Breast carcinoma
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Oct 30, 2014
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About This Presentation
ppt for all
Slide Content
BREAST CARCINOMA
Presented by
Dr Praveen Kumar Tripathi
Moderator
Dr C.P.Singh(M.S.,F.I.A.M.S.)
Dr Sanjeev kumar(M.S.) praveen tripathi
Presented by
Dr Praveen Kumar Tripathi
Moderator
Dr C.P.Singh(M.S.,F.I.A.M.S.)
Dr Sanjeev kumar(M.S.) praveen tripathi
•The breast is a group of large glands derived from the
epidermis
• It lies in a network of fascia derived from the dermis
and the superficial fascia of the ventral surface of the
thorax
•Breast formation begins in the 6th weeks of fetal
development.
•Mammary gland originates from milk streaks, bilateral
ectodermal thickenings that extend from the axilla to
the groin.
•The ectoderm invaginates into the surrounding
mesenchyme.
DEVELOPMENT OF BREAST
epidermis
• It lies in a network of fascia derived from the dermis
and the superficial fascia of the ventral surface of the
thorax
•Breast formation begins in the 6th weeks of fetal
development.
•Mammary gland originates from milk streaks, bilateral
ectodermal thickenings that extend from the axilla to
the groin.
•The ectoderm invaginates into the surrounding
mesenchyme.
DEVELOPMENT OF BREAST
DEVELOPMENT OF BREAST praveen tripathi
•During the later part of pregnancy this fetal epithelium
further canalizes.
•At term birth, the breasts has 6-10 ducts. The ducts
contain one layer of epithelium and one layer of
myoepithelial
•The initial fetal stages of breast development are
independent of sex steroid influence.
•At birth the withdrawal of maternal steroids results in
secretion of neonatal prolactin (PRL) that stimulates
newborn breast secretion.
DEVELOPMENT OF BREAST
further canalizes.
•At term birth, the breasts has 6-10 ducts. The ducts
contain one layer of epithelium and one layer of
myoepithelial
•The initial fetal stages of breast development are
independent of sex steroid influence.
•At birth the withdrawal of maternal steroids results in
secretion of neonatal prolactin (PRL) that stimulates
newborn breast secretion.
DEVELOPMENT OF BREAST
•Thelarche: the beginning of adult breast
development (10 years)
•Ductal growth phase: Club-shaped terminal
end buds (TEBs)
•Lobuloalveolar phase: TEBs form alveolar buds.
9-10 alveolar buds empty into terminal ductal
lobular units (TDLUs)
•In early puberty, the TDLU is termed a virginal
lobule or lobule type 1 (Lob1)
development (10 years)
•Ductal growth phase: Club-shaped terminal
end buds (TEBs)
•Lobuloalveolar phase: TEBs form alveolar buds.
9-10 alveolar buds empty into terminal ductal
lobular units (TDLUs)
•In early puberty, the TDLU is termed a virginal
lobule or lobule type 1 (Lob1)
•Under cyclic influence of ovarian hormones:
some of the Lob1 will undergo further division
and differentiate into a lobule type 2 (Lob 2).
•In Lob 2 the alveolar buds become smaller but
four times more numerous than Lob1; these
buds are termed ductules or alveoli.
•Lobs develop during late teens but then
decline after the mid twenties.
some of the Lob1 will undergo further division
and differentiate into a lobule type 2 (Lob 2).
•In Lob 2 the alveolar buds become smaller but
four times more numerous than Lob1; these
buds are termed ductules or alveoli.
•Lobs develop during late teens but then
decline after the mid twenties.
praveen tripathi
ANATOMY OF BREAST
BLOOD SUPPLY
1.Axillary
artery(lateral)
•the supreme
thoracic branch
• pectoral br. of
thoracoacromial a.
• lateral thoracic a.
• mammary br.
2.Internal thoracic
a. (medialupper)
3.Intercostal
arteries
1.Axillary
artery(lateral)
•the supreme
thoracic branch
• pectoral br. of
thoracoacromial a.
• lateral thoracic a.
• mammary br.
2.Internal thoracic
a. (medialupper)
3.Intercostal
arteries
LYMPHATIC DRAINAGE
surgeons typically identify six groups at
three anatomic levels.
•The axillary vein group or lateral group,
lateral and posterior to the axillary vein.
Identified at
anatomic confluence of the lateral vein
with the latissimus dorsi.
•These nodes receive the majority of
lymphatic contents from the upper
extremity and ipsilateral back with the
exception of lymph that drains into the
deltopectoral lymph nodes, a group also
referred to as the infraclavicular nodes
•The external mammary group, or
pectoral group along lower and lateral
border of pectoralis minor in association
with the lateral thoracic vessels.
•These nodes receive the principal volume
of lymph drainage from the breast
parenchyma praveen tripathi
surgeons typically identify six groups at
three anatomic levels.
•The axillary vein group or lateral group,
lateral and posterior to the axillary vein.
Identified at
anatomic confluence of the lateral vein
with the latissimus dorsi.
•These nodes receive the majority of
lymphatic contents from the upper
extremity and ipsilateral back with the
exception of lymph that drains into the
deltopectoral lymph nodes, a group also
referred to as the infraclavicular nodes
•The external mammary group, or
pectoral group along lower and lateral
border of pectoralis minor in association
with the lateral thoracic vessels.
•These nodes receive the principal volume
of lymph drainage from the breast
parenchyma praveen tripathi
•The scapular group, near the posterior
wall of the axilla in
juxtaposition to the lateral border of the
scapula and contiguous with the
subscapular vessels
•The central group, nodes that are
embedded in the fat of the axilla, usually
behind the pectoralis minor muscle.
•These nodes receive lymph from the
preceding nodal
groups (axillary, external mammary, and
scapular nodal sites).
•This nodal group is the most palpable
and numerous of axillary
lymphatics, and because of its superficial
position may provide accurate clinical
assessment
of metastatic disease.
wall of the axilla in
juxtaposition to the lateral border of the
scapula and contiguous with the
subscapular vessels
•The central group, nodes that are
embedded in the fat of the axilla, usually
behind the pectoralis minor muscle.
•These nodes receive lymph from the
preceding nodal
groups (axillary, external mammary, and
scapular nodal sites).
•This nodal group is the most palpable
and numerous of axillary
lymphatics, and because of its superficial
position may provide accurate clinical
assessment
of metastatic disease.
•The subclavicular group, posterior and
partially above the upper border of the
pectoralis minor muscle. These nodes
receive lymph from all the other axillary
lymph node groups.
•Thereafter, these efferent lymphatic
vessels from the subclavicular lymph
nodes unite to form the
subclavian trunk.
•The interpectoral or Rotter group,
between the pectoralis major and minor
muscles.
•This group is contiguous with pectoral
branches of the thoracoacromial
vessels.
• Lymph from these nodes enters the
central and subclavicular nodes.
partially above the upper border of the
pectoralis minor muscle. These nodes
receive lymph from all the other axillary
lymph node groups.
•Thereafter, these efferent lymphatic
vessels from the subclavicular lymph
nodes unite to form the
subclavian trunk.
•The interpectoral or Rotter group,
between the pectoralis major and minor
muscles.
•This group is contiguous with pectoral
branches of the thoracoacromial
vessels.
• Lymph from these nodes enters the
central and subclavicular nodes.
SUBAREOLAR PLEXUS
LATERAL COLLECTING ROUTE
EXTERNAL MAMMARY
NODES
SUBSCAPULAR NODE
LATERAL NODE
CENTRAL NODE
SUBCAPULAR NODES
APICAL
SYSTEMIC DISSEMINATION
ROTTER’S
TO CONTRALATERAL BREAST
RECTUS SHEATH AND SUB
PERITONEAL PLEXUS
LATERAL COLLECTING ROUTE
EXTERNAL MAMMARY
NODES
SUBSCAPULAR NODE
LATERAL NODE
CENTRAL NODE
SUBCAPULAR NODES
APICAL
SYSTEMIC DISSEMINATION
ROTTER’S
TO CONTRALATERAL BREAST
RECTUS SHEATH AND SUB
PERITONEAL PLEXUS
praveen tripathi
BREAST CARCINOMA -OVERVIEW
•Breast cancer is most common malignancy in
female
•Second to lung cancer as a cause of death
•Now the mortality rate is decreasing owing to
early detection
•Surgery is considered primary treatment for
breast cancer
•Etiology of the vast majority of breast cancer
is unknown
•Breast cancer is most common malignancy in
female
•Second to lung cancer as a cause of death
•Now the mortality rate is decreasing owing to
early detection
•Surgery is considered primary treatment for
breast cancer
•Etiology of the vast majority of breast cancer
is unknown
RISK FACTORS OFBREAST CARCINOMA
•Epidemiologic studies have identified many
risk factors to develop breast carcinoma
• The common denominator for many of these
risk factors is their effect on the level and
duration of exposure to endogenous estrogen.
•Age and female gender are the most
significant risk factors for breast cancer
•Epidemiologic studies have identified many
risk factors to develop breast carcinoma
• The common denominator for many of these
risk factors is their effect on the level and
duration of exposure to endogenous estrogen.
•Age and female gender are the most
significant risk factors for breast cancer
Risk Factors Estimated Relative Risk
Advanced age >4
Family history
Family history of ovarian cancer in women < 50y >5
One first-degree relative >2
Two or more relatives (mother, sister) >2
Personal history
Personal history 3-4
Positive BRCA1/BRCA2 mutation >4
Breast biopsy with atypical hyperplasia 4-5
Breast biopsy with LCIS or DCIS 8-10
Reproductive history
Early age at menarche (< 12 y) 2
Late age of menopause 1.5-2
Late age of first term pregnancy (>30 y)/nulliparity 2
Use of combined estrogen/progesterone HRT 1.5-2
Current or recent use of oral contraceptives 1.25
Lifestyle factors
Adult weight gain 1.5-2
Sedentary lifestyle 1.3-1.5
Alcohol consumption 1.5
Advanced age >4
Family history
Family history of ovarian cancer in women < 50y >5
One first-degree relative >2
Two or more relatives (mother, sister) >2
Personal history
Personal history 3-4
Positive BRCA1/BRCA2 mutation >4
Breast biopsy with atypical hyperplasia 4-5
Breast biopsy with LCIS or DCIS 8-10
Reproductive history
Early age at menarche (< 12 y) 2
Late age of menopause 1.5-2
Late age of first term pregnancy (>30 y)/nulliparity 2
Use of combined estrogen/progesterone HRT 1.5-2
Current or recent use of oral contraceptives 1.25
Lifestyle factors
Adult weight gain 1.5-2
Sedentary lifestyle 1.3-1.5
Alcohol consumption 1.5
Syndrome Gene Inheritance Cancers Other Features
Breast/ovarian BRCA1 AD Breast, ovarian
Cancer syndrome BRCA2 AD Breast, ovarian,
prostate, pancreatic
Fanconi anemia in
homozygotes
Li-Fraumeni
syndrome
TP53 AD Breast, brain, soft-
tissue sarcomas,
leukemia,
adrenocortical,
others
Cowden disease PTEN AD Breast, ovary,
follicular thyroid,
colon
Adenomas of thyroid,
fibroids, GI polyps
Peutz-Jeghers
syndrome
STKII/LKB1 AD GI, breast Hamartomas of bowel,
pigmentation of buccal
mucosa
Ataxia-
telangiectasia
ATM AD Breast Homozygotes: leukemia,
lymphoma, cerebella
ataxia, immune
deficiency,
telangiectasias
Site-specific CHEK2 AD Breast Low penetrance
Muir-Torre MSH2/MLH1 AD Colorectal, breast
Breast/ovarian BRCA1 AD Breast, ovarian
Cancer syndrome BRCA2 AD Breast, ovarian,
prostate, pancreatic
Fanconi anemia in
homozygotes
Li-Fraumeni
syndrome
TP53 AD Breast, brain, soft-
tissue sarcomas,
leukemia,
adrenocortical,
others
Cowden disease PTEN AD Breast, ovary,
follicular thyroid,
colon
Adenomas of thyroid,
fibroids, GI polyps
Peutz-Jeghers
syndrome
STKII/LKB1 AD GI, breast Hamartomas of bowel,
pigmentation of buccal
mucosa
Ataxia-
telangiectasia
ATM AD Breast Homozygotes: leukemia,
lymphoma, cerebella
ataxia, immune
deficiency,
telangiectasias
Site-specific CHEK2 AD Breast Low penetrance
Muir-Torre MSH2/MLH1 AD Colorectal, breast
PATHOGENESIS OF BREAST CANCER
•Invasive cancers arise through a series of
molecular alterations at the cellular level.
•Resulting in the outgrowth and spread of
breast epithelial cells with immortal features
and uncontrolled growth.
•Genomic profiling has demonstrated the
presence of discrete breast tumor subtypes
with distinct clinical behavior .
•Invasive cancers arise through a series of
molecular alterations at the cellular level.
•Resulting in the outgrowth and spread of
breast epithelial cells with immortal features
and uncontrolled growth.
•Genomic profiling has demonstrated the
presence of discrete breast tumor subtypes
with distinct clinical behavior .
•Proposed molecular subtypes on the basis of
DNAmicroarray include:
Basal-like: ER-, PR- and HER2-; also called triple negative
breast cancer (TNBC)
Most BRCA1 breast cancers are basal-like TNBC.
Luminal A: ER+ and low grade
Luminal B: ER+ but often high grade
ERBB2/HER2+: has amplified HER2/neu
Normal breast-like
Claudin low: a more recently described class; often triple-
negative, but distinct in that there is low expression of cell-
cell junctionproteins including E-cadherin and frequently
there is infiltration with lymphocytes
DNAmicroarray include:
Basal-like: ER-, PR- and HER2-; also called triple negative
breast cancer (TNBC)
Most BRCA1 breast cancers are basal-like TNBC.
Luminal A: ER+ and low grade
Luminal B: ER+ but often high grade
ERBB2/HER2+: has amplified HER2/neu
Normal breast-like
Claudin low: a more recently described class; often triple-
negative, but distinct in that there is low expression of cell-
cell junctionproteins including E-cadherin and frequently
there is infiltration with lymphocytes
Luminal A
Luminal B
HER2+
Basal-like
Intrinsic Breast Cancer
Subtypes
Express ↑ amounts Of luminal
cyto-Keratins & genetic Markers
of luminalEpithelial cells
ofNormal tissue
Express ↑ levels of
EGFR,
c-kit, & growth
factors like
hepatocyte growth
factor
and IGF
Luminal B
HER2+
Basal-like
Intrinsic Breast Cancer
Subtypes
Express ↑ amounts Of luminal
cyto-Keratins & genetic Markers
of luminalEpithelial cells
ofNormal tissue
Express ↑ levels of
EGFR,
c-kit, & growth
factors like
hepatocyte growth
factor
and IGF
•Long arm Chm17(17q21)
•autosomal dominant trait
with high penetrance
•a role in transcription,
cell-cycle control, and
DNA damage repair
•90% lifetime risk of
breast cancer
•40% lifetime risk of
ovarian cancer
•Basal like breast cancer
•Chm 13q
• autosomal dominant
trait and has a high
penetrance
•role in DNA damage
response pathways
•Carrier male100-fold
increase over the risk in
the general male
population
•Invasive ductal
carcinomas
BRCA1 BRCA2
•autosomal dominant trait
with high penetrance
•a role in transcription,
cell-cycle control, and
DNA damage repair
•90% lifetime risk of
breast cancer
•40% lifetime risk of
ovarian cancer
•Basal like breast cancer
•Chm 13q
• autosomal dominant
trait and has a high
penetrance
•role in DNA damage
response pathways
•Carrier male100-fold
increase over the risk in
the general male
population
•Invasive ductal
carcinomas
BRCA1 BRCA2
•High grade,hormone
negative
receptor,aneuploid,inc
reased S fraction
•early age of onset
•a higher prevalence of
bilateral breast cancer;
and the presence of
associated cancers
BRCA2
•well differentiated
• commonly hormone
receptor positive
•early age of onset
•a higher prevalence
of bilateral breast
cancer; and the
presence of
associated cancers
BRCA1
negative
receptor,aneuploid,inc
reased S fraction
•early age of onset
•a higher prevalence of
bilateral breast cancer;
and the presence of
associated cancers
BRCA2
•well differentiated
• commonly hormone
receptor positive
•early age of onset
•a higher prevalence
of bilateral breast
cancer; and the
presence of
associated cancers
BRCA1
The EGFR (erbB) family
Membrane
Extracellular
Intracellular
Receptor
domain
K
EGF
TGF-
Amphiregulin
Tyrosine
kinase
domain
erbB4
HER4
erbB3
HER3
erbB1
HER1
EGFR
erbB2
HER2
neu
Ligands
K
No specific
ligands
Heregulins
K
NRG2
NRG3
Heregulins
Membrane
Extracellular
Intracellular
Receptor
domain
K
EGF
TGF-
Amphiregulin
Tyrosine
kinase
domain
erbB4
HER4
erbB3
HER3
erbB1
HER1
EGFR
erbB2
HER2
neu
Ligands
K
No specific
ligands
Heregulins
K
NRG2
NRG3
Heregulins
Histopathology of Breast Cancer
•On the basis of invasion of basement
membrane
•CARCINOMA IN SITU
Ductal carcimoma in situ(DCIS)
Lobular carcinoma in situ(LCIS)
•INVASIVE CARCINOMA
•On the basis of invasion of basement
membrane
•CARCINOMA IN SITU
Ductal carcimoma in situ(DCIS)
Lobular carcinoma in situ(LCIS)
•INVASIVE CARCINOMA
Normal Breast
Breast profile
A ducts
B lobules
C dilated section of duct to hold milk
D nipple
E fat
F pectoralis major muscle
G chest wall/rib cage
32
Enlargement
A normal duct cells
B basement membrane (duct wall)
C lumen (center of duct)
Illustration © Mary K. Bryson praveen tripathi
Breast profile
A ducts
B lobules
C dilated section of duct to hold milk
D nipple
E fat
F pectoralis major muscle
G chest wall/rib cage
32
Enlargement
A normal duct cells
B basement membrane (duct wall)
C lumen (center of duct)
Illustration © Mary K. Bryson praveen tripathi
Ductal carcinoma in situ
•Discrete spaces surrounded by basement membrane
that are filled with malignant cells and usually with a
recognizable, basally located cell layer made up of
presumably normal myoepithelial cells.
