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Breast cancer
SpecialtyOncology Edit this on Wikidata

Breast cancer is a cancer that starts in the breast, usually in the inner lining of the milk ducts or lobules. There are different types of breast cancer, with different stages (spread), aggressiveness, and genetic makeup. With best treatment, 10-year disease-free survival varies from 98% to 10%. Treatment includes surgery, drugs (hormone therapy and chemotherapy), and radiation.[1].

In the United States, there were 216,000 cases of invasive breast cancer and 40,000 deaths in 2004.[2] Worldwide, breast cancer is the second most common type of cancer after lung cancer (10.4% of all cancer incidence, both sexes counted)[3] and the fifth most common cause of cancer death.[4] In 2004, breast cancer caused 519,000 deaths worldwide (7% of cancer deaths; almost 1% of all deaths).[4]

Breast cancer is about 100 times as frequent among women as among men, but survival rates are equal in both sexes.[5][6][7]

Some breast cancers require the hormones estrogen and progesterone to grow, and have receptors for those hormones. Those cancers are treated with drugs that interfere with those hormones, usually tamoxifen, and with drugs that shut off the production of estrogen in the ovaries or elsewhere; this may damage the ovaries and end fertility. Low-risk, hormone-sensitive breast cancers may be treated with hormone therapy and radiation alone. Breast cancers without hormone receptors, or which have spread to the lymph nodes in the armpits, or which express certain genetic characeristics, are higher-risk, and are treated more aggressively. One standard regimen, popular in the U.S., is cycophosphamide plus doxorubicin (Adriomycin), known as CA; these drugs damage DNA in the cancer, but also in fast-growing normal cells where they cause serious side effects. Sometimes a taxane drug, such as docetaxel, is added, and the regime is then known as CAT; taxane attacks the microtubules in cancer cells. An equivalent treatment, popular in Europe, is cyclophosphamide, methotrexate, and fluorouracil (CMF).[8] Monoclonal antibodies, such as trastuzumab, are used for cancer cells that have the HER2 mutation. Radiation is usually added to the surgical bed to control cancer cells that were missed by the surgery, which usually extends survival, although radiation exposure to the heart may cause damage and heart failure in the following years.[9]

Classification

Main article: Breast cancer classification

Breast cancers are described along four different classification schemes, or groups, each based on different criteria and serving a different purpose:

  • Pathology - Each tumor is classified by its histological (microscopic anatomy) appearance and other criteria.[10]
  • Grade of tumor - The histological grade of a tumor is determined by a pathologist under a microscope. A well-differentiated (low grade) tumor resembles normal tissue. A poorly differentiated (high grade) tumor is composed of disorganized cells and, therefore, does not look like normal tissue. Moderately differentiated (intermediate grade) tumors are somewhere in between.
  • Protein & gene expression status - Currently, all breast cancers should be tested for expression, or detectable effect, of the estrogen receptor (ER), progesterone receptor (PR) and HER2/neu proteins. These tests are usually done by immunohistochemistry and are presented in a pathologist's report. The profile of expression of a given tumor helps predict its prognosis, or outlook, and helps an oncologist choose the most appropriate treatment. More genes and/or proteins may be tested in the future.
  • Stage of a tumor - The currently accepted staging scheme for breast cancer is the TNM classification. This considers the Tumor itself, whether it has spread to lymph Nodes, and whether there are any Metastases to locations other than the breast and lymph nodes.

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.[11] In the future, some pathologic classifications may be changed.

Signs and symptoms

The first symptom, or subjective sign, of breast cancer is typically a lump that feels different from the surrounding breast tissue. According to the The Merck Manual, more than 80% of breast cancer cases are discovered when the woman feels a lump.[12] According to the American Cancer Society, the first medical sign, or objective indication of breast cancer as detected by a physician, is discovered by mammogram.[13] Lumps found in lymph nodes located in the armpits[12] 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 ("mastodynia") is an unreliable tool in determining the presence or absence of breast cancer, but may be indicative of other breast health issues.[12][13][14]

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.[12]

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.[15]

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. Common sites of metastasis include bone, liver, lung and brain.[16] 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.[17]

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.[18]

Risk factors

Main article: Risk factors of breast cancer

The primary risk factors that have been identified are sex,[19] age,[20] childbearing, hormones,[21] a high-fat diet,[22] alcohol intake,[23][24] obesity,[25] and environmental factors such as tobacco use, radiation[26], endocrine disruptors and shiftwork.[27] However, studies of environmental and lifestyle factors only attribute a small increase in breast cancer to each factor. Furthermore, these studies are not randomized, controlled trials, and so they may associate breast cancer with factors that don't actually cause breast cancer.[original research?]

