c
 


MIMS Class : Antiasthmatic & COPD Preparations, Drugs Acting on the Uterus
See available brands of salbutamol

See related salbutamol information

Indication & 2

Dosage a  

c c
a

mg (up to 8 mg) 3
times daily. As modified release tablet: 8
mg bid.
 1 mth  yr: 100 mcg/kg (max:  mg),   yr: 1  mg, > yr:  mg.
Doses to be taken 3
times daily.

Initially,  mg 3
times daily.
„



a  

c c
a
As aerosol: 100 or 00 mcg (1  puffs) 3
times daily.  puffs may
be given prior to exertion to prevent exercise induced bronchospasm.
„



a c  c

a
As MDI:
 inhalations may be given every 10 0 min via a large
volume spacer.
`
 

›  

c c
a
0 mcg (as a solution of 0 mcg/ml) via IV inj, or via IV infusion of
a solution containing  mg in 00 ml at a rate of 3 0 mcg/min adjusted
according to patient's need. Higher dosages may be used in respiratory
failure. IM/SC: 00 mcg, repeated every
hr if necessary.
„ 
 
!

   

a
or arrest of preterm labor between 
and 33 wk of gestation:
Initially, 10 mcg/min using a dilute solution of 0 mcg/ml in glucose 
(00 mcg/ml of salbutamol if using a syringe pump), increase rate gradually
at 10 min intervals until there is response; then increase slowly until
contractions cease. Maintain rate for 1 hr after contractions have stopped,
then gradually reduce rate by 0 at intervals of  hr. Usual dose: 10

mcg/min. Avoid prolonged therapy.
„



›  

c c
a
Via nebuliser: .  mg, may repeat up to
times daily.
Alternatively, may be given continuously at a rate of 1  mg/hr. Patients
with asthma may require supplemental oxygen.
 >18 mth: Via nebuliser: .  mg, may repeat up to
times daily.
Alternatively, may be given continuously at a rate of 1  mg/hr. Patients
 with asthma may require supplemental oxygen.
Administration Should be taken on an empty stomach. (Take 1 hr before or  hr after
meals.)
Overdosage May lead to tachycardia, tremor, CNS stimulation, hypokalaemia and
hyperglycaemia. Symptomatic treatment is recommended.
Contraindications Eclampsia and severe pre eclampsia; intra uterine infection, intra uterine
foetal death, antepartum haemorrhage, placenta praevia and cord
compression, threatened miscarriage, cardiac disease.
Special Pregnancy; mild to moderate pre eclampsia. Arrhythmias, hyperthyroidism,
Precautions hypertension, DM, myocardial insufficiency, susceptibility to QT interval
prolongation. Monitor serum potassium levels. In women treated for
premature labour, monitor hydration status, cardiac and respiratory function.
Minimise volume of infusion fluid. Discontinue treatment if patient
develops signs of pulmonary oedema.
Adverse Drug ine skeletal muscle tremor especially hands, tachycardia, palpitations,
Reactions muscle cramps, headache, paradoxical bronchospasm, angioedema,
urticaria, hypotension and collapse.
`


 
Potentially serious hypokalaemia after large doses.
Drug Interactions Diuretics, corticosteroids and xanthines may augment hypokalaemia. CV
effects potentiated by MAOIs, TCAs, sympathomimetics. Increases
absorption of sulfamethoxazole when used together. May markedly increase
heart rate and BP when used with atomoxetine. Reduces serum levels of
digoxin. Hypokalaemia induced by salbutamol increases the risk of digitalis
toxicity. BP should be closely monitored if linezolid is used concurrently
with salbutamol.
Click to view more Drug Interactions
Pregnancy
Category (US
DA)   : Either studies in animals have revealed adverse effects on
the foetus (teratogenic or embryocidal or other) and there are no controlled
studies in women or studies in women and animals are not available.
Drugs should be given only if the potential benefit justifies the potential
risk to the foetus.
Storage 


 
Store between  C (3 ). 
 
cStore below
30C. Protect from light. 
Store at 0 C (8 ). ` 


Store below 30C. Protect from light.
Mechanism of Salbutamol is a direct acting sympathomimetic with ȕ adrenergic activity
Action and selective action on ȕ receptors, producing bronchodilating effects. It
also decreases uterine contractility.

cInhalation:  1 min; oral: 30 min.
  
Inhalation: 3  hr; oral: 8 hr; modified release preparation: 1 hr.
ac  
Readily absorbed from the GI tract.
 
cHepatic and in the gut wall.
 Π 
Via the urine as metabolites and unchanged drug. Some
excretion in the faeces.
MIMS Class Antiasthmatic & COPD Preparations / Drugs Acting on the Uterus
ATC R03AC0 salbutamol; Belongs to the class of adrenergic inhalants,
Classification selective beta  adrenoreceptor agonists. Used in the treatment of
obstructive airway diseases.
R03CC0 salbutamol; Belongs to the class of adrenergics for systemic use,
selective beta  adrenoreceptor agonists. Used in the treatment of
obstructive airway diseases.
?

 
 c


 
UAP [ United Lab ]
MIMS Class : Antiasthmatic & COPD Preparations

See related Duavent Metered dose inhaler information

Contents ` 


 Ipratropium Br 00 mcg, salbutamol sulfate .
mg. `    
Ipratropium Br 1 mcg, salbutamol sulfate 10 mcg
Indications Management of reversible bronchospasm associated with obstructive
airway diseases (eg, bronchial asthma).

or patients with chronic obstructive pulmonary disease (COPD) on a

regular inhaled bronchodilator who continue to have evidence of
bronchospasm and who require a second bronchodilator.
Dosage `
  Each pulmoneb of ipratropium bromide salbutamol contains
00 mcg (. mg) of salbutamol base (with each drop containing 0
mcg).

a
 
 


 a 



]  
 a a c 1 pulmoneb (. mL) is sufficient for
prompt symptom relief in many cases;  pulmonebs ( mL) may be
required in severe cases where an attack has not been relieved by 1
pulmoneb.




]  
1 pulmoneb (. mL) every  8 hrs daily.

 

 3 drops/kg/dose, maximum dose 00 mcg (.
mg) of salbutamol every  8 hrs.

a
c  
 The solution is intended only for inhalation with
suitable nebulizing devices and should not be taken orally.

Prepare the nebulizer for use. Remove the pulmoneb from the labeled
strip by twisting and pulling. Hold the pulmoneb upright and twist off the
cap, transfer the contents to the reservoir of the nebulizer. (Note: In most
studies, a volume fill of
mL in the nebulizer chamber, using sterile
normal saline as diluent, is recommended to ensure high aerosol output,
small respirable particle size and acceptably short treatment time.)