• DCIS is divided into
noncomedo cribriform, micropapillary low grade
solid
comedo subtypes high grade
•Five times increased risk of invasive cancer in female
•Discrete spaces surrounded by basement membrane
that are filled with malignant cells and usually with a
recognizable, basally located cell layer made up of
presumably normal myoepithelial cells.
• DCIS is divided into
noncomedo cribriform, micropapillary low grade
solid
comedo subtypes high grade
•Five times increased risk of invasive cancer in female
34
Range of
Ductal Carcinoma in situ
Illustration © Mary K. Bryson
Range of
Ductal Carcinoma in situ
Illustration © Mary K. Bryson
35
Ductal Carcinoma in situ (DCIS)
Illustration © Mary K. Bryson
Ductal
cancer
cells
Normal
ductal
cell
Ductal Carcinoma in situ (DCIS)
Illustration © Mary K. Bryson
Ductal
cancer
cells
Normal
ductal
cell
DCIS
Characteristic
Comedo Noncomedo
Nuclear grade High Low
Estrogen receptor Negative Positive
HER2
overexpression
Present Absent
Distribution Continuous Multifocal
Necrosis Present Absent
Local recurrence High Low
Prognosis Worse Better
Characteristic
Comedo Noncomedo
Nuclear grade High Low
Estrogen receptor Negative Positive
HER2
overexpression
Present Absent
Distribution Continuous Multifocal
Necrosis Present Absent
Local recurrence High Low
Prognosis Worse Better
Lobular carcinoma in situ
• Originates from the terminal duct lobular units
and develops only in the female breast
•Normal nuclear:cytoplasmic ratio.
•Cytoplasmic mucoid globules are a distinctive
cellular feature
• Approximately, 20% of women with LCIS develop
invasive breast cancer within 15 years
•Risk of invasive cancers is equal in both breasts
•Pleomorphic variant has great potential to
become malignant
• Originates from the terminal duct lobular units
and develops only in the female breast
•Normal nuclear:cytoplasmic ratio.
•Cytoplasmic mucoid globules are a distinctive
cellular feature
• Approximately, 20% of women with LCIS develop
invasive breast cancer within 15 years
•Risk of invasive cancers is equal in both breasts
•Pleomorphic variant has great potential to
become malignant
Lobular carcinoma in situ(LCIS)
•A. Breast Duct System
•B. Lobules
•C. Breast Duct System
•D. Nipple
•E. Fat
•F. Chest Muscle
•G. Ribs
•A. Cells lining lobule
•B. Cancer cells, but all contained
within the lobules
•C. Basement membrane
•A. Breast Duct System
•B. Lobules
•C. Breast Duct System
•D. Nipple
•E. Fat
•F. Chest Muscle
•G. Ribs
•A. Cells lining lobule
•B. Cancer cells, but all contained
within the lobules
•C. Basement membrane
Foot and Stewart Classification for
invasive breast cancer
I. Paget's disease of the nipple
II. Invasive ductal carcinoma
A. Adenocarcinoma with productive fibrosis
(scirrhous, simplex, NST) 80%
B. Medullary carcinoma 4%
C. Mucinous (colloid) carcinoma 2%
D. Papillary carcinoma 2%
E. Tubular carcinoma (and ICC) 2%
III. Invasive lobular carcinoma 10%
IV. Rare cancers (adenoid cystic, squamous cell, apocrine)
invasive breast cancer
I. Paget's disease of the nipple
II. Invasive ductal carcinoma
A. Adenocarcinoma with productive fibrosis
(scirrhous, simplex, NST) 80%
B. Medullary carcinoma 4%
C. Mucinous (colloid) carcinoma 2%
D. Papillary carcinoma 2%
E. Tubular carcinoma (and ICC) 2%
III. Invasive lobular carcinoma 10%
IV. Rare cancers (adenoid cystic, squamous cell, apocrine)
Paget's disease of the nipple
•Chronic, eczematous eruption of the nipple,
which may progress to an ulcerated, weeping
lesion.
• Usually is associated with extensive DCIS and
rarerly with an invasive cancer.
• Nipple biopsy shows a cells identical to the
underlying DCIS cells (pagetoid features or
pagetoid change).
• Pathognomonic of this cancer is the presence
of large, pale, vacuolated cells (Paget cells) in
the rete pegs of the epithelium
•Chronic, eczematous eruption of the nipple,
which may progress to an ulcerated, weeping
lesion.
• Usually is associated with extensive DCIS and
rarerly with an invasive cancer.
• Nipple biopsy shows a cells identical to the
underlying DCIS cells (pagetoid features or
pagetoid change).
• Pathognomonic of this cancer is the presence
of large, pale, vacuolated cells (Paget cells) in
the rete pegs of the epithelium
Invasive Ductal Carcinoma
Adenocarcinoma of the breast with productive
fibrosis (scirrhous, simplex, NST)
•Accounts for 80% of breast cancers
•Axillary lymph node metastases present in up
to 60% of cases.
• Occurs in the fifth to sixth decades of life as a
solitary, firm mass.
Adenocarcinoma of the breast with productive
fibrosis (scirrhous, simplex, NST)
•Accounts for 80% of breast cancers
•Axillary lymph node metastases present in up
to 60% of cases.
• Occurs in the fifth to sixth decades of life as a
solitary, firm mass.
Invasive Ductal Carcinoma (IDC –
80% of breast cancer)
43
•The cancer has spread to the
surrounding tissues
Illustration © Mary K. Bryson
Ductal cancer cells
breaking through
the wall
80% of breast cancer)
43
•The cancer has spread to the
surrounding tissues
Illustration © Mary K. Bryson
Ductal cancer cells
breaking through
the wall
INVASIVE CARCINOMA…..
Medullary carcinoma
• frequent phenotype of BRCA1 hereditary
breast cancer.
•Grossly, the cancer is soft and hemorrhagic.
• A Roughly 30% of patients have lymph node
metastasis.
• Typical medullary carcinomas are often
associated with a good prognosis despite the
unfavorable prognostic features associated
with this type of breast cancer.
Medullary carcinoma
• frequent phenotype of BRCA1 hereditary
breast cancer.
•Grossly, the cancer is soft and hemorrhagic.
• A Roughly 30% of patients have lymph node
metastasis.
• Typical medullary carcinomas are often
associated with a good prognosis despite the
unfavorable prognostic features associated
with this type of breast cancer.
•Mucinous carcinoma
Excellent prognosis, with a greater than 80% 10-
year survival.
66% of mucinous carcinomas display hormone
receptors.
Lymph node metastases occur in 33%
•Tubular carcinoma
Low incidence of lymph node involvement and
a very high overall survival rate thus patients
are often treated with only breast-conserving
surgery and local radiation therapy.
Excellent prognosis, with a greater than 80% 10-
year survival.
66% of mucinous carcinomas display hormone
receptors.
Lymph node metastases occur in 33%
•Tubular carcinoma
Low incidence of lymph node involvement and
a very high overall survival rate thus patients
are often treated with only breast-conserving
surgery and local radiation therapy.
•Papillary carcinoma
Cystic papillary carcinoma has a low mitotic activity, which results in
a more indolent course and good prognosis.
Invasive micropapillary ductal carcinoma has a more aggressive
phenotype, even though approximately 70% of cases are ER-
positive.
rarely attain a size of 3 cm in diameter
Additionally, lymph node metastasis is seen frequently in this
subtype (70-90% incidence), and the number of lymph nodes
involved appears to correlate with survival
Cystic papillary carcinoma has a low mitotic activity, which results in
a more indolent course and good prognosis.
Invasive micropapillary ductal carcinoma has a more aggressive
phenotype, even though approximately 70% of cases are ER-
positive.
rarely attain a size of 3 cm in diameter
Additionally, lymph node metastasis is seen frequently in this
subtype (70-90% incidence), and the number of lymph nodes
involved appears to correlate with survival
•Invasive lobular carcinoma
accounts for 10% of breast cancers.
Special stains may confirm the presence of
intracytoplasmic mucin, which may displace the nucleus
(signet-ring cell carcinoma).
It is frequently multifocal, multicentric, and bilateral.
Because of its insidious growth pattern and subtle
mammographic features, it is difficult to detect.
accounts for 10% of breast cancers.
Special stains may confirm the presence of
intracytoplasmic mucin, which may displace the nucleus
(signet-ring cell carcinoma).
It is frequently multifocal, multicentric, and bilateral.
Because of its insidious growth pattern and subtle
mammographic features, it is difficult to detect.
Invasive Lobular Carcinoma (ILC)
48
Illustration © Mary K. Bryson
Lobular cancer
cells breaking
through the wall
48
Illustration © Mary K. Bryson
Lobular cancer
cells breaking
through the wall
Cancer Can also Invade Lymph or
Blood Vessels
49
Illustration © Mary K. Bryson
Cancer cells
invade
lymph duct
Cancer cells
invade
blood vessel
Blood Vessels
49
Illustration © Mary K. Bryson
Cancer cells
invade
lymph duct
Cancer cells
invade
blood vessel
Diagnosis of breast cancer
Diagnosis of breast cancer
Clinical examination
History
This should include the following elements:
• breast mass
• breast pain
• nipple discharge
• nipple or skin retraction
• axillary mass or pain
• arm swelling
• symptoms of possible metastatic spread
Clinical examination
History
This should include the following elements:
• breast mass
• breast pain
• nipple discharge
• nipple or skin retraction
• axillary mass or pain
• arm swelling
• symptoms of possible metastatic spread
2. Past medical history of breast disease in detail.
3. Family history of breast and other cancers with
emphasis on gynaecological cancers.
4. Reproductive history:
• age at menarche
• age at first delivery
• number of pregnancies, children and
miscarriages
• age at onset of menopause
• history of hormonal viz OCP/HRT
5. Past medical history.
3. Family history of breast and other cancers with
emphasis on gynaecological cancers.
4. Reproductive history:
• age at menarche
• age at first delivery
• number of pregnancies, children and
miscarriages
• age at onset of menopause
• history of hormonal viz OCP/HRT
5. Past medical history.
Physical examination
Careful physical examination should cover the following:
1. Performance status.
2. Weight, height and surface area.
3. General examination of other systems.
Careful physical examination should cover the following:
1. Performance status.
2. Weight, height and surface area.
3. General examination of other systems.
4. Local examination:
• breast mass
– size
– location (specified by clock position and distance from the
edge of the areola)
– shape
– consistency
– fixation to skin, pectoral muscle and chest wall
– multiplicity
• skin changes
– erythema (location and extent)
– oedema (location and extent)
– dimpling
– infiltration
– ulceration
– satellite nodules
• breast mass
– size
– location (specified by clock position and distance from the
edge of the areola)
– shape
– consistency
– fixation to skin, pectoral muscle and chest wall
– multiplicity
• skin changes
– erythema (location and extent)
– oedema (location and extent)
– dimpling
– infiltration
– ulceration
– satellite nodules
• nipple changes
– retraction
– erythema
– erosion and ulceration
– discharge (specify)
• nodal status
– axillary nodes on both sides (number, size, location and fixation to
other nodes
or underlying structures)
– supraclavicular nodes
• local examination of possible metastatic sites.
– retraction
– erythema
– erosion and ulceration
– discharge (specify)
• nodal status
– axillary nodes on both sides (number, size, location and fixation to
other nodes
or underlying structures)
– supraclavicular nodes
• local examination of possible metastatic sites.
Signs and Symptoms
Most common:
lump or
thickening in
breast. Often
painless
Change in color
or appearance
of areola
Redness or pitting
of skin over the
breast, like the
skin of an orange
Discharge
or
bleeding
Change in size
or contours of
breast
Most common:
lump or
thickening in
breast. Often
painless
Change in color
or appearance
of areola
Redness or pitting
of skin over the
breast, like the
skin of an orange
Discharge
or
bleeding
Change in size
or contours of
breast
Laboratory investigations
• Complete blood count with differential (CBCD), and renal and hepatic profile.
• Bilateral mammography and/or ultrasound.
• Chest X-ray ― computed tomography i(CT) of chest if needed.
• Abdominal ultrasound } CT of abdomen.
• Bone scan if indicated.
• Electrocardiogram (ECG) and echocardiogram or multiple gated acquisition
(MUGA)scan if age > 60.
• Positron emission tomography (PET) scan optional
• Complete blood count with differential (CBCD), and renal and hepatic profile.
• Bilateral mammography and/or ultrasound.
• Chest X-ray ― computed tomography i(CT) of chest if needed.
• Abdominal ultrasound } CT of abdomen.
• Bone scan if indicated.
• Electrocardiogram (ECG) and echocardiogram or multiple gated acquisition
(MUGA)scan if age > 60.
• Positron emission tomography (PET) scan optional
RADIOLOGICAL INVESTIGATIONS
•Mammography
•Nuclear Imaging(scintimammography)
•Ultrasonography
•Doppler Flow Studies
•Thermography
•Magnetic resonance imaging
•PET Scan
•Mammography
•Nuclear Imaging(scintimammography)
•Ultrasonography
•Doppler Flow Studies
•Thermography
•Magnetic resonance imaging
•PET Scan
Mammography
•Mammography is a special type of low-dose
(0.1 cGy per study) x ray imaging used to
create detailed images of the breast.
• Mammography can demonstrate
microcalcifications smaller than 100 µm;
•Reveals a lesion , 1-2 years before it is
palpable by BSE.
•Each chest roentgenogram delivers one-
quarter of this radiation volume
• Not a substitute for biopsy; rather is an
adjunctive
•Mammography is a special type of low-dose
(0.1 cGy per study) x ray imaging used to
create detailed images of the breast.
• Mammography can demonstrate
microcalcifications smaller than 100 µm;
•Reveals a lesion , 1-2 years before it is
palpable by BSE.
•Each chest roentgenogram delivers one-
quarter of this radiation volume
• Not a substitute for biopsy; rather is an
adjunctive
The technique is useful for
1) A screening tool for early detection in asymptomatic female
2) An indeterminate mass that presents as a solitary lesion that
may be a neoplasm
3)Indeterminate mass that cannot be considered a dominant
nodule, especially when multiple cysts or other vague
masses are present and the indication for biopsy is uncertain
4)Follow-up examination of breast cancer treated by segmental
mastectomy and radiation therapy
5) Follow-up examination of the contralateral breast after
segmental or total mastectomy
6) Evaluation of the large, fatty breast in the symptomatic
patient in whom nodules are not palpable
1) A screening tool for early detection in asymptomatic female
2) An indeterminate mass that presents as a solitary lesion that
may be a neoplasm
3)Indeterminate mass that cannot be considered a dominant
nodule, especially when multiple cysts or other vague
masses are present and the indication for biopsy is uncertain
4)Follow-up examination of breast cancer treated by segmental
mastectomy and radiation therapy
5) Follow-up examination of the contralateral breast after
segmental or total mastectomy
6) Evaluation of the large, fatty breast in the symptomatic
patient in whom nodules are not palpable
Types of mammography :
• screening
• diagnostic.
Screening mammography is done in
asymptomatic womenwhen cancer not
suspected
Diagnostic mammography is performed in
symptomatic women (eg, when a breast lump
or nipple discharge is found during self-
examination or an abnormality is found during
screening mammography
• screening
• diagnostic.
Screening mammography is done in
asymptomatic womenwhen cancer not
suspected
Diagnostic mammography is performed in
symptomatic women (eg, when a breast lump
or nipple discharge is found during self-
examination or an abnormality is found during
screening mammography
FINDINGS IN MAMMOGRAPHY
•DENSITY- Space occupying lesion seen in only
one projection
- no clinical significance
•MASSES- Space occupying lesion seen in two
projections
Round or oval- benign
Irregular or lobulated- malignant
•CALCIFICATIONS – Malignant calcifications are
usually<0.5mm, pleomorphic or heterogenous
and grouped
•DENSITY- Space occupying lesion seen in only
one projection
- no clinical significance
•MASSES- Space occupying lesion seen in two
projections
Round or oval- benign
Irregular or lobulated- malignant
•CALCIFICATIONS – Malignant calcifications are
usually<0.5mm, pleomorphic or heterogenous
and grouped
mass
microcalcifications
microcalcifications
•Benign
–Pure and intensely
hyperechoic
–Elliptical shape (wider
than tall)
–Lobulated
–Complete tine capsule
–Skin calcifications
–Vascular
–Popcorn
–Punctate
–Eggshell
•Malignant
–Hypoechoic,
spiculated,heterogenous
–Taller than wide
–Duct extension
–Microlobulation
–Fine
–Fine and linear
–Linear and branching
–Pure and intensely
hyperechoic
–Elliptical shape (wider
than tall)
–Lobulated
–Complete tine capsule
–Skin calcifications
–Vascular
–Popcorn
–Punctate
–Eggshell
•Malignant
–Hypoechoic,
spiculated,heterogenous
–Taller than wide
–Duct extension
–Microlobulation
–Fine
–Fine and linear
–Linear and branching
Mammogram – Difficult Case
66
•Heterogeneously dense breast
•Cancer can be difficult to detect with
this type of breast tissue
•The fibroglandular tissue (white areas)
may hide the tumor
•The breasts of younger women contain
more glands and ligaments resulting in
dense breast tissue
66
•Heterogeneously dense breast
•Cancer can be difficult to detect with
this type of breast tissue
•The fibroglandular tissue (white areas)
may hide the tumor
•The breasts of younger women contain
more glands and ligaments resulting in
dense breast tissue
Mammogram – Easier Case
67
•With age, breast tissue
becomes fattier and has
fewer glands
•Cancer is relatively easy to
detect in this type of breast
tissue
67
•With age, breast tissue
becomes fattier and has
fewer glands
•Cancer is relatively easy to
detect in this type of breast
tissue
Xeromammography
• Identical with mammography except that the image is
recorded on a xerographic plate rather than a
conventional transparency.
