DEVELOPMENT OF BREAST

On each side of the ventral surface of young embryos, a

thickened band of ectoderm develops(the milk ridge).
It extends obliquely from axilla to inguinal region.
In human, the whole of these ridge atrophies, excepting only
small portion in each pectoral region from which breast
arises.

CONGENITAL ANOMALY OF
BREAST

Amastia: bilateral absence of breast tissue & nipple. When

breast tissue is absent unilaterally, the pectoral muscle is often
absent.(3)

Polymastia: more than one breast in one or both sides.(1)

Polythelia: supranumerary nipples are situated irregularly
over the breast & not on milk ridge.(2)

EVALUATION

A. Clinical Manifestation:
B. Physical Examination:

IMAGENES

RELEVANCIA DE LA MAMOGRAFA
La consulta mdica luego
de los 40 aos debe efectuarse
anualmente
Lo ideal es detectar el cncer antes que
se palpe.
La Mamografa es el nico mtodo por
excelencia para la deteccin del cncer
de mama.
Conlleva una mnima preparacin y se
realiza
en pocos minutos.

Indicaciones de
mamografia
Control anual a partir de los 40 aos
Con antecedentes familiares apartir de los
35 aos o 10 aos antes del familiar ms
joven
Paciente de cualquier edad con diagnstico
de cncer de mama
Paciente de cualquier edad con enfermedad
metastsica demostrada sin tumor primario.
Previo a cualquier intervencion quirurgica
mamaria
Durante la terapia hormonal con
periodicidad anual
En el varn para diferenciar ginecomastia-

Ecografia mamaria
Es un estudio complementario.
No es mtodo de screening.
til en premenopausicas, embarazadas, en
lactancia
Diag.dif.de lesiones qusticas-slidas
Mamas densas
Evaluacin de prtesis
Procesos inflamatorios
Gua de procedimientos intervencionistas
Primera evaluacin de mujeres de 30-35
aos.
Lesiones axilares adenopatas.
Complemento de lesin palpable

Resonancia magnetica
nuclear

Evaluar la extensin de la enfermedad

preoperatoria.
Prtesis
Carcinoma oculto por imgenes
habituales
Mama operada-irradiada
Monitoreo pos tratamiento.
Sospecha de enfermedad metastsica.
Paciente de alto riesgo bcra1-2.

Signos Mamogrficos

Ndulo / Masa
Microcalcificaciones
Deformidad del parnquima
Asimetra
Lesin Espiculada

Lesin espiculada

Carcinoma ductal infiltrante

Calcificaciones

Benignas
Redondas
Dispersas
Bilaterales
Grandes

Malignas
Irregulares
Agrupadas
Unilaterales
Muy pequeas

microcalcificaciones

Hallazgos Ecogrficos
en Cncer de Mama
Bordes irregulares, redondeados
Estructura interna heterognea,
irregular
Sombra acstica posterior
Hay dificultad a veces con los
ndulos slidos para diferenciar :
benigno / maligno

3.
PROCEDIMIENTOS
INTERVENCIONISTAS
Punciones citohistolgicas bajo
control
ECOGRFICO o
ESTEREOTXICO (RX)
Marcaje prequirurgico de lesiones no
palpables:
BIOPSIA DIRIGIDA CON ARPON

S Radiologa CHA

30

Carcinoma ductal infiltrante

Classification

85% of ca arises in ducts, thus ductal ca is most common variant

Most frequently upper outer quadrant is involved
lobular ca occur in up to 15% of cases
Breast cancers are divided in to

NoDCIS
n Invasive (IN SITU)

LCIS

2-Invasive

Ductal
Lobular
Medullary
Colloid
Tubular
Inflammatory Ca
Pagets Disease

DIAGNOSIS
Diagnosis should be made by combination of
1:clinical assessments
2:radiological imaging
3:cytological or thru histological analysis

BREAST CANCER STAGING

ACCORDING TO TNM CLASSIFICATION

Stage 0: Tis

No

Mo

Tis = carcinoma in situ

N o= no reginal lymph
node metastasis

M o= no distant metastasis

BREAST CANCER STAGING

ACCORDING TO TNM CLASSIFICATION

Stage 1: T1 N o M o
T 1 = tumor 2cm or less
in greatest dimension

Stage 2a:
To N1 Mo

T1 N1 Mo

T2 N o Mo

N1= metastasis
to ipsilateral
ax. Nodes
mobile

T2= tumor>2cm
but <5cm in
greatest
dimention

Stage 2b:

T2 N1 Mo

T3 N o Mo

T3= tumor size

> 5cm in
greatest
dimention

Stage 3a
T o N2 M o

T1 N2 Mo

T2 N2 Mo

T3 N1 Mo

T3 N2 Mo

N2a =met to ipsilat axillary

node , fixed or matted

N2b= met to ipsilat int mammary

node in absence of ax. node

Stage 3b

T4 No Mo

T4 N1 Mo

T4 N2 Mo

T4 N2 Mo

T4a= extension
to chest wall

T4b=
edema(Peaud
Orange),

T4c= both T4a

& T4b

T4d=
inflammatory
carcinoma

Stage 3 c

Any T
N3
Mo

N3a= met to
N3b= ipsilat
N3c= ipsilat
ipsilat
Internal mammary supraclavicular LN
infraclavicular LN & axillary LN

Stage 4 : Any T any N + M1

M1= distant metastasis

Positive axillary lymph node versus T stage

Silverstein, The Breast Journal 4:324, 1998

SKELETAL
L - Lumber vertebrate
F - Femur
T - T.vertebrae
R- RIBS
S- Skull
Metastasis may
occur in liver,lungs &
brain

SKELETAL

PET Scan

PET scan Normal

45

PET Scan

PET scan
abnormal

PET in woman with breast CA

that has spread to 46bone

PROGNOSTIC FACTORS
Anatomic and cellular prognostic factors

Name

Literature
support

Properties

Tumor size, extent (T)

Regional lymph node involvement (N)

+
+

Pathologic more reliable than clinical

Pathologic more reliable than clinical

Metastasis (M)
Histology: type
Grade
Chromatin
Tumor necrosis
Mitotic counts
DNA ploidy
Thymidine labeling index

+
+
+
+
+
+
0
+

S-phase; flow cytometry

Ki-67 antibody

+
0

Profilerating cell nuclear antigen

PCNA)

Angiogenesis

Peritumoral lymphatic vessel invasion

Radiographic tests acceptable

Most breast cancer is ductal
Problems with uniformity of criteria
Nuclear morphology
Cell degeneration and death
Cell activity, fixative problems, only M-phase cells
Conflicting results
Cell proliferation, thymidine a DNA precursor, thymidine
analogue 5-bromodeoxyuridine also used, predicts
recurrence
Cell proliferation, no standardized cutoff point
Recognizes nuclear antigen expressed only in
proliferating cells
Cell cycle-dependent protein that accumulates in the
nucleus of replicating cells during S-phase, conflicting
results
Related to tumor angiogenesis factors
Significant for relapse-free survival but not overall
survival

FACTORES

Factores Tumorales
Compromiso ganglionar
Tamao Tumoral
Grado Histologico y nuclear
Invasion Linfatica y vascular
Expresion her 2 neu
Receptores hormonales (ER/PR)

PRONOSTICOS

Factores del Huesped

Edad
Estado Menopausico
Historia Familiar
Enfermedad neoplasica previa
Immunosupresion
Respuesta inflamatoria
Nutricion
Quimioterapia previa
Radioterapia previa

Earlier stage - better survival

Stage

Survival Rates for patients w/ Breast Cancer

Relative to Histologic Stage
Histologic Staging
(NSABP)

Crude
survival (%)
5yr
10yr

5-yr
Disease-free
survival (%)

All patients

63.5

45.9

60.3

Negative axillary lymph nodes

78.1

64.9

82.3

Positive axillary lymph nodes

46.5

24.9

34.9

1 - 3 positive axillary lymph

nodes

62.2

37.5

50.0

> 4 positive axillary lymph

nodes

32.0

13.4

21.1

50

TRATAMIENTO

Clasificacion de riesgo

Low Risk

Intermediate Risk

High Risk

MANAGEMENT

sic principles of treatment

To reduce the chance of local recurrence
To reduce the risk of metastatic spread

EATMENT MODALITIES
Surgery
Radiotherapy
Adjuvant systemic therapy

Locoregional
Ciruga
Radioterapia

Sistmico
Quimioterapia
Hormonoterapia
A.C Monoclonales

Therapeutic Approach for Breast Cancer

A. Carcinoma in Situ:
1.

2.

