BREAST

CARCINOMA
CANCER BREAST
ANATOMY
 INTRODUCTION

 Mammary glands are modified sweat

glands gaining importance because
of the fear of malignancy and this
fear psychosis causing mental agony
if there is any change such as
discharge of the nipple, pain and
presence of lump
 The breast is located within the
superficial fascia of the anterior chest
wall housing mainly 15 – 20 lobes of
tubuloalveolar glandular tissue, fibrous
connective tissue supporting the lobes
and adipose tissue covering the gap
between the lobes.
 Subcutaneous tissue placed in between
the lobes and lobules provide support to
the glandular elements.
 Distinct space, retromammary space
gives the free mobility of the chest wall
 Coopers ligament are supporting
connecting tissue interdigitate between
the parenchymal tissue of the breast
extend from deep layer to attach to the
dermis of the skin.
 The mature female breast extend from
the second rib to the inframammary
fold (7th rib) and from side to side
between the lateral part of the sternum
to the anterior axillary fold. The deep
surface of the breast rests on portions
of pectoralis major serratus anterior and
external oblique muscles and also upper
portion of anterior rectus sheath.
 ANATOMY OF THE AXILLA
 The axilla is the pyramidal
compartment located between
upper extremity and the thoracic
wall. The structure has four
boundaries, the base formed by
the axillary fascia, the apex is the
aperture that extends into the
posterior triangle of the neck.
 The canal is cervicoaxillary canal
bounded anteriorly by the clavicle,
medially by the first rib and
posteriorly by the scapula.
 The axilla contains great vessels and
nerves of the upper extremity being
enclosed within the axillary sheath.
 The axillary artery can be divided into
three parts within the axilla. The first part
medial to the pectoralis minor giving rise
to superior thoracic. The second part
posterior to the pectoralis minor giving rise
to lateral thoracic and thoracoacromial.
The third part located lateral to the
pectoralis minor and give rise to anterior
and posterior circumflex humeral and the
subscapular arteries.
 The tributaries of the axillary vein
follow the course of the branches of
the axillary artery, the cephalic vein
passes in the groove between deltoid
and pectoralis major muscle and
thereafter enters the axillary vein
 Three nerves of importance are
• Long thoracic nerve located on the medial wall
of the axilla which face accidental division while
fascia is dissected during lymphatic dissection
of the axilla. This nerve even though
diminutive has long course and division results
in winging of the scapula.
• Thoracodorsal nerve from the posterior cord of
the brachial plexus innervating the latismus
dorsi muscle attains importance for the survival
of the myocutaneous flap.
• Intercosto brachial nerve providing sensory
innervation of the skin of axilla and the upper
medial aspect of the arm may get sacrificed
during level II clearance.
BLOOD SUPPLY OF THE
BREAST
 Perforating branch from the
internal mammary artery, lateral
branches of the posterior
intercostal arteries and several
branches of the axillary artery.
 Major venous drainage of the
breast is directed towards the
axilla and a three principal group
of veins carries the same name as
that of the arteries.
 INNERVATION OF THE
BREAST

 Sensory innervation of the breast

primarily from the lateral and
anterior cutaneous branches from
the second to sixth intercostal nerve.
 LYMPHATIC DRAINAGE OF
THE BREAST
 Lymph drainage from the breast is important
in relation to malignant disease and is via
the axillary and internal mammary nodes.
To a lesser extent lymph also drains by
intercostal routes to nodes adjacent to the
vertebrae. Even though the nodes are
commonly coming into the various group
such as lateral, anterior or pectoral group,
posterior or subscapular group, central
group, apical group and the inter pectoral or
Rotters group, the simplification could come
in the form of level I node lies lateral to the
muscle, level II behind and level III medial.
 There are an average of 20 nodes in the
axilla, 13 being at level I, 4 – 5 at level
II and 2 or 3 at level III.