• The image produced is positive rather than negative
• Edge enhancement and wide recording latitude allow
details of the soft tissues of the breast, chest wall, and
thinner peripheral portions of the breast to be
recorded with one exposure.
• Identical with mammography except that the image is
recorded on a xerographic plate rather than a
conventional transparency.
• The image produced is positive rather than negative
• Edge enhancement and wide recording latitude allow
details of the soft tissues of the breast, chest wall, and
thinner peripheral portions of the breast to be
recorded with one exposure.
Magnification Mammography
•This technique enhances the sharpness of detail and
increases diagnostic accuracy for breast cancer.
•The optimal magnification is 1.5 times life size
• margins of breast masses and the degree and specificity
of microcalcifications are clearly defined
•may significantly reduce the number of patients referred
for biopsy
•This technique enhances the sharpness of detail and
increases diagnostic accuracy for breast cancer.
•The optimal magnification is 1.5 times life size
• margins of breast masses and the degree and specificity
of microcalcifications are clearly defined
•may significantly reduce the number of patients referred
for biopsy
Ultrasonography
•Useful adjunct to mammography in the
clinical setting
•As a screening device, ultrasound is limited
by a number of factors, most notably by the
failure to detect microcalcifications and by
poor specificity (34%).
•performed primarily to differentiate cystic
from solid lesions
•Ultrasonography is also useful for guiding the
aspiration of cysts to provide cytologic
specimens in FNAC
•Useful adjunct to mammography in the
clinical setting
•As a screening device, ultrasound is limited
by a number of factors, most notably by the
failure to detect microcalcifications and by
poor specificity (34%).
•performed primarily to differentiate cystic
from solid lesions
•Ultrasonography is also useful for guiding the
aspiration of cysts to provide cytologic
specimens in FNAC
Magnetic Resonance Imaging
• MRI has been explored as a modality for
detecting breast cancer in women at high risk
and in younger women.
Indications for MRI
•Characterization of an indeterminate lesion
after a full assessment with physical
examination, mammography, and
ultrasonography
•Detection of occult breast carcinoma in a
patient with carcinoma in an axillary lymph
node
• MRI has been explored as a modality for
detecting breast cancer in women at high risk
and in younger women.
Indications for MRI
•Characterization of an indeterminate lesion
after a full assessment with physical
examination, mammography, and
ultrasonography
•Detection of occult breast carcinoma in a
patient with carcinoma in an axillary lymph
node
•Evaluation of suspected multifocal or bilateral tumor
•Evaluation of invasive lobular carcinoma, which has a high incidence of
multifocality
•Evaluation of suspected, extensive, high-grade intraductal carcinoma
•Detection of occult primary breast carcinoma in the presence of
metastatic adenocarcinoma of unknown origin
•Monitoring of the response to neoadjuvant chemotherapy
•Detection of recurrent breast cancer and to differentiate from scar
• Best imaging modality for the breasts of women with implants
•Evaluation of invasive lobular carcinoma, which has a high incidence of
multifocality
•Evaluation of suspected, extensive, high-grade intraductal carcinoma
•Detection of occult primary breast carcinoma in the presence of
metastatic adenocarcinoma of unknown origin
•Monitoring of the response to neoadjuvant chemotherapy
•Detection of recurrent breast cancer and to differentiate from scar
• Best imaging modality for the breasts of women with implants
•Contraindications to MRI
Contraindication to gadolinium-based contrast media (eg, allergy,
pregnancy)
Patient's inability to lie prone(Marked kyphosis or kyphoscoliosis)
Marked obesity
Extremely large breasts
Severe claustrophobia
•LIMITATIONS AS SCREENING TOOL
Cost and unreliable depiction of microcalcifications
Above contraindications
Contraindication to gadolinium-based contrast media (eg, allergy,
pregnancy)
Patient's inability to lie prone(Marked kyphosis or kyphoscoliosis)
Marked obesity
Extremely large breasts
Severe claustrophobia
•LIMITATIONS AS SCREENING TOOL
Cost and unreliable depiction of microcalcifications
Above contraindications
Positron Emission Tomography
Scanning
•PET scanning is the most sensitive and specific
of all the imaging modalities for breast disease
•At present, its main use to detect recurrences
in scarred breasts
•Also useful in multifocal disease, in detecting
axillary involvement, and in equivocal cases of
systemic metastases.
Scanning
•PET scanning is the most sensitive and specific
of all the imaging modalities for breast disease
•At present, its main use to detect recurrences
in scarred breasts
•Also useful in multifocal disease, in detecting
axillary involvement, and in equivocal cases of
systemic metastases.
• Assist in identification of nonaxillary lymph
node metastasis (ie, internal mammary or
supraclavicular lymph nodes) for staging
locally advanced and inflammatory breast
cancer before starting neoadjuvant therapy
•Most expensive and least widely available.
node metastasis (ie, internal mammary or
supraclavicular lymph nodes) for staging
locally advanced and inflammatory breast
cancer before starting neoadjuvant therapy
•Most expensive and least widely available.
Modality Sensitivity Specificity P p value Indications
Mammogra
phy
63-95%
(>95% palpable,
50%
impalpable,
83-92% in
women older
than 50 y)
(decreases to
35% in dense
breasts)
14-90%
(90% palpable)
10-50%
(94% palpable)
Initial investigation
for symptomatic
breast in women
older than 35 years
and for screening;
investigation of
choice for
microcalcification
Ultrasonogr
aphy
68-97%
(palpable)
74-94%
(palpable)
92% (palpable) Initial investigation
for palpable lesions
in women younger
than 35 years
Mammogra
phy
63-95%
(>95% palpable,
50%
impalpable,
83-92% in
women older
than 50 y)
(decreases to
35% in dense
breasts)
14-90%
(90% palpable)
10-50%
(94% palpable)
Initial investigation
for symptomatic
breast in women
older than 35 years
and for screening;
investigation of
choice for
microcalcification
Ultrasonogr
aphy
68-97%
(palpable)
74-94%
(palpable)
92% (palpable) Initial investigation
for palpable lesions
in women younger
than 35 years
Modality Sensitivity Specificity P PV Indications
MRI 86-100% 21-97%
(< 40% primary
cancer)
52% Scarred breast, implants, multifocal
lesions, and borderline lesions for
breast conservation; may be useful in
screening high-risk women
Scintigraph
y
76-95%
(palpable)
52-91%
(impalpabl
e)
62-94%
(94% impalpable)
70-83%
(83%
palpable,
79%
impalpab
le)
Lesions larger than 1 cm and axilla
assessment; may help predict drug
resistance
PET
scanning
96%
(90%
axillary
metastases)
100% Axilla assessment, scarred breast, and
multifocal lesions
MRI 86-100% 21-97%
(< 40% primary
cancer)
52% Scarred breast, implants, multifocal
lesions, and borderline lesions for
breast conservation; may be useful in
screening high-risk women
Scintigraph
y
76-95%
(palpable)
52-91%
(impalpabl
e)
62-94%
(94% impalpable)
70-83%
(83%
palpable,
79%
impalpab
le)
Lesions larger than 1 cm and axilla
assessment; may help predict drug
resistance
PET
scanning
96%
(90%
axillary
metastases)
100% Axilla assessment, scarred breast, and
multifocal lesions
Thermography
•Transmission of detectable heat from the breast is
nonspecific, and in malignant lesions results from the
hypervascularity that frequently accompanies carcinoma.
•Three thermographic methods are used: telethermography,
contact thermography, and computed tomography.
•Using special heat scanners it is possible to delineate these
“hot” perfusion sites on film.
• Results are variable and inaccurate, Sensitivity is less than
50 percent and it is not advocated as a routine screening
method, because it is unable to detect minimal breast cancer.
•Transmission of detectable heat from the breast is
nonspecific, and in malignant lesions results from the
hypervascularity that frequently accompanies carcinoma.
•Three thermographic methods are used: telethermography,
contact thermography, and computed tomography.
•Using special heat scanners it is possible to delineate these
“hot” perfusion sites on film.
• Results are variable and inaccurate, Sensitivity is less than
50 percent and it is not advocated as a routine screening
method, because it is unable to detect minimal breast cancer.
DIAGNOSTIC BIOPSY
NONPALPABLE LESIONS
•Image-guided breast biopsies are frequently
required to diagnose nonpalpable lesion
•Ultrasound localization techniques are used
when a mass is present, whereas stereotactic
techniques are used when no mass is present
(microcalcifications only).
• Combination of diagnostic mammography,
ultrasound or stereotactic localization, and
FNAB achieves almost 100% accuracy in the
diagnosis of breast cancer.
NONPALPABLE LESIONS
•Image-guided breast biopsies are frequently
required to diagnose nonpalpable lesion
•Ultrasound localization techniques are used
when a mass is present, whereas stereotactic
techniques are used when no mass is present
(microcalcifications only).
• Combination of diagnostic mammography,
ultrasound or stereotactic localization, and
FNAB achieves almost 100% accuracy in the
diagnosis of breast cancer.
Fine-needle aspiration cytology (FNAC)
• Rapid and least invasive technique of
obtaining a cell diagnosis
• 80% diagnostic accuracy
• Invasive cancer cannot be distinguished
from in situ disease
• Rapid and least invasive technique of
obtaining a cell diagnosis
• 80% diagnostic accuracy
• Invasive cancer cannot be distinguished
from in situ disease
core-needle Biopsy
•Permits the analysis of breast tissue architecture and
allows the pathologist to determine whether invasive
cancer is present.
• Core-needle biopsy is preferred over open biopsy for
nonpalpable breast lesions because a single surgical
procedure can be planned based on the results of the core
biopsy.
• The advantages of core-needle biopsy include a low
complication rate, avoidance of scarring, and a lower cost.
•Permits the analysis of breast tissue architecture and
allows the pathologist to determine whether invasive
cancer is present.
• Core-needle biopsy is preferred over open biopsy for
nonpalpable breast lesions because a single surgical
procedure can be planned based on the results of the core
biopsy.
• The advantages of core-needle biopsy include a low
complication rate, avoidance of scarring, and a lower cost.
Palpable masses
•FNAC can be done in out patient setting
•USG guided FNAC is preferred in cystic masses
and aspirate is sent for cytology if bloody
•Percutaneous vacuum-assisted large-gauge
core biopsy (VACNB) with image guidance is
preferred
•Incision biopsy can be done in ulcerating
masses
•FNAC can be done in out patient setting
•USG guided FNAC is preferred in cystic masses
and aspirate is sent for cytology if bloody
•Percutaneous vacuum-assisted large-gauge
core biopsy (VACNB) with image guidance is
preferred
•Incision biopsy can be done in ulcerating
masses
Histology
The following features are all important in deciding on a
course of treatment :
•Size
•Status of surgical margin
•Presence or absence of estrogen receptors and
progesterone receptors
•Nuclear and histologic grade
•DNA content
•S-phase fraction
•Vascular invasion
•Tumor necrosis
•Quantity of intraductal component
The following features are all important in deciding on a
course of treatment :
•Size
•Status of surgical margin
•Presence or absence of estrogen receptors and
progesterone receptors
•Nuclear and histologic grade
•DNA content
•S-phase fraction
•Vascular invasion
•Tumor necrosis
•Quantity of intraductal component
Additional Testing
HER2 testing
•Breast cancer specimens should initially undergo HER2
testing by a validated immunohistochemistry (IHC)
•The scoring method for HER2 expression is based on
the cell membrane staining pattern and is as follows:
3+: Positive HER2 expression - Uniform intense
membrane staining of more than 30% of invasive
tumor cells
2+: Equivocal for HER2 protein expression - Complete
membrane staining that is either nonuniform or weak
in intensity but has circumferential distribution in at
least 10% of cells
0 or 1+: Negative for HER2 protein expression
HER2 testing
•Breast cancer specimens should initially undergo HER2
testing by a validated immunohistochemistry (IHC)
•The scoring method for HER2 expression is based on
the cell membrane staining pattern and is as follows:
3+: Positive HER2 expression - Uniform intense
membrane staining of more than 30% of invasive
tumor cells
2+: Equivocal for HER2 protein expression - Complete
membrane staining that is either nonuniform or weak
in intensity but has circumferential distribution in at
least 10% of cells
0 or 1+: Negative for HER2 protein expression
Current assay of HER2/neu
Immunohistochemistry
‘0’ (negative) ‘1+’ (negative) ‘2+’ (equivocal) ‘3+’ (positive)
Fluorescence in situ hybridization (FISH)
HER2 gene no amplification
FISH negative :FISH ratio <1.8
HER2 gene amplification FISH positive
FISH ratio >2.2
Immunohistochemistry
‘0’ (negative) ‘1+’ (negative) ‘2+’ (equivocal) ‘3+’ (positive)
Fluorescence in situ hybridization (FISH)
HER2 gene no amplification
FISH negative :FISH ratio <1.8
HER2 gene amplification FISH positive
FISH ratio >2.2
Oncotype DX
•RT-PCR assay of 16 cancer-related genes and 5 normal comparator
reference genes, and is therefore sometimes known as the 21-gene
assay.
• It was designed for use in estrogen receptor positive tumors. The
test is run on formalin fixed, paraffin-embedded tissue.
• Oncotype results are reported as a Recurrence Score (RS) .
< 18 are considered low risk
18-30 is considered intermediate risk
> 30 is considered high risk.
• where a higher RS is associated with a worse prognosis, referring to
the likelihood of recurrence without treatment.
•higher RS is also associated with a higher probability of response
to chemotherapy, which is termed a positive predictive factor.
•RT-PCR assay of 16 cancer-related genes and 5 normal comparator
reference genes, and is therefore sometimes known as the 21-gene
assay.
• It was designed for use in estrogen receptor positive tumors. The
test is run on formalin fixed, paraffin-embedded tissue.
• Oncotype results are reported as a Recurrence Score (RS) .
< 18 are considered low risk
18-30 is considered intermediate risk
> 30 is considered high risk.
• where a higher RS is associated with a worse prognosis, referring to
the likelihood of recurrence without treatment.
•higher RS is also associated with a higher probability of response
to chemotherapy, which is termed a positive predictive factor.
NCCN guidelines include Oncotype DX
®
testing in the
treatment-decision pathway for node-negative and
micrometastatic disease
Adapted from NCCN Practice Guidelines in Oncology – v.1.2010.
•Tumor 0.6-1.0 cm,
moderately or poorly
differentiated,
intermediate or high
grade, or vascular
invasion
•Tumor > 1 cm with
favorable or
unfavorable
pathologic features
Consider
Oncotyp
e DX
Hormone receptor-positive, HER2-negative disease
pT1, pT2, or pT3 and pN1mi
No test
RS <
18
RS 18-
30
RS ≥
31
Adjuvant endocrine
therapy
± adjuvant chemotherapy
Adjuvant endocrine
therapy
endocrine therapy
± adjuvant chemotherapy
Adjuvant Adjuvant
endocrine therapy
+ adjuvant chemotherapy
®
testing in the
treatment-decision pathway for node-negative and
micrometastatic disease
Adapted from NCCN Practice Guidelines in Oncology – v.1.2010.
•Tumor 0.6-1.0 cm,
moderately or poorly
differentiated,
intermediate or high
grade, or vascular
invasion
•Tumor > 1 cm with
favorable or
unfavorable
pathologic features
Consider
Oncotyp
e DX
Hormone receptor-positive, HER2-negative disease
pT1, pT2, or pT3 and pN1mi
No test
RS <
18
RS 18-
30
RS ≥
31
Adjuvant endocrine
therapy
± adjuvant chemotherapy
Adjuvant endocrine
therapy
endocrine therapy
± adjuvant chemotherapy
Adjuvant Adjuvant
endocrine therapy
+ adjuvant chemotherapy
MammaPrint
•The MammaPrint test analyzes 70 genes from an early-stage breast
cancer tissue sample to figure out if the cancer has a low or high risk
of coming back (recurrence) within 10 years after diagnosis.
• A diagnostic test used by physicians to assess the risk that a breast
tumor will metastasize to other parts of the body
• This helps physicians determine whether or not each patient will
benefit from chemotherapy
• MammaPrint can be used on cancers that are:
stage I or stage II
invasive
smaller than 5 centimeters
in three or fewer lymph nodes
•The MammaPrint test analyzes 70 genes from an early-stage breast
cancer tissue sample to figure out if the cancer has a low or high risk
of coming back (recurrence) within 10 years after diagnosis.
• A diagnostic test used by physicians to assess the risk that a breast
tumor will metastasize to other parts of the body
• This helps physicians determine whether or not each patient will
benefit from chemotherapy
• MammaPrint can be used on cancers that are:
stage I or stage II
invasive
smaller than 5 centimeters
in three or fewer lymph nodes
SET (sensitivity to endocrine therapy) index:
•A multigene expression profile that was
developed to measure estrogen receptor–
related transcription in breast cancer.
RCB (residual cancer burden):An index to
estimate the extent of residual invasive cancer
in the breast and regional lymph nodes after
neoadjuvant chemotherapy.
•A multigene expression profile that was
developed to measure estrogen receptor–
related transcription in breast cancer.
RCB (residual cancer burden):An index to
estimate the extent of residual invasive cancer
in the breast and regional lymph nodes after
neoadjuvant chemotherapy.