Use the nebulizer as instructed by the manufacturer. After use, discard

any remaining solution and thoroughly clean the nebulizer.

Other Information: Since the solution contains no preservatives, it is

important to use the content soon after opening. A new pulmoneb should
be used for each administration to avoid microbial contamination.
Discard partly used, opened or damaged pulmoneb. Do not mix the
inhalation solution with other drugs in the same nebulizer.

m   „

  a
  


  actuations
every  hrs.

Patients may have additional inhalations as required but should not

exceed 1 actuations in 
hrs.

Directions for Use:

1. Before using the inhaler for the 1st time, or if it has not been used for a
week or longer, shake it well and then "test fire" by releasing 1 actuation
into the air. Avoid spraying in the eyes.

. Shake the inhaler well before each use.

3. Remove the mouthpiece cover, and check if it is clean.

. Hold the inhaler between the index and thumb. Breathe out deeply
through the mouth and immediately place the mouthpiece in the mouth
between the teeth and close lips around it.
 . Tilt head slightly backwards. Keep the eyes closed because ocular
undesirable effects (ie, temporary blurring of vision, precipitation or
worsening of narrow angle glaucoma, eye pain) may result after contact
of the aerosol with the eyes.

. Start breathing in slowly and deeply through the mouth. Press down
the canister while breathing in to release 1 dose while continuing to
breathe in steady and deeply.

. Remove the inhaler from the mouth and hold breath for 10 seconds, or
for as long as comfortable. Breathe out slowly.

8. or the nd dose, wait for at least 1 min and repeat steps
.

9. After use, replace the mouthpiece cover.

Cleaning Instructions: Clean inhaler at least once a week.

1. Gently pull the metal canister out of the inhaler's adapter. Remove the
mouthpiece cover.

. Rinse the adapter and the mouthpiece cover in warm water. Do not put
the metal canister in water.

3. Shake well to remove excess water.

. Leave to dry in warm place. Avoid excess heat.

. Replace the canister and mouthpiece cover correctly.

Overdosage ›c Metered Dose Inhaler: Signs and symptoms of overdose are
associated with salbutamol since ipratropium bromide is not well
absorbed after oral inhalation. These include extensions of salbutamol's
common undesirable effects (eg, angina, hypertension or hypotension,
arrhythmias, palpitation, tachycardia, nervousness, dizziness, tremor,
headache, sleeplessness or insomnia, dry mouth and nausea).
Hypokalemia has also been reported; thus, plasma potassium
concentrations should be monitored.

]  
 Discontinue the use of Duavent and institute appropriate
symptomatic therapy in cases of overdosage. Administration of a ȕ
adrenergic blocking agent may be appropriate, but use with caution if the
patient is asthmatic. There is no adequate evidence to support the use of
dialysis in the treatment of salbutamol overdose.
Contraindications Hypersensitivity to soya lecithin or related food products eg, soybeans or
peanuts; and to any component of Duavent or to atropine and its
 derivatives. Hypertrophic obstructive cardiomyopathy or
tachyarrhythmia.
Warnings Pulmoneb: Ipratropium bromide salbutamol combination can produce
paradoxical bronchospasm that can be life threatening. If it occurs,
discontinue the preparation immediately and institute alternative therapy.
It should be recognized that paradoxical bronchospasm, when associated
with inhaled formulations, frequently occurs with the first use of a new
pulmoneb.

Salbutamol sulfate contained in the formulation, like other ȕ adrenergic

agonists, can produce a clinically significant cardiovascular effect in
some patients as measured by pulse rate, blood pressure and/or other
symptoms. Such effects are uncommon after administration of the
combination at recommended doses.

Metered Dose Inhaler: If a previously effective dose fails to provide the

usual relief, symptoms become worse, or the usual duration of action is
reduced, consult a physician for medicinal advice as this would require
reassessment of therapy.

Excessive use of sympathomimetic oral inhalations has been associated

with fatalities in asthmatic patients. The exact cause of death in unknown
but cardiac arrest following severe, acute asthmatic crisis and hypoxia is
suspected.

Paradoxical bronchospasm, a potentially life threatening event,

frequently occurs with the 1st use of a new canister. If it occurs,
discontinue the use of Duavent immediately.

Therapy with salbutamol and other ȕ agonists may produce decrease in

plasma potassium concentration possibly through intracellular shunting
resulting in cardiovascular undesirable effects.

Immediately hypersensitivity reactions including urticaria, angioedema,

rash, bronchospasm, anaphylaxis and oropharyngeal edema may occur
rarely after administration of Duavent.
Special Precautions Patients should avoid spraying the aerosol into the eyes since this may
result in precipitation or worsening of narrow angle glaucoma, eye pain
or discomfort, temporary blurring of vision, visual halos or colored
images in association of red eyes from conjunctival and corneal
congestion. Consult a physician if any combination of these symptoms
develops. Use with caution in patients with the following conditions:
Prostatic hypertrophy or bladder neck obstruction; convulsive disorders,
hyperthyroidism or diabetes mellitus and in patients who are unusually
responsive to sympathomimetic amines (ȕ adrenergic agents may also
 produce significant hypokalemia in some patients, possibly through
intracellular shunting, which has the potential to produce adverse
cardiovascular effects. The decrease in serum potassium is usually
transient, not requiring supplementation.); hepatic or renal disease, since
use of Duavent in these patients has not been studied.

!c
 

!
  
 Safety and efficacy of Duavent during
pregnancy has not yet been established. The inhibitory effect of Duavent
on uterine contraction should be taken into account.

It is not known whether the components (ipratropium bromide and

salbutamol sulfate) of the DC are excreted in human milk. Although
lipid insoluble quaternary bases pass into breast milk, it is unlikely that
ipratropium bromide would reach the infant to an important extent,
especially when taken as a nebulized solution. Because of the potential
for tumorigenicity shown for salbutamol sulfate in some animals, a
decision should be made whether to discontinue nursing or discontinue
the drug, taking into account the importance of the drug to the mother.

Labor and Delivery: Since ȕ agonists may interfere with uterine

contraction, Duavent should be used in labor only if the potential benefit
justifies the potential risk.

!c


 
 The safety and efficacy of the DC in patients <18
years have not been established.
Adverse Drug Pulmoneb: The following adverse effects were reported by • in
Reactions patients with COPD in a 1 week controlled clinical trial on ipratropium
bromide salbutamol sulfate combination (N=38):

Body as a Whole (General Disorders): Headache, pain, influenza, chest

pain.