 The drainage from level I node passes

into the central nodes and on into the
apical nodes. An alternate route being
the interpectoral node. The so called
skip metastasis are seen in less than 5%
of the patients.
MICROSCOPIC ANATOMY OF
THE BREAST
 Each lobe of the mammary gland ends in
the lactiferous ducts 2 – 4 mm in diameter
emptying into the subareolar ampula and
on to the nipple. Beneath the areola each
duct has lactiferous sinus. At the opening
they are lined with stratified squamous
epithelium. Morphology varies from time
to time during pregnancy and lactation.
These events are accompanied by relative
decreases in the volume of connective and
adipose tissue.
 ETIOPATHOGENESIS
BREAST CANCER – EPIDIMIOLOGY, RISK
FACTOR AND GENETICS
 With 570 thousands new cases in the

world each year breast cancer remains

the commonest malignancy in human
and constitute 18% of all cancers that
occur in women. Of every 1000 women
age 52 would have recently had breast
cancer and about 15 would be
undergoing treatment before the age of
50.
 AGE
 The incidence increases with age
doubling about every 10 years till
menopause and slows down
dramatically. Compared with the
lung cancer, cancer of the breast is
higher at younger age with the
flattening of the age – incidence
curve after the menopause.
GEOGRAPHICAL VARIATION
 The difference between Eastern and
Western countries is still about 5 – 6
fold even though the difference
appears to be diminishing. The
migrating population assuming the
rate in the host country significantly
indicates the environmental factors.
 AGE AT MENARCHE AND
MENOPAUSE
 Women who attain menarche early
and late menopause show an
increased risk. The women who
have natural menopause after the
age of 50 seem to be the candidates
with 2 fold increase compared to
women who experience menopause
before the age of 45.
 AGE AT FIRST PREGNANCY
 Nulliparity and late age at first birth have
a significant increase of incidence of
breast cancer.
 The high risk group are those who get
children after the age of 35. Quite
interestingly these women appear to be at
even higher risk than nulliparous women.
 An early age at birth of the second child
further reduces the risk of breast cancer.
 FAMILY HISTORY
 Genetic predisposition carries 10% of
breast cancers. It is generally inherited
as autosomal dominant with limited
peneterance, this means that it can be
transmitted through either sex and
some of the members transmit the
abnormal genes without being affected.
 About the third of the familial cases are
thought to be due to mutation in BRCA
1 gene on the long arm of chromosome
17 and second being BRCA 2 on the
long arm of chromosome13. In addition
a few cases arise from mutation from
p53 gene on the short arm of
chromosome 17. p53 is affectionately
called ‘Angel’ of the gene.
 Many families affected by breast cancer
show an excess of ovarian, colon,
prostatic and other cancers attributable
to the same inherited mutations. Most
breast cancers that are due to genetic
mutation can occur before the age of 65
and a women with a strong family
history of breast cancer of early onset
may not get after the age of 65. This
could be probably due to non
inheritance of genetic mutation.
 A women’s risk of breast cancer is 2 or
more times greater if she has a first
degree of relative who develop the
disease before the age of 50, the
younger the age the greater the risk.
 PREVIOUS BENIGN
BREAST DISEASE

 Women with severe atypical

epithelial hyperplasia have a 4 – 5
fold increase of incidence. Women
with this change and a family history
have many fold increase.
 RADIATION
 The cancer risk doubles among teenage
girls if exposed to radiation which has
been proved beyond doubt towards
Second World War. This gains
importance since mammographic
screening is associated with net increase
in mortality from breast cancer among
women aged over 50 and the same
effect is not clear on younger women.
 LIFE STYLE
 DIET
 OBESITY