DCIS:
a.

Breast conserving surgery + radiation therapy w/ or w/o

tamoxifen

b.

Total mastectomy w/ or w/o tamoxifen

c.

Breast-conserving surgery w/o radiation therapy

Lobular Carcinoma in Situ:

a.

Observation after diagnostic biopsy

b.

Tamoxifen to decrease the incidence of subsequent breast

cancer

c.

Study, Tamoxifen versus raloxifene in high-risk

postmenopausal women

d.

Bilateral prophylactic total mastectomy, w/o axillary

dissection
55

Therapeutic Approach for Breast Cancer

B.

Stage I & II
Modified radical mastectomy

(+) LN

(-) LN
Low risk

(-) LN
High risk

.
.

Hormonal /

chemotherapy

observe

chemotherapy

High Risk Patients (Stage I):

A.

Histologic criteria:
1. Poor cytologic differentiation, 2. Lymphatic
permeation, 3. Blood vessel invasion, 4. Poor circumscritption

B.

Rapid growth rate, by clinical history or thymidine labeling index

C.

Youth of the patient

D.

Estrogen receptor negative

56

Therapeutic Approach for Breast Cancer

3. Advance Breast Cancer (III / IV):
.

Palliative Mastectomy
(+) Estrogen
Chemotherapy/Hormonal/
Chemotherapy/Radiotherapy

(-) Estrogen
Radiotherapy

57

SITUATION

The breast lies in the superficial fascia of the pectoral region.

foramen of langer

A small extension called the axillary tail(of Spence) pierces the deep fascia and
lies in the axilla
In some normal subjects it can be palpable or seen premanstrually or during
lactation.
A well developed axillary tail sometimes mistaken for mass of enlarge lymph
nodes.

EXTENT

Vertically: it extends from the 2nd to 6th rib.

Horizontally: it extends from the lateral

border of the sternum to the mid- axillary line.

DEEP RELATIONS OF THE

BREAST

The breast lies on the deep fascia (pectoral

fascia) covering the pectoralis major.

pectoral fascia
pectoralis
major

DEEP RELATIONS OF THE

BREAST

Still deeper there are parts of four muscles,

namely pectoralis major, the serratus anterior,
latissimus dorsi and external oblique muscle.
pectoralis major

Serratus
anterior
latissimus dorsi

external oblique

DEEP RELATIONS OF THE

BREAST

Located deep to pectoralis muscle, the pectoralis minor muscle is

enclosed in clavipectoral fascia.

clavipectoral fascia

pecroralis minor
axillary fascia
clavipectoral fascia extends laterally to fuse with axillary fascia

DEEP RELATIONS OF THE

BREAST
Breast is separated from pectoralis fascia by loose areolar tissue(retromammary space).
It is thin layer of loose areolar tissue that contains lymphatics & small vessels.

retromammary
space

pectorali
minor
clavipectoral
fascia

axillary fascia

Because of this loose tissue the normal breast can be moved freely over the pectoralis
major
Surgical importence: during removal of breast the breast is separeted from pectoral muscle
in plane of retromammary space.

STRUCTURE OF THE BREAST

Structure of the breast can be studied under following heading skin,

parenchyma, & stroma.
Skin
- nipple &
- areola

4th IC space

Nipple : erectile structure, covered with thick pigmented skin(which increases

during pregnancy)
It contains smooth muscle fiber arranged concentrically & longitudinally.
Near its apex lies orifices of lactiferous ducts.

Areola: epithelium of areola contains

numerous modified sweat glands and
sebacious glands.
These glands enlarge during
pregnancy(Glands of Montogomery).
It contains involuntary muscles arranged in
concentric rings as well as radially in
subcutaneous tissue.

ARCHITECTURE OF THE
PARENCHYMA

Parenchyma consist of 10 to 100 lobules,

each loblues is cluster of alveoli, drained by
lactiferous duct, which near its termination
it dilate to form lactiferous sinus.
alveoli

lactiferous
duct

lactiferous sinus

Different portions of duct system are

associated with different diseases.
Large ductduct papilloma
duct ectasia
Smaller duct-(during development of breast)
- fibroadenoma
-(during involution of breast)
- cyst formation
- sclerosing adenosis

THE STROMA

It forms the supporting framework of the gland. It is partly fibrous &

partly fatty
Fibrous part: Ligament of Cooper-hollow conical projection of
fibrous tissue filled with breast tissue, the apices of cones firmly
attached to superficial fascia & to the skin.