LEVELS OF INTERVENTION IN BREAST CARCINOMA
1.RISK IDENTIFICATION AND RISK
REDUCTION THERAPY
2.SCREENING
3.STAGING AND MANAGEMENT OF BREAST
CARCINOMA
•SURGERY
•HORMONAL THERAPY
•CHEMOTHERAPY
•RADIOTHERAPY
4. FOLLOW UP
1.RISK IDENTIFICATION AND RISK
REDUCTION THERAPY
2.SCREENING
3.STAGING AND MANAGEMENT OF BREAST
CARCINOMA
•SURGERY
•HORMONAL THERAPY
•CHEMOTHERAPY
•RADIOTHERAPY
4. FOLLOW UP
· Familial/genetic factors
Criteria for further risk evaluation:
• Family history
• Early-age-onset breast cancer
Two breast primaries or breast and ovarian/fallopian
tube/primary peritoneal cancer in a single individual
or
• Two or more breast primaries or breast and ovarian/fallopian
tube/primary peritoneal cancers in close relative(s) from the same
side of family (maternal or paternal)
• A combination of breast cancer with one or more of the following:
thyroid cancer, sarcoma, adrenocortical carcinoma, endometrial cancer,
pancreatic cancer, brain tumors, diffuse gastric cancer dermatologic
manifestations or leukemia/lymphoma on the same side of family
• Member of a family with a known mutation in a breast cancer
susceptibility gene
• Populations at risk
• Male breast cancer
• Ovarian/fallopian tube/primary peritoneal cancer
• Known BRCA1/2, p53, PTEN, or other gene mutation associated
with breast cancer risk
Criteria for further risk evaluation:
• Family history
• Early-age-onset breast cancer
Two breast primaries or breast and ovarian/fallopian
tube/primary peritoneal cancer in a single individual
or
• Two or more breast primaries or breast and ovarian/fallopian
tube/primary peritoneal cancers in close relative(s) from the same
side of family (maternal or paternal)
• A combination of breast cancer with one or more of the following:
thyroid cancer, sarcoma, adrenocortical carcinoma, endometrial cancer,
pancreatic cancer, brain tumors, diffuse gastric cancer dermatologic
manifestations or leukemia/lymphoma on the same side of family
• Member of a family with a known mutation in a breast cancer
susceptibility gene
• Populations at risk
• Male breast cancer
• Ovarian/fallopian tube/primary peritoneal cancer
• Known BRCA1/2, p53, PTEN, or other gene mutation associated
with breast cancer risk
· Demographics
• Age.
• Ethnicity/race
Increased incidence of specific BRCA1/2 mutations in Ashkenazi Jewish
decent.
• Body mass index
•· Reproductive history
• Age at menarche
• Parity
• Age at first live birth
• Age at menopause
•· Environmental factors
• Current or prior estrogen and progesterone hormone replacement therapy
• Alcohol consumption
• Other
Atypical hyperplasia
Number of prior breast biopsies
Procedure done with the intent to diagnose cancer, multiple biopsies of the
same lesion are scored as one biopsy.
Breast density
Prior thoracic RT
History of lobular carcinoma in situ (LCIS)
• Age.
• Ethnicity/race
Increased incidence of specific BRCA1/2 mutations in Ashkenazi Jewish
decent.
• Body mass index
•· Reproductive history
• Age at menarche
• Parity
• Age at first live birth
• Age at menopause
•· Environmental factors
• Current or prior estrogen and progesterone hormone replacement therapy
• Alcohol consumption
• Other
Atypical hyperplasia
Number of prior breast biopsies
Procedure done with the intent to diagnose cancer, multiple biopsies of the
same lesion are scored as one biopsy.
Breast density
Prior thoracic RT
History of lobular carcinoma in situ (LCIS)
The Gail model
Developed by Gail and
colleagues at the National
Cancer Institute now
modified
Estimates likelihood that a
woman of given age with
certain riskfactors will
develop breast cancer over
a specified time interval
•Current age,
•Race,
•Age at menarche,
•Age at first live birth or nulliparity,
•Number of first-degree relatives with breast cancer,
•Number of previous breast biopsies, and histology of the breast biopsies
The modified Gail model is
a computer-based
multivariate logistic
regression model that uses
Developed by Gail and
colleagues at the National
Cancer Institute now
modified
Estimates likelihood that a
woman of given age with
certain riskfactors will
develop breast cancer over
a specified time interval
•Current age,
•Race,
•Age at menarche,
•Age at first live birth or nulliparity,
•Number of first-degree relatives with breast cancer,
•Number of previous breast biopsies, and histology of the breast biopsies
The modified Gail model is
a computer-based
multivariate logistic
regression model that uses
Limitations?
It over-predicts the risk of breast cancer among women age 35 to 61 who do not
receive annual mammograms
The overestimation is more marked in pre-menopausal women and in those with
an extensive family history.
Underestimate the risk for a BRCA1 or BRCA2 mutation carrier and overestimate
the risk in a noncarrier.
Not an appropriate breastcancer risk assessment tool for women who received
prior thoracicradiation to treat Hodgkin’s disease (eg, mantle radiation),LCIS
It over-predicts the risk of breast cancer among women age 35 to 61 who do not
receive annual mammograms
The overestimation is more marked in pre-menopausal women and in those with
an extensive family history.
Underestimate the risk for a BRCA1 or BRCA2 mutation carrier and overestimate
the risk in a noncarrier.
Not an appropriate breastcancer risk assessment tool for women who received
prior thoracicradiation to treat Hodgkin’s disease (eg, mantle radiation),LCIS
The Claus model
• include second-degree relatives and the age of onset,
• does not include nonfamilial risk factors such as
hormonal factors
•Neither model takes into account bilateral breast cancer
or ovarian cancer.
The newest model is the Tyler-Cuzick model.
•This model not only takes into account many of the
relevant details of family history and hormonal factors, but
also includes BMI and the presence of LCIS.
•A computerized version of this model is not yet available.
• include second-degree relatives and the age of onset,
• does not include nonfamilial risk factors such as
hormonal factors
•Neither model takes into account bilateral breast cancer
or ovarian cancer.
The newest model is the Tyler-Cuzick model.
•This model not only takes into account many of the
relevant details of family history and hormonal factors, but
also includes BMI and the presence of LCIS.
•A computerized version of this model is not yet available.
FAMILIAL RISK ASSESSMENT
Woman meets one or more of the familial risk
criteria
YES NO
Lifetime risk > 20% based on models
largely dependent on family history
or
Pedigree suggestive of genetic
predisposition
or
Known gene mutation associated
with breast cancer risk
and
Life expectancy 10 y
•Prior thoracic RT
•H/O LCIS
•Gail model s/o 1.7%
increased risk of breast
ca. in 5 yr
and
Life expectancy 10 y
Risk reduction counselling
Woman meets one or more of the familial risk
criteria
YES NO
Lifetime risk > 20% based on models
largely dependent on family history
or
Pedigree suggestive of genetic
predisposition
or
Known gene mutation associated
with breast cancer risk
and
Life expectancy 10 y
•Prior thoracic RT
•H/O LCIS
•Gail model s/o 1.7%
increased risk of breast
ca. in 5 yr
and
Life expectancy 10 y
Risk reduction counselling
Risk reduction counseling
Woman does not desire risk-reduction
therapy
Woman desire risk-reduction therapy
Breast screening as per NCCN Breast
Cancer Screening and Diagnosis Guidelines
if not done in previous year
Breast screening as per
NCCN Breast Cancer
Screening and Diagnosis
Guidelines
normal
abnormal
1.Risk reduction mastectomy
2.Risk reduction salpingo
opherectomy with peritoneal wash
3.Risk reduction agent
m/m accordingly
Woman does not desire risk-reduction
therapy
Woman desire risk-reduction therapy
Breast screening as per NCCN Breast
Cancer Screening and Diagnosis Guidelines
if not done in previous year
Breast screening as per
NCCN Breast Cancer
Screening and Diagnosis
Guidelines
normal
abnormal
1.Risk reduction mastectomy
2.Risk reduction salpingo
opherectomy with peritoneal wash
3.Risk reduction agent
m/m accordingly
SCREENING OF BREAST CANCER
•Done to detect disease as early as possible
•Components of screening depends on
1.pt. age medical and family history,
2. breast awareness,
3.Clinical breast examination& physical
examination
4.risk assessment,
5. screening mammograpy and MRI in selected
cases
•Done to detect disease as early as possible
•Components of screening depends on
1.pt. age medical and family history,
2. breast awareness,
3.Clinical breast examination& physical
examination
4.risk assessment,
5. screening mammograpy and MRI in selected
cases
BREAST CANCER SCREENING RECOMMENDATIONS
American College of Surgeons:
•Begin self-examinations and every 3 years clinical breast
examination
at age 20.
•Begin annual mammograms and yearly clinical breast examination
at age 40
American College of Radiology
•Begin annual mammograms and
•yearly clinical breast examination at age 40.
American College of Surgeons:
•Begin self-examinations and every 3 years clinical breast
examination
at age 20.
•Begin annual mammograms and yearly clinical breast examination
at age 40
American College of Radiology
•Begin annual mammograms and
•yearly clinical breast examination at age 40.
history and
physical
examination
s/o
asymptomatic
and no
physical
findings
normal
risk
age 20-40
clinical breast
examination every 1-
3 years
age >40 years
clinical breast examination
annually
annual mammogram
increased risk viz.
-prior thoracic RT
-5yr risk of invasive
breast ca. >1.7% in
women of>35 yr
-genetic predisposition
-LCIS/atypical hyperplasia
recommendations
accordingly
physical
examination
s/o
asymptomatic
and no
physical
findings
normal
risk
age 20-40
clinical breast
examination every 1-
3 years
age >40 years
clinical breast examination
annually
annual mammogram
increased risk viz.
-prior thoracic RT
-5yr risk of invasive
breast ca. >1.7% in
women of>35 yr
-genetic predisposition
-LCIS/atypical hyperplasia
recommendations
accordingly
RISK FACTORS
MAMMOGRAPHY
SCREENING
RECOMMENDATIONS PREVENTIVE OPTIONS
Factors Conferring Moderate to High Risk
Age >60 yr Annual Not usually recommended
Atypical hyperplasia (ductal
or lobular)
Annual after diagnosis Tamoxifen, 20 mg/day × 5 yr
LCIS Annual after diagnosis Tamoxifen, 20 mg/day × 5 yr
Personal history of either
DCIS or invasive cancer, age
>40 yr
Annual after diagnosis No specific preventive
recommended
[*]
Family history of breast
cancer (1st-degree relative,
age <50 yr; two relatives on
same side of family)
Annual after age 40 Referral for genetic
counseling
Significant Risk Factors for Breast Cancer in Women: Assessment and Recommendations
MAMMOGRAPHY
SCREENING
RECOMMENDATIONS PREVENTIVE OPTIONS
Factors Conferring Moderate to High Risk
Age >60 yr Annual Not usually recommended
Atypical hyperplasia (ductal
or lobular)
Annual after diagnosis Tamoxifen, 20 mg/day × 5 yr
LCIS Annual after diagnosis Tamoxifen, 20 mg/day × 5 yr
Personal history of either
DCIS or invasive cancer, age
>40 yr
Annual after diagnosis No specific preventive
recommended
[*]
Family history of breast
cancer (1st-degree relative,
age <50 yr; two relatives on
same side of family)
Annual after age 40 Referral for genetic
counseling
Significant Risk Factors for Breast Cancer in Women: Assessment and Recommendations
Factors Conferring Very High Risk
Therapeutic thoracic radiation
(age <30 yr)
Annual at 10 yr after
radiotherapy
No specific preventive
recommended
[*]
Personal history of DCIS or
invasive cancer, age <40 yr
Annual after diagnosis No specific preventive
recommended
[*]
Family history of breast
cancer (two 1st-degree
relatives, age <50)
Annual after age 35-40 Referral for genetic
counseling
Family history of breast and
ovarian cancer (1st-degree
relatives)
Annual after age 35-40 Referral for genetic
counseling
Known carrier of a mutation
in BRCA1 or BRCA2 or a 1st-
degree relative with a
mutation
Annual after age 25; consider
annual MRI
Genetic testing for relatives;
discuss prophylactic
mastectomy or oophorectomy
for carriers
Therapeutic thoracic radiation
(age <30 yr)
Annual at 10 yr after
radiotherapy
No specific preventive
recommended
[*]
Personal history of DCIS or
invasive cancer, age <40 yr
Annual after diagnosis No specific preventive
recommended
[*]
Family history of breast
cancer (two 1st-degree
relatives, age <50)
Annual after age 35-40 Referral for genetic
counseling
Family history of breast and
ovarian cancer (1st-degree
relatives)
Annual after age 35-40 Referral for genetic
counseling
Known carrier of a mutation
in BRCA1 or BRCA2 or a 1st-
degree relative with a
mutation
Annual after age 25; consider
annual MRI
Genetic testing for relatives;
discuss prophylactic
mastectomy or oophorectomy
for carriers
Indications of MRI for screening
BRCA mutation
First degree relative of BRCA carrier
Lifetime risk of 20-25% as defined by BRCAPRO or any other model which depend on family
history
Radiation to chest between 10-30 yr age
Li Fraumeni syndrome in first degree relative
Cowden syndrome in first degree relative
BRCA mutation
First degree relative of BRCA carrier
Lifetime risk of 20-25% as defined by BRCAPRO or any other model which depend on family
history
Radiation to chest between 10-30 yr age
Li Fraumeni syndrome in first degree relative
Cowden syndrome in first degree relative
STAGING, GRADING
AND MANAGEMENT
OF BREAST
CARCINOMA
AND MANAGEMENT
OF BREAST
CARCINOMA
(p)T (Primary Tumor)
Tis Carcinoma in situ (lobular or ductal)
T1 Tumor ≤2 cm
T1a Tumor ≥0.1 cm, ≤0.5 cm
T1b Tumor >0.5 cm, ≤1 cm
T1c Tumor >1 cm, ≤2 cm
T2 Tumor >2 cm, ≤5 cm
T3 Tumor >5 cm
T4 Tumor any size with extension to the chest wall or
skin
T4a Tumor extending to the chest wall (excluding the
pectoralis)
T4b Tumor extending to the skin with ulceration, edema,
satellite nodules
T4c Both T4a and T4b
T4d Inflammatory carcinoma
American Joint Committee on Cancer Staging System for Breast Ca.
Tis Carcinoma in situ (lobular or ductal)
T1 Tumor ≤2 cm
T1a Tumor ≥0.1 cm, ≤0.5 cm
T1b Tumor >0.5 cm, ≤1 cm
T1c Tumor >1 cm, ≤2 cm
T2 Tumor >2 cm, ≤5 cm
T3 Tumor >5 cm
T4 Tumor any size with extension to the chest wall or
skin
T4a Tumor extending to the chest wall (excluding the
pectoralis)
T4b Tumor extending to the skin with ulceration, edema,
satellite nodules
T4c Both T4a and T4b
T4d Inflammatory carcinoma
American Joint Committee on Cancer Staging System for Breast Ca.
(p)N (Nodes)
N0 No regional node involvement, no special studies
N0 (i
-
) No regional node involvement, negative IHC
N0 (i
+
) Node(s) with isolated tumor cells spanning <0.2 mm
N0 (mol
-
) Negative node(s) histologically, negative PCR
N0 (mol
+
) Negative node(s) histologically, positive PCR
N1 Metastasis to 1-3 axillary nodes and/or int. mammary
positive by biopsy
N1(mic) Micrometastasis (>0.2 mm, none >2.0 mm)
N1a Metastasis to 1-3 axillary nodes
N1b Metastasis in int. mammary by sentinel biopsy
N1c Metastasis to 1-3 axillary nodes and int. mammary by
biopsy
N0 No regional node involvement, no special studies
N0 (i
-
) No regional node involvement, negative IHC
N0 (i
+
) Node(s) with isolated tumor cells spanning <0.2 mm
N0 (mol
-
) Negative node(s) histologically, negative PCR
N0 (mol
+
) Negative node(s) histologically, positive PCR
N1 Metastasis to 1-3 axillary nodes and/or int. mammary
positive by biopsy
N1(mic) Micrometastasis (>0.2 mm, none >2.0 mm)
N1a Metastasis to 1-3 axillary nodes
N1b Metastasis in int. mammary by sentinel biopsy
N1c Metastasis to 1-3 axillary nodes and int. mammary by
biopsy
N2 Metastasis to 4-9 axillary nodes or int. mammary clinically
positive, without axillary metastasis
N2a Metastasis to 4-9 axillary nodes, at least 1 >2.0 mm
N2b Int. mammary clinically apparent, negative axillary nodes
N3 Metastasis to ≥10 axillary nodes or combination of axillary and
int. mammary metastasis
N3a ≥10 axillary nodes (>2.0 mm), or infraclavicular nodes
N3b Positive int. mammary clinically with ≥1 axillary nodes or >3
positive axillary nodes with int. mammary positive by biopsy
N3c Metastasis to ipsilateral supraclavicular nodes
positive, without axillary metastasis
N2a Metastasis to 4-9 axillary nodes, at least 1 >2.0 mm
N2b Int. mammary clinically apparent, negative axillary nodes
N3 Metastasis to ≥10 axillary nodes or combination of axillary and
int. mammary metastasis
N3a ≥10 axillary nodes (>2.0 mm), or infraclavicular nodes
N3b Positive int. mammary clinically with ≥1 axillary nodes or >3
positive axillary nodes with int. mammary positive by biopsy
N3c Metastasis to ipsilateral supraclavicular nodes
M (Metastasis)
M0 No distant metastasis
M1 Distant metastasis
M0 No distant metastasis
M1 Distant metastasis
STAGE TNM
5-YEAR RELATIVE
SURVIVAL RATE (%)
[*]
0 Tis, N0, M0 100
I T1, N0, M0 100
IIA T0, N1, M0 92
T1, N1, M0
T2, N0, M0
IIB T2, N1, M0 81
T3, N0, M0
IIIA T0, N2, M0 67
T1, N2, M0
T2, N2, M0
T3, N1, M0
T3, N2, M0
IIIB T4, N0, M0 54
T4, N1, M0
T4, N2, M0
IIIC Any T, N3, M0
[†]
IV Any T, any N, M1 20
5-YEAR RELATIVE
SURVIVAL RATE (%)
[*]
0 Tis, N0, M0 100
I T1, N0, M0 100
IIA T0, N1, M0 92
T1, N1, M0
T2, N0, M0
IIB T2, N1, M0 81
T3, N0, M0
IIIA T0, N2, M0 67
T1, N2, M0
T2, N2, M0
T3, N1, M0
T3, N2, M0
IIIB T4, N0, M0 54
T4, N1, M0
T4, N2, M0
IIIC Any T, N3, M0
[†]
IV Any T, any N, M1 20
Score
1 2 3
A.Tubule formation
>75% 10-75% < 10%
B. Mitotic count per high-
power field
< 7 7-12 >12
C. Nuclear size and
pleomorphism
Near normal
Little variation
Slightly enlarged
Moderate variation
Markedly
enlarged
Marked
variation
Grading System in Invasive Breast Cancer
(Modified Bloom and Richardson) )
1 2 3
A.Tubule formation
>75% 10-75% < 10%
B. Mitotic count per high-
power field
< 7 7-12 >12
C. Nuclear size and
pleomorphism
Near normal
Little variation
Slightly enlarged
Moderate variation
Markedly
enlarged
Marked
variation
Grading System in Invasive Breast Cancer
(Modified Bloom and Richardson) )
Grade I cancer if the total score (A + B + C) is 3-5
Grade II cancer if the total score (A + B + C) is 6 or 7
Grade III cancer if the total score (A + B + C) is 8 or 9
Grade II cancer if the total score (A + B + C) is 6 or 7
Grade III cancer if the total score (A + B + C) is 8 or 9
Sentinel Lymph Node Biopsy
•Sentinel lymph node (SLN) biopsy is a minimally
invasive procedure designed to stage the axilla in breast
cancer patients who have clinically negative nodes.