 SMOKING

 ALCOHOL INTAKE

Seem to be play a part but evidence is not

convincing. Interestingly obesity shows 2
fold increase in post menopausal women
whereas among premenopausal the
reverse hold good.
 ORAL CONTRACEPTIVE
 The use of oral contraceptive is four
years or more by younger women
before their first term pregnancy
almost certainly increases the risk.
Other than that the oral
contraceptive does not play any
significant role.
 HORMONE REPLACEMENT
THERAPY
 Studies of unopposed estrogen for
HRT the risk of breast cancer
increases upto 50% after 10 – 15
years use. Other important aspect is
increase in breast density with a
hormone replacement therapy
causing problem in detection of
breast cancer.
 PREVENTION OF BREAST
CANCER
 Hormonal control – The use of Tamoxifen
seem to playing a role but is it due to delay
in presentation ?
 Other preventive agents – Retinoids affect
the growth and differentiation of epithelial
cells and they have definitely a roll in
preventing breast cancer.
 Selenium is another possible cancer
preventive agents.
 PATHOLOGY OF
BREAST CANCER
 Breast cancers are from the
epithelial cells that line terminal
duct lobular unit. They remain
within the basement membrane of
either the lobular unit and or the
draining duct are classified as in
situ or non invasive. Once they
breach the basement membrane
and spread into the adjacent
surrounding normal tissue, it is
known as invasive breast cancer.
 CLASSIFICATION OF
PRIMARY BREAST CANCERS
 NON – INVASIVE EPITHELIAL
CANCERS

 INVASIVE EPITHELIAL CANCERS

 MIXED CONNECTIVE &

EPITHELIAL CANCERS
 NON – INVASIVE EPITHELIAL
CANCERS
 LCIS
 DCIS :
- papillary
- cribriform
- solid
- comedo
 INVASIVE EPITHELIAL
CANCERS
 INVASIVE LOBULAR CARCINOMA
 INVASIVE DUCTAL CARCINOMA :
- invasive ductal carcinoma - NOS
- tubular
- mucinous or colloid
- medullary
- invasive cribriform
- invasive papillary
- adenoid cystic
- metaplastic carcinoma
 MIXED CONNECTIVE &
EPITHELIAL CANCERS
 Phyllodes tumour :
- benign
- malignant
 Carcinosarcoma
 angiosarcoma
 DUCTAL AND LOBULAR
TYPES
 This classification was based on
the belief that they are arising
from the respective area of origin.
The modern concept is they arise
from the terminal duct lobular unit
and this terminology is no longer
appropriate.
 Since some tumors show distinct
patterns of growth and cellular
morphology and on this basis
special types are identified. Rest
are called No Special Type.
 TUMOR DIFFERENTIATION
 Among the cancers of no special type
prognostic information can be gained by
following features.
1. Degree of glandular formation.
2. Nuclear pleomorphism.
3. Frequency of mitosis.
This comes under Bloom and Richardson
Grade – A good predictor of both disease
free and
over all survival.
 OTHER FEATURES
 Lymphatic and vascular invasion

 Extensive In situ component

This gains importance because the tumor

recurrence occurs after breast conserving
treatment.
 TNM CLASSIFICATION OF
BREAST TUMORS
International union against cancer recommends TNM classification.

Tis Cancer In situ N0 No regional node

metastasis
T1 < 2 cm N1 Palpable mobile
nodes
T2 2 – 5 cm N2 Fixed nodes
T3 > 5 cm N3 Internal
mammary node
T4A Involvement of Chest wall M0 No metastasis
T4B Involvement of Skin M2 Distant metastasis
includes
T4C T4A and T4B combined (ipsilateral
supraclavicular
T4D Inflammatory cancer nodes)
 AJCC STAGING FOR BREAST
CARCINOMA
Tis - carcinoma in situ
T1 - tumour ≤ 2 cm
T2 - tumor >2 cm;≤5 cm
T3 - tumor >5 cm
T4 - tumor any side with extension to
chest wall or skin
T4a - tumor extending to chest wall
(excluding pectoralis)
T4b - tumor extending to skin with
ulceration, edema, satellite nodules
T4c - both T4a and T4b
T4d - inflammatory carcinoma
 AJCC STAGING FOR BREAST
CARCINOMA
 N0 - no regional node involvement, no special
studies
 N1 - metastasis to 1-3 axillary nodes and/ or
int.mammary positive by biopsy
 N2 - metastasis to 4-9 axillary nodes or
int.mammary clinically positive, without
axillary metastasis
 N3 - metastasis to ≥ 10 axillary nodes or
combination of axillary or int. mammary
metastasis
 N3a - ≥ 10 axillary nodes( >2 mm), or
infraclavicular nodes
 N3b - positive int. mammary clinically with ≥ 1
axillary node or > 3 positive axillary nodes
with int. mammary by positive by biopsy
 N3c - metastasis to ipsilateral supraclavicular nodes
 AJCC STAGING FOR BREAST
CARCINOMA
 M0 – no distance metastasis
 M1 – distance metastasis
A System of combining T N M Staging
subsets with clinical staging.
T0 T1 T2 T3 T4
N0 Stag
eI
N1 Stage II
N3 Stage IIIB
M1 Stage IV
The Manchester System (1940)
 Stage I – Tumour confined to the breast. Any
skin involvement covers area less than the the
size of tumor.
 Stage II – Tumour confined to breast. Palpable ,
mobile axillary nodes.
 Stage III – Tumour extends beyond breast tissue
because of skin fixation in an area greater than
the size of the tumour or because of ulceration.
Tumour fixity underlying fascia.
 Stage IV – Fixed axillary nodes, Supraclavicular
nodal involvement, satellite nodules or distant
metastasis.
 POINT OF IMPORTANCE