Gastrointestinal: Nausea.

Respiratory: Bronchitis, dyspnea, coughing, pneumonia, bronchospasm,

pharyngitis, sinusitis, rhinitis.

Additional adverse reactions, reported in < of patients include edema,

fatigue, hypertension, dizziness, nervousness, paresthesia, tremor,
dysphonia, insomnia, diarrhea, dry mouth, dyspepsia, vomiting,
arrhythmia, palpitation, tachycardia, arthralgia, angina, increased
sputum, taste perversion and urinary tract infection/dysuria. Allergic
type reactions eg, skin rash, angioedema of the tongue, lips and face,
urticaria, laryngospasm and anaphylactic reaction have also been
reported.
 Metered Dose Inhaler: The most frequently reported undesirable effects
of ipratropium bromide salbutamol combination include bronchitis,
dyspnea, cough, lower respiratory tract disorders, pneumonia,
bronchospasm, upper respiratory tract disorders, sinusitis, pharyngitis,
rhinitis, influenza, nasal congestion, wheezing, central nervous system
stimulation, tremor, nervousness, dizziness, headache, sleeplessness or
insomnia, tachycardia, palpitation, angina, pain, weakness, nausea,
vomiting, diarrhea, dyspepsia, dry mouth, dysphonia, increased sputum,
unusual taste/taste perversion and urinary tract infection/dysuria.

Cases of skin rash, angioedema of the tongue, lips and face, urticaria,
laryngospasm, oropharyngeal edema, anaphylactic reactions and
paradoxical bronchospasm have also been reported.

The following adverse effects have been noted after oral inhalation of
ipratropium bromide: Precipitation or worsening of narrow angle
glaucoma, blurred vision, acute eye pain, drowsiness, coordination
difficulty, hypotension, exacerbation of respiratory symptoms, fatigue,
paresthesia, pruritis, flushing, alopecia, irritation, drying of secretions,
GI distress, mucosal ulcers and urinary retention/difficulty.

The following adverse effects have been observed after administration of

inhaled salbutamol: Edema, hypertension or hypotension, arrhythmias
(including atrial fibrillation, supraventricular tachycardia and
extrasystoles), heartburn, sweating and rarely muscle cramos. Potentially
serious hypokalemia has been reported.
Click to view ADR Monitoring Website
Drug Interactions Anticholinergic Agents: Although ipratropium bromide is minimally
absorbed into the systemic circulation, there is some potential for an
additive interaction with concomitantly used anticholinergic medications.

Beta Adrenergic Agents: Co administration with other sympathomimetic

agents may increase risk of adverse cardiovascular events.

Beta Receptor Blocking Agents: Salbutamol and a ȕ receptor blocking

agent inhibit each other's effect.

Diuretics: The ECG changes and/or hypokalemia which may result from
the administration of non potassium sparing diuretics (eg, loop or
thiazide diuretics) can be acutely worsened by ȕ agonists, especially
when the recommended dose of the ȕ agonist is exceeded.

Monoamine Oxidase Inhibitors (MAOI) or Tricyclic Antidepressant

(TCAs): Concomitant administration with these agents may potentiate
salbutamol's effect on the cardiovascular system.
View more drug interactions for Duavent
Pregnancy Category
(US DA)
  : Either studies in animals have revealed adverse effects on
the foetus (teratogenic or embryocidal or other) and there are no
controlled studies in women or studies in women and animals are not
available. Drugs should be given only if the potential benefit justifies
the potential risk to the foetus.
Storage Store at temperatures not exceeding 30C. Protect from direct sunlight or
heat. Do not freeze or refrigerate.

Pulmoneb: Do not use if the solution is discolored.

Metered Dose Inhaler: Exposure to temperatures >
8C (10) may

cause bursting. Do not break, puncture or burn the canister even when
apparently empty.
Description Pulmoneb: Each . mL pulmoneb contains ipratropium bromide
anhydrous 00 mcg and salbutamol sulfate . mg.

Metered Dose Inhaler: Each actuation delivers ipratropium bromide BP

monohydrate 1 mcg (equivalent to 0 mcg ipratropiun bromide
anhydrous) and salbutamol sulfate 10 mcg (equivalent to 100 mcg
salbutamol BP).

Duavent 0 mcg/100 mcg/actuation metered dose inhaler is a milky

white homogenous suspension filled in aluminum container in propellant
gases with suitable surface active agent. The aluminum container is fitted
with a metering valve and a plastic oral actuator.
Mechanism of `
 
 Ipratropium bromide: Ipratropium bromide is a
Action quaternary ammonium compound with anticholinergic
(parasympatholytic) properties. Similar to atropine, it is a nonselective
competitive antagonist of muscarinic receptors present in airways and
other organs. Ipratropium bromide relaxes smooth muscles of bronchi
and bronchioles by blocking acetylcholine induced stimulation of guanyl
cyclase, thus reducing formation of cyclic guanosine monophosphate
(cGMP), a mediator of bronchoconstriction. Ipratropium generally
exhibits greater antimuscarinic activity of bronchial smooth muscle than
on secretory (eg, salivary, gastric) glands.

Ipratropium bromide is a potent bronchodilator, particularly in large

bronchial airways; however, some evidence suggests that it also has
bronchodilator activity in small airways. Bronchodilation results from
relaxation of smooth muscles of the bronchial tree. The extent of
bronchodilation produced by ipratropium appears to be determined by
the level of cholinergic parasympathetic bronchomotor tone and by
inhibition of bronchoconstriction resulting from neural reflex activation
of cholinergic pathways.

Salbutamol: Salbutamol stimulates adenyl cyclase, the enzyme which

catalyzes the formation of cyclic 3', ' adenosine monophosphate
(cAMP) from adenosine triphosphate (ATP). The cAMP thus formed
mediates the cellular response eg, bronchial smooth muscle relaxation. „ 
  and   pharmacologic studies have demonstrated that
salbutamol has a preferential effect on ȕ adrenergic receptors that are
especially found in respiratory tract compared with isoproterenol.
Salbutamol has been shown in most controlled studies to have more
effect on respiratory tract, in the form of bronchial smooth muscle
relaxation, than isoproterenol at comparable doses while producing fewer
cardiovascular effects.

