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Malignan

cy

Group I

4th year – Medicine


2008
Module II
Dr.Murgany
Epidemiology of breast cancer

WHAT IS CANCER?

Cancer is a generic term for a group of more than 100 diseases


that can affect any part of the body. Other terms used are
malignant tumours and neoplasms. One defining feature of
cancer is the rapid creation of abnormal cells which grow
beyond their usual boundaries, and which can invade adjoining
parts of the body and spread to other organs, a process referred
to as metastasis. Metastases are the major cause of death from
cancer.

FACTS ABOUT CANCER

Cancer is a leading cause of death worldwide. From a total of 58


million deaths worldwide in 2005, cancer accounts for 7.6
million (or 13%) of all deaths. The main types of cancer leading
to overall cancer mortality are:

• lung (1.3 million deaths/year);

• Stomach (almost 1 million deaths/year);

• Liver (662,000 deaths/year);

• Colon (655,000 deaths/year) and

• Breast (502,000 deaths/year).

More than 70% of all cancer deaths in 2005 occurred in low and
middle income countries. Deaths from cancer in the world are
projected to continue rising, with an estimated 9 million people
dying from cancer in 2015 and 11.4 million dying in 2030.
The most frequent cancer types world wide are:

• Among men (in order of number of global deaths): lung,


stomach, liver, colorectal, oesophagus and prostate.

• Among women (in order of number of global deaths):


breast, lung, stomach, colorectal and cervical.

QUICK CANCER FACTS

• 40% of cancer can be prevented (by a healthy diet,


physical activity and not using tobacco).

• Tobacco use is the single largest preventable cause of


cancer in the world. Tobacco use causes cancer of the
lung, throat, mouth, pancreas, bladder, stomach, liver,
kidney and other types; Environmental tobacco smoke
(passive smoking) causes lung cancer.

• One-fifth of cancers worldwide are due to chronic


infections, mainly from hepatitis B viruses HBV (causing
liver), human papilloma viruses HPV (causing cervix),
Helicobacter pylori (causing stomach), schistosomes
(causing bladder), the liver fluke (bile duct) and human
immunodeficiency virus HIV (Kaposi sarcoma and
lymphomas).
Frequency: The American Cancer Society estimated that
211,240 new cases of breast cancer (32.1% of all cancers in
women) would be diagnosed in 2005 in the United States,
making breast cancer the most-diagnosed cancer in women.
Male breast cancer is a rare disease and 1690 cases were
expected for 2005 in the US. The true incidence rates of breast
cancer have been stable from 1987-1996 after a constant
increase since 1979 (increase of 1% per year from 1979-1982;
4% per y from 1982-1987). The lack of decline of breast cancer
incidence in the 1990s contrasts with a slight decline (decline of
1.3% per y from 1992-1997) of the incidence rate of cancer for
all sites. Up to 40,870 cases of breast cancer-related deaths
were expected for 2005 in the US.

Based on cancer cases diagnosed from 1995-1997, the


probability of developing invasive cancer is 0.44% (1 in 225) for
women younger than 39 years, 4.15% (1 in 24) for women aged
40-59 years, and 7.02% (1 in 14) for women aged 60-79 years.
The estimated lifetime probability of developing breast cancer is
12.83% (~1 in 8). The likelihood of developing breast cancer is
higher in white women than in women of any other racial or
ethnic group.

Although the death rate from breast cancer has decreased an


average of 2.2% per year from 1990-1997, the recorded number
of deaths from breast cancer has remained stable, at
approximately 43,000 per year. Deaths dropped to 41,737 in
1998 after reaching the highest number, 43,844, in 1995.
Among women aged 20-59 years, breast cancer is the leading
cause of death from cancer. However, lung cancer remains the
leading cause of death from cancer in women aged 60 years or
older.
Geographical variations worldwide

Worldwide, more than one million new cases of female breast


cancer are diagnosed each year. It is the most commonly
occurring neoplasm in women, accounting for over one-fifth of
the estimated annual 4.7 million cancer diagnoses in females,
and the second most common tumour, after lung cancer, in both
sexes . It is also the most common female cancer in both
developing and developed countries, with most (55%) occurring
in the latter regions, where age-standardised rates are three
times higher than in developing areas.