•Sentinel nodes are the first node or first group of nodes
that drain from the breast to the axilla.
•SLN biopsy has become the preferred SLN technique for
axillary staging, because it offers accuracy equivalent to
that of axillary lymph node dissection with less
morbidity.
•According to the American College of Breast Surgeons
(ACBS), SLN biopsy is suitable for virtually all clinically
node-negative T1-2 invasive breast cancers
•Sentinel lymph node (SLN) biopsy is a minimally
invasive procedure designed to stage the axilla in breast
cancer patients who have clinically negative nodes.
•Sentinel nodes are the first node or first group of nodes
that drain from the breast to the axilla.
•SLN biopsy has become the preferred SLN technique for
axillary staging, because it offers accuracy equivalent to
that of axillary lymph node dissection with less
morbidity.
•According to the American College of Breast Surgeons
(ACBS), SLN biopsy is suitable for virtually all clinically
node-negative T1-2 invasive breast cancers
SLN biopsy technique
•The best results with SLN biopsy are
achieved with the combination of
careful intraoperative digital
examination and lymphatic
mapping.
• Technique involves injecting
radioisotope (technetium-99m
sulfur colloid) alone or radioisotope
plus a patent blue dye (Lymphazurin
or methylene blue) into the tissues
of the breast.
•With SLN dissection, typically 1-3
lymph nodes are removed and
tested for nodal metastasis with
hematoxylin and eosin (H&E) stain
and IHC with an anticytokeratin
cocktail.
•The best results with SLN biopsy are
achieved with the combination of
careful intraoperative digital
examination and lymphatic
mapping.
• Technique involves injecting
radioisotope (technetium-99m
sulfur colloid) alone or radioisotope
plus a patent blue dye (Lymphazurin
or methylene blue) into the tissues
of the breast.
•With SLN dissection, typically 1-3
lymph nodes are removed and
tested for nodal metastasis with
hematoxylin and eosin (H&E) stain
and IHC with an anticytokeratin
cocktail.
Relative contraindications
•any procedure that potentially alters lymphatic
drainage to the axilla.e.g.
breast augmentation, particularly when the implants
reside in a subglandular position
reduction mammoplasty
•Allergy to blue dye or radiocolloid
•Pregnancy
Absolute contraindications
•Inflammatory breast cancer
•presence of biopsy proven metastatic axillary
lymphadenopathy
•any procedure that potentially alters lymphatic
drainage to the axilla.e.g.
breast augmentation, particularly when the implants
reside in a subglandular position
reduction mammoplasty
•Allergy to blue dye or radiocolloid
•Pregnancy
Absolute contraindications
•Inflammatory breast cancer
•presence of biopsy proven metastatic axillary
lymphadenopathy
Indications and Contraindications for Breast-Conserving
Surgery
Indications
•T1, T2 (<4 cm), N0, N1, M0
•T2 >4 cm in large breasts
•Single clinical and mammographic lesion
Contraindications
•T4, N2, or M1 (some localized T4 disease and some patients with limited
metastatic disease may be suitable for breast-conserving surgery)
•Patients who prefer mastectomy
•Clinically evident multifocal/multicentric disease ·
• Prior radiation therapy to the breast or chest wall
• Diffuse suspicious or malignant appearing microcalcifications
• Widespread disease that cannot be incorporated by local excision through a single
incision that achieves negative margins with a
satisfactory cosmetic result.
• Positive pathologic margin
Surgery
Indications
•T1, T2 (<4 cm), N0, N1, M0
•T2 >4 cm in large breasts
•Single clinical and mammographic lesion
Contraindications
•T4, N2, or M1 (some localized T4 disease and some patients with limited
metastatic disease may be suitable for breast-conserving surgery)
•Patients who prefer mastectomy
•Clinically evident multifocal/multicentric disease ·
• Prior radiation therapy to the breast or chest wall
• Diffuse suspicious or malignant appearing microcalcifications
• Widespread disease that cannot be incorporated by local excision through a single
incision that achieves negative margins with a
satisfactory cosmetic result.
• Positive pathologic margin
Relative contraindications
• Active connective tissue disease involving the skin (especially scleroderma
and lupus)
•Tumors > 5 cm (category 2B)
• Focally positive margin
• Women < 35 y or premenopausal women with a known BRCA 1/2 mutation:
May have an increased risk of ipsilateral breast recurrence or contralateral
breast cancer with breast conserving therapy
Prophylactic bilateral mastectomy for risk reduction may be considered
•Large or central tumors in small breasts
• Active connective tissue disease involving the skin (especially scleroderma
and lupus)
•Tumors > 5 cm (category 2B)
• Focally positive margin
• Women < 35 y or premenopausal women with a known BRCA 1/2 mutation:
May have an increased risk of ipsilateral breast recurrence or contralateral
breast cancer with breast conserving therapy
Prophylactic bilateral mastectomy for risk reduction may be considered
•Large or central tumors in small breasts
Lobular Carcinoma in Situ
Lobular carcinoma in situ (LCIS) identified on breast biopsy
Stage 0 Tis, N0, M0
surgical biopsy
LCIS without other
cancer
Counseling regarding risk reduction
And
observation
6-12 monthly CBE and annual mammogram
pleomorphic LCIS may have a similar biological behavior to that of DCIS.
• may consider complete excision with negative margins
Lobular carcinoma in situ (LCIS) identified on breast biopsy
Stage 0 Tis, N0, M0
surgical biopsy
LCIS without other
cancer
Counseling regarding risk reduction
And
observation
6-12 monthly CBE and annual mammogram
pleomorphic LCIS may have a similar biological behavior to that of DCIS.
• may consider complete excision with negative margins
Ductal carcinoma in situ (DCIS)
Stage 0 Tis, N0, M0
Lumpectomy without lymph node surgery + whole breast radiation therapy
or
Total mastectomy with or without sentinel node biopsy ± reconstruction
or
Lumpectomy without lymph node surgery without radiation therapy
Consider tamoxifen for 5 years for:
Patients treated with breast-conserving therapy (lumpectomy) and radiation
therapy especially for those with ER-positive DCIS. The benefit of tamoxifen
for ER-negative DCIS is uncertain
Patients treated with excision alone
Interval history and physical exam every 6-12 mo for 5 y, then annually
Mammogram every 12 mo
If treated with tamoxifen, monitor
Stage 0 Tis, N0, M0
Lumpectomy without lymph node surgery + whole breast radiation therapy
or
Total mastectomy with or without sentinel node biopsy ± reconstruction
or
Lumpectomy without lymph node surgery without radiation therapy
Consider tamoxifen for 5 years for:
Patients treated with breast-conserving therapy (lumpectomy) and radiation
therapy especially for those with ER-positive DCIS. The benefit of tamoxifen
for ER-negative DCIS is uncertain
Patients treated with excision alone
Interval history and physical exam every 6-12 mo for 5 y, then annually
Mammogram every 12 mo
If treated with tamoxifen, monitor
INDICATIONS FOR SENTINEL LYMPH NODE BIOPSY IN DCIS
• Patients with microinvasion
• Patients undergoing mastectomy for diffuse disease
• Patients with a high suspicion of harboring invasive disease
• Extensive high-grade disease or necrosis on core biopsy
• Imaging studies suggesting invasion
INDICATIONS FOR MASTECTOMY IN DUCTAL CARCINOMA IN SITU
1. Multicentric disease
2. Diffuse microcalcifications on mammography
3. Large tumor size with predictably bad cosmetic outcome
4. Contraindication to radiation
Pregnancy
Connective tissue disorder(scleroderma)
Previous radiation therapy
Patient preference
• Patients with microinvasion
• Patients undergoing mastectomy for diffuse disease
• Patients with a high suspicion of harboring invasive disease
• Extensive high-grade disease or necrosis on core biopsy
• Imaging studies suggesting invasion
INDICATIONS FOR MASTECTOMY IN DUCTAL CARCINOMA IN SITU
1. Multicentric disease
2. Diffuse microcalcifications on mammography
3. Large tumor size with predictably bad cosmetic outcome
4. Contraindication to radiation
Pregnancy
Connective tissue disorder(scleroderma)
Previous radiation therapy
Patient preference
RADIATION THERAPY AFTER LUMPECTOMY FOR DUCTAL CARCINOMA IN SITU
• Radiation therapy (XRT) reduces ipsilateral breast tumor recurrence by 50% to 60%.
• After XRT, the annual rate of an invasive recurrence is 0.5% to 1% per year.
• XRT does not improve necessarily survival.
PEARLS IN M/M OF DCIS
•Complete axillary lymph node dissection should not be performed in the
absence of evidence of invasive cancer or proven metastatic disease
•Patients found to have invasive disease at total mastectomy or re-excision
should be managed as stage l or stage ll disease, including lymph node staging
•Margins greater than 10 mm are widely accepted as negative
•Margins less than 1 mm are considered inadequate.
•There is no evidence that survival differs between the three treatment Options
• Radiation therapy (XRT) reduces ipsilateral breast tumor recurrence by 50% to 60%.
• After XRT, the annual rate of an invasive recurrence is 0.5% to 1% per year.
• XRT does not improve necessarily survival.
PEARLS IN M/M OF DCIS
•Complete axillary lymph node dissection should not be performed in the
absence of evidence of invasive cancer or proven metastatic disease
•Patients found to have invasive disease at total mastectomy or re-excision
should be managed as stage l or stage ll disease, including lymph node staging
•Margins greater than 10 mm are widely accepted as negative
•Margins less than 1 mm are considered inadequate.
•There is no evidence that survival differs between the three treatment Options
Stage I
T1, N0, M0
or
Stage IIA
T0, N1, M0
T1, N1, M0
T2, N0, M0
or
Stage IIB
T2, N1, M0
T3, N0, M0
or
Stage IIIA
T3, N1, M0
General workup
If clinical stage
lllA (T3, N1, M0)
consider:
Bone scan
(category 2B)
Abdominal ±
pelvis CT or US or
MRI
Chest imaging
Lumpectomy with surgical
axillary staging (category 1)
(Preferred)
OR
Total mastectomy with
surgical axillary
staging(category 1) ±
reconstruction
Or
If T2 or T3 and fulfills criteria
for breast conserving therapy
except for size
Preoperative Chemotherapy
TREATMENT OF CLINICAL STAGE I, IIA, OR IIB DISEASE OR T3, N1, M0
T1, N0, M0
or
Stage IIA
T0, N1, M0
T1, N1, M0
T2, N0, M0
or
Stage IIB
T2, N1, M0
T3, N0, M0
or
Stage IIIA
T3, N1, M0
General workup
If clinical stage
lllA (T3, N1, M0)
consider:
Bone scan
(category 2B)
Abdominal ±
pelvis CT or US or
MRI
Chest imaging
Lumpectomy with surgical
axillary staging (category 1)
(Preferred)
OR
Total mastectomy with
surgical axillary
staging(category 1) ±
reconstruction
Or
If T2 or T3 and fulfills criteria
for breast conserving therapy
except for size
Preoperative Chemotherapy
TREATMENT OF CLINICAL STAGE I, IIA, OR IIB DISEASE OR T3, N1, M0
Lumpectomy with surgical axillary staging
Positive axillary
nodes
Negative axillary
nodes
•Radiation therapy to whole breast with
or without boost (by photons,
brachytherapy, or electron beam) to
tumor bed
• Strongly consider radiation therapy to
infraclavicular region and
supraclavicular area , internal mammary
nodes
•Radiation therapy should follow
chemotherapy when chemotherapy
indicated.
•Radiation therapy to whole breast
with or without boost m (by photons,
brachytherapy, or electron beam) to
tumor bed or
• consideration of partial breast
irradiation (PBI) in selected patients
•Radiation therapy should follow
chemotherapy when chemotherapy
indicated.
+/-Trastuzumab +/- endocrine therapy +/- adjuvant chemotherapy
Positive axillary
nodes
Negative axillary
nodes
•Radiation therapy to whole breast with
or without boost (by photons,
brachytherapy, or electron beam) to
tumor bed
• Strongly consider radiation therapy to
infraclavicular region and
supraclavicular area , internal mammary
nodes
•Radiation therapy should follow
chemotherapy when chemotherapy
indicated.
•Radiation therapy to whole breast
with or without boost m (by photons,
brachytherapy, or electron beam) to
tumor bed or
• consideration of partial breast
irradiation (PBI) in selected patients
•Radiation therapy should follow
chemotherapy when chemotherapy
indicated.
+/-Trastuzumab +/- endocrine therapy +/- adjuvant chemotherapy
SYSTEMIC ADJUVANT TREATMENT according to
ER/PR, Her/Neu, histology,
ER/PR, Her/Neu, histology,
•Endocrine therapy is indicated in all ER/PR positive cases
•Trastuzumab is added in all Her2 positive cases except microinvasive <0.5cm with Pn0
•Adjuvant chemotherapy is individualised above age 70yrs
UNFAVOURABLE HISTOLOGY
•Trastuzumab is added in all Her2 positive cases except microinvasive <0.5cm with Pn0
•Adjuvant chemotherapy is individualised above age 70yrs
UNFAVOURABLE HISTOLOGY
Adjuvant Endocrine Therapy
pT1, pT2, or pT3
and pN0 or pN1mi
(≤2 mm axillary
node metastasis)
Node positive (≥1 metastases >2
mm to ≥1 ipsilateral axillary lymph
nodes)
Tumor ≤0.5 cm or
Microinvasive or
Tumor 0.6-1.0 cm, well
differentiated, no
unfavorable features
Tumor 0.6-1.0 cm,
moderate/poorly
differentiated or
unfavorable features
Tumor >1 cm
pN0
pN1mi
Adjuvant endocrine
therapy ± adjuvant
chemotherapy
Adjuvant endocrine
therapy
Consider adjuvant endocrine therapy
No adjuvant therapy
Adjuvant endocrine
therapy + adjuvant
chemotherapy +
trastuzumab if HER2+
Consider 21-
gene RT-PCR
assay
Low score (<18)
Intermediate
Score (18-30)
Not done
High score (≥31)
HR positive disease
pT1, pT2, or pT3
and pN0 or pN1mi
(≤2 mm axillary
node metastasis)
Node positive (≥1 metastases >2
mm to ≥1 ipsilateral axillary lymph
nodes)
Tumor ≤0.5 cm or
Microinvasive or
Tumor 0.6-1.0 cm, well
differentiated, no
unfavorable features
Tumor 0.6-1.0 cm,
moderate/poorly
differentiated or
unfavorable features
Tumor >1 cm
pN0
pN1mi
Adjuvant endocrine
therapy ± adjuvant
chemotherapy
Adjuvant endocrine
therapy
Consider adjuvant endocrine therapy
No adjuvant therapy
Adjuvant endocrine
therapy + adjuvant
chemotherapy +
trastuzumab if HER2+
Consider 21-
gene RT-PCR
assay
Low score (<18)
Intermediate
Score (18-30)
Not done
High score (≥31)
HR positive disease
•Team includes surgeon, radiologists, nuclear medicine physician,pathologist, and prior discussion
with medical and radiation oncologists on use of sentinel node for treatment decisions.
•Consider pathologic confirmation of malignancy in clinically positive nodes using ultrasound
guided FNA or core biopsy in determining if patient needs axillary lymph node dissection.
•Axillary sentinel node biopsy in all cases; internal mammary sentinel node biopsy optional if
drainage maps to internal mammary nodes
with medical and radiation oncologists on use of sentinel node for treatment decisions.
•Consider pathologic confirmation of malignancy in clinically positive nodes using ultrasound
guided FNA or core biopsy in determining if patient needs axillary lymph node dissection.
•Axillary sentinel node biopsy in all cases; internal mammary sentinel node biopsy optional if
drainage maps to internal mammary nodes
MANAGEMENT OF LOCALLY ADVANCED BREAST CA.
•LABC is defined as either large, bulky
primary tumors or extensive adenopathy.
•Patients with AJCC T3 or T4 tumors
(associated with chest wall fixation, skin
ulceration, or both) are classified as LABC.
•Patients with AJCC N2 or N3 disease
(matted axillary nodes, supraclavicular or
internal mammary metastases)
•LABC is defined as either large, bulky
primary tumors or extensive adenopathy.
•Patients with AJCC T3 or T4 tumors
(associated with chest wall fixation, skin
ulceration, or both) are classified as LABC.
•Patients with AJCC N2 or N3 disease
(matted axillary nodes, supraclavicular or
internal mammary metastases)
•Interval history and physical exam every 4-6 mo for 5 y, then every 12 mo
Annual mammography
Women on tamoxifen: annual gynecologic assessment every 12 mo if
uterus present
Women on an aromatase inhibitor or who experience ovarian failure
secondary to treatment should have monitoring of bone health with a
bone mineral density determination at baseline and periodically thereafter
Assess and encourage adherence to adjuvant endocrine therapy.