Rationale of Combination: Ipratropium bromide salbutamol fixed dose

combination (DC) maximizes the response to treatment in patients with
bronchial asthma and chronic obstructive pulmonary disease (COPD) by
increasing bronchodilation through  distinctly different mechanisms ie,
anticholinergic (parasympatholytic) and ȕ agonist (sympathomimetic)
effects. Simultaneous administration of both an anticholinergic
(ipratropium bromide) and a ȕ sympathomimetic (salbutamol sulfate)
produces a greater bronchodilator effect than when either drug is used
alone.

`
 
 c Pulmoneb: Two 3 month double blind, randomized,
parallel, multicenter clinical trials were done in a total of 10 patients
with stable COPD comparing ipratropium bromide salbutamol
combination with each individual component. Pulmonary function test
(PT) response rates were analyzed using 1 and 1 increases in
EV, compared with baseline values and were measured in various
treatment groups on days 1, 9,  and 8 in these trials. Regardless of
whether a 1 or a 1 increase in EV was used to define a positive
response, the ipratropium bromide salbutamol combination was superior
to the individual agents (p<0.0; all comparisons within 30 min). A
•1 increase in EV was seen in >80 of patients who received the
ipratropium and salbutamol sulfate combination administered as a single
inhalation aerosol.

Studies demonstrate that each component of the DC contributed to the

improvement of pulmonary function produced by the combination
especially during the 1st
 hrs after the dosing, and that the ipratropium
bromide salbutamol inhalation was significantly more effective than
ipratropium bromide or salbutamol administered alone.

In a crossover pharmacokinetic study in 1 healthy male volunteers

comparing the pattern of absorption and excretion of  inhalations of the
 ipratropium bromide salbutamol DC to the  active components
individually, the co administration of ipratropium bromide from a single
inhalation preparation did not significantly alter the systemic absorption
of either component. Ipratropium bromide levels remained below
detectable limits (<100 pg/mL). Peak salbutamol level obtained within 3
hrs post administration was
913 pg/mL. ollowing this single
administration .1. of the estimated mouthpiece dose was
excreted unchanged in the 
hr urine. rom pharmacokinetic
perspective, the synergistic efficacy of the DC is likely to be due to a
local effect on the muscarinic and ȕ adrenergic receptors in the lung.

Ipratropium bromide is minimally bound (0 9   ) to plasma

albumin and Į1 acid glycoprotein. It is partially metabolized to inactive
ester hydrolysis products.

Salbutamol is extensively metabolized in the liver, mainly to salbutamol

' O sulfate which has little or no ȕ adrenergic stimulating effect and no
ȕ adrenergic blocking effect. Unlike isoproterenol, salbutamol is not
metabolized by the enzyme catechol O methyl transferase and is not a
substrate for catecholamine cellular uptake processes.

Metered Dose Inhaler: After oral inhalation of ipatropium bromide

salbutamol sulfate combination in patients with COPD, the onset of
bronchodilation is evident within 1 min, with peak effect in 1 hr.
Bronchodilation persists for
 hrs with the combination compared with

hrs with ipratropium bromide alone and 3 hrs for salbutamol alone.
Ipratropium's peak plasma concentration remains below detectable limits
(<100 pg/mL) white maximum salbutamol concentration is
9 pg/mL
occurring within 3 hrs after administration; .1 of the estimated
mouthpiece dose of ipratropium salbutamol combination is excreted in
urine as unchanged drug within 
hrs.

Ipratropium is 0 9 bound to lasma albumin and Į1 acid glycoproteins

  . It is partially metabolized to N isopropylnortropium
methobromide, an inactive ester hydrolysis product.

Salbutamol is metabolized in the liver, being converted to salbutamol
'

2 sulafet which has little or no ȕ adrenergic stimulating effect and no ȕ
adrenergic blocking effect.

Animal studies show that salbutamol can cross the blood brain barrier
and the placenta. It may be secreted in breast milk, but the concentrations
are not known.
MIMS Class Antiasthmatic & COPD Preparations
ATC Classification R03AK0
Salbutamol and other drugs for obstructive airway diseases ;
 Belongs to the class of adrenergics and other inhalants used in the
treatment of obstructive airway diseases.
Poison Schedule Rx
Presentation/Packing Pulmoneb . mL x 0's. Metered dose inhaler 00 doses.
?

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M  c
 (malignant breast neoplasm) is cancer originating from breast tissue, most
commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk.
Cancers originating from ducts are known as ductal carcinomas; those originating from lobules
are known as lobular carcinomas.

Prognosis and survival rate varies greatly depending on cancer type and staging.[1] Computerized
models are available to predict survival.[] With best treatment and dependent on staging, 10 year
disease free survival varies from 98 to 10. Treatment includes surgery, drugs (hormonal
therapy and chemotherapy), and radiation.

Worldwide, breast cancer comprises 10.
 of all cancer incidence among women, making it the
most common type of non skin cancer in women and the fifth most common cause of cancer
death.[3] In 00
, breast cancer caused 19,000 deaths worldwide ( of cancer deaths; almost
1 of all deaths).[
] Breast cancer is about 100 times more common in women than in men,
although males tend to have poorer outcomes due to delays in diagnosis.[][][][8]

Some breast cancers are sensitive to hormones such as estrogen and/or progesterone, which
makes it possible to treat them by blocking the effects of these hormones in the target tissues.
Estrogen and progesterone receptor positive tumors have better prognosis and require less
aggressive treatment than hormone negative cancers.

Breast cancers without hormone receptors, or which have spread to the lymph nodes in the
armpits, or which express certain genetic characteristics, are higher risk, and are treated more
aggressively. One standard regimen, popular in the U.S., is cyclophosphamide plus doxorubicin
(Adriamycin), 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
(CM).[9] Monoclonal antibodies, such as trastuzumab (Herceptin), are used for cancer cells that
have HER/neu overexpressed. 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.[10]
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Breast cancers can be classified by different schemata. Every aspect influences treatment
response and prognosis. Description of a breast cancer would optimally include multiple
classification aspects, as well as other findings, such as signs found on physical exam.
Classification aspects include stage (TNM), pathology, grade, receptor status, and the presence
or absence of genes as determined by DNA testing:

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The first noticeable symptom of breast cancer is typically a lump that feels different from the rest
of the breast tissue. More than 80 of breast cancer cases are discovered when the woman feels
a lump.[1
] The earliest breast cancers are detected by a mammogram.[1] Lumps found in lymph
nodes located in the armpits[1
] 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.[1
][1][1]

Inflammatory breast cancer is a special type of breast cancer which can pose a substantial
diagnostic challenge. Symptoms may resemble a breast inflammation and may include pain,
swelling, nipple inversion, warmth and redness throughout the breast, as well as an orange peel
texture to the skin referred to as i
 
.[1
]

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.[1]

In rare cases, what initially appears as a fibroadenoma (hard movable 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.[18]

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.[19] 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.[0]

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.[1]

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The primary epidemiologic and risk factors that have been identified are sex,[] age,[3] lack of
childbearing or breastfeeding,[
][] higher hormone levels,[][] race, economic status and also
dietary iodine deficiency.[8][9][30]

In ood, Nutrition, Physical Activity and the Prevention of Cancer: a Global Perspective, a 00
report by American Institute for Cancer Research/ World Cancer Research und, it concluded
women can reduce their risk by maintaining a healthy weight, drinking less alcohol, being
physically active and breastfeeding their children.[31] This was based on an review of 83
separate studies.