No cause is known for 95% of breast cancer cases, while approximately 5% of new breast cancers are attributable to hereditary syndromes.[28] 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.[29]

  • Personal history of breast cancer: A woman who had breast cancer in one breast has an increased risk of getting cancer in her other breast.
  • Family history: A woman's risk of breast cancer is higher if her mother, sister, or daughter had breast cancer. The risk is higher if her family member got breast cancer before age 40. Having other relatives with breast cancer (in either her mother's or father's family) may also increase a woman's risk.
  • Certain breast changes: Some women have cells in the breast that look abnormal under a microscope. Having certain types of abnormal cells (atypical hyperplasia and lobular carcinoma in situ [LCIS]) increases the risk of breast cancer.
  • Race: Breast cancer is diagnosed more often in Caucasian women than Latina, Asian, or African American women.
  • No physical activity: Women who are physically inactive throughout life may have an increased risk of breast cancer. Being active may help decrease risk.
  • Tamoxifen may interact unfavorably with certain antidepressants when used for prevention of breast cancer recurrence.[30]
  • Abortion-breast cancer hypothesis: Mainstream organizations such as the American Cancer Society and National Cancer Institute have concluded there is no link between induced abortion and breast cancer, although a minority of doctors continue to disagree.

Pathophysiology

Main article: Carcinogenesis

Breast cancer, like other forms of cancer, is the outcome of multiple environmental and hereditary factors. Some of these factors include:

  1. Lesions to DNA such as genetic mutations. Mutations that can lead to breast cancer have been experimentally linked to estrogen exposure.[31]
  2. Failure of immune surveillance, a theory in which the immune system removes malignant cells throughout one's life.[32]
  3. Abnormal growth factor signaling in the interaction between stromal cells and epithelial cells can facilitate malignant cell growth.
  4. Inherited defects in DNA repair genes, such as BRCA1, BRCA2[26] and TP53.[33] People in less-developed countries report lower incidence rates than in developed countries.

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. Mutations in either of two major susceptibility genes, breast cancer susceptibility gene 1 (BRCA1) and breast cancer susceptibility gene 2 (BRCA2), 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. However, mutations in these genes account for only 2 to 3 percent of all breast cancers.[34]

Diagnosis

While screening techniques discussed above 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.

In a clinical setting, breast cancer is commonly diagnosed using a "triple test" of clinical breast examination (breast examination by a trained medical practitioner), mammography, and fine needle aspiration cytology. Both mammography and clinical breast exam, also used for screening, can indicate an approximate likelihood that a lump is cancer, and may also identify any other lesions. Fine Needle Aspiration and Cytology (FNAC), which 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.

Screening

Main article: Breast cancer screening
Mammograms showing a normal breast (left) and a breast cancer (right).

Breast cancer screening is an attempt to find cancer in otherwise healthy individuals. The most common screening method for women is a combination of x-ray mammography and clinical breast exam. In women at higher than normal risk, such as those with a strong family history of cancer, additional tools may include genetic testing or breast Magnetic Resonance Imaging.

Breast self-examination was a form of screening that was heavily advocated in the past, but has since fallen into disfavour since several large studies have shown that it does not have a survival benefit for women and often causes considerable anxiety. This is thought to be because cancers that could be detected tended to be at a relatively advanced stage already, whereas other methods push to identify the cancer at an earlier stage where curative treatment is more often possible.

X-ray mammography uses x-rays to examine the breast for any uncharacteristic masses or lumps. Regular mammograms are recommended by several countries in women over a certain age as a screening tool.

Genetic screening involves testing for mutations in the BRCA genes. This is recommended only for those with family history of breast cancer.[citation needed]

Treatment

Main article: Breast cancer treatment
Chest appearance after right breast mastectomy.