Evidence suggests that active lifestyle, achieving and maintaining an
ideal body weight (20-25 BMI) may lead to optimal breast cancer
outcomes.
SURVEILLANCE/FOLLOW -UP
Annual mammography
Women on tamoxifen: annual gynecologic assessment every 12 mo if
uterus present
Women on an aromatase inhibitor or who experience ovarian failure
secondary to treatment should have monitoring of bone health with a
bone mineral density determination at baseline and periodically thereafter
Assess and encourage adherence to adjuvant endocrine therapy.
Evidence suggests that active lifestyle, achieving and maintaining an
ideal body weight (20-25 BMI) may lead to optimal breast cancer
outcomes.
SURVEILLANCE/FOLLOW -UP
Intervention Year 1 Year 2 Year 3-5 Year 6+
History &
physical
examination
q3-4mo q4mo q6mo Annually
Mammography Annually(or 6
mo after post –
BCS*
irradiation)
Annually
Annually
Annually
CXR Not
recommended
Not
recommended
Not
recommended
Not
recommended
Pelvic
examination
Annually
Annually
Annually
Annually
Bone density q1-2y
History &
physical
examination
q3-4mo q4mo q6mo Annually
Mammography Annually(or 6
mo after post –
BCS*
irradiation)
Annually
Annually
Annually
CXR Not
recommended
Not
recommended
Not
recommended
Not
recommended
Pelvic
examination
Annually
Annually
Annually
Annually
Bone density q1-2y
BREAST CANCER
Stage IV
Any T any N M1
Examples of distant mestastatic disease
Stage IV
Any T any N M1
Examples of distant mestastatic disease
DEFINITIONS Of LOCOREGIONAL RECURRENCE
Recurrence: Reappearance of a treated cancer in a patient previously considered
NED.
Local recurrence: Recurrence in the remaining breast after breast conservation or
in the soft tissues of the anterior chest after mastectomy.
In-breast tumor recurrence (IBTR): Local recurrence in the breast after breast-
conserving therapy although it is not always possible to differentiate IBTR from a
second primary tumor.
Regional recurrence: Recurrence in the ipsilateral axillary, internal mammary, or
supraclavicular lymph nodes.
Distant recurrence: Recurrence anywhere outside the ipsilateral breast, chest
wall, or regional lymph node basins.
Recurrence: Reappearance of a treated cancer in a patient previously considered
NED.
Local recurrence: Recurrence in the remaining breast after breast conservation or
in the soft tissues of the anterior chest after mastectomy.
In-breast tumor recurrence (IBTR): Local recurrence in the breast after breast-
conserving therapy although it is not always possible to differentiate IBTR from a
second primary tumor.
Regional recurrence: Recurrence in the ipsilateral axillary, internal mammary, or
supraclavicular lymph nodes.
Distant recurrence: Recurrence anywhere outside the ipsilateral breast, chest
wall, or regional lymph node basins.
Diagnosis of metastatic breast cancer
Determine site and extent of disease, ER/PR status, age and micronodal status
Hormone responsive or no life
threatening disease
Hormone unresponsive or life threatening
First line hormone therapy
First line chemotherapy
Progress of
disease
No progress of disease
second line chemotherapy
Progress of
disease
No progress of
disease
third line chemotherapy
Progress of disease
No progress of
disease
Progress of
disease
second line hormone therapy
No progress of
disease
Progress of
disease
third line hormone therapy
Progress of disease Supportive care
Determine site and extent of disease, ER/PR status, age and micronodal status
Hormone responsive or no life
threatening disease
Hormone unresponsive or life threatening
First line hormone therapy
First line chemotherapy
Progress of
disease
No progress of disease
second line chemotherapy
Progress of
disease
No progress of
disease
third line chemotherapy
Progress of disease
No progress of
disease
Progress of
disease
second line hormone therapy
No progress of
disease
Progress of
disease
third line hormone therapy
Progress of disease Supportive care
MEMORABLE PEARLS
•LOCAL RECURRENCE: resection if possible with
ALND +/- RT
•REGIONAL : Radiotherapy
•SYSTEMIC: Chemotherapy+/- endocrine
therapy +/- trastuzumab +/- bisphosphonates
•LOCAL RECURRENCE: resection if possible with
ALND +/- RT
•REGIONAL : Radiotherapy
•SYSTEMIC: Chemotherapy+/- endocrine
therapy +/- trastuzumab +/- bisphosphonates
• Inflammatory breast cancer is a clinical syndrome in women with invasive breast cancer that is
characterized by erythema and edema (peau d'orange) of a third or more of the skin of the breast and with a
palpable border to the erythema.
• The differential diagnosis includes cellulitis of the breast or mastitis. Pathologically, tumor is typically present
in the dermal lymphatics of the involved skin, but dermal lymphatic involvement is neither required for, nor
sufficient for by itself, a diagnosis of Inflammatory breast cancer
characterized by erythema and edema (peau d'orange) of a third or more of the skin of the breast and with a
palpable border to the erythema.
• The differential diagnosis includes cellulitis of the breast or mastitis. Pathologically, tumor is typically present
in the dermal lymphatics of the involved skin, but dermal lymphatic involvement is neither required for, nor
sufficient for by itself, a diagnosis of Inflammatory breast cancer
•Chemotherapy should not be administered during the first trimester of pregnancy and
radiation therapy should not be administered during any trimester of pregnancy.
•Combinations of doxorubicin, cyclophosphamide and fluorouracil can be used
•Radiolabeled sulfur colloid appears safe for sentinel node biopsy in pregnancy.
•The use of trastuzumab is contraindicated during pregnancy
radiation therapy should not be administered during any trimester of pregnancy.
•Combinations of doxorubicin, cyclophosphamide and fluorouracil can be used
•Radiolabeled sulfur colloid appears safe for sentinel node biopsy in pregnancy.
•The use of trastuzumab is contraindicated during pregnancy
(Neoadjuvant) Preoperative Chemotherapy Guidelines
Stage IIA
T2, N0, M0
Stage IIB
T2, N1, M0
T3, N0, M0
Stage lllA
T3, N1, M0
Fulfills criteria for
breast
conserving surgery
except for tumor size
Desires breast preservation
Core biopsy of breast tumor, localization of tumor bed for future surgical
management
Clinically negative axillary
lymph node(s), consider
sentinel lymph node
procedure Consider axillary
ultrasound
Clinically positive axillary lymph
node(s), consider core biopsy or
FNA;
Or
consider sentinel lymph node
procedure if FNA or core biopsy
Negative
Stage IIA
T2, N0, M0
Stage IIB
T2, N1, M0
T3, N0, M0
Stage lllA
T3, N1, M0
Fulfills criteria for
breast
conserving surgery
except for tumor size
Desires breast preservation
Core biopsy of breast tumor, localization of tumor bed for future surgical
management
Clinically negative axillary
lymph node(s), consider
sentinel lymph node
procedure Consider axillary
ultrasound
Clinically positive axillary lymph
node(s), consider core biopsy or
FNA;
Or
consider sentinel lymph node
procedure if FNA or core biopsy
Negative
Preoperative Chemotherapy Guideline
•Lumpectomy or Mastectomy and surgical axillary staging ± reconstruction.
• If sentinel lymph node biopsy performed prechemotherapy and negative
findings, may omit axillary lymph node staging
Consider additional chemotherapy if
recommended
ADJUVANT TREATMENT
Adjuvant radiation therapy post-mastectomy is based on prechemotherapy
tumor characteristics
Endocrine therapy if ER-positive and/or PR- positive
Complete up to one year of trastuzumab therapy if HER2-positive . May be
administered concurrent with radiation therapy and withendocrine therapy if
indicated.
Surveillance/Follow-up
•Lumpectomy or Mastectomy and surgical axillary staging ± reconstruction.
• If sentinel lymph node biopsy performed prechemotherapy and negative
findings, may omit axillary lymph node staging
Consider additional chemotherapy if
recommended
ADJUVANT TREATMENT
Adjuvant radiation therapy post-mastectomy is based on prechemotherapy
tumor characteristics
Endocrine therapy if ER-positive and/or PR- positive
Complete up to one year of trastuzumab therapy if HER2-positive . May be
administered concurrent with radiation therapy and withendocrine therapy if
indicated.
Surveillance/Follow-up
Definitions for response evaluation of primary systemic therapy
Clinical definition
• Complete: no palpable mass detectable (cCR)
• Partial: reduction of tumour area to < 50% (cPR)
Imaging definition
• No tumour visible by mammogram and/or ultrasound and/or MRI
Pathological definition
• Only focal invasive tumour residuals in the removed breast tissue
• Only in situ tumour residuals in the removed breast tissue (pCR inv)
• No invasive or in situ tumour cells (pCR)
• No malignant tumour cells in breast and lymph nodes (pCR breast and nodes).
Clinical definition
• Complete: no palpable mass detectable (cCR)
• Partial: reduction of tumour area to < 50% (cPR)
Imaging definition
• No tumour visible by mammogram and/or ultrasound and/or MRI
Pathological definition
• Only focal invasive tumour residuals in the removed breast tissue
• Only in situ tumour residuals in the removed breast tissue (pCR inv)
• No invasive or in situ tumour cells (pCR)
• No malignant tumour cells in breast and lymph nodes (pCR breast and nodes).
POTENTIAL ADVANTAGES TO NEOADJUVANT
CHEMOTHERAPY
•May allow for breast-conservation therapy in a woman who would otherwise require
a mastectomy.
• May improve the aesthetic outcome of a lumpectomy by decreasing the volume of
tissue needing to be resected.
• Allows for an assessment of the response of the tumor to chemotherapy. This may
allow for modifications of therapy based on response. In addition, a demonstrable
response may also have a positive effect on the patient’s compliance with further
treatment and on the patient’s willingness to accept some adverse events.
• Allows patients to delay surgery so they have more time to accept the need for
mastectomy, consider reconstructive options, or undergo genetic counseling and
testing if prophylactic mastectomies are considered.
• Allows women in their second or third trimester of pregnancy to delay the surgery
and radiotherapy until after delivery.
• May reduce distant metastases compared with classic adjuvant systemic therapy.
CHEMOTHERAPY
•May allow for breast-conservation therapy in a woman who would otherwise require
a mastectomy.
• May improve the aesthetic outcome of a lumpectomy by decreasing the volume of
tissue needing to be resected.
• Allows for an assessment of the response of the tumor to chemotherapy. This may
allow for modifications of therapy based on response. In addition, a demonstrable
response may also have a positive effect on the patient’s compliance with further
treatment and on the patient’s willingness to accept some adverse events.
• Allows patients to delay surgery so they have more time to accept the need for
mastectomy, consider reconstructive options, or undergo genetic counseling and
testing if prophylactic mastectomies are considered.
• Allows women in their second or third trimester of pregnancy to delay the surgery
and radiotherapy until after delivery.
• May reduce distant metastases compared with classic adjuvant systemic therapy.
ADJUVANT CHEMOTHERAPY
•Adjuvant chemotherapy demonstrated reductions in recurrence and
death in women 70 years of age with stage I, IIA, or IIB breast cancer
•Minimal benefit to women with negative nodes and cancers 0.5 cm in size
and is not recommended.
•Women with negative nodes and cancers 0.6 to 1.0 cm with adverse
prognostic factors include blood vessel or lymph vessel invasion, high
nuclear grade, high histologic grade, HER-2/neu overexpression, and
negative hormone receptor status. Adjuvant chemotherapy is
recommended
•Hormone receptor–negative cancers that are >1 cm in size,
•Node-positive tumors or with a special-type cancer that is >3 cm, the use
of chemotherapy is appropriate.
• Trastuzumab should also be considered for patients with HER2 positive
lymph node negative tumors greater than or equal to 1 cm.
•Adjuvant chemotherapy demonstrated reductions in recurrence and
death in women 70 years of age with stage I, IIA, or IIB breast cancer
•Minimal benefit to women with negative nodes and cancers 0.5 cm in size
and is not recommended.
•Women with negative nodes and cancers 0.6 to 1.0 cm with adverse
prognostic factors include blood vessel or lymph vessel invasion, high
nuclear grade, high histologic grade, HER-2/neu overexpression, and
negative hormone receptor status. Adjuvant chemotherapy is
recommended
•Hormone receptor–negative cancers that are >1 cm in size,
•Node-positive tumors or with a special-type cancer that is >3 cm, the use
of chemotherapy is appropriate.
• Trastuzumab should also be considered for patients with HER2 positive
lymph node negative tumors greater than or equal to 1 cm.
PRINCIPLES OF ADJUVANT CHEMOTHERAPY
•Chemotherapy kills a constant fraction of tumor cells (first-orderkinetics) rather
than a constant number of cells (log kill hypothesis).Thus, repetitive cycles of
therapy are necessary.
•Combination therapy is superior to single-agent therapy by overcoming drug
resistance.
• A dose-response effect exists, thus requiring adequate doses of drug.
•Outcome is dependent on the number of malignant cells present when therapy is
initiated. Even a single metastatic cancer cell, left alive, can lead to death.
•Evidence suggests that anthracycline-based chemotherapy regimens may be
superior to non-anthracycline-based regimens in patients with HER2 positive
tumors.
• In patients with HER2 positive and axillary lymph node positive breast cancer,
trastuzumab should be incorporated into the adjuvant therapy
•Chemotherapy regimens should be given prior to radiotherapy
•If Chemotherapy and tamoxifen used as adjuvant therapy should be given
sequentially with tamoxifen following chemotherapy
•Chemotherapy kills a constant fraction of tumor cells (first-orderkinetics) rather
than a constant number of cells (log kill hypothesis).Thus, repetitive cycles of
therapy are necessary.
•Combination therapy is superior to single-agent therapy by overcoming drug
resistance.
• A dose-response effect exists, thus requiring adequate doses of drug.
•Outcome is dependent on the number of malignant cells present when therapy is
initiated. Even a single metastatic cancer cell, left alive, can lead to death.
•Evidence suggests that anthracycline-based chemotherapy regimens may be
superior to non-anthracycline-based regimens in patients with HER2 positive
tumors.
• In patients with HER2 positive and axillary lymph node positive breast cancer,
trastuzumab should be incorporated into the adjuvant therapy
•Chemotherapy regimens should be given prior to radiotherapy
•If Chemotherapy and tamoxifen used as adjuvant therapy should be given
sequentially with tamoxifen following chemotherapy
Cardiac assessment and anthracyclines
Routine pre-anthracycline assessment of left ventricular function is advised for
all patients who:
• have a cardiac history
• are treated for a cardiovascular condition including hypertension
• have an obviously abnormal ECG
• are 65 or older.
•Anthracyclines should be avoided in patients with a baseline left ventricular
ejection fraction (LVEF) of < 50%. LVEF should be rechecked after a cumulative
epirubucin dose of not more than 400 mg/m2
Routine pre-anthracycline assessment of left ventricular function is advised for
all patients who:
• have a cardiac history
• are treated for a cardiovascular condition including hypertension
• have an obviously abnormal ECG
• are 65 or older.
•Anthracyclines should be avoided in patients with a baseline left ventricular
ejection fraction (LVEF) of < 50%. LVEF should be rechecked after a cumulative
epirubucin dose of not more than 400 mg/m2
NON-TRASTUZUMAB CONTAINING COMBINATIONS
PREFERRED ADJUVANT REGIMENS
TAC chemotherapy
Docetaxel 75 mg/m 2 IV day 1
Doxorubicin 50 mg/m 2 IV day 1
Cyclophosphamide 500 mg/m 2 IV day 1
Cycled every 21 days for 6 cycles.
Dose-dense AC followed by paclitaxel
chemotherapy
Doxorubicin 60 mg/m 2 IV day 1
Cyclophosphamide 600 mg/m 2 IV day 1
Cycled every 14 days for 4 cycles.
Followed by
Paclitaxel 175 mg/m 2 by 3 h IV infusion day 1
Cycled every 14 days for 4 cycles.
AC followed by paclitaxel chemotherapy
Doxorubicin 60 mg/m 2 IV day 1
Cyclophosphamide 600 mg/m 2 IV day 1
Cycled every 21 days for 4 cycles.
Followed by
Paclitaxel 80 mg/m 2 by 1 h IV infusion
weeklyfor 12 wks.
OTHER ADJUVANT REGIMENS
FAC chemotherapy
5-Fluorouracil 500 mg/m 2 IV days 1 & 8
or
days 1 & 4
Doxorubicin 50 mg/m 2 IV day 1
(or by 72 h continuous infusion)
Cyclophosphamide 500 mg/m 2 IV day 1
Cycled every 21 days for 6 cycles.
CMF chemotherapy
Cyclophosphamide 100 mg/m 2 PO
days 1-14
Methotrexate 40 mg/m 2 IV days 1 & 8
5-Fluorouracil 600 mg/m 2 IV days 1 &
8
Cycled every 28 days for 6 cycles.
PREFERRED ADJUVANT REGIMENS
TAC chemotherapy
Docetaxel 75 mg/m 2 IV day 1
Doxorubicin 50 mg/m 2 IV day 1
Cyclophosphamide 500 mg/m 2 IV day 1
Cycled every 21 days for 6 cycles.
Dose-dense AC followed by paclitaxel
chemotherapy
Doxorubicin 60 mg/m 2 IV day 1
Cyclophosphamide 600 mg/m 2 IV day 1
Cycled every 14 days for 4 cycles.
Followed by
Paclitaxel 175 mg/m 2 by 3 h IV infusion day 1
Cycled every 14 days for 4 cycles.
AC followed by paclitaxel chemotherapy
Doxorubicin 60 mg/m 2 IV day 1
Cyclophosphamide 600 mg/m 2 IV day 1
Cycled every 21 days for 4 cycles.
Followed by
Paclitaxel 80 mg/m 2 by 1 h IV infusion
weeklyfor 12 wks.
OTHER ADJUVANT REGIMENS
FAC chemotherapy
5-Fluorouracil 500 mg/m 2 IV days 1 & 8
or
days 1 & 4
Doxorubicin 50 mg/m 2 IV day 1
(or by 72 h continuous infusion)
Cyclophosphamide 500 mg/m 2 IV day 1
Cycled every 21 days for 6 cycles.