It anchor the skin & gland to the pectoral fascia.

Fatty stroma forms the main bulk of the gland. It is distributed all over
the breast, except beneath the areola & nipple.

THE STROMA
In cancer of the breast, the malignant cells may
invade these ligaments & consequent contraction
of these strands may cause dimpling of the skin.

THE STROMA

If the underlying growth attached to the skin, it cannot be

pinched up from the lump

THE STROMA
If cancer cells grow along the ligament of cooper binding
the breast to the pectoral fascia breast
fixed to
pectoralis major

It cannot then moved in the long axis of the muscle.

THE STROMA
If cancer cells grow along the ligament of cooper binding
the breast to the pectoral fascia breast
fixed to
pectoralis major

It cannot then moved in the long axis of the muscle.

BLOOD SUPPLY
internal thoracic art.(br. of
subclavian art)

axillary
artery

supirior thoracic artery

acromiothoracic artery
lateral thoracic artery

branches from intercostal artery

Venous drainage: the superficial veins radiate from breast & are
characterized by their proximity to skin.
They are accompanied by lymphatics & drain to axillary, internal mammary &
intercostal vessels.
Phlebitis of one of these superficial veins feel like a cord immediately beneath
the skin. The condition produces no discoloration & may be tensed like
bowstring by putting traction on it (Mondors disease).
Nerve supply: the secreting tissue is supplied by sympathetic nerves(2 nd-6th
intercostal nerves). The overlying skin is supplied by the ant & lat branches
of 4th, 5th & 6th intercostal nerves.

AXILLARY LYMPH NODES

The breast drains mainly to the axillary nodes, of which there are 5 sets
axillary vein
apical axillary nodes

lat ax.nodes
pectoralis minor
interpectoral nodes(Rotters)
anterior axillary nodes
post ax.nodes
lat thoracic v.
central axilary nodes
subscapular vein

internal mammary chain

AXILLARY LYMPH NODES

Anterior set:
situation- along the lateral thoracic vein under anterior axillary fold. They lie manly
on 3rd r

The axillary tail of Spence is in close contact with these nodes & therefore , cancer
involving this process may be misdiagnosed as enlarged node with an apparently
healthy breast.
Anterior axillary nodes may be involved, by continuity of the tissue

AXILLARY LYMPH NODES

Central set:
Situation- in the fat of upper part of axilla.
Intercostobrachial nerve passes outwards amongst these nodes

Intercostobrachial nerve

Enlargement of these nodes(in cancer) by pressure on the nerve, cause

pain in the distribution of the nerve along the inner border of the arm.

AXILLARY LYMPH NODES

Apical set(infraclavicular nodes):
situation- bounded below by 1st intercostal space, behind by axillary vein, in front by
the costocoracoid membrane.

They are of great importance

because they receive one vessel directly from upper part
of the breast & ultimately most of the lymph from the breast
A single trunk leaves the apical group on each side of the subclavian trunk, & enters the
junction of jugular & subclavian vein
or may join the thoracic duct on the left.

AXILLARY LYMPH NODES LEVELS

Level 1: lateral to lateral border of pectoralis minor

Level 3(apical groups)

Level 2 (central groups)
Level 1
(lateral groups)

Level 2: central axillary nodes located under pectoralis minor muscle.

Level 3: subclavicular nodes medial to pectoralis minor muscle. It is difficult
to visualised & remove unless pectoralis muscles are sacrifised or divided.

THE AXILLARY FASCIAL TENT

Axillary lymph nodes are enclosed by layers of fascia which
resembles tent lying on its side

THE AXILLARY FASCIAL TENT

Axillary lymph nodes are enclosed by layers of fascia which resembles tent lying on its side
Anterior wall: pectoralis minor & clavipectoral fascia
Posterior wall: subscapularis muscle lying on the scapula
Medial wall: deep fascia covering chest wall, upper ribs, intercostal
surgical importance:
n. to serratus ant.
lies here

Apex : points upwards &

medially where