In 009 World Cancer Research und announced the results of a further review that took into
account a further 81 studies published subsequently. This did not change the conclusions of the
00 Report. In 009, WCR/ AICR published Policy and Action for Cancer Prevention, a
Policy Report that included a preventability study.[3] This estimated that 38 of breast cancer
cases in the US are preventable through reducing alcohol intake, increasing physical activity
levels and maintaining a healthy weight. It also estimated that
 of breast cancer cases in the
UK could be prevented in this way, as well as 8 in Brazil and 0 in China.

In a study of attributable risk and epidemiological factors published in 199, later age at first
birth and nulliparity accounted for 9. of U.S. breast cancer cases, family history of breast
cancer accounted for 9.1 and factors correlated with higher income contributed 18.9 of
cases.[33] Attempts to explain the increased incidence (but lower mortality) correlated with higher
income include epidemiologic observations such as lower birth rates correlated with higher
income and better education, possible overdetection and overtreatment because of better access
to breast cancer screening and the postulation of as yet unexplained lifestyle and dietary factors
correlated with higher income. One such factor may be past hormone replacement therapy that
was typically more widespread in higher income groups.

Genetic factors usually increase the risk slightly or moderately; the exception is women and men
who are carriers of BRCA mutations. These people have a very high lifetime risk for breast and
ovarian cancer, depending on the portion of the proteins where the mutation occurs. Instead of a
1 percent lifetime risk of breast cancer, women with one of these genes has a risk of
approximately 0 percent.[3
] In more recent years, research has indicated the impact of diet and
other behaviors on breast cancer. These additional risk factors include a high fat diet,[3] alcohol
intake,[3][3] obesity,[38] and environmental factors such as tobacco use, radiation,[39] endocrine
disruptors and shiftwork.[
0] Although the radiation from mammography is a low dose, the
cumulative effect can cause cancer.[
1] [
]

In addition to the risk factors specified above, demographic and medical risk factors include:

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A National Cancer Institute (NCI) study of ,000 women found that those who had a normal
body mass index at age 0 and gained weight as they aged had nearly double the risk of
developing breast cancer after menopause in comparison to women who maintained their weight.
The average 0 year old woman's risk of developing breast cancer by age  is about  percent;
her lifetime risk is 13 percent.[

]

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Exercise may decrease breast cancer risk.[
] Also avoiding alcohol and obesity. Prophylactic
bilateral mastectomy may be considered in patients with BRCA1 and BRCA mutations.[
][
]

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Breast cancer, like other cancers, occurs because of an interaction between the environment and
a defective gene. 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 mutations destroy their ability to
stop dividing, to attach to other cells and to stay where they belong. When cells divide, their
DNA is normally copied with many mistakes. Error correcting proteins fix those mistakes. The
mutations known to cause cancer, such as p3, BRCA1 and BRCA, occur in the error
correcting mechanisms. These mutations are either inherited or acquired after birth. Presumably,
they allow the other mutations, which allow uncontrolled division, lack of attachment, and
metastasis to distant organs.[39][
8] Normal cells will commit cell suicide (apoptosis) 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 cell suicide. 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.[
9]

Mutations that can lead to breast cancer have been experimentally linked to estrogen
exposure.[0]

ailure of immune surveillance, the removal of malignant cells throughout one's life by the
immune system.[1]

Abnormal growth factor signaling in the interaction between stromal cells and epithelial cells can
facilitate malignant cell growth.[][3]

In the United States, 10 to 0 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  (BRCA), confer a lifetime risk of breast cancer of between 0 and 8
percent and a lifetime risk of ovarian cancer of between 1 and
0 percent. However, mutations
in these genes account for only  to 3 percent of all breast cancers.[
]

î



While screening techniques (which are further discussed below) 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.

Very often the results of noninvasive examination, mammography and additional tests that are
performed in special circumstances such as ultrasound or MR imaging are sufficient to warrant
excisional biopsy as the definitive diagnostic and curative method.

Both mammography and clinical breast exam, also used for screening, can indicate an
approximate likelihood that a lump is cancer, and may also detect some other lesions.[] When
the tests are inconclusive ine Needle Aspiration and Cytology (NAC) may be used. NAC
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.

In addition vacuum assisted breast biopsy (VAB) may help diagnose breast cancer among
patients with a mammographically detected breast in women.[]
 ? ? ?
Excised human ? ?
High grade Micrograph
breast tissue, invasive ductal showing a lymph
showing an Neuropilin  Lymph nodes
carcinoma, with node invaded by
irregular, dense, expression in which drain the
minimal tubule ductal breast
white stellate area normal breast and breast
formation, marked carcinoma and
of cancer  cm in breast carcinoma
pleomorphism, and with extranodal
diameter, within tissue.
prominent mitoses, extension of
yellow fatty tissue.
0x field. tumour.

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 18 DG
PET/CT:
Metastasis of a
mamma carcinoma
in the right scapula

î 



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Breast cancer screening refers to testing otherwise healthy women for breast cancer in an attempt
to achieve an earlier diagnosis. The assumption is that early detection will improve outcomes. A
number of screening test 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.
Research evidence does not support the effectiveness of either type of breast exam, because by
the time a lump is large enough to be found it is likely to have been growing for several years
and will soon be large enough to be found without an exam.[] Mammographic screening for
breast cancer uses x rays to examine the breast for any uncharacteristic masses or lumps. The
Cochrane collaboration in 009 concluded that mammograms reduce mortality from breast
cancer by 1 percent but also result in unnecessary surgery and anxiety, resulting in their view
that it is not clear whether mammography screening does more good or harm.[8] Many national
organizations recommend regular mammography, nevertheless. or the average woman, the U.S.
Preventive Services Task orce recommends mammography every two years in women between
the ages of 0 and 
.[9] The Task orce points 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.[0]

In women at high risk, such as those with a strong family history of cancer, mammography
screening is recommended at an earlier age and additional testing may include genetic screening
that tests for the BRCA genes and / or magnetic resonance imaging.