 All patients with invasive breast

cancer should undergo full blood
count, liver function test, and chest
radiograph. If they are negative in
stage 1 and 2 further tests are not
indicated. Otherwise they have to
undergo bone and liver scans.
Diagnosis and Investigations
of
Carcinoma of Breast
Breast Self Examination
 Clinical Symptoms
•Breast lump.
•Mastalgia.
•Discharge from nipple.
•Axillary and/or neck Lump.
•Nipple Ulcer.
•Breast asymmetry.
•Metastatic Bone or Brain Symptoms.
Clinical Examination
Mastalgia
Usually painless, rarely pain in the lump
premenstrual discomfort ; Heaviness in
the breast in Lobular Ca

Discharge from Nipple

 Usually blood stained and watery in
Intraductal Ca compared to tenacious
discharge in duct ectasia.
Clinical Examination
Axillary and neck nodes
The clinical assessment of axillary nodes is notoriously
unreliable
Focus attention on
•Number of axillary nodes affected
•Level of axillary nodal disease
•Level I External mammary, axillary vein, scapular group
•Level II Central group
•Level III Subclavicular group
•Rotter’s nodes – Intra mammary group.
•Presence of supraclavicular nodes

Nipple ulceration/ Fungation

Occur in neglected cases of Ca breast also in Paget’s
nipple and Adenomas of Nipple
Clinical Examination
Breast Asymmetry
•Diffuse enlargement in lobular Ca
•Nipple retraction in infiltating dutal Ca
•Large ulcerated mobile tumors without
axillary nodes – Cystosarcoma Phyllodes

Metastatic Bone Brain Lung

Abdominal Symptoms.
•Commonest is Bone metastasis – Vertebral,upper
end of femur – Bone pain, Pathological fracture
•Peritoneal in Lobular cacinoma – Ascites,
Hepatoslenomegaly, Jaundice.
•Lung – Haemoptysis, Dyspnoea.
 Clinical Staging
Many clinical systems have been proposed
none has been shown to be significantly
better than others.
Investigations and Work-up
Options for Non palpable masses
•Picked up by screening mammography
•FNAC not advisable
•USG guided or Sterotactic core needle biopsy is
preferred
•If not possible incision biopsy and needle
localization for lesions close to chest wall or
areola
•Any finding of atypia is an indication for wire
localised open biopsy
•Tunneling and piece meal removal to be avoided
in open biopsy.
 Options for Palpable
I ) FNAC masses
• Out patient procedure.
• Gives cellular sample of the lesion
• Done with 21G needle in cystic lesions and
22-25G needle in solid lesions
• Oscillation of the needle several times inside the
tumour with suction effect with 10-20ml syringe
gives good results
• Better suited for lesions larger than 1cm
• False negative results (5%) occur in inexperienced
hands, fibrotic tumours, Infiltrating lobular Ca,
Tubular Ca and Cribriform Ca.
• False positive results (2%) can occur in
Hypercellular fibroadenoma, Hormone therapy,
pregnancy, Lactation and normal breast.
 Options for Palpable masses
FNAC-(contd)