The estimated number of deaths from female breast cancer in


2000 is considerably lower – about 375,000 deaths – reflecting
the reasonably good overall survival. Prognosis is heavily
dependant on stage of disease at presentation, however. In the
Surveillance, Epidemiology, and End Results (SEER) registries in
the USA, 5-year survival for localised cases in 1994 was about
97% but was only about 25% for cases with metastatic disease .
In developing countries, the differences in survival by stage at
diagnosis are also very marked . In Europe, 5-year relative
survival rates vary from 83% in Sweden to 61% in Slovakia , and
although trends show clear improvement over time, the utility of
survival in monitoring patient outcome has been questioned in
countries affected by artefactual increases in registrations due
to screening .

Above figure shows the geographical variation in breast cancer


incidence worldwide, as estimated for the year 2000. The
highest incidence rates occur in northern and western Europe,
northern America, Australia and New Zealand, and in southern
countries of South America, notably Uruguay and Argentina.
Clear geographical differences in risk are apparent within
Europe, with elevated rates in northern and western Europe,
whereas rates in most southern and eastern European countries
are low to intermediate . Incidence is low throughout Africa, Asia
and most of Central and South America .

Age-specific variations worldwide

Breast cancer incidence has a distinctive age-specific curve .


The rapid rate of increase before the menopause (ages 40–50)
slows down after that, probably owing to diminishing levels of
circulating oestrogens. In low-incidence countries, the slope of
the curve after the menopause may be flat, or even negative .
This is a consequence of increasing risks of occurrence in
consecutive generations of women rather than a real decline in
risk with age . The young age structure of populations in
developing countries coupled with a rather flat age-incidence
curve implies that the mean age at diagnosis in developing
countries is lower than that of European and American
populations.

‫انتشار سرطان الثدي بين السعوديات‬


30/12/1426 - ‫سي ان ان‬

‫ أظهرت إحدى الحصائيات الصادرة في السعودية أن‬--)CNN( ‫ السعودية‬،‫الرياض‬


‫ سيدة من بين‬11.8 ‫عدد حالت الصابة بسرطان الثدي لدى السعوديات يقدر بـ‬
.‫ ألف‬100 ‫كل‬

‫وذكرت وكالة النباء السعودية نقل عن الحصائية التي أصدرها السجل الوطني‬
‫ حيث يقدر‬،‫للورام أن سرطان الثدي هو السرطان الكثر شيوعا بين السعوديات‬
.‫ حالة‬2741 ‫عددهن في السعودية بنحو‬

‫ كما‬،‫غير أن هذا الرقم يبقى أقل بكثير من عدد الصابات في المجتمعات الغربية‬
.‫ذكرت الحصائية‬
Being 40 or younger is an independent risk factor for relapse in
operable breast cancer patients: The Saudi Arabia
experience
Naser Elkum, Said Dermime, Dahish Ajarim, Ali Al-Zahrani, Adher Alsayed,
Asma Tulbah, Osama Al Malik, Mohamed Alshabanah, Adnan Ezzat and Taher
Al-Tweigeri

Department of Biostatistics, Epidemiology, and Scientific Computing, King


Faisal Specialist Hospital and Research Center, PO Box 3354, Riyadh 11211,
Saudi Arabia

Results

Median age at presentation was 45 years. A total of 288 (33.2%)


patients were aged ≤ 40 years. Hormone receptors were
positive in 69% of patients 40 and 78.2% of patients above 40
(p = 0.009). There was a significantly higher incidence of grade
III tumor in younger patients compared to older patients (p =
0.0006). Stage, tumor size, lymphatic/vascular invasion, number
of nodes and axillary lymph node status, did not differ
significantly between the two age groups. Younger patients had
a greater probability of recurrence at all time periods (p =
0.035). Young age had a negative impact on survival of patients
with positive axillary lymph nodes (p = 0.030) but not on
survival of patients with negative lymph nodes (p = 0.695).
Stage, tumor size, nodal status and hormonal receptors had
negative impact on survival. Adjuvant chemotherapy was
administered to 87.9% of younger and 65.6% of older patients
(p < 0.0001). In terms of hormone therapy, the proportion of
tamoxifen treated patients was significantly lower in young age
group (p < 0.0001). No significant difference in radiation
therapy between the two groups.