î



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Breast cancer is  
 treated with surgery and then possibly with chemotherapy or radiation,
or both. Hormone positive cancers are treated with long term hormone blocking therapy.
Treatments are given with increasing aggressiveness according to the prognosis and risk of
recurrence.
Stage 1 cancers (and DCIS) have an excellent prognosis and are generally treated with
lumpectomy and sometimes radiation.[1] HER cancers should be treated with the trastuzumab
(Herceptin) regime,[]chemotherapy is uncommon for other types of stage 1 cancers.
Stage  and 3 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 trastuzumab for HER 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. 10 year survival rate is  without treatment and 10 with optimal treatment.[3]

î



'?*'
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Drugs used after and in addition to surgery are called adjuvant therapy. Chemotherapy prior to
surgery is called neo adjuvant therapy. There are currently 3 main groups of medications used
for adjuvant breast cancer treatment:
 ½? ! ?"

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One or all of these groups can be used.

Hormone Blocking Therapy: Some breast cancers require estrogen to continue growing. They
can be identified by the presence of estrogen receptors (ER) and progesterone receptors (PR)
on their surface (sometimes referred to together as hormone receptors). These ER cancers can
be treated with drugs that either block the receptors, e.g. tamoxifen, or alternatively block the
production of estrogen with an aromatase inhibitor, e.g. anastrozole (Arimidex) or letrozole
(emara). Aromatase inhibitors, however, are only suitable for post menopausal patients.

Chemotherapy: Predominately used for stage 
disease, being particularly beneficial in

estrogen receptor negative (ER ) disease. They are given in combinations, usually for 3±
months. One of the most common treatments is cyclophosphamide plus doxorubicin
(Adriamycin), known as AC. The mechanism of action of chemotherapy is to destroy fast
growing an or fast replicating cancer cells either by causing DNA damage upon replication or
other mechanisms; these drugs also damage fast growing normal cells where they cause serious
side effects. Damage to the heart muscle is the most dangerous complication of doxorubicin.
Sometimes a taxane drug, such as docetaxel, is added, and the regime is then known as CAT;
taxane attacks the microtubules in cancer cells. Another common treatment, which produces
equivalent results, is cyclophosphamide, methotrexate, and fluorouracil (CM). (Chemotherapy
can literally refer to any drug, but it is usually used to refer to traditional non hormone
treatments for cancer.)

Monoclonal antibodies: A relatively recent development in HER breast cancer treatment.

Approximately 1 0 percent of breast cancers have an amplification of the ÿ
  gene or
overexpression of its protein product.[
] This receptor is normally stimulated by a growth factor
which causes the cell to divide; in the absence of the growth factor, the cell will normally stop
growing. Overexpression of this receptor in breast cancer is associated with increased disease
recurrence and worse prognosis. Trastuzumab (Herceptin), a monoclonal antibody to HER, has
improved the  year disease free survival of stage 1±3 HER breast cancers to about 8
(overall survival 9).[] Trastuzumab, however, is expensive, and approx  of patients suffer
significant heart damage; it is otherwise well tolerated, with far milder side effects than
conventional chemotherapy.[] Other monoclonal antibodies are also undergoing clinical trials.

A recent analysis of a subset of the Nurses' Health Study data indicated that Aspirin may reduce
mortality from breast cancer.[]

î




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 tumour microenvironment.[8][9] Radiation therapy can be delivered as external beam
radiotherapy or as brachytherapy (internal radiotherapy). Conventionally radiotherapy is given

 the operation for breast cancer. Radiation can also be given at the time of operation on the
breast cancer intraoperatively. The largest randomised trial to test this approach was the
TARGIT A Trial[0] which found that targeted intraoperative radiotherapy was equally effective
at
years as the usual several weeks' of whole breast external beam radiotherapy.[1] Radiation
can reduce the risk of recurrence by 0  (1/ /3rds reduction of risk) when delivered in
the correct dose[] and is considered essential when breast cancer is treated by removing only the
lump (Lumpectomy or Wide local excision)

î 


A prognosis is a prediction of outcome and the probability of progression free survival (PS) or
disease free survival (DS). These predictions are based on experience with breast cancer
patients with similar classification. A 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 0 of patients
survive, or the percentage of patients that are alive after 1, , 1, and 0 years. Prognosis 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 extensive
mastectomy and one or more chemotherapy drugs.

Prognostic factors include staging, (i.e., tumor size, location, grade, whether disease has spread
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. or example, Ductal Carcinoma In Situ (DCIS) involving the entire
breast will still be stage zero and consequently an excellent prognosis with a 10yr disease free
survival of about 98.[3]

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 , while poor or undifferentiated is given a higher grade of 3 or

(depending upon the scale used). The most widely used grading system is the Nottingham
Modification of the Bloom Richardson system,[
] which grades breast carcinomas by adding up
scores for tubule formation, nuclear pleomorphism, and mitotic count, each of which is given 1
to 3 points, which add to a final score as follows: 3  points = Grade I;   points = Grade II; and
8 9 points = Grade III. The grading criteria is as follows:

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Note: The overall appearance of the tumor has to be considered.

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Note: The tumor areas having cells with the greatest atypia should be evaluated.

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Note: Mitotic figures are counted only at the periphery of the tumor, and counting should begin
in the most mitotically active areas.

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.[]

The presence of estrogen and progesterone receptors in the cancer cell is important in guiding
treatment. Those who do not test positive for these specific receptors will not be able to respond
to hormone therapy, and this can affect their chance of survival depending upon what treatment
options remain, the exact type of the cancer, and how advanced the disease is.