CMF chemotherapy
Cyclophosphamide 100 mg/m 2 PO
days 1-14
Methotrexate 40 mg/m 2 IV days 1 & 8
5-Fluorouracil 600 mg/m 2 IV days 1 &
8
Cycled every 28 days for 6 cycles.
TRASTUZUMAB CONTAINING COMBINATIONS
AC followed by T chemotherapy with Trastuzumab
Doxorubicin 60 mg/m 2 IV day 1
Cyclophosphamide 600 mg/m 2 IV day 1
Cycled every 21 days for 4 cycles.
Followed by
Paclitaxel 80 mg/m2by 1 h IV weekly for 12 wks With
Trastuzumab 4 mg/kg IV with first dose of paclitaxel
Followed by
Trastuzumab 2 mg/kg IV weekly to complete 1 y of treatment.
As analternative, trastuzumab 6 mg/kg IV every 3 wk may be used following thecompletion of
paclitaxel, and given to complete 1y of trastuzumab.
Cardiac monitoring at baseline, 3, 6, and 9 mo.
Dose-dense AC followed by paclitaxel chemotherapy
Doxorubicin 60 mg/m 2 IV day 1
Cyclophosphamide 600 mg/m 2 IV day 1
Cycled every 14 days for 4 cycles.
Followed by
Paclitaxel 175 mg/m 2 by 3 h IV infusion day 1
Cycled every 14 days for 4 cycles.
With
Trastuzumab 4 mg/kg IV with first dose of paclitaxel
Followed by
Trastuzumab 2 mg/kg IV weekly to complete 1 y of treatment. As an alternative, trastuzumab 6
mg/kg IV every 3 wk may be used following the completion of paclitaxel, and given to complete 1y
of trastuzumab
AC followed by T chemotherapy with Trastuzumab
Doxorubicin 60 mg/m 2 IV day 1
Cyclophosphamide 600 mg/m 2 IV day 1
Cycled every 21 days for 4 cycles.
Followed by
Paclitaxel 80 mg/m2by 1 h IV weekly for 12 wks With
Trastuzumab 4 mg/kg IV with first dose of paclitaxel
Followed by
Trastuzumab 2 mg/kg IV weekly to complete 1 y of treatment.
As analternative, trastuzumab 6 mg/kg IV every 3 wk may be used following thecompletion of
paclitaxel, and given to complete 1y of trastuzumab.
Cardiac monitoring at baseline, 3, 6, and 9 mo.
Dose-dense AC followed by paclitaxel chemotherapy
Doxorubicin 60 mg/m 2 IV day 1
Cyclophosphamide 600 mg/m 2 IV day 1
Cycled every 14 days for 4 cycles.
Followed by
Paclitaxel 175 mg/m 2 by 3 h IV infusion day 1
Cycled every 14 days for 4 cycles.
With
Trastuzumab 4 mg/kg IV with first dose of paclitaxel
Followed by
Trastuzumab 2 mg/kg IV weekly to complete 1 y of treatment. As an alternative, trastuzumab 6
mg/kg IV every 3 wk may be used following the completion of paclitaxel, and given to complete 1y
of trastuzumab
PREFERRED CHEMOTHERAPY REGIMENS FOR RECURRENT OR METASTATIC
BREAST CANCER
CAF chemotherapy
Cyclophosphamide 100 mg/m 2 PO days 1-14
Doxorubicin 30 mg/m 2 IV days 1 & 8
5-Fluorouracil 500 mg/m 2 IV days 1 & 8
Cycled every 28 days.
FAC chemotherapy
5-Fluorouracil 500 mg/m 2 IV days 1 & 8 or
days 1 & 4
Doxorubicin 50 mg/m 2 IV day 1
Cyclophosphamide 500 mg/m 2 IV day 1
Cycled every 21 days.
FEC chemotherapy
Cyclophosphamide 400 mg/m 2 IV days 1 & 8
Epirubicin 50 mg/m 2 IV days 1 & 8
5-Fluorouracil 500 mg/m 2 IV days 1 & 8
Cycled every 28 days.
PREFERRED CHEMOTHERAPY
COMBINATIONS
CAF/FAC
(cyclophosphamide/doxorubicin/fluorouracil)
FEC
(fluorouracil/epirubicin/cyclophosphamide)
AC (doxorubicin/cyclophosphamide)
EC (epirubicin/cyclophosphamide)
AT (doxorubicin/docetaxel;
doxorubicin/paclitaxel)
CMF
(cyclophosphamide/methotrexate/fluorouracil
Docetaxel/capecitabine
GT (gemcitabine/paclitaxel)
Docetaxel/capecitabine chemotherapy
Docetaxel 75 mg/m 2 IV day 1
Capecitabine 950 mg/m 2 PO twice daily
days 1-14
Cycled every 21 days.
BREAST CANCER
CAF chemotherapy
Cyclophosphamide 100 mg/m 2 PO days 1-14
Doxorubicin 30 mg/m 2 IV days 1 & 8
5-Fluorouracil 500 mg/m 2 IV days 1 & 8
Cycled every 28 days.
FAC chemotherapy
5-Fluorouracil 500 mg/m 2 IV days 1 & 8 or
days 1 & 4
Doxorubicin 50 mg/m 2 IV day 1
Cyclophosphamide 500 mg/m 2 IV day 1
Cycled every 21 days.
FEC chemotherapy
Cyclophosphamide 400 mg/m 2 IV days 1 & 8
Epirubicin 50 mg/m 2 IV days 1 & 8
5-Fluorouracil 500 mg/m 2 IV days 1 & 8
Cycled every 28 days.
PREFERRED CHEMOTHERAPY
COMBINATIONS
CAF/FAC
(cyclophosphamide/doxorubicin/fluorouracil)
FEC
(fluorouracil/epirubicin/cyclophosphamide)
AC (doxorubicin/cyclophosphamide)
EC (epirubicin/cyclophosphamide)
AT (doxorubicin/docetaxel;
doxorubicin/paclitaxel)
CMF
(cyclophosphamide/methotrexate/fluorouracil
Docetaxel/capecitabine
GT (gemcitabine/paclitaxel)
Docetaxel/capecitabine chemotherapy
Docetaxel 75 mg/m 2 IV day 1
Capecitabine 950 mg/m 2 PO twice daily
days 1-14
Cycled every 21 days.
TRASTUZUMAB(HERCEPTIN)
Mechanism of Action
• Recombinant humanized monoclonal antibody directed against the extracellular domain
of the HER-2/neu growth factor receptor. This receptor is overexpressed in several human
cancers, including 25%–30% of breast cancers and up to 20% of gastric cancers.
• Downregulates expression of HER-2/neu receptor.
• Inhibits HER-2/neu intracellular signaling pathways.
• Induction of apoptosis through as yet undetermined mechanisms.
• Immunologic mechanisms may also be involved in antitumor activity, and they include
recruitment of antibody-dependent cellular cytotoxicity (ADCC) and/or complement-
mediated cell lysis.
Mechanism of Resistance
• Mutations in the HER-2/neu growth factor receptor leading to
decreased binding affinity to trastuzumab.
• Decreased expression of HER-2/neu receptors.
• Activation/induction of alternative cellular signaling pathways, such as IGF-1R.
Dosage Range
1. Recommended loading dose of 4 mg/kg IV administered over 90 minutes, followed by
maintenance dose of 2 mg/kg IV on a weekly basis.
2. Alternative schedule is to give a loading dose of 8 mg/kg IV administered over 90
minutes, followed by maintenance dose of 6 mg/kg IV every 3 weeks.
Mechanism of Action
• Recombinant humanized monoclonal antibody directed against the extracellular domain
of the HER-2/neu growth factor receptor. This receptor is overexpressed in several human
cancers, including 25%–30% of breast cancers and up to 20% of gastric cancers.
• Downregulates expression of HER-2/neu receptor.
• Inhibits HER-2/neu intracellular signaling pathways.
• Induction of apoptosis through as yet undetermined mechanisms.
• Immunologic mechanisms may also be involved in antitumor activity, and they include
recruitment of antibody-dependent cellular cytotoxicity (ADCC) and/or complement-
mediated cell lysis.
Mechanism of Resistance
• Mutations in the HER-2/neu growth factor receptor leading to
decreased binding affinity to trastuzumab.
• Decreased expression of HER-2/neu receptors.
• Activation/induction of alternative cellular signaling pathways, such as IGF-1R.
Dosage Range
1. Recommended loading dose of 4 mg/kg IV administered over 90 minutes, followed by
maintenance dose of 2 mg/kg IV on a weekly basis.
2. Alternative schedule is to give a loading dose of 8 mg/kg IV administered over 90
minutes, followed by maintenance dose of 6 mg/kg IV every 3 weeks.
Drug Interactions
Anthracyclines, taxanes—Increased risk of cardiotoxicity when trastuzumab is used in
combination with anthracyclines and/or taxanes.
Special Considerations
1. Caution should be exercised in treating patients with pre-existing cardiac dysfunction. Careful
baseline assessment of cardiac function (LVEF) before treatment and frequent monitoring (every
3 months)of cardiac function while on therapy. Trastuzumab should be held for ≥16% absolute
decrease in LVEF from a normal baseline value.
•cardiac function should be assessed every 6 months for at least 2 years following the
completion of therapy.
2. Carefully monitor for infusion reactions, which typically occur during or within 24 hours of
drug administration.
IMPORTANT FACTS
•Trastuzumab may be given beginning either concurrent with paclitaxel as part of the AC
followed by paclitaxel regimen, or alternatively after the completion of chemotherapy.
•Trastuzumab should not be given concurrent with an anthracycline because of cardiac toxicity,
except as part of the neoadjuvant trastuzumab with paclitaxel followed by CEF regimen.
•Trastuzumab should be given for one year, (with the exception of the docetaxel + trastuzumab
followed by FEC regimen in which trastuzumab is given for 9 weeks), with cardiac monitoring,
and by either the weekly or every three weekly schedule.
Anthracyclines, taxanes—Increased risk of cardiotoxicity when trastuzumab is used in
combination with anthracyclines and/or taxanes.
Special Considerations
1. Caution should be exercised in treating patients with pre-existing cardiac dysfunction. Careful
baseline assessment of cardiac function (LVEF) before treatment and frequent monitoring (every
3 months)of cardiac function while on therapy. Trastuzumab should be held for ≥16% absolute
decrease in LVEF from a normal baseline value.
•cardiac function should be assessed every 6 months for at least 2 years following the
completion of therapy.
2. Carefully monitor for infusion reactions, which typically occur during or within 24 hours of
drug administration.
IMPORTANT FACTS
•Trastuzumab may be given beginning either concurrent with paclitaxel as part of the AC
followed by paclitaxel regimen, or alternatively after the completion of chemotherapy.
•Trastuzumab should not be given concurrent with an anthracycline because of cardiac toxicity,
except as part of the neoadjuvant trastuzumab with paclitaxel followed by CEF regimen.
•Trastuzumab should be given for one year, (with the exception of the docetaxel + trastuzumab
followed by FEC regimen in which trastuzumab is given for 9 weeks), with cardiac monitoring,
and by either the weekly or every three weekly schedule.
Toxicity
•Infusion-related symptoms with fever, chills, urticaria, flushing, fatigue, headache,
bronchospasm, dyspnea, angioedema, and hypotension.
•Nausea and vomiting, diarrhea. Generally mild.
•Cardiotoxicity in the form of dyspnea, peripheral edema, and reduced leftventricular
function.. In most instances, cardiac dysfunction is readily reversible.
•Myelosuppression,Generalized pain, asthenia, and headache. pleural effusions
•Infusion-related symptoms with fever, chills, urticaria, flushing, fatigue, headache,
bronchospasm, dyspnea, angioedema, and hypotension.
•Nausea and vomiting, diarrhea. Generally mild.
•Cardiotoxicity in the form of dyspnea, peripheral edema, and reduced leftventricular
function.. In most instances, cardiac dysfunction is readily reversible.
•Myelosuppression,Generalized pain, asthenia, and headache. pleural effusions
Class Toxicity
5-Fluorouracil Antimetabolite Myelosuppression, Mucositis and/or diarrhea, Hand-foot syndrome
(palmar-plantar erythrodysesthesia) , Cardiac symptoms of chest pain,
Metallic taste in mouth
Cyclophosphamide Alkylating agent Myelosuppression, Bladder toxicity in the form of hemorrhagic cystitis,
Nausea and vomiting, Alopecia
Capecitabine Oral fluoro pyrimidine Rash, hand-foot syndrome,diarrhea, mucositis
Docetaxel Antimicrotubule Myelosuppression, alopecia,skin reaction, mucositis,
and fluid retention
Doxorubicin Anthracycline
(antitumor antibiotic)
Myelosuppression, nausea/vomiting, mucositis, diarrhea
cardiotoxicity, alopecia
Doxil (liposomal
encapsulated
doxorubicin)
Anthracycline Less cardiotoxicity, neutropenia, alopecia, stomatitis, hand-foot syndrome
Epirubicin Anthracycline Myelosuppression, mucositis, nausea, vomiting, cardiotoxicity
Gemcitabine Antimetabolite Myelosuppression, nausea/vomiting, flulike syndrome,
elevated LFTs
Paclitaxel Antimicrotubule Myelosuppression, alopecia,neuropathy, allergic reaction
Trastuzumab Monoclonal antibody Fever, allergic reaction cardiotoxicity/congestive heart failure
Vinorelbine Vinca alkaloid Myelosuppression, nausea/vomiting, constipation, fatigue,stomatitis,
anorexia
5-Fluorouracil Antimetabolite Myelosuppression, Mucositis and/or diarrhea, Hand-foot syndrome
(palmar-plantar erythrodysesthesia) , Cardiac symptoms of chest pain,
Metallic taste in mouth
Cyclophosphamide Alkylating agent Myelosuppression, Bladder toxicity in the form of hemorrhagic cystitis,
Nausea and vomiting, Alopecia
Capecitabine Oral fluoro pyrimidine Rash, hand-foot syndrome,diarrhea, mucositis
Docetaxel Antimicrotubule Myelosuppression, alopecia,skin reaction, mucositis,
and fluid retention
Doxorubicin Anthracycline
(antitumor antibiotic)
Myelosuppression, nausea/vomiting, mucositis, diarrhea
cardiotoxicity, alopecia
Doxil (liposomal
encapsulated
doxorubicin)
Anthracycline Less cardiotoxicity, neutropenia, alopecia, stomatitis, hand-foot syndrome
Epirubicin Anthracycline Myelosuppression, mucositis, nausea, vomiting, cardiotoxicity
Gemcitabine Antimetabolite Myelosuppression, nausea/vomiting, flulike syndrome,
elevated LFTs
Paclitaxel Antimicrotubule Myelosuppression, alopecia,neuropathy, allergic reaction
Trastuzumab Monoclonal antibody Fever, allergic reaction cardiotoxicity/congestive heart failure
Vinorelbine Vinca alkaloid Myelosuppression, nausea/vomiting, constipation, fatigue,stomatitis,
anorexia
DEFINITION OF MENOPAUSE
•Menopause is generally the permanent cessation of menses,and as the term is utilized in breast cancer
management includes a profound and permanent decrease in ovarian estrogen synthesis.
Reasonable criteria for determining menopause include any of the following:
• Prior bilateral oophorectomy
• Age ≥ 60 y
• Age < 60 y and amenorrheic for 12 or more months in the absence of chemotherapy, tamoxifen, toremifene,
or ovarian suppression and FSH and estradiol in the postmenopausal range
• If taking tamoxifen or toremifene, and age < 60 y, then FSH and plasma estradiol level in postmenopausal
ranges
•Menopause is generally the permanent cessation of menses,and as the term is utilized in breast cancer
management includes a profound and permanent decrease in ovarian estrogen synthesis.