Conclusion

Young age (≤ 40) is an independent risk factor for relapse in


operable Saudi breast cancer patients. The fundamental biology
of young age breast cancer patients needs to be elucidated.
Risk factors
The clinical evaluation should include an assessment of specific
risk factors for breast cancer, as follows:

• Age

o Breast cancer is rare in women younger than 25


years.

o Incidence increases with age, with a plateau in


women aged 50-55 years.

o Age is the most significant risk factor.

• Genetics

o Family history is a risk factor. The lifetime risk is up


to 4 times higher if a mother and sister are affected.
The family history characteristics that suggest
increased risk of cancer are as follows:

 Two or more relatives with breast or ovarian


cancer

 Breast cancer occurring in an affected relative


younger than 50 years

 Relatives with both breast cancer and ovarian


cancer

 One or more relative with 2 cancers (breast


and ovarian cancer or two independent breast
cancers)

 Male relatives with breast cancer


o Individuals of Ashkenazi Jewish descent have a 2-
times greater risk.

o Japanese and Taiwanese woman have one fifth the


risk when compared with US women.

o BRCA1 and BRCA2 mutations are associated with


higher risk.

o Ataxia telangiectasia heterozygotes are at 4-times


increased risk.

• Other pathology

o Risk is increased with previous breast cancer,


ovarian cancer, endometrial cancer, ductal
carcinoma in situ, lobular carcinoma in situ,
hyperplasia (unless mild), complex fibroadenoma,
radial scar, papillomatosis, sclerosing adenosis, and
microglandular adenosis.

o Risk is decreased with cervical cancer.

• Years menstruating

o Factors increasing the number of menstrual cycles


increase the risk, probably due to increased
endogenous estrogen exposure.

o Such factors include (1) nulliparity, (2) first full


pregnancy when older than 30 years, (3) menarche
when younger than 13 years (2 times the risk), (4)
menopause when older than 50 years, and (5) not
breastfeeding.

• Obesity: Increased risk is probably due to adipose


conversion of androgens to estrogens.

• Socioeconomic class: Incidence is increased in


individuals in a higher socioeconomic class.

• Exogenous factors

o Hormone replacement therapy increases risk (1.35


times for 10 y use, normalizing 5 y from
discontinuing).

o The use of oral contraceptive pills increases risk


(1.24 times for 10 y use, normalizing 10 y from
discontinuing). The progesterone-only pill is not
associated with increased risk.

o The use of diethylstilbestrol increases risk.

o Alcohol consumption is associated with an increased


risk, probably through increasing estrogen levels.

o Irradiation, particularly in first decade of life, is


associated with an increased risk of breast cancer.

o Dichlorodiphenyldichloroethylene, a metabolite of
the insecticide dichlorodiphenyltrichloroethane
(DDT), exposure increases risk.

o Exposure to some viral agents (eg, mouse


mammary tumor virus) is associated with increased
risk.

• Other dietary, cultural, and/or geographic


influences

o High-risk regions include North America and


northern Europe.

o Low-risk regions include Japan and Hawaii; however,


descendants migrating to the United States take on
the higher US risk.

DDx of painful breast


PAINFUL AND TENDERNESS BUT NO LUMP :

1 – CYCLICAL BREAST PAIN

Breast tenderness just prior to the menstrual period during the


reproductive years is a common finding.

The cyclicity and bilaterality usually parallel hormonal changes


or the menstrual cycle. Both growth of the breast can be
associated with or cause breast pain. In the second half of the
menstrual cycle both of these hormone levels are high.

2 – NON- CYCLICAL BREAST PAIN

There are two types of non-cyclical breast pain:


• true breast pain that comes from the breast but is not
linked to the menstrual cycle

• extra mammary pain that is felt in the breast but in fact


comes from somewhere else such as the muscles, bones
or joints (musculoskeletal pain).

Both of these can result in continuous pain both before and after
the menopause. The pain can be in the whole of the breast, in a
specific area, or in both breasts at the same time.

Causes

The cause of non-cyclical breast pain is often unknown. It can


sometimes be related to specific benign breast conditions,
previous surgery or underlying conditions that are unrelated to
the breasts.

