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Breast cancer

DEFINITION :
Breast cancer
is cancer that develops from breast tissue. 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, or a red scaly patch of skin. In those with distant spread of the disease
, there may be bone pain
, swollen lymph nodes
, shortness of breath, or yellow skin.
FREQUENCY :
Breast cancer is the top cancer in women worldwide and is increasing particularly in
developing countries where the majority of cases are diagnosed in late stages.
Breast cancer is the most common cancer in women both in the developedand less
developed world. It is estimated that worldwide over 508 000 women died in 2011
due to breast cancer (Global Health Estimates, WHO 2013). Although breast cancer
is thought to be a disease of the developed world, almost 50% of breast cancer
cases and 58% of deaths occur in less developed countries (GLOBOCAN 2008).
ILLUSTRATION :
Mammograms showing a normal breast (left) and a breast with cancer (right, white
arrows).
DIAGNOSIS AND MANAGEMENT :
Most types of breast cancer are easy to diagnose by microscopic analysis of a
sampleor biopsy
of the affected area of the breast. !lso, there are types of breast cancer that
re"uire speciali#ed lab e$ams. %he two most commonly used screening methods,
physical e$amination of the breasts by a healthcare provider and mammography,
can offer an appro$imate likelihood that a lump is cancer, and may also detect
some other lesions, such as a simple cyst
. &hen these e$aminations 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'!) to help establish the diagnosis. %he
needle aspiration may be performed in a healthcare provider*s office or clinic using
local anaesthetic if re"uired.
! 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.
%ogether, physical e$amination of the breasts, mammography, and '! can be
used to diagnose breast cancer with a good degree of accuracy+ther options for
biopsy include a core biopsy
or vacuumassisted breast biopsy
-/0
which are procedures in which a section of the breast lump is removed1 or an
e$cisional biopsy
, in which the entire lump is removed. 2ery often the results of physical e$amination
by a healthcare provider, mammography, and additional tests that may be
performed in special circumstances (such as imaging by ultrasoundor M3I) are
sufficient to warrant e$cisional biopsy as the definitive diagnostic and primary
treatment method.
showing a normal breast (left) and a breast with cancer (right, white arrows).

Breast cancers are classified by several grading systems. 4ach of these influences
the prognosis and can affect treatment response. 5escription of a breast cancer
optimally includes all of these factors.
Histopatholog
. 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 lowgrade 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.
-6
Gra!e
. 7rading compares the appearance of the breast cancer cells to the appearance of
normal breast tissue. ormal cells in an organ like the breast become differentiated,
meaning that they take on specific shapesand forms that reflect their function as
part of that organ. ancerous cells lose that differentiation. In cancer, the cells that
would normally line up in an orderly way to make up the milk ducts become
disorgani#ed. ell division becomes uncontrolled. ell nuclei become less uniform.
8athologists 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. 8oorly
differentiated cancers (the ones whose tissueis least like normal breast tissue) have
a worse prognosis
Stage
. Breast cancer staging using the %M system is based on the si#e of the tumor (
T
), whether or not the tumor has spread to the lymph nodes (
N
) in the armpits, and whether the tumor has metastasi#ed (
M
) (i.e. spread to a more distant part of the body). 9arger si#e, nodal spread, and
metastasis have a larger stage number and a worse prognosis.%he main stages are:
Stage / is a precancerous or marker condition, either ductal carcinoma in situ
(5IS) or lobular carcinoma in situ (9IS).
Stages 6;< are within the breast or regional lymph nodes.
Stage = is *metastatic* cancer that has a less favorable prognosis since it has
spread beyond the breast and regional lymph nodes.&here available, imaging
studies may be employed as part of the staging process in select cases to look for
signs of metastatic cancer. >owever, in cases of breast cancer with low risk for
metastasis, the risks associated with 84% scans, % scans, or bone scans outweigh
the possible benefits, as these procedures e$pose the patient to a substantial
amount of potentially dangerous ioni#ing radiation.