Reasonable criteria for determining menopause include any of the following:
• Prior bilateral oophorectomy
• Age ≥ 60 y
• Age < 60 y and amenorrheic for 12 or more months in the absence of chemotherapy, tamoxifen, toremifene,
or ovarian suppression and FSH and estradiol in the postmenopausal range
• If taking tamoxifen or toremifene, and age < 60 y, then FSH and plasma estradiol level in postmenopausal
ranges
Postmenopausal: Aromatase inhibitors
•Produce most of their estrogen outside the
ovaries
•Generated through androgen hormones store
in fatty tissue and adrenal glands
•In a biochemical process started by the
enzyme aromatase, androgen is converted
into estrogen, into bloodstream and to breast
•Aromatase inhibitors “block” the process
•Produce most of their estrogen outside the
ovaries
•Generated through androgen hormones store
in fatty tissue and adrenal glands
•In a biochemical process started by the
enzyme aromatase, androgen is converted
into estrogen, into bloodstream and to breast
•Aromatase inhibitors “block” the process
Aromatase Inhibitors (AIs)
•Steroidal Ais
– Exemestane
•Nonsteroidal AIs
•Anastrazole
•letrozole
•Many clinical trials showing significant results in both
reduced breast cancer relapse, as well as reduced
rates of metastatic disease
•Now being studied in various scenarios with
Tamoxifen
•Steroidal Ais
– Exemestane
•Nonsteroidal AIs
•Anastrazole
•letrozole
•Many clinical trials showing significant results in both
reduced breast cancer relapse, as well as reduced
rates of metastatic disease
•Now being studied in various scenarios with
Tamoxifen
postmenopausal
agents dose shedule
1 antiestrogen Tamoxifen 20mg Orally
everyday
2 Aromatase
inhibitor
Anastrazole 1mg Orally
everyday
Letrazole 2.5mg Orally
everyday
exemestane 25mg Orally
everyday
Fulvestrand
Megestrol
500mg
250mg
40mg
IM satat f/b
IM every
month
Orally qid
agents dose shedule
1 antiestrogen Tamoxifen 20mg Orally
everyday
2 Aromatase
inhibitor
Anastrazole 1mg Orally
everyday
Letrazole 2.5mg Orally
everyday
exemestane 25mg Orally
everyday
Fulvestrand
Megestrol
500mg
250mg
40mg
IM satat f/b
IM every
month
Orally qid
Premenopausal: Tamoxifen
•Ovaries produce estrogen, sent through
bloodstream directly to the breast
•Tamoxifen mimics estrogen
•Attached to receptors, keeping real hormones
out
•Ovaries produce estrogen, sent through
bloodstream directly to the breast
•Tamoxifen mimics estrogen
•Attached to receptors, keeping real hormones
out
ER
X
Selective Estrogen-Receptor
Modulators (SERMs): Mechanism
SERMS
•Chemical structure resembles estrogen
•Compete with estrogen for ER binding
•Effective treatment for ER+ breast cancer
Tamoxifen
•First SERM
•Approved for
–Early and advanced ER+ breast
cancer and women at high risk for breast
cancer
Raloxifene
•Currently under investigation for prevention of
breast cancer in postmenopausal women at high
risk for breast cancer
Estrogen
SERM
ER-dependent Cell Proliferation
X
Selective Estrogen-Receptor
Modulators (SERMs): Mechanism
SERMS
•Chemical structure resembles estrogen
•Compete with estrogen for ER binding
•Effective treatment for ER+ breast cancer
Tamoxifen
•First SERM
•Approved for
–Early and advanced ER+ breast
cancer and women at high risk for breast
cancer
Raloxifene
•Currently under investigation for prevention of
breast cancer in postmenopausal women at high
risk for breast cancer
Estrogen
SERM
ER-dependent Cell Proliferation
Premenopausal
- bilateral oophorectomy
followed by
class agents dose schedule
Antiestrogen tamoxifen 20mg Orally everyday
Aromatase
inhibitor + LHRH
7.5mg IM depot (q28d)
Leuprolide 22.5mg IM (q4mo)
Gosereline 3.6mg s/c depot q28d
Megestrol 40mg Orally qid
- bilateral oophorectomy
followed by
class agents dose schedule
Antiestrogen tamoxifen 20mg Orally everyday
Aromatase
inhibitor + LHRH
7.5mg IM depot (q28d)
Leuprolide 22.5mg IM (q4mo)
Gosereline 3.6mg s/c depot q28d
Megestrol 40mg Orally qid
Post-mastectomy radiotherapy
Objectives
• Post-mastectomy radiotherapy reduces the risk of locoregional failure and increases the
long-term survival rate for a substantial proportion of women with positive axillary nodes
treated with systemic therapy.
Indications
• Four or more positive axillary lymph nodes.
• Tumour > 5 cm in size.
• Close or positive margins.
• Inadequate axillary surgery (the removal of less than 10 nodes).
Consideration
• 1 to 3 positive axillary lymph nodes.
Objectives
• Post-mastectomy radiotherapy reduces the risk of locoregional failure and increases the
long-term survival rate for a substantial proportion of women with positive axillary nodes
treated with systemic therapy.
Indications
• Four or more positive axillary lymph nodes.
• Tumour > 5 cm in size.
• Close or positive margins.
• Inadequate axillary surgery (the removal of less than 10 nodes).
Consideration
• 1 to 3 positive axillary lymph nodes.
Treatment modality: beam energy
• Super voltage equipment (4, 6, or 8 MV or cobalt-60) is preferred.
• In the patient where the field separation is greater than 22 cm, higher beam energy (10
MV) may give a more homogenous dose distribution.
Dosimetry
• The aim is to create a homogeneous dose distribution throughout this irregular shaped
treatment volume (― 5% variation).
Dose/fractionation
• A whole breast dose of 45 Gy–50 Gy is prescribed.
• This is given in 1.8 Gy–2.0 Gy fractions per day, 5 days per week.
Boost
• In patients with negative margins, randomized trials demonstrate that the use of a
boost is effective, on local control and survival.
• This effect was clearer in patients < 50 years of age.
• Via the boost, the dose at the tumour bed is increased to 60 Gy–66 Gy.
• A boost may be give by electron beam (10 Gy in 5 fractions or 16 Gy/8f) or interstitial
implant.
• Photons can be used as well.
• Super voltage equipment (4, 6, or 8 MV or cobalt-60) is preferred.
• In the patient where the field separation is greater than 22 cm, higher beam energy (10
MV) may give a more homogenous dose distribution.
Dosimetry
• The aim is to create a homogeneous dose distribution throughout this irregular shaped
treatment volume (― 5% variation).
Dose/fractionation
• A whole breast dose of 45 Gy–50 Gy is prescribed.
• This is given in 1.8 Gy–2.0 Gy fractions per day, 5 days per week.
Boost
• In patients with negative margins, randomized trials demonstrate that the use of a
boost is effective, on local control and survival.
• This effect was clearer in patients < 50 years of age.
• Via the boost, the dose at the tumour bed is increased to 60 Gy–66 Gy.
• A boost may be give by electron beam (10 Gy in 5 fractions or 16 Gy/8f) or interstitial
implant.
• Photons can be used as well.
Radiotherapy technique
Target volume
• Target definition includes the majority of the breast tissue, and is best done by both clinical
assessment and CT-based treatment planning.
• The target volume must include the chest wall.
• Supraclavicular lymph node group for patients with 4 or more positive axillary lymph
nodes.
• Axilla if inadequate axillary surgery was done.
In addition, the following areas may be included even though there is insufficient evidence to
made recommendations:
• Drain sites.
• Internal mammary chain (IMC).
accelerated partial breast irradiation (APBI)
RECOMMENDATIONS FROM THE AMERICAN SOCIETY indicate that APBI may be suitable in
selected patients with early stage breast cancer and may be comparable to treatment with
standard whole breast RT
Patients who may be suitable for APBI are:
• women 60 years and older who are not carriers of a known BRCA1/2 mutation, have been
treated with primary surgery for a unifocal Stage I, ER positive cancer.
•Tumors should be infiltrating ductal or a favorable histology, not be associated with an
extensive intraductal component or LCIS, and margins should be negative.
•34 Gy in 10 fractions delivered twice per day with brachytherapy or 38.5 Gy in 10 fractions
delivered twice per day with external beam photon therapy to the tumor bed is recommended
Target volume
• Target definition includes the majority of the breast tissue, and is best done by both clinical
assessment and CT-based treatment planning.
• The target volume must include the chest wall.
• Supraclavicular lymph node group for patients with 4 or more positive axillary lymph
nodes.
• Axilla if inadequate axillary surgery was done.
In addition, the following areas may be included even though there is insufficient evidence to
made recommendations:
• Drain sites.
• Internal mammary chain (IMC).
accelerated partial breast irradiation (APBI)
RECOMMENDATIONS FROM THE AMERICAN SOCIETY indicate that APBI may be suitable in
selected patients with early stage breast cancer and may be comparable to treatment with
standard whole breast RT
Patients who may be suitable for APBI are:
• women 60 years and older who are not carriers of a known BRCA1/2 mutation, have been
treated with primary surgery for a unifocal Stage I, ER positive cancer.
•Tumors should be infiltrating ductal or a favorable histology, not be associated with an
extensive intraductal component or LCIS, and margins should be negative.
•34 Gy in 10 fractions delivered twice per day with brachytherapy or 38.5 Gy in 10 fractions
delivered twice per day with external beam photon therapy to the tumor bed is recommended
Radiotherapy for metastatic disease
Radiotherapy can be effective symptomatic treatment for:
• pain relief from bony metastases;
• spinal cord compression;
• brain metastases;
• leptomeningeal disease;
• superior vena caval obstruction;
• local control of primary tumour/local or chest wall recurrence;
• symptomatic skin metastases.
Radiotherapy can be effective symptomatic treatment for:
• pain relief from bony metastases;
• spinal cord compression;
• brain metastases;
• leptomeningeal disease;
• superior vena caval obstruction;
• local control of primary tumour/local or chest wall recurrence;
• symptomatic skin metastases.
Bisphosphonates can reduce the incidence of skeletal events and also reduce
bone pain in patients with bony metastases.
• Their use should be considered in all patients with bony metastases
Four bisphosphonates are currently available
• Clodronate (800 mg b.d.), a first-generation oral bisphosphonate.
• Pamidronate (90 mg i.v. over 90 min every 3–4 weeks), a potent intravenous
bisphosphonate.
• Zoledronate (4 mg i.v. over 15 min every 3–4 weeks), a potent intravenous
bisphosphonate.
• Ibandronate, a potent bisphosphonate available in both oral and intravenous
preparations
•The use of bisphosphonates should be accompanied by calcium and vitamin D
supplementation with daily doses of calcium of 1200 to 1500mg and Vitamin D3 400
– 800 IU.
• The risk of renal toxicity necessitates monitoring of serum creatinine prior to
administration of each dose
•Current clinical trial results support the use of bisphosphonates for up to two years
•The bisphosphonates are associated with the occurance of osteonecrosis of the jaw
bone pain in patients with bony metastases.
• Their use should be considered in all patients with bony metastases
Four bisphosphonates are currently available
• Clodronate (800 mg b.d.), a first-generation oral bisphosphonate.
• Pamidronate (90 mg i.v. over 90 min every 3–4 weeks), a potent intravenous
bisphosphonate.
• Zoledronate (4 mg i.v. over 15 min every 3–4 weeks), a potent intravenous
bisphosphonate.
• Ibandronate, a potent bisphosphonate available in both oral and intravenous
preparations
•The use of bisphosphonates should be accompanied by calcium and vitamin D
supplementation with daily doses of calcium of 1200 to 1500mg and Vitamin D3 400
– 800 IU.
• The risk of renal toxicity necessitates monitoring of serum creatinine prior to
administration of each dose
•Current clinical trial results support the use of bisphosphonates for up to two years
•The bisphosphonates are associated with the occurance of osteonecrosis of the jaw
PRINCIPLES OF BREAST RECONSTRUCTION
FOLLOWING SURGERY
•The breast can be reconstructed in conjunction with mastectomy using breast implants,
autologous tissue (“flaps”) or a combination of the two (e.g., latissimus / implant
composite reconstructions).
• Breast reconstruction
Immediate
delayed
• As with any mastectomy, there is a risk of local and regional cancer recurrence, and
evidence suggests skin sparing mastectomy is probably equivalent to standard
mastectomy in this regard.
• The nipple-areolar complex is sacrificed with skin sparing mastectomy for cancer
therapy.
•When post-mastectomy radiation is required, delayed reconstruction is generally
preferred after completion of radiation therapy in autologous tissue reconstruction,
because of reported loss in reconstruction cosmesis
•When implant reconstruction is used,immediate rather than delayed reconstruction is
preferred to avoid tissue expansion of radiated skin flaps
•. Immediate implant reconstruction in patients requiring post-operative radiation has an
increased rate of capsular contracture.
•Smoking increases the risk of complications for all types of breast reconstruction
whether with implant or flap
FOLLOWING SURGERY
•The breast can be reconstructed in conjunction with mastectomy using breast implants,
autologous tissue (“flaps”) or a combination of the two (e.g., latissimus / implant
composite reconstructions).
• Breast reconstruction
Immediate
delayed
• As with any mastectomy, there is a risk of local and regional cancer recurrence, and
evidence suggests skin sparing mastectomy is probably equivalent to standard
mastectomy in this regard.
• The nipple-areolar complex is sacrificed with skin sparing mastectomy for cancer
therapy.
•When post-mastectomy radiation is required, delayed reconstruction is generally
preferred after completion of radiation therapy in autologous tissue reconstruction,
because of reported loss in reconstruction cosmesis
•When implant reconstruction is used,immediate rather than delayed reconstruction is
preferred to avoid tissue expansion of radiated skin flaps
•. Immediate implant reconstruction in patients requiring post-operative radiation has an
increased rate of capsular contracture.
•Smoking increases the risk of complications for all types of breast reconstruction
whether with implant or flap
SURGICAL PRINCIPLES OF THE SKIN-SPARING MASTECTOMY
•Excision of the nipple-areolar complex
•Excision of the biopsy/lumpectomy incision
•Total glandular mastectomy, adhering to the same surgical principles of a
total mastectomy
•Sentinel node biopsy or axillary node dissection through breast incision
(with possible lengthening) or separate incision in the axilla
•Excision of the nipple-areolar complex
•Excision of the biopsy/lumpectomy incision
•Total glandular mastectomy, adhering to the same surgical principles of a
total mastectomy
•Sentinel node biopsy or axillary node dissection through breast incision
(with possible lengthening) or separate incision in the axilla
NOVEL AGENTS
•bevacizumab, a humanized monoclonal antibody against the vascular
endothelial growth factor (VEGF) in the treatment of metastatic breast cancer.
•Eribulin is a non-taxane microtubule inhibitor approved by the FDA in
November of 2010 for the treatment of patients with metastatic breast cancer
who have previously received at least two chemotherapeutic regimens for the
treatment of metastatic disease.
•Ixabepilone, an epothilone B analogue, is a newer agent for treatment of
recurrent or metastatic breast cancer as a single agent or in combination with
capecitabine
•Dasatinib (Sprycel) is a novel oral kinase inhibitor that targets the Src family
kinases and BCR-abl effective in basal cell type
•HSP90 inhibitor tanespimycin
•Axitinib, another oral Tyrosine Kinase Inhibitor of VEGFR, showed promising
antitumor activity in combination with docetaxel
•Other VEGFR TKIs such as pazopanib, vatalanib, cediranib, and motesanib are
under investigation.
•bevacizumab, a humanized monoclonal antibody against the vascular
endothelial growth factor (VEGF) in the treatment of metastatic breast cancer.
•Eribulin is a non-taxane microtubule inhibitor approved by the FDA in
November of 2010 for the treatment of patients with metastatic breast cancer
who have previously received at least two chemotherapeutic regimens for the
treatment of metastatic disease.
•Ixabepilone, an epothilone B analogue, is a newer agent for treatment of
recurrent or metastatic breast cancer as a single agent or in combination with
capecitabine
•Dasatinib (Sprycel) is a novel oral kinase inhibitor that targets the Src family
kinases and BCR-abl effective in basal cell type
•HSP90 inhibitor tanespimycin
•Axitinib, another oral Tyrosine Kinase Inhibitor of VEGFR, showed promising
antitumor activity in combination with docetaxel
•Other VEGFR TKIs such as pazopanib, vatalanib, cediranib, and motesanib are
under investigation.
TREATMENT IN A VIEW
NONINVASIVE CA. BREAST
•DCIS BCT+RT+/-Tamoxifen
•LCIS Observation+risk reduction counselling
INVASIVE BREAST CARCINOMA
EARLY
•Stage I,IIa, or IIb lumpectomy/mastectomy+/-
ALND+Adjuvant chemo+/-tamoxifen+/-trastuzumab
LATE
•LABC Preop chemo. Mastectomy+axillary staging
+adjuvant chemo+RT+/-Tamoxifen+/-trastuzumab
•INFLAMMATORY
•METASTATIC/RECURRENT indvidualised
NONINVASIVE CA. BREAST
•DCIS BCT+RT+/-Tamoxifen
•LCIS Observation+risk reduction counselling
INVASIVE BREAST CARCINOMA
EARLY
•Stage I,IIa, or IIb lumpectomy/mastectomy+/-
ALND+Adjuvant chemo+/-tamoxifen+/-trastuzumab
LATE
•LABC Preop chemo. Mastectomy+axillary staging
+adjuvant chemo+RT+/-Tamoxifen+/-trastuzumab
•INFLAMMATORY
•METASTATIC/RECURRENT indvidualised
SUMMARY
•Routine use of screening mammography in women 50 years of age
reduces mortality from breast cancer by 33%.
• Tumor estrogen receptor concentration, nuclear grade, histologic
grade, tumor type, and markers of proliferation should be
considered in patients before choosing between the use of
chemotherapy and hormonal therapy
• Anthracycline-based chemotherapy regimens may be superior to
non-anthracycline-based regimens in patients with HER2 positive
tumors.
•Surgery is mainstay of treatment ,BCT is to be done if possible and
pt. can be followed.
•SLN can avoid unnecessary axillary dissection and morbidity
•Routine use of screening mammography in women 50 years of age
reduces mortality from breast cancer by 33%.
• Tumor estrogen receptor concentration, nuclear grade, histologic
grade, tumor type, and markers of proliferation should be
considered in patients before choosing between the use of
chemotherapy and hormonal therapy
• Anthracycline-based chemotherapy regimens may be superior to
non-anthracycline-based regimens in patients with HER2 positive
tumors.
•Surgery is mainstay of treatment ,BCT is to be done if possible and
pt. can be followed.
•SLN can avoid unnecessary axillary dissection and morbidity
•Surgery should not be performed until leukocyte counts and
hemoglobin and hematocrit levels are back to normal, which typically
takes 3 to 4 weeks after the last cycle of chemotherapy.
•Concurrent radiotherapy and chemotherapy is not used because of
increased acute and late local toxicity resulting in a poor cosmetic
result.
•There is no good evidence that concurrent radiotherapy and
endocrine therapy is detrimental. However, concurrent chemotherapy
and tamoxifen compromises survival.
•Start adjuvant chemotherapy or radiotherapy as soon as clinically
possible within 31 days of completion of surgery in patients with early
breast cancer having these treatments.
• loco-regional recurrence is more likely if radiotherapy is delayed
more than 8 weeks following surgery.
•Delayed reconstruction is preferred if postmastectomy RT is to be
given.
hemoglobin and hematocrit levels are back to normal, which typically
takes 3 to 4 weeks after the last cycle of chemotherapy.
•Concurrent radiotherapy and chemotherapy is not used because of
increased acute and late local toxicity resulting in a poor cosmetic
result.
•There is no good evidence that concurrent radiotherapy and
endocrine therapy is detrimental. However, concurrent chemotherapy
and tamoxifen compromises survival.
•Start adjuvant chemotherapy or radiotherapy as soon as clinically
possible within 31 days of completion of surgery in patients with early
breast cancer having these treatments.
• loco-regional recurrence is more likely if radiotherapy is delayed
more than 8 weeks following surgery.
•Delayed reconstruction is preferred if postmastectomy RT is to be
given.
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