3 – VERY RARLY CARCINOMA

PAINFUL LUMP :

1- An area of fibroadenosis

A benign neoplasm composed of glandular and fibrous tissues,


with a relatively large proportion of glands.

2 – cyst

are fluid-filled sacs that develop in the breast tissue. Cysts


naturally occur as the breast ages and changes.

Galactocele is a milk – containing cyst and occur during or


shortly after lactation .
3 – periductal mastitis :

Periductal mastitis is a benign mammary duct disease that


begins with periductal inflammation and progresses to ductal
dilatation with minimal inflammation (ductal ectasia).

4 – abscess

A local accumulation of pus within the breast due to infection .


Symptoms may include painful local swelling of the breast, a
breast lump

Breast abscesses are reasonably common during breast feeding


It is thought that the mode of entry of the causative organism
(Staphylococcus aureus) is via cracked or damaged skin around
the nipple caused by the infant's sucking.

Abscesses can also occur in women who are not breast-feeding.

These non-lactational abscesses are usually associated with


periductal mastitis and therefore tend to occur in women over
30 years of age

5 – sometimes carcinoma
‫س‬
‫عيد‬
History & General examination of
Breast

History
• Age : rare in young women (most common in 70 yrs old
female)

• Previous pregnancies

Parity & breast – feeding reduce incidance of breast cancer

• Menstrual pattern

» Regularity

» Duration

» Quantity of bleeding

• Medication

– Is the patient taking drugs containing female sex


hormones ?

E.g. : OCP,hormone replacement therapy .

• Association symptoms

Breast Lung
Hotness cough
Ulcer Dyspnea
Skin change Bloody sputum
Dnipple discharge

GI Lymph nodes
Jundice Axillary L.N
Neck L.N
Wt. loss
Inguinal L.N
Abdominal distention
Nausea & vomiting CNS
Constipation Headach
Acitis Dizziness
photophobia
• And can cause:

Fever Respiratory system


Bloody sputum
Locally :
Dyspnea
Hotness
Cough
Skin change
Ulcer Musculoskeletal
problem
CNS
Headach / dizziness Enlargment of L.N
Photophopia
Overies
Cranial and cerebral
Hormonal disturbance
disturbance Hair distribution
Menstrual cycle
GI
Liver disease
Nausea/vomiting

----------------------------------------------------------------------
----------------

Physical Examination
• Hand & Nail

Clubbing è respiratory tumor

Koilonychia è Fe deficiency

» Due to affecting Bone marrow

» Anorexia

Pale nail bed è anemia

Leuconchia and muehrcke’s line è albuminaemia

Scratch mark

Hair distribution è endocrine dist.

tremur
• Respiratory system
Cyanosis

– Skin & mucous membrane

– Tongue

Dyspnea

Sputum

Inspection the shape & symmetry of chest


Musculoskeletal system
Can cause :
•Bone
deformity

•Muscular
problem

•Skull
•Vertebae
•Ribs
•Sternum
Can affect bone marrow •Pelvis
And cause : •Upper femur
•Anemia •Upper
And cause pallor humerus

• GI examination
Jaundice

Pruritus

Wt. loss

Nail

– Leuconchia

– Transverse opaque white band (muehrcke’s line)

– Pale nail bed

• Spider nevi

• Ascitis

• Palpation :

– Liver

– Spleen

• liver
Jaundice

– Sclera

– Scratch mark ( pruritus )

– Leuconychia è hypo-albuminaemia

– Transverse opaque white band è hypo-


albuminaemia

enlarged

Spider nevi

Ascitis

Flapping tremor

liver
ed
n
u
Ja
ic

Breast lump
Examination of
Breast
- Anatomy
Inspection:
Look for :

• Size, symmetry, and contour of both sides

• Skin appearance:

dimpling, peau d’ orange, discoloration, nodules, and


ulceration

• Characteristics of the nipples and areolae:

size and shape, direction in which they point, rashes,


ulceration, and discharge

Inspect the breast in different positions:

• Arms at sides

• Arms over the head

• Hands pressed against hips

• Leaning forward

Inspection in different positions is very important


because some signs will appear or be obvious in specific
position.