In addition to hormone receptors, there are other cell surface proteins that may affect prognosis
and treatment. HER status directs the course of treatment. Patients whose cancer cells are
positive for HER have more aggressive disease and may be treated with the 'targeted therapy',
trastuzumab (Herceptin), a monoclonal antibody that targets this protein and improves the
prognosis significantly. Tumors overexpressing the Wnt signaling pathway co receptor low
density lipoprotein receptor related protein  (LRP) may represent a distinct subtype of breast
cancer and a potential treatment target.[]
î 



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. actors 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.[8] As the incidence of breast cancer in women over 0
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.[8]

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Worldwide, breast cancer is the most common cancer in women, after skin cancer, representing
1 of all female cancers.[80] Mortality worldwide is  greater than that of lung cancer in
women.[3] In 00
, breast cancer caused 19,000 deaths worldwide ( of cancer deaths; almost
1 of all deaths).[
] The number of cases worldwide has significantly increased since the 190s,
a phenomenon partly attributed to the modern lifestyles.[81][8]

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: in Eastern Asia, 18; South
Central Asia, ; sub Saharan Africa, ; South Eastern Asia, ; North Africa and Western
Asia, 8; South and Central America,
; Eastern Europe,
9; Southern Europe, ; Northern
Europe, 3; Oceania, 
; Western Europe, 8; and in North America, 90.[83]

Breast cancer is strongly related to age with only  of all breast cancers occur in women under

0 years old.[8
]

î
 


The lifetime risk for breast cancer in the United States is usually given as 1 in 8 (1.) with a 1
in 3 (3) chance of death.[8] A recent analysis however has called this estimate into question
when it found a risk of only  in healthy women.[8]

The United States has the highest annual incidence rates of breast cancer in the world; 18. per
100,000 in whites and 11. per 100,000 among African Americans.[8][8] It is the second most
common cancer (after skin cancer) and the second most common cause of cancer death (after
lung cancer).[8] In 00, breast cancer was expected to cause
0,910 deaths in the US ( of
cancer deaths; almost  of all deaths).[1] This figure includes
0 00 annual deaths among
men out of 000 cancer cases.[88]

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.[1][89] Nevertheless, a US study conducted in
00 indicated that breast cancer remains the most feared disease,[90] even though heart disease is
a much more common cause of death among women.[91] Many doctors say that women
exaggerate their risk of breast cancer.[9]
Cancer occurrence in females in the United
States. Breast cancer is seen in light green at By mortality.[93]
left.[93]
î 

,000 cases diagnosed and 1,00 deaths per annum. 0 of cases are treated with Tamoxifen,
of these the drug becomes ineffective in 3.[9
]

î 
 


As developing countries grow and adopt Western culture they also accumulate more disease that
has arisen from Western culture and its habits (fat/alcohol intake, smoking, exposure to oral
contraceptives, the changing patterns of childbearing and breastfeeding, low parity). or
instance, as South America has developed so has the amount of breast cancer. "Breast cancer in
less developed countries, such as those in South America, is a major public health issue. It is a
leading cause of cancer related deaths in women in countries such as Argentina, Uruguay, and
Brazil. The expected numbers of new cases and deaths due to breast cancer in South America for
the year 001 are approximately 0,000 and 30,000, respectively." [9] However, because of a
lack of funding and resources, treatment is not always available to those suffering with breast
cancer.
î! 

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Because of its visibility, breast cancer was the form of cancer most often described in ancient
documents.[9] 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.[9]

The oldest description of cancer was discovered in Egypt and dates back to approximately 100
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."[9] or
centuries, physicians described similar cases in their practises, with the same conclusion. Ancient
medicine, from the time of the Greeks through the 1th 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.[98] Alternatively, patients often saw it
as divine punishment.[99] 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.[98][100] 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.[100]

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.[100] Additionally, early and frequent childbearing and breastfeeding probably reduced the
rate of breast cancer development in those women who did survive to middle age.[100]

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 poisons hemlock
or arsenic, were relatively common.

Mastectomy for breast cancer was performed at least as early as 
8 CE, when it was proposed
by the court physician Aetios of Amida to Theodora.[9] It was not until doctors achieved greater
understanding of the circulatory system in the 1th century that they could link breast cancer's
spread to the lymph nodes in the armpit. The rench surgeon Jean Louis Petit (1
±10) and
later the Scottish surgeon Benjamin Bell (1
9±180) were the first to remove the lymph nodes,
breast tissue, and underlying chest muscle.[101]

Their successful work was carried on by William Stewart Halsted who started performing radical
mastectomies in 188, 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.[10] Before the
advent of the Halsted radical mastectomy, 0 year survival rates were only 10; Halsted's
surgery raised that rate to 0.[103] Extending Halsted's work, Jerome Urban promoted
superradical mastectomies, taking even more tissue, until 193, when the ten year survival rates
proved equal to the less damaging radical mastectomy.[10]

Radical mastectomies remained the standard of care in America until the 190s, but in Europe,
breast sparing procedures, often followed radiation therapy, were generally adopted in the
190s.[10] 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.[10]
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.[10] American health insurance companies also paid surgeons more to
perform radical mastectomies than they did to perform more intricate breast sparing
surgeries.[10]

Breast cancer staging systems were developed in the 190s and 1930s.[10]

During the 190s, 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.

The rench surgeon Bernard Peyrilhe (13±180
) realized the first experimental transmission
of cancer by injecting extracts of breast cancer into an animal.
Prominent women who died of breast cancer include Anne of Austria, the mother of Louis XIV
of rance; Mary Washington, mother of George, and Rachel Carson, the environmentalist.[10
]

The first case controlled study on breast cancer epidemiology was done by Janet Lane Claypon,
who published a comparative study in 19 of 00 breast cancer cases and 00 control patients
of the same background and lifestyle for the British Ministry of Health.[10][ 
    ][10]

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 1±0 of women
died because of the brutal treatment.[10]

The 199 reports from the Nurses' Health Study and the 00 conclusions of the Women's
Health Initiative trial conclusively proved that hormone replacement therapy significantly
increased the incidence of breast cancer.[10]

î 

 

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(?"?

?$ ?

Before the 0th 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 ield Army", run by the American Society for the Control of Cancer
(the forerunner of the American Cancer Society) during the 1930s and 19
0s was one of the first
organized campaigns. In 19, 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.[108]

The breast cancer movement of the 1980s and 1990s developed out of the larger feminist
movements and women's health movement of the 0th century.[109] 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 patient care.[110]

î


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In most countries, October is recognized as National Breast Cancer Awareness Month

(NBCAM). The primary purpose is to promote screening mammography as the most effective
way to save lives by detecting breast cancer at early stages.[111]

The month features many events, especially fundraisers. Cosmetics company Estée Lauder has
sponsored the illumination of landmarks with pink lights. Lee National Denim Day encourages
employers to offer a relaxed dress code in return for a small donation to a breast cancer charity.
Susan G. Komen for the Cure and other breast cancer organizations hold walkathons and other
sponsored athletic events. The ubiquitious presence of pink ribbons and other pink objects has
prompted the title "Pinktober". Typically, relatively little money from pink ribbons and tie in
merchandise is donated to the cause.[11]

Some critics call NBCAM the "National Breast Cancer Industry Month" to highlight the conflict
of interest between corporations promoting breast cancer awareness while profiting from the
resulting increased diagnoses and treatments. Breast Cancer Action says that October is a slick
public relations campaign that distracts people from discovering the causes and means of
preventing breast cancer and instead focuses on raising awareness as a way to sell
mammography equipment and chemotherapy drugs. The term ` 

  describes the actions
of companies that manufacture and use chemicals which may cause breast cancer while
simultaneously and hypocritically giving money to breast cancer organizations.[113]

î



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 ?

