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) and the fifth most common cause of
cancer death. In 2004, breast cancer caused 519,000 deaths worldwide (7% of cancer
deaths; almost 1% of all deaths). Breast cancer is about 100 times as frequent among
women as among men, but survival rates are equal in both sexes.
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.
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. 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).[citation needed]
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.
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. Lumps found
in lymph nodes located in the armpits and/or collarbone[citation needed] 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 health issues such as mastodynia.

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.
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.

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. 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.

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.
Epidemiology and etiology
There is no cure for breast cancer.
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. [verification needed]

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:
Lesions to DNA such as genetic mutations. Mutations that can lead to breast cancer have
been experimentally linked to estrogen exposure. Beyond the contribution of estrogen,
research has implicated viral transformation and the contribution of ionizing radiation in
causing genetic mutations.[citation needed]
Failure of immune surveillance, a theory in which the immune system removes malignant
cells throughout one's life.
Abnormal growth factor signaling in the interaction between stromal cells and epithelial
cells can facilitate malignant cell growth. For example, tumors can induce blood vessel
growth (angiogenesis) by secreting various growth factors further facilitating cancer
growth.[citation needed]
Inherited defects in DNA repair genes, such as BRCA1, BRCA2 and p53.[citation needed]
People in less-developed countries report lower incidence rates than in developed
countries.

Experts believe that 95 percent of inherited breast cancer can be traced to one of two
genes, which they call Breast Cancer 1 (BRCA1) and Breast Cancer 2 (BRCA2). Hereditary
breast cancers can take the form of a site-specific hereditary breast cancer- cancers
affecting the breast only- or breast- ovarian and other cancer syndromes. Breast cancer
can be inherited both from female and male relatives.

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, age, childbearing, hormones, a
high-fat diet, alcohol intake, obesity, and environmental factors such as tobacco use,
radiation and shiftwork.

No etiology is known for 95% of breast cancer cases, while approximately 5% of new
breast cancers are attributable to hereditary syndromes. 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.

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

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.

Racial disparities in diagnosis and treatment

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. 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. Some studies suggest that the racial disparity in breast cancer
outcomes may reflect cultural biases more than biological disease differences. Research
is currently ongoing to define the contribution of both biological and cultural factors.
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%.
Prevention
Several factors can influence breast cancer incidence either positively or negatively.

Screening
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.

Fine Needle Aspiration Cytology (FNAC) is commonly used as a diagnostic tool in

detecting malignancy in a breast lump. This procedure involves inserting a very fine
needle into the lump and removing some cells, which will then be screened and tested for
malignancy. Anestesia is rarely needed for this procedure given the fineness of the
needle.

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.

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.

Diagnosis This section does not cite any references or sources. Please help improve
this article by adding citations to reliable sources (ideally, using inline citations).
Unsourced material may be challenged and removed. (October 2007)
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.

Staging
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. For a more detailed discussion on staging of breast cancer, see here.

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.

Hormone receptors
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+). Receptor status modifies the treatment as, for
instance, only ER-positive tumors, not ER-negative tumors, are sensitive to hormonal
therapy.

HER2
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. HER2 status can be assessed by immunohistochemistry,
fluorescent/chromogenic/silver in situ hybridization (FISH/CISH/SISH), or virtual
karyotyping.

Treatment
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.

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.

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.

Prognosis This section does not cite any references or sources. Please help improve
this article by adding citations to reliable sources (ideally, using inline citations).
Unsourced material may be challenged and removed. (October 2007)

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. 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 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.

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.

Psychological aspects of diagnosis and treatment

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.

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. 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.
Metastasis
A micrograph showing breast cancer (dark pink) in and around a lymph node (purple).

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.[56] 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.

In 2008, scientists discovered that breast cancer becomes more invasive when a specific
trio of cells are present together in the same anatomic region: an endothelial cell (a type
of cell that lines the blood vessels), a perivascular macrophage (a type of immune cell
found near blood vessels), and a tumor cell that produces the protein Mena. This
important finding could potentially alter the way in which breast cancer is treated.