The mainstay of breast cancer treatment is surgery. Adjuvant hormonal therapy (with tamoxifen or an aromatase inhibitor) is given when the tumor expresses estrogen receptors or progesterone receptors. Chemotherapy is given for more advanced stages of disease. Monoclonal antibodies are sometimes used, especially for HER2-positive tumors. Radiotherapy is given after surgery to the region of the tumor bed, to destroy microscopic tumors that may have escaped surgery. Treatments are constantly being 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 American Society of Clinical Oncology and St. Gallen, Switzerland.[citation needed] These studies are reviewed by professional societies and other organizations, and formulated into guidelines for specific treatment groups and risk category.

In planning treatment, doctors can also use PCR tests like Oncotype DX or microarray tests that predict breast cancer recurrence risk based on gene expression. In February 2007, the first breast cancer predictor test won 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.[35]

Radiation therapy 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. [36]

In 2008, the American College of Surgeons Oncology Group began a National Cancer Institute funded study to explore the success of cryoablation therapy in the treatment of Invasive Breast Carcinoma. The Visica 2TM Treatment System from Sanarus Technologies was chosen as the exclusive cryoablation treatment technology for the study, which is currently in Phase 2. [37]

Prognosis

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, tumor 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. The stage is raised by the invasiveness of disease to lymph nodes, chest wall, skin or beyond, and the aggressiveness of the cancer cells. The stage is lowered by the presence of cancer-free zones and close-to-normal cell behaviour (grading). Size is not a factor in staging unless the cancer is invasive. Ductal Carcinoma in situ throughout the entire breast is stage zero.

Grading is based on how biopsied, cultured cells behave. The closer to normal cancer cells are, the slower their growth and the better the prognosis. If cells are not well differentiated, they will appear immature, will divide more rapidly, and will tend to spread. Well differentiated is given a grade of 1, moderate is grade 2, while poor or undifferentiated is given a higher grade of 3 or 4 (depending upon the scale used).

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.[38]

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.

Elevated CA15-3, in conjunction with alkaline phosphatase, was shown to increase chances of early recurrence in breast cancer.[39]

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. [40]

On the other hand, 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.[41] 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.[41]

Incidence and death rates

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.[3] In 2004, breast cancer caused 519,000 deaths worldwide (7% of cancer deaths; almost 1% of all deaths).[4] The number of cases worldwide has significantly increased since the 1970s, a phenomenon partly blamed on modern lifestyles in the Western world.[42][43]

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.[44]

Breast cancer can strike at any age, but only 5% of all breast cancers occur in women under 40 years old.[45]

United States

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.[46][47] Among women in the US, breast cancer is the second-most common cancer (after skin cancer) and the second-most common cause of cancer death (after lung cancer).[47] 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.[47] In 2007, breast cancer was expected to cause 40,910 deaths in the US (7% of cancer deaths; almost 2% of all deaths).[13] This figure includes 450-500 men who die annually in the U.S. out of approximately 2000 who contract it.[48]

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.[13][49] Nevertheless, a US study conducted in 2005 by the Society for Women's Health Research indicated that breast cancer remains the most feared disease,[50] even though heart disease is a much more common cause of death among women.[51] Many doctors say that women exaggerate their risk of breast cancer.[52]

Racial disparities

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.[53][54][55] 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.[56] Some studies suggest that the racial disparity in breast cancer outcomes may reflect cultural biases more than biological disease differences.[57] Research is currently ongoing to define the contribution of both biological and cultural factors.[54][58]

UK

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%.[59]

History

Breast cancer may be one of the oldest known forms of cancerous 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."[60] For centuries, physicians described similar cases in their practises, with the same conclusion. It was not 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.[61] 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 died of breast cancer include Empress Theodora, wife of Justinian; Anne of Austria, mother of Louis XIV of France; Mary Washington, mother of George, and Rachel Carson, the environmentalist.[62]


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.[63][verification needed][64]

Prevention

Regular exercise, weight loss, and avoidance of stressors, toxic chemicals and environmental pollutants are all helpful measures in the prevention of breast cancer. Dietary inclusion of dried beans, cruciferous vegetables, and whole grains have also proven beneficial.

Cultural references

In the month of October, the National Breast Cancer Awareness Month is recognized by survivors, family and friends of survivors and/or victims of the disease.[65] A pink ribbon is worn to recognize the struggle that sufferers face when battling with the cancer.[66]

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.[67]

The patron saint of breast cancer is Agatha of Sicily.[68]

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!"[69]

See also

References

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