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?$  ?

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 cancer²usually white, middle aged, middle class, educated women.

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.[11
]
Promotion of the pink ribbon as a symbol for breast cancer has not been credited with saving any
lives. Wearing or displaying a pink ribbon has been denounced as a kind of slacktivism, because
it has no practical positive effect and as hypocrisy among those who 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.[11][11] 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.[11] It is also criticized for reinforcing gender stereotypes
and objectifying women and their breasts.[118] Breast Cancer Action launched the "Think Before
You Pink" campaign, and charged that companies have co opted the pink campaign to promote
products that encourage breast cancer, such as high fat Kentucky ried Chicken and alcohol.[119]

î"


 

Breast cancer culture, or pink ribbon culture, is the set of activities, attitudes, and values that
surround and shape breast cancer in public. The dominant values are selflessness, cheerfulness,
unity, and optimism. Appearing to have suffered bravely is the passport into the culture.

The woman with breast cancer is given a cultural template that constrains her emotional and
social responses into a socially acceptable discourse: She is to use the emotional trauma of being
diagnosed with breast cancer and the suffering of extended treatment to transform herself into a
stronger, happier and more sensitive person who is grateful for the opportunity to become a
better person. Breast cancer thereby becomes a rite of passage rather than a disease.[10] To fit
into this mold, the woman with breast cancer needs to normalize and feminize her appearance,
and minimize the disruption that her health issues cause anyone else. Anger, sadness and
negativity must be silenced.[10]

As with most cultural models, people who conform to the model are given social status, in this
case as cancer survivors. Women who reject the model are shunned, punished and shamed.[10]

The culture is criticized for treating adult women like little girls, as evidenced by "baby" toys
such as pink teddy bears given to adult women.[10]

The primary purposes or goals of breast cancer culture are to maintain breast cancer's dominance
as the preëminent women's health issue, to promote the appearance that society is "doing
something" effective about breast cancer, and to sustain and expand the social, political, and
financial power of breast cancer activists.[11]

î%
&

Compared to other diseases or other cancers, breast cancer receives a disproportionate share of
resources and attention. In 001 MP Ian Gibson, chairman of the UK House of Commons all
party group on cancer stated "The treatment has been skewed by the lobbying, there is no doubt
about that. Breast cancer sufferers get better treatment in terms of bed spaces, facilities and
doctors and nurses."[1] Breast cancer also receives significantly more media coverage than
other, equally prevalent cancers, with a study by Prostate Coalition showing . breast cancer
stories for each one covering cancer of the prostate.[13] Ultimately there is a concern that
favoring sufferers of breast cancer with disproporionate research on their behalf may well be
costing lives elsewhere.[1] Partly because of its relatively high prevalence and long term
survival rates, research is biased towards breast cancer. Some subjects, such as cancer related
fatigue, have been studied in little except women with breast cancer.

One result of breast cancer's high visibility is that most women significantly overestimate their
personal risk of dying from it. Misleading statistics, such as the claim that one in eight women
will develop breast cancer during their lives²a claim that depends on the patently unrealistic
assumption that no woman will die of any other disease before the age of 9[1
]²obscure the
reality, which is that about ten times as many women will die from heart disease or stroke than
from breast cancer.[1]

The emphasis on breast cancer screening may be harming women by subjecting them to
unnecessary radiation, biopsies, and surgery. One third of diagnosed breast cancers might recede
on their own.[1] Screening mammography efficiently finds non life threatening, asymptomatic
breast cancers and pre cancers, even while overlooking serious cancers. According to H. Gilbert
Welch of the Dartmouth Institute for Health Policy and Clinical Practice, research on screening
mammography has taken the "brain dead approach that says the best test is the one that finds the
most cancers" rather than the one that finds dangerous cancers.[1]

î#

Several historical paintings show anomalies that have been interpreted as visible evidence of
breast cancer; retrospective diagnoses are discussed in the medical literature. Possible signs of
breast cancer such as a typical lump, differences in breast size or shape and the peau d'orange
skin texture can be found for example in works by Raphael, Rembrandt and
Rubens.[1][18][19][9]

The paintings and the historical context do not give enough information to conclude whether or
not the visible changes are really signs of breast cancer[130] and alternative explanations such as
tuberculous mastitis or a chronic lactational breast abscess need to be considered.[131]

'? ??

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Raffaelo Sanzio (1
83±10): Rembrandt van Rijn (10±
Peter Paul Rubens (1±
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A considerable part of the current knowledge on breast carcinomas is based on in vivo and in
vitro studies performed with breast cancer cell (BCC) lines. These provide an unlimited source
of homogenous self replicating material, free of contaminating stromal cells, and often easily
cultured in simple standard media. The first line described, BT 0, was established in 198.
Since then, and despite sustained work in this area, the number of permanent lines obtained has
been strikingly low (about 100). Indeed, attempts to culture BCC from primary tumors have been
largely unsuccessful. This poor efficiency was often due to technical difficulties associated with
the extraction of viable tumor cells from their surrounding stroma. Most of the available BCC
lines issued from metastatic tumors, mainly from pleural effusions. Effusions provided generally
large numbers of dissociated, viable tumor cells with little or no contamination by fibroblasts and
other tumor stroma cells. Many of the currently used BCC lines were established in the late
190s. A very few of them, namely MC , T
D, and MDA MB 31, account for more than
two thirds of all abstracts reporting studies on mentioned BCC lines, as concluded from a
Medline based survey.

Treatments are constantly 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, San Antonio Breast Cancer Symposium,[13] and the St. Gallen Oncology
Conference in St. Gallen, Switzerland.[133] These studies are reviewed by professional societies
and other organizations, and formulated into guidelines for specific treatment groups and risk
category.

-
? ?
?
?

Mainly based on Lacroix and Leclercq (00
).[13
] or more data on the nature of TP3
mutations in breast cancer cell lines, see Lacroix et al. (00).[13]

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