Receptor stat"s
. Breast cancer cells have receptors on their surface and in their cytoplasm and
nucleus. hemical messengers such as hormones bind to receptors, and this
causes changes in the cell. Breast cancer cells may or may not have three
important receptors: estrogen receptor (43), progesterone receptor (83), and
>43?.43@ cancer cells (that is, cancer cells that have estrogen receptors) depend
on estrogen for their growth, sothey can be treated with drugs to block estrogen
effects (e.g.tamo$ifen), and generally have a better prognosis. Antreated, >43?@
breast cancers are generally more aggressive than >43? breast cancers,
-=0-0
but >43?@ cancer cells respond to drugs such as the monoclonal antibody
trastu#umab (in combination with conventional chemotherapy), and this has
improved the prognosis significantly.
-C0
ells that do not haveany of these three receptor types (estrogen receptors,
progesterone receptors, or >43?) are called triple negative, although they
fre"uently do e$press receptors for other hormones, such as androgen receptor and
prolactin receptor .
DNA assas
. 5! testing of various types including 5! microarrays have compared normal cells
to breastcancer cells. %he specific changes in a particular breast cancer can be
used to classify the cancer in severalways, and may assist in choosing the most
effective treatment for that 5! type.%he management of breast cancer depends on
various factors, including the stage of the cancer and the age of the patient.
Increasingly aggressive treatments are employed in accordance with the poorer the
patient*s prognosis and the higher the risk of recurrence of the cancer following
treatment.Breast cancer is usually treated with surgery, which may be followed by
chemotherapy or radiation therapy, or both. ! multidisciplinary approach is
preferable.
-66?0
>ormone receptorpositive cancers are often treated with hormone blocking
therapy over courses of several years. Monoclonal antibodies, or other
immunemodulating treatments, may be administered in certain cases of
metastatic and other advanced stages of breast cancer.
SURGER# :
Surgery involves the physical removal of the tumor, typically along with some of the
surrounding tissue. +ne or morelymph nodes may be biopsied during the surgery1
increasingly the lymph node sampling is performed by a sentinel lymph node
biopsy.
MEDICATION :
5rugs used after and in addition to surgery are called adDuvant therapy.
hemotherapy or other types of therapy prior to surgery are called neoadDuvant
therapy. !spirin may reduce mortality from breast cancer .
-66<0
%here are currently three main groups of medications used for adDuvant breast
cancer treatment: hormoneblocking agents, chemotherapy, and monoclonal
antibodies.
HORMONE BLO$%ING THERA&H#
Some breast cancers re"uire estrogen to continue growing. %hey can be identified
by the presence of estrogen receptors (43@) and progesterone receptors (83@) on
their surface (sometimes referred to together as hormone receptors).
$HEMOTHERA&H#
hemotherapy is predominantly used for cases of breast cancer in stages ?;=, and
is particularly beneficial in estrogen receptornegative (43 ) disease. %he
chemotherapy medications are administeredin combinations, usually for periods of
<;C months
MONO$LONAL ANTIBODIES
%rastu#umab, a monoclonal antibody to >43? (a cell receptor that is especially
active in some breast cancer cells), has improved the year disease free survival
of stage 6;< >43?positive breast cancers to about EF (overall survival G F).
RADIATION THERA&H# :
3adiotherapy
is given after surgery to the region of the tumor bed and regional lymph nodes, to
destroy microscopictumor cells that may have escaped surgery. It may also have a
beneficial effect on tumor microenvironment. 3adiation therapy can be delivered
ase$ternal beam radiotherapy or as brachytherapy (internal radiotherapy).
onventionally radiotherapy is give after
the operation for breast cancer. 3adiation can also be given at the time of
operation on the breast cancer. 3adiation can reduce the risk of recurrence by
/;CCF (6H? ; ?H< reduction of risk) when delivered in the correct dose
-6?=0
and is considered essential when breast cancer is treatedby removing only the
lump (9umpectomy or &ide local e$cision).
