Content: Introduction Pathophysiology and classification Diagnostis Treatment

Defination
Breast cancer is a cancer that starts in the

breast, usually in the inner lining of the milk ducts or lobules. There are different types of breast cancer, with different stages (spread), aggressiveness, and genetic makeup.

 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).

Anatomy of breast

 The interior of the female breast consists

mostly of fatty and fibrous connective tissues. It is divided into about 20 sections called lobes. Each lobe is further subdivided into a collection of lobules, structures that contain small milk-producing glands. These glands secrete milk into a complex system of tiny ducts.

 The ducts carry the milk through the breast

and converge in a collecting chamber located just below the nipple. Breast cancer is either noninvasive (referred to as in situ, confined to the site of origin) or invasive (spreading). The female breast is either of two mammary glands (organs of milk secretion) on the chest.


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Statistic in U.S
In 2011, an estimated 230,480 new cases of

invasive breast cancer were expected to be diagnosed in women in the U.S., along with 57,650 new cases of non-invasive (in situ) breast cancer. About 2,140 new cases of invasive breast cancer were expected to be diagnosed in men in 2011. A mans lifetime risk of breast cancer is about 1 in 1,000.

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About 39,520 women in the U.S. were

expected to die in 2011 from breast cancer In 2011, there were more than 2.6 million breast cancer survivors in the US

 Breast pain. Deformity. Nipple discharge or inversion. Erythema. Skin ulceration. Axillary lump.

 Pagets disease: (eczematoid rash of the nipple-areola complex,

itching, tenderness, burning, and occasional bloody discharge from the nipple.)

Symptoms related to distant metastases : Breathing difficulties ,Bone pain ,Symptoms of

hypercalcemia ,Abdominal distension ,Jaundice ,Localizing neurologic signs ,Altered cognitive function.

Presentation:

 Painless lump (67%) Pain (5 %) Nipple (deviation, retraction, destroyed) (4 %) Nipple discharge (2 %) Skin retraction (1 %) Axillarys mass (1 %) Swelling of arm (1 %)

history

Nipple discharge. Fever. Pain. Rapid growth. Duration of the mass. Changes with menses.

Examination and diagnosis

Physical examination should include

inspection of the patient in the upright as well as supine positions.

Motwakil. A. H. Moneer

Gezira 2005

Examination and diagnosis

In the upright position patient is inspected for

suggestive findings: (Symmetry , Skin and nipple changes, size

discrepancy, nipple inversion, skin dimpling, scaling, and edema (peau d'orange) ).

And for Supraclavicular, infraclavicular, and axillary lymphadenopathy .

Motwakil. A. H. Moneer

Gezira 2005

 A complete examination includes examination of the chest and sites of skeletal pain, and an abdominal and neurological

examination.

What if we find a lump in the breast?

Frequently small Firm, rubbery mass Frequently painful Regular

Larger Hard Painless ( in 85%) Irregular

Nil Nil
Nil
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Possible Present
Present
Motwakil. A. H. Moneer

Nil

Present

what about the Characteristics of Discharge?

Gezira 2005

Motwakil. A. H. Moneer

1)

3-Diagnostic tests Lab Studies

2) Imaging Studies 3) Other Tests

4) Diagnostic Procedures

Lab Studies
CBC count with differential and platelet count

Chemistry and renal function studies

Liver function tests Calcium and phosphorus evaluations

 The normal range for WBC count is 4,300 to

10,800 cells per cubic millimeter (cmm) or 4.3 to 10.8 x 109 cells per liter. The range for a normal RBC count (expressed in million red cells per microliter {uL} of blood) is Women: 4.2 to 5.4 million/uL A normal platelet count is between 150,000 and 450,000 - 266,000 per mcL in women. onemillionth of a liter, normal blood calcium level range is 9.0 to 10.5 mg/dL

 Normal phosphorus on a routine blood test

for the general public and CKD non-dialysis is 2.7 to 4.6 mg/dL. For dialysis patients the target range is 3.5 to 5.5 mg/dL.