Lump Look for any new lump


or hard knot found in
the breast or armpit

Discolorati Look for any change in


on Skin Color, Size or
Texture
Skin Look for any dimpling,
Dimpling puckering or indention
in the breast

Changes Look for any redness, scaliness of


the nipple or breast skin, nipple
in Nipple tenderness or pain,
nipple retraction, turning or drawing
inward or pointing in a new
direction

Nipple Look for any fluid coming from


the nipples, particularly if the
Discharge discharge is bloody, clear and
sticky, dark or occurs without
squeezing the nipple

• Change in skin colour


( redness )

• Change in contour of the


breast
• Ulceration and obvious
skin dimpling in breast
cancer

Palpation:
• The breast tissue is flattened when the patient is lying
supine.

• Use the finger pad of the 2nd , 3rd , and 4th fingers.

• It is important to be systematic to cover all parts of the


breast; the four quadrants, the tail, and the nipple and
areola.

• You can use circular pattern or vertical strip pattern, no


matter.

Finger Use:

Use the pads of your middle


three fingers to feel the texture
of the breast.

Your finger pads are the top


third of each finger, not the
tips.
• examine the breast carefully for:

• Consistency ( normal variation: proportion of firm


glandular tissue and soft fat ).

• Tenderness.

• Nodules:

- Location ( quadrant and distant from the nipple )

- Size

- Shape ( round, cystic, disc-like, or irregular )

- Consistency ( soft, firm, or hard )

- Delimitation ( well circumscribed or not )

- Tenderness

- Mobility:
 first in relation to skin; moving breast à
dimpling

 second in relation to pectoral fascia, and


chest wall;fixed with relaxed arm à
attached to the ribs and intercostal
muscles, fixed with hand pressed against
the hip à attached to the pectoral fascia

• The nipple and areola

The axilla
• Inspection:
inspect the skin of the axilla looking for :

- Rash

- infection ( sweat gland infection )

- Unusual pigmentation
• Palpation:

groups of lymph nodes: central, apical, medial, lateral,


pectoral, subscapular. Also, infraclavicular group of lymph
nodes.
— Pathohistological types of
breast CA
—

— DCIS
• It is Pre invasive cancer.

• Consist of Malignant population of cells limited to the


ducts.

• Early detection now is possible , thanks to mammographic


screening (accounts for 20% of cancers detection.)

• Classified as low,intermediate or high grade.

• Grade based on nuclear features and assessment of


comedo necrosis.
• Subtypes : caomedo,cribiform,micropapillary and solid

• Often micro-calcifications on mammogram; usually not


palpable.

• Paget’s disease. Rare manifestation.

— LCIS
• Incidental finding.

• Multifocal and bilateral .

• More common in young women(80% occurs prior to


menopause).

• Has family Hx .

• 20% will develop into invasive carcinoma within 20 years !

— -----------------------------------------------------------------------------------

— Invasive types
• Palpaple mass …50% will have axillary LN metastasis.

• Fixation to chest wall & dimpling of skin.

• Retraction of nipple.

• lymphedema & thickened skin “peau d’ orange” .

• Calcification or density on mammography.

— Invasive types are :

— Ductal – most common


Lobular
Medullary
Mucinous
Tubular
Papillary

— Invasive ductal carcinoma


• MC of breast CA (80%).

• Most common is NST.

• Hard in consistency and irrigular borders on palpation


(schirrhous carcinoma).

• Mass retracted below cut surface.

• May attached to underlying tissue à dimpling of skin ,


nipple retraction.

— Invasive lobular carcinoma


• 10% of breast CA.

• Often bilateral , multicentric.

• Firm to hard

• MS : single file or bull’s eye pattern.

— Medullary carcinoma
• 1-5 % of breast cancers.

• Soft fleshy tumor (no fibrosis).

• Well Circumscribed mass.

• LN metastasis is infrequent.

• Better prognosis.

• ER -

• BRCA1

— Mucinous )colloidal( carcinoma


• 2% of breast carcinoma.
• Postmenopausal, +60

• Gross: soft pale grey blue gelatinous material.

• MS: pools of mucin with small islands of tumor cells.

• Majority ER +

• May associated with DCIS.

• Pure colloid carcinoma have better prognosis.


— Rare histological variants
• Usually carry better prognosis.