- FNAC is alchol fixed and is stained
using Giemsa stain and studied by
Papanicolo’s techinque.
• FNAC does not differentiate between
invasive and insitu carcinoma.
• But differentiates ductal and lobular
Ca.
• Tripple negative criteria.
Options for Palpable masses
II) Tru –Cut Biopsy,
• Required for FNAC negative lesions.
• FNAC gives a cellular sample but TRU-CUT
gives a histo-pathological sample.
• Done under local anaesthesia after making a
nick in the skin with 11 blade and targetting
the lesion with tru-cut needle after fixing the
lump between the thumb and index finger of
the non dominant hand.
• Fixative is formalin
• Can be used even to assess the ER status and
HER-2 NEU status
 TRU-CUT Bx
 10 Ficomol/mg of tissue is positive of
ER status.
Tru- Cut Biopsy.

 Pappilary variant of
Ductal Carcinoma.
 Options for Palpable masses
 OPEN BIOPSY
• Incisional biopsy - Can be done for
ulcerated and fungated masses.
• Excisional biopsy – Done under GA the
tumour is excised with 1 cm margin of
normal tissue.
• Frozen section biopsy – Though
advocated has the difficulty in explaining
to the patient about mastectomy.
Natural history of Ca Breast
Normal

Hyperplasia

Atypia

Carcinoma in Situ

Microinvasive Carcinoma

Clinically invasive Carcinoma

 Micro- Invasion
It is defined as extension
of the malignant cells beyond the
basement membrane into the
adjacent tissues with no focus more
than 0.1 cm in greatest dimension
and are staged as T1 mic .
A subset of the T1 Breast
carcinoma
 Investigations to Know the extent
of Disease

Loco Regional
 Mammography
 Ultrasonography
 MRI Breast
 Mammography
 Primarily for screening
 Always bilateral
 Reduces mortality by 20-30%
Indications
 Evaluation of pain, mass, nipple retraction
 Pre op mammography detects potential multicentricity
and identifies synchronous cancers
 Detects very early breast cancers as small as 5mm
 Stereotactic mammo guided core needle biopsy of non
palpable masses when USG guidance fails
 Post-op mammo of the same breastafter breast
conservation surgery and contralateral breast after total
mastectomy.
 Types of Mammography
 Conventional mammography-
delivers dose of 0.1cGy per study
 Xero mammography
 Magnification Mammography
 Full field digital mammography
 Mammography
Views
 Cranio caudal
 Mediolateral oblique
 Exaggerated oblique
 Slight rotational magnified
 Mammography
Classic features of breast cancer
 Mass effect
Most reliable
 Micro calcifications combination
 Architectural distortions