WBC RBC

4,300 to 10,800 cells per cubic millimeter (cmm) Women: 4.2 to 5.4 million/uL (million red cells per microliter {uL}) 150,000 and 450,000 - 266,000 per mcL in women. one-millionth of a liter,

PLATELET GFR(kidney function test)

PHOSPHROUS CALCIUM

60-120 for someone with good kidney function, and 350-600 for someone approaching dialysis.
general public and CKD non-dialysis is 2.7 to 4.6 mg/dL. For dialysis patients the target range is 3.5 to 5.5 mg/dL. 9.0 to 10.5 mg/dL

Estimated GFR calculator

The value will be roughly 60-120 for someone

with good kidney function, and 350-600 for someone approaching dialysis. Creatinine clearance = 1.2 x (140 - age in years) x weight in kg Plasma creatinine Note: if the patient is female the result of the formula is multiplied by 0.85; if the patient is of black ethnicity the result of the formula is multiplied by 1.18.

Liver function test

Albumin (ALB): Normal values: 3.5-5

grams/100 ml Alkaline Phosphatase (ALK PHOS): Normal values: 13-39 units/liter Alanine Aminotransferase (ALT or SGPT): Normal values: 5-40 units per liter of blood serum Total Bilirubin (TBIL): Normal values: less than 1mg per 100 m.

imaging

Imaging Studies
Mammography and ultra sound . Mammography: It is an x-ray of the breast . It has more than one type depending on

accuracy.

 Diagnostic mammography:
is often used to assess whether a mass seen on

screening mammogram is benign (noncancerous) or malignant (cancerous).

Screening Mammography:

Studies over the past 30 years clearly indicate that regular screening mammography significantly reduces the death rate from breast cancer.

 In fact, high-quality screening mammography is the most effective tool now available to detect breast cancer before symptoms appear.
Mammography can often locate an abnormality

when it is very small, years before a lump can be felt (i.e. it is nonpalpable).

Mammography:
Initial investigation for symptomatic breast in

women older than 35 years and for screening; investigation of choice for microcalcification. Malignant and benign breast lesions have the following mammographic characteristics:

A)Malignant breast lesions : Irregular speculated mass . Clustered calcifications . Calcifications - Smaller than 0.5 mm in diameter . Architectural distortion. (is an abnormal arrangement of tissue strands of the breast, often a radial or perhaps a somewhat random pattern) Focal asymmetric density.

asymmetry
The breast X-ray below certain appears to

have a nodule of some sort, but since it may or may not be a real nodule, one label it as an 'asymmetric density' or a 'developing '.

Focal asymmetry
means the suspected asymmetry-mass is

much smaller, and has a similar shape on two views. It lacks the clear borders that we see in a true mass, and it usually is found to be an 'island' of normal , yet dense fibroglandular tissue, especially when it is interspersed with fat. The liklihood of malignancy with focal asymmetry is less than 1%.

Focal asymmetry

Irregular speculated mass .

Architectural distortion

Calcification less than 0.5mm in diameter

Calcification larger than 0.5mm

B) Benign breast lesions :

Solid- or lucent-centered spheres. Smooth and round calcifications . Calcifications - Larger than 1 mm in

diameter . Architectural distortion - Usually not

present.

(A) Mammography shows typical oil cysts with calcified walls in a patient with a history of mammoplasty performed 12 years earlier.

(B) Patient with a history of mammoplasty performed 5 years earlier. Mammography shows typically benign coarse calcifications with lucent centers and variable size, corresponding to calcified fat necrosis. Suture calcifications are also visible (arrow).

Ultrasound

 2) Ultrasound :
Ultrasonic features of malignancy include the following: Poorly defined borders Heterogeneous internal echoes Disruption of the tissue layers Irregular shadowing Superficial echo enhancement Depth greater than height High vascular density and flow rates on Doppler images

Other imaging techniques

MRI PET CT scan

Diagnostic Procedures
A) Surgical procedures for nonpalpable

lesions :

1) Image-guided core-needle biopsy. 2) Open biopsy with needle localization.

B) Surgical procedures for palpable

lesions :

1) Fine-needle aspiration biopsy. 2) Cutting-needle (core-needle) biopsy. 3) Excision (open) biopsy. 4) Incisional biopsy.

Fine needle aspiration

Open biobcy

1) Ductal : Intraductal (in situ). Invasive with predominant intraductal component. Invasive, not otherwise specified Scirrhous Tubular Medullary with lymphocytic infiltrate Mucinous (colloid) Papillary Inflammatory Comedo Other
Motwakil. A. H. Moneer Gezira 2005

Histologic Findings

 2) Lobular : In situ . Invasive with predominant in situ component. Invasive. 3) Nipple : Paget disease, not otherwise specified . Paget disease with intraductal carcinoma. Paget disease with invasive ductal carcinoma.