• colloid carcinoma whose cells produce abundant mucin

• medullary carcinoma with solid sheets of large cells often


associated with a marked lymphocytic reaction and
tubular carcinoma. Invasive lobular carcinoma is
commonly multi-focal and/or bilateral.

—
— Prognosis
• In-situ VS invasive
in situ is curable

• Invasive ... Metastasis (locally or distally) is common.

• Special types have better prognosis than NST

• HR = slightly better prognosis. (+ predict respose to


therapy)

• ER and PR (prognosis + endocrine therapy).

• Postmenopausal patients.

• Lobular , papillary , tubular.

Staging
1 - T N M Staging:

— This separately assesses the:

1 - Tumor size )T(,

2 - Lymph Nodes involvement )N(, and


3 - Distal Metastases )M(.

Tumour )T(

Tx Primary tumor cannot be assessed

T0 No evidence of primary tumor

Tis Carcinoma in situ: DCIS, LCIS, or Paget's disease of the


nipple with no tumor

T1 Tumor 2 cm or less in greatest dimension

T2 Tumor more than 2 cm but not more than 5 cm in


greatest dimension

T3 Tumor more than 5 cm in greatest dimension

T4 Tumor of any size with direct extension to chest wall or


skin and divided into subcategories:

T4a - fixed to the chest wall

T4b - fixed to the skin

T4c - fixed to both the skin and the chest wall

T4d - Inflammatory carcinoma

Nodes )N(
— Nx Regional lymph nodes cannot be assessed

— N0 No cancer cells found in any nodes

— N1 lymph nodes in the auxilla but not stuck to other


structures.

— N2: which divided to:

1- N2a - lymph nodes in the auxilla, which are


stuck to each other and to other structures

2- N2b - there are cancer cells in the internal


mammary nodes.

N3 : Metastasis to contralateral mediastinal, contralateral


hilar, ipsilateral or contralateral scalene, or supraclavicular
lymph node(s)

— Metastases )M(
— Mx Presence of distant metastasis cannot be assessed
M0 No sign of cancer spread
M1 Cancer has spread to another part of the body:
1- lungs, 2- liver, 3- bone, or
4- brain.

2 - Staging of breast cancer

based on:

Tumor Size.

Lymph nodes involvement.

Metastasized spread.

To 5 stages: 1 - stage 0 2 - stage I


3 - stage II
4 - stage III 5 - stage IV

Stage 0:

No invasion of neighboring normal tissue.

No lymph nodes involvement or distal metastasis.

E.g. DCIS & LCIS

Stage I:

— There is invading of neighboring normal tissue.

— The tumor measures up to 2cm but not more.

— No lymph nodes or distal metastasis involvement.

Stage II:

divided into subcategories as II a and II b:

Stage II a: Invasive carcinomas 2 cm or less in size.


Metastatic to lymph node of the same side. Or Invasive
carcinoma 2 to 5 cm in size. No lymph node metastasis.
Stage II b: Invasive carcinoma 2 to 5 cm in size and
metastatic to lymph node of the axilla of same side. Or
Invasive carcinomas 5 cm or more in size and no lymph node
metastasis.

- Lymph nodes have not invade one another or to the


surrounding tissues and no distal metastasis in stage II.

Stage III:

divided into subcategories as III a and III b:

— Stage III a:

the tumor measures is larger then 5 cm. with metastasis to


axillary lymph node only. invasion of surrounding lymph
nodal and Surrounding structure.

— Or the tumor measures is less then 5 cm. with


involvement of axillary and other lymph group lymph
node metastasis. No extra nodal invasion.
Stage III b:

— It is an inflammatory breast cancer

distinguishing feature of inflammatory breast


cancer is redness, Swelling, and pain.

— A lump is present only half of the time.

There is invading to:

— 1 - Chest wall

— 2 - Skin (’’peau d'orange“)

— 3 - Internal mammary lymph node.

— Stage IV:

— Carcinoma has metastasize to internal mammary


lymph nodes and:

— 1 - supraclavicular lymph nodes, 2 – lungs,

3 – liver, 4 – bone, or 5 – brain.

