each risk category following different rules for therapy. Treatment possibilities include radiation therapy, chemotherapy, hormone therapy, and immune therapy.
In planning treatment, doctors can also use PCR tests like Oncotype DX or microarray tests like MammaPrint that predict breast cancer recurrence risk based on gene expression. In February 2007, the MammaPrint test became the first breast cancer predictor to win formal approval from the Food and Drug Administration. This is a new gene test to help predict whether women with early-stage breast cancer will relapse in 5 or 10 years, this could help influence how aggressively the initial tumor is treated.[73]
Interstitial laser thermotherapy (ILT) is an innovative method of treating breast cancer in a minimally invasive manner and without the need for surgical removal, and with the absence of any adverse effect on the health and survival of the patient during intermediate followup [74].
Radiation treatment is also used to help destroy cancer cells that may linger after surgery. Radiation can reduce the risk of recurrence by 50-66% (1/2 - 2/3rds reduction of risk) when delivered in the correct dose. [75]
A prognosis is the medical team's "best guess" in how cancer will affect a patient. There are many prognostic factors associated with breast cancer: staging, tumour size and location, grade, whether disease is systemic (has metastasized, or traveled to other parts of the body), recurrence of the disease, and age of patient.
Stage is the most important, as it takes into consideration size, local involvement, lymph node status and whether metastatic disease is present. The higher the stage at diagnosis, the worse the prognosis. Invasiveness of disease to lymph nodes, chest wall, skin or beyond, and aggressiveness of the cancer cells raise the stage, while cancer-free zones, and close to normal cell behaviour (grading) lower it. Size is not a factor in staging unless it is invasive. Ductal Carcinoma in situ throughout the entire breast is stage zero.
Grading is based on how cultured biopsied cells behave. The closer to normal cancer cells are, the slower their growth and a better prognosis. If cells are not well differentiated, they appear immature, divide more rapidly, and 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).
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.
The presence of estrogen and progesterone receptors in the cancer cell, while not prognostic, is important in guiding treatment. Those who do not test positive for these specific receptors will not respond to hormone therapy.
Likewise, HER2/neu status directs the course of treatment. Patients whose cancer cells are positive for HER2/neu have more aggressive disease and may be treated with trastuzumab, a monoclonal antibody that targets this protein.
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. For example, a recent study conducted by researchers at the College of Public Health of the University of Georgia showed that older women may face a more difficult recovery from breast cancer than their younger counterparts.[76] As the incidence of breast cancer in women over 50 rises and survival rates increase, breast cancer is increasingly becoming a geriatric issue that warrants both further research and the expansion of specialized cancer support services tailored for specific age groups.[76]
Several studies have found that black women in the U.S. are more likely to die from breast cancer even though white women are more likely to be diagnosed with the disease. Even after diagnosis, black women are less likely to get treatment compared to white women.[77][78][79] Scholars have advanced several theories for the disparities, including inadequate access to screening, reduced availability of the most advanced surgical and medical techniques, or some biological characteristic of the disease in the African American population.[80] Some studies suggest that the racial disparity in breast cancer outcomes may reflect cultural biases more than biological disease differences.[81] Research is currently ongoing to define the contribution of both biological and cultural factors.[82][78]
Most people understand breast cancer as something that happens in the breast. However it can metastasize (spread) via lymphatics to nearby lymph nodes, usually those under the arm. That is why surgery for breast cancer always involves some type of surgery for the glands under the arm — either axillary clearance, sampling, or sentinel node biopsy.
Breast cancer can also spread to other parts of the body via blood vessels or the lymphatic system. So it can spread to the lungs, pleura (the lining of the lungs), liver, brain, and most commonly to the bones.[83] Seventy percent of the time that breast cancer spreads to other locations, it spreads to bone, especially the vertebrae and the long bones of the arms, legs, and ribs. Usually when breast cancer spreads to bone, it eats away healthy bone, causing weak spots, where the bones can break easily. That is why breast cancer patients are often seen wearing braces or using a wheelchair, and have aching bones.
When breast cancer is found in bones, it has usually spread to more than one site. At this stage, it is treatable, often for many years, but it is not curable. Like normal breast cells, these tumors in the bone often thrive on female hormones, especially estrogen. Therefore treatment with medicines that lower estrogen levels may be prescribed.
Breast cancer may be one of the oldest known forms of cancer tumors in humans. The oldest description of cancer was discovered in Egypt and dates back to approximately 1600 BC. 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."[84] For centuries, physicians described similar cases in their practises, with the same sad conclusion. It wasn't until doctors achieved greater understanding of the circulatory system in the 17th century that they could establish a link between breast cancer and the lymph nodes in the armpit. The French surgeon Jean Louis Petit (1674-1750) and later the Scottish surgeon Benjamin Bell (1749-1806) were the first to remove the lymph nodes, breast tissue, and underlying chest muscle. Their successful work was carried on by William Stewart Halsted who started performing mastectomies in 1882. The Halsted radical mastectomy often involved removing both breasts, associated lymph nodes, and the underlying pectoral muscles. This often led to long-term pain and disability, but was seen as necessary in order to prevent the cancer from recurring.[85] Radical mastectomies remained the standard until the 1970s, when 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.
Prominent women who lost their lives because of breast cancer include Empress Theodora, wife of Justinian; Anne of Austria, mother of Louis XIV of France; Mary Washington, mother of George and the environmentalist Rachel Carson.[86]
In the month of October, breast cancer is recognized by survivors, family and friends of survivors and/or victims of the disease.[87] A pink ribbon is worn to recognize the struggle that sufferers face when battling the cancer.[88]
Pink for October is an initiative started by Matthew Oliphant, which asks that any sites willing to help make people aware of breast cancer, change their template or layout to include the color pink, so that when visitors view the site, they see that the majority of the site is pink. Then after reading a short amount of information about breast cancer, or being redirected to another site, they are aware of the disease itself.[89]
The patron saint of breast cancer is Saint Agatha of Sicily.[90]
The pink and blue ribbon was designed in 1996 by Nancy Nick, President and Founder of the John W. Nick Foundation to bring awareness that "Men Get Breast Cancer Too!"[91]
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