Motwakil. A. H. Moneer

Gezira 2005

Most important

Breast self examination

 No effect on mortality by breast cancer High programmatic cost (training, reinforcement, management of false positive). For women: time consuming (training), adverse psychological effects. Potential harmful effect (delayed presentation).

BSE: a deceiving screening tool

However Breast awareness cannot be overemphasized. Women do not have to worry about BSE procedure but have to be breast aware and ready to report anything suspicious to a practitioner.

TREATMENT
What is good care for breast cancer? When deciding what treatment is best for you, your doctors will consider: the stage and grade of your cancer The main treatments for breast cancer are: 1.surgery 2.radiotherapy 3.chemotherapy 4.hormone therapy 5.biological therapy (targeted therapy) .

1.surgery
The type of surgery depends on the type of

breast cancer you have. Surgery is usually followed by chemotherapy or radiotherapy or, in some cases, hormone or biological treatments. Sometimes, chemotherapy or hormone therapy will be the first.

There are two types of surgery for breast cancer.

1. remove just the cancerous lump (tumour), known as breast-conserving surgery,. 2.surgery toremove the whole breast, which is called a mastectomy. In many cases, a mastectomy can be followed by reconstructive surgery to recreate the breast that was removed:

A.Breast-conserving surgery

Breast-conserving surgery ranges from a

lumpectomy or wide local excision, in which just the tumour and a little surrounding breast tissue is removed, to a partial mastectomy or quadrantectomy, in which up to a quarter of the breast is removed. If you have breast-conserving surgery, the amount of breast tissue you have removed will depend on

 the type of cancer you have the size of the tumour and where it is in your

breast the amount of surrounding tissue that needs to be removed the size of your breasts

1- Surgical treatment of breast cancer

B/ Mastectomy:-Removal of all breast tissue with some overlying skin (including the nipple) but leaves the chest wall muscle intact + axillary surgery. Used in:1- large multifocal operable breast cancer 2- when there is a wish to avoid radiotherapy 3- extensive non invasive disease. 4- large tumour more than 4cm in diameter.

1- Surgical treatment of breast cancer

2.Radiotherapy
Radiotherapy uses controlled doses of radiation to

kill cancer cells. It is generally given after surgery and chemotherapy to kill any remaining cancer cells. If you need radiotherapy, your treatment will begin about a month after your surgery or chemotherapy to give your body a chance to recover. You will probably have radiotherapy sessions three to five days a week, for three to six weeks. Each session will only last a few minutes. The type of radiotherapy you have depends on. the type ofcancer and the type of surgery .

 . Radiotherapy is aimed at the armpit (axilla)

and the surrounding area to kill any cancer that may be present in the lymph nodes

The side effects of radiotherapy include:

irritation and darkening of the skin on your

breast, which may lead to sore, red, weepy skin fatigue (extreme tiredness) lymphoedema (excess fluid build-up

3- Chemical treatment
- Combination of drugs more effective. - At least four cycles postoperatively (every six months). - Better result in women under 50 years old. - Common regimens : CMF ,also there is AC,FEC and toxaues.

 Several different drugs are used for

chemotherapy and often three are given at once. The choice of drugs and the combination depends on the type of breast cancer and how much it has spread

 The drugs are usually given through a drip

straight into the blood through a vein. In some cases, you may be given tablets that you can take at home. You may receive chemotherapy sessions once every two to three weeks, over a period of four to eight months, to give your body a rest in between treatments

 Side effects include: infections loss of appetite nausea and vomiting tiredness hair loss sore mouth

 3. Hormonal Therapy:
HT is indicated only in the presence of hormone receptors (ER and/or PR) on cancer tissue .

Modalities:

1) Estrogen receptor modulators.(Tamoxifen) 2)Suppression of estrogen synthesis:

a) Aromatase inhibitors (anastrozole).in postmenopausals b) luteinizing hormone-releasing hormone analogues.
(goserelin) in premenopausals.

3) ovarian ablation ( surgical /RT).

Treatment with Tamoxifen (20mg/d for 5 yrs) reduced the risk of invasive breast cancer by 49%. Moreover, a 50% reduction in the risk of noninvasive cancers was demonstrated.28% reduction of mortality.