 Skin thickening

 Duct dilatations

 Asymmetry of the breast

 Fibro-nodular densities
Mammography
 Ultrasonography
 Cannot replace mammo for
screening.
 No ionising radiation
 High patient acceptability
 Mainly diagnoses cystic lesions
 Can be used for core needle biopsy
of non palpable lesions when more
than 1 cm
 MRI Breast
 Its potential value in screening is questionable
 Indicated when mammography is compromised
 Evaluation of residual cancer before re-excision
 Dense breast
 To know int. mammary node ststus
 Silicone augmented breast
 Scarring – to differentiate from local recurrance
 To assess effect of induction of chemotherapy
 High resolution MRI pick up Ca in situ
 Recently been used to evaluate axillary nodal
status.
 Metastatic Work-up
 X-ray Chest
 USG Abdomen
 Skeletal survey
 CT scan chest
 CT scan abdomen
 Bone scan
 Indications – Advanced local disease T3,T4
- Lymph node metastasis N1,N2,N3
- Distant metastasis M1
- Positive skeletal survey
- Bone symptoms alone
 Limitations False positive e.g in osteo arthritis
 Prognostic indicators
 Genetic study BRCA1 and BRCA2
 Axillary nodal status – No, Level, inv on HPE
 ER status values more 10fmol/mg – ER positive
 Post menopausal 60% ER positive
 PR status Pre menopausal strongly PR positive
but may be ER negative
 Proliferative rate – Thymidine labelling indices
 S- Phase fraction
 Incompletely defined risk factors Her 2/neu or
Erb-2 is overexpression in small percentage of
tumours
 Sentinel Node Biopsy
 Done only when axillary is clinically
negative
 Contraindications
• Previous mammoplasty
• Inflammatory breast Ca
 Carcinoma of Male Breast
 0.5% of all male cancers
 Often in seventh decade often ductal
adeno ca , Lobular Ca never occurs
 Strong hormonal basis 80% ER,PR positive
 Positive correlation between breast Ca and
Prostate Ca
 Genetic defects – BRCA2 and AR gene
 Gynaecomastia is not a predisposing factor
 Paget’s Disease
 Eczematoid eruption of nipple
 Tenderness, itching, burning and
intermittent bleeding
 Underlying lump usually DCIS or invasive
 Always unilateral
 Axillary nodes in one third cases
 D/D –Superficial melanoma (S-100 protein
and CEA)
 HPE pagets cells in the Rete pegs of
epithelium
Inflammatory Breast Carcinoma
 Common in pregnant and lactating
mothers but can occur in any age
 Breast is red and warm mimics cellulitis
 Poor prognosis
 HPE tumour emboli in dermal
lymphatics and characteristic absence
of polmorphs and lymphocytes near
tumour
Treatment of Ca. Breast
Prevention
GAIL model – Calculates
future development of breast
cancer in high risk population
 Gail model based on:
1. Race
2. Age
3. Reproductive Risk Factors
4. Maternal Family History
5. Previous Bx status
Gail model Trial- random assignment of
women to receive Tamoxifen/Placebo
Claus Model – Predicts a woman’s chance of
developing breats cancer based on her
family history
 Breast Conserving Surgery
 Cosmetically less damaging, reduces
emotional and psychological after-effects
 Indication: Pts who have DCIS/LCIS and
stages I and II have a choice of
BCS/Mastectomy
 Subsect of stage I and II Ca breast
patients are benefited by adjuvant
Chemotherapy and/or Hormonal therapy
 Local therapy consists of surgery alone or
surgery followed by RT.
 Accepted Treatment Options for
Stage I&II Ca breast
 Surgery
 Adjuvant Chemo/Hormonal Therapy

 Radioation Therapy

Concept of BCS
Refers to wide local excision of cancer (1-2 cm)
leaving the breast largly intact, with or without
Post op RT/ALND
Modern treatment of breast Cancer is
multimodal – following limited surgical
procedures – 4500Gy RT for the whole breats and
Booster Radiation to the Tumour bed, Sentinel
Node sampling and ALND ( done via separate
incisions)
 Treatment Options for DCIS
 Mastectomy or wide local excision with RT
or wide local excision along with
Tamoxifen for ER +ve tumours.
Early stage Br. Cancer Rx (Stage I &II)
 BCS/Mastectomy

 Sentinel Node BX with/without ALND

 Followed by RT - based on whether the

cancer is multi-centric or if margins are
+ve
 Node –ve pts – benefited by
chemo/Hormone therapy
 Wide local excision
 Removal of the malignancy along
with a rim of grossly normal
parenchyma( 1-2 cm)
 Quadrentectomy (Vernoci) – more
aggressive local procedure, removes
the tumour , 1-2 cm of adjacent Br.
Tissue( quadrant) and the overlying
skin.
 Treatment For LABC

 LABC- advanced on chestwall, regional

lymph nodes but no distant
metastasis(Mo)
Trimodal Treatment
 Pre op Chemotherapy (FAC)-3 cycles to
downsize the disease
 Followed by M.R.M with ALND for +ve
sentinel node Bx or clinically palpable
Axillary nodes with RT
 Treatment for Inflammatory Ca
(stage IV d)
 Intensive chemotherapy followed by
mastectomy ALND with RT

Rx for Paget’s disease

 Simple mastectomy with or without
ALND
 Mastectomy
 Refers to the complete removal of mammary gland along
with nipple-areola complex, sacrificing variable amount of
surrounding skin depending on site(?)/size and behaviour
of the primary tumour.

Modified Radical Mastectomy (M.R.M)

 Extending the operation lateral to the pectoralis major
muscle and extending upto the axially vein, removing the
axillary pad of fat with ALND (level I and II)

 HDCT
 Hormonal Treatment