Stage Group T Value N Value M Value


Stage 0 Tis N0 M0
Stage I T1 N0 M0
T1 N1 M0
Stage II a T1 N1 M0
T2 N0 M0
T2 N1 M0
Stage II b T3 N0 M0
T0 N2 M0
T1 or T1 N2 M0
Stage III a T2 N2 M0
T3 N1 M0
T3 N2 M0
T4 N0 M0
T4 N1 M0
Stage III b T4 N2 M0
Any T N3 M0
Stage IV Any T Any N M1
Histological Grading of Breast Cancer
Classified to 3 grad:

1. Low grad (I)

2. Intermediate grade (II)

3. High grade (III)

According to:

1- Tubule formation.

a) Majority of tumor ( > 75 % ) score 1

b) Moderate degree ( 10 – 75 % ) score 2

c) Little or none (< 10 % ) score 3

2- Nuclear pleomorphism.

a) minimal variation score 1


Small regular uniform cell

b) Moderate to mild nuclear variation score 2

c) Marked severe nuclear variation score 3

3- Mitotic Activity.

a) 0 – 9 mitoses / 10 hpf. score 1

b) 10 – 19 mitoses / 10 hpf. score 2

c) > 20 mitoses / 10 hpf. score 3

Combined Histologic Grade

Add scores for tubular formation, nuclear pleomorphism and


mitosis count. Total score must be in the range 3–9.

Low grad (I) 3–5

Well-differentiated breast cells.


cells generally appear normal and are not growing rapidly.
cancer arranged in small tubules.
Intermediate grade (II) 6–7

Moderately-differentiated breast cells.


have characteristics between grade 1 and Grade 3 tumors.

High grade (III) 8–9

Poorly differentiated tuomor cells.


Cells do not appear normal and tend to grow and spread
more aggressively.
Investigations
The laboratory investigation of breast carcinoma

1. CBC

2. LFT

3. LDH

4. tumor markers

CBC

 NORMALY the RBC and the WBC are normal in the breast
carcinoma but when it metastasize to the bone marrow
there may be change

 Hb concentration

 Packed cell volume 40-52%

 Mean corpuscular volume80-95fl

 Mean corpuscular HB 27-34pg

 Red blood cell distribution width

 White blood count

Differential count
Neutro.
Lymph.
Eosino.
Mono.
Baso.

LFT
The LFT is normal in the breast carcinoma except when it is
metastasize to the liver there will be elevation to the liver
enzymes

1-Alanine transaminase (ALT)


2-Aspartate transaminase (AST)

3-Alkaline phosphatase (ALP)

4-Total bilirubin (TBIL)

5-Direct bilirubin

6-Gamma glutamyltranspeptidase (GGT)

Lactate dehydrogenises )LDH(

 When there is destruction to the bone marrow there will


be increase in the LDH

 This probably occur due to destruction of the bone marrow


and the RBCS that release It.

1-hemolysis

2-cardiac infarction

3-carcinoma (lymphoma)

4-empysema

5-maningiitis

6-HIV

Tumor markers
These are some of the markers that may indicate breast
carcinoma

 CA15.3

 CA125

 CA27.29

 TRU-Quant
Radiological Investigation for breast cancer

Modality Sensitivity Specificity Indications

Mammography 63-95% 90% Initial


(>95% investigation
palpable, for
50% symptomatic
impalpable, breast in
83-92% in women older
women older than 35 years
than 50 y) and for
(decreases to screening
35% in dense
breasts)
Ultrasonograph 68-97% 92% Initial
y (palpable) investigation
for palpable
lesions in
women
younger than
35 years

MRI 86-100% 21-97% Scarred breast,


implants,
multifocal
lesions, and
borderline
lesions for
breast
conservation
Positron 96% 100% Axilla
emission (90% axillary assessment,
tomography metastases) scarred breast,
(PET) and multifocal
lesions

Mammography

 uses a low-dose x-ray system to examine breasts


 Two-view mammography (ie, craniocaudal and oblique)
 tool of choice for breast screening for women older than
40y
 inappropriate in patients younger than 35 years
§ A mammogram is usually
performed with the patient standing
§ The breast tissue is compressed
and x-rays are taken from different
angles
Ultrasonography

 Determining the Nature of a Breast Abnormality


 Doppler ultrasound is used to assess blood supply in
breast lesions.
 use as a screening tool for women who :
1. dense breasts
2. scarred breasts
3. pregnant

Ultrasonographic 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

Features of benign lesions include the following:

• Cyst - Absence of internal echoes, marked deep


enhancement
• Fibroadenoma - Well-defined borders, well-defined internal
echoes, and displacement of tissue planes
• Lymph node - Well-defined peripheral blood flow on
Doppler images

MRI

 detect lesions as small as 2-3 mm

 cancers, it is useful in defining the precise size of the


tumor and in detecting multifocal disease

 MRI allows for the construction of tridimensional images,


and its versatility is enhanced by the use of different
sequences, including high-resolution, rapid-imaging, fat-
suppression, subtraction, and dynamic sequences.
 Improved staging and treatment planning
 Better detection of recurrence
 help distinguish between benign and malignant
lesions
 Improved screening in high-risk patients

Positron emission tomography )PET(

 most sensitive and specific of all the imaging modalities


for breast disease
 most expensive and least widely available
 Using a wide range of labeled metabolites :
-changes in metabolic activity, vascularization, oxygen
consumption, and tumor receptor status can be detected.

 scarred breasts, multifocal disease and detect axillary


involvement.

Biopsy

 80% of all breast biopsies turn out to be benign


 With early diagnosis women’s chances of surviving are
very good

Fine-needle aspiration

 The least invasive method of biopsy


 If fluid comes out, a cyst was present.
 If lump is solid, will get no fluid. Individual cells will come
out, and can be sprayed onto a microscope slide.
 Pathologist can examine cells to see if cancerous or not,
but cannot tell what type.
 risk of causing a pneumothorax is important

Core Needle Biopsy

 8 – 18 gauge needles. Large enough to withdraw “chunks”


of tissue, with cellular layers undisturbed.
 Pathologist can give more info about tumor – can see if is
invading surrounding tissue or still within ducts
 Can use for palpable AND non-palpable lumps

Histology showing Histology showing


invasive lobular ductal carcinoma in
cancer situ
Breast Cancer Treatment
1- Surgical
2- Radiotherapy
3- Adjuvant (Endocrine therapy , Chemotherapy ,
Herceptin)

Surgical intervention
Operable Breast tumours
Those tumors:
1- Restricted to the breast
2- Associated with axillary lymph nodes.

There are two accepted methods

1- Breast-conserving treatment :
Is usually only suitable for single cancers measuring less than 4cm.

Wide excision should be combined with an axillary node removing .


All so wide excision should be followed by radiotherapy
to the hole breast .

2-Mastectomy

 Mastectomy removes all the breast tissue with some overlying skin but
leaves the chest wall muscle intact.

- Use in multifocal cancer grade 3 or more than 4cm in diameter.

Surgery consists of total mastectomy with axillary node sampling or clearance.


 Radiotherapy
 Always after conservative surgery

 Sometimes after mastectomy

Types!

1-External

2-Internal

 Adjuvant Systemic
Immediately following surgery

Types!

1- Endocrine Therapy

ER/PgR +ve (60%)

 Tamoxifen

 Aromatase Inhibitors

 Ovarian Ablation

2- Chemotherapy

Higher risk

Several options ( CMF )

3- Herceptin

HER2 +ve (20%)

1- Endocrine Therapy

2- Only for ER+ve or PgR+ve (60%)

3- Low toxicity

4- Long term 5 years

5- Around 10% survival gain after 10 years


Chemotherapy
• High toxicity

• Short term 3-6months

• 1-25% survival gain after 10 years

• Careful selection of patients!


FOLLOW UP OF BREAST CA

- Provide patient with support and counseling.


- Detection of early recurrence.
- Support the patient.

1- Provide patient with support and counseling.

Necessary in the early months after the end of primary


treatment :

• - screening.

• - recurrence and plan of follow up

• - Management of early symptoms

Detection of early recurrence.2

• - early detection improve outcome


• - Procedures of early detection
Group I
 Hussain Al-Sheef
 Ahmed Al-Faraj
 Abdullah Al-Rashid
 Hussain Al-Abdul Ghani
 Bassam Al-Bassri
 Hassan Al-Mustafa
 Ali Al-Shammasi
 Abdulhadi Al-Jawad
 Ali Almatrouk
 Hassan Altalaq
 Hassan Al-Zaher
 Saeed Al-Abdul Jabbar