&ROGNOSIS :
8rognosis is usually given for the probability of progression free survival (8'S) or
diseasefree survival (5'S). %hese predictions are based on e$perience with breast
cancer patients with similar classification. ! prognosis is an estimate, as patients
with the same classification will survive a different amount of time, and
classifications are not always precise. Survival is usually calculated as an average
number of months (or years) that /F of patients survive, or the percentage of
patients that are alive after 6, , 6, and ?/ years. 8rognosis is important for
treatment decisions because patients with a good prognosis are usually offered less
invasive treatments, such as lumpectomy and radiation or hormone therapy, while
patients with poor prognosis are usually offered more aggressive treatment,such as
more e$tensive mastectomy and one or more chemotherapy drugs.8rognostic
factors are reflected in the classification scheme for breast cancer including stage,
(i.e., tumor si#e, location, whether disease has spread to lymph nodes and other
parts of the body), grade, recurrence of the disease,and the age and health of the
patient. %he ottingham 8rognostic Inde$ is a commonly used prognostic tool.
Stage 6 cancers (and 5IS, 9IS) have an e$cellent prognosis and are generally
treated with lumpectomy and sometimes radiation. >43?@ cancers should be
treated with the trastu#umab (>erceptin) regime. hemotherapy is uncommon for
other types of stage 6 cancers
Stage ? and < cancers with a progressively poorer prognosis and greater risk of
recurrence are generally treated with surgery (lumpectomy or mastectomy with or
without lymph node removal), chemotherapy (plus trastu#umab for >43?@
cancers) and sometimes radiation (particularly following large cancers, multiple
positive nodes or lumpectomy).
Stage =, metastatic cancer, (i.e. spread to distant sites) has poor prognosis and is
managed by various combination of all treatments from surgery, radiation,
chemotherapy and targeted therapies. %enyear survival rate is F without
treatment and 6/F with optimal treatment.ounger women with an age of less than
=/ years or women over / years tend to have a poorer prognosis than
postmenopausal women due to several factors. %heir breasts may change with
their menstrual cycles, they may be nursing infants, and they may be unaware of
changes in their breasts. %herefore, younger women are usually at a more
advanced stage when diagnosed. %here may also be biologic factors contributing to
a higher risk of disease recurrence for younger women with breast cancer.>igh
mammographic breast density, which is a marker of increased risk of developing
breast cancer, may not mean an increased risk of death among breast cancer
patients, according to a ?/6? report of a study involving G?<? women by the
ational ancer Institute (I). +n the other hand, more recent research has
shown that women withe$tremely low mammographic densities (J6/F) hold a
significantly worse prognosis compared to women with other densities, irrespective
of all possible confounding factors.Since breast cancer in males is usually detected
at later stages, outcomes are typically worse.
&RE'ENTION :LIFE ST#LE :
&omen may reduce their risk of breast cancer by maintaining a healthy weight,
drinking less alcohol, being physically active and breastfeeding their children. %he
benefits with moderate e$ercise such as brisk walking are seen at all age groups
including postmenopausal women. >igh levels of physical activity reduce the risk of
breast cancer by about 6=F.
Strategies that encourage regular physical activity and reduce obesity could also
have other benefits, such as reduced risks of cardiovascular disease and
diabetes.>igh intake of citrus fruit has been associated with a 6/F reduction in the
risk of breast cancer.Marine omega< polyunsaturated fatty acids appear to
reduce the ris >igh consumption of soybased foods may reduce risk.
&RE ( EM&TI'E SURGER# :
3emoval of both breasts before any cancer has been diagnosed or any suspicious
lump or other lesion has appeared (a procedure known as prophylactic bilateral
mastectomy) may be considered in people with B3 !6 and B3 !? mutations, which
are associated with a substantially heightened risk for an eventual diagnosis of
breast cancer. 4vidence is not strong enough to support this procedure in anyone
but those at the highest risK .
B3! testing is recommended in those with a high family risk after genetic
counseling. It is not recommended routinely.
%his is because there are many forms of changes in
BRCA
genes, ranging from harmless polymorphisms to obviously dangerous frameshift
mutations. %he effect of most of the identifiable changes in the genes is uncertain.
%esting in an averagerisk person is particularly likely to return one of these
indeterminate, useless results. It is unclear if removing the second breast in those
who have breast cancer in one is beneficial.
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