Side efect including

tiredness changes to your periods nausea and vomiting hot flushes aching joints headaches

weight gain

aromatase inhibitors
Three aromatase inhibitors may be offered. These are anastrozole, exemestane and

letrozole. These are taken as a tablet once a day. Side effects include: hot flushes and sweats loss of interest in sex nausea and vomiting tiredness aching joints and bone pain headaches skin rashes

Anastrazole(ARIMIDEX)
Recommended Dose The dose of ARIMIDEX is one 1 mg tablet

taken once a day. For patients with advanced breast cancer, ARIMIDEX should be continued until tumor progression. ARIMIDEX can be taken with or without food. The optimal duration is unkonown

Drug Interaction Classification

The classifications below are a general

guideline only. It is difficult to determine the relevance of a particular drug interaction to any individual given the large number of variables.

Drug Interaction Classification

Major Highly clinically significant: Avoid combinations; the risk of the

interaction outweighs the benefit

Drug Interaction Classification

.ModerateModerately clinically significant:

Usually avoid combinations; use it only under special circumstances. MinorMinimally clinically significant: Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.

Ovarian suppression
Ovarian suppression involves using a drug

called goserelin, which is a luteinising hormone-releasing hormone agonist (LHRHa). . Goserelin is taken as an injection once a month and can cause menopausal side effects, including: hot flushes and sweats mood swings trouble sleeping

Complication are greater in premenopausal patient

There is :1-vaginal dryness 2- vaginal discharge 3- loss of libido 4- hot flushes.

goserelin
Usual Adult Dose for Breast Cancer-Palliative For use in the palliative treatment of advanced breast cancer: 3.6 mg subcutaneously into the upper abdominal wall once. The 3.6 mg dosage may be repeated every 28

days.
Intended for long-term administration unless clinically inappropriate.

5.Biological therapy
breast cancers are stimulated to grow by a protein called human epidermal growth factor

receptor 2 (HER2). These cancers are called HER2-positive. Biological therapy works by stopping the effects of HER2 and by helping your immune system to fight off cancer cells. If you have high levels of the HER2 protein and are able to have biological therapy, you will probably be prescribed a medicine called trastuzumab. Trastuzumab, also known by the brand name Herceptin, is usually used after chemotherapy.

Recommended Doses and Schedules of herceptin

Do not administer as an intravenous push or

bolus. Do not mix Herceptin with other drugs. Adjuvant Treatment, Breast Cancer: Administer according to one of the following doses and schedules for a total of 52 weeks of Herceptin therapy:

Recommended Doses and Schedules of herceptin

During and following paclitaxel, docetaxel, or

docetaxel/carboplatin:

Recommended Doses and Schedules of herceptin

Initial dose of 4 mg/kg as an intravenous

infusion over 90 minutes then at 2 mg/kg as an intravenous infusion over 30 minutes weekly during chemotherapy for the first 12 weeks (paclitaxel or docetaxel) or 18 weeks (docetaxel/carboplatin). One week following the last weekly dose of Herceptin, administer Herceptin at 6 mg/kg as an intravenous infusion over 3090 minutes every three weeks.

Side efect
, including heart problems. This means that it is not suitable if you have a heart problem, such as

angina, uncontrolled high blood pressure (hypertension) or heart valve disease Other side effects . an initial allergic reaction to the drug, which can cause nausea, wheezing, chills and fever diarrhoea tiredness aches and pains

prevention
Limit alcohol. The more alcohol you drink,

the greater your risk of developing breast cancer. If you choose to drink alcohol including beer, wine or liquor limit yourself to no more than one drink a day. Control your weight. Being overweight or obese increases the risk of breast cancer. This is especially true if obesity occurs later in life, particularly after menopause

 Get plenty of physical activity. Being physically active can help you maintain a healthy weight,

which, in turn, helps prevent breast cancer. For most healthy adults, the Department of Health and Human Services recommends at least 150 minutes a week of moderate aerobic activity (think brisk walking or swimming) or 75 minutes of vigorous aerobic activity (such as running), in addition to strength training exercises at least twice a week

 Breast-feed. Breast-feeding may also play a

role in breast cancer prevention. The longer you breast-feed, the greater the protective effect.

 Discontinue hormone therapy. Long-term

combination hormone therapy increases the risk of breast cancer. If you're taking hormone therapy for menopausal symptoms, ask your doctor about other options

 Avoid exposure to environmental pollution.

While further studies are needed, some research suggests a link between breast cancer and exposure to the polycyclic aromatic hydrocarbons found in vehicle exhaust and air pollution. .diet including antioxidant .tamoxifen

For those with cancer .... of tomorrow; for God is Do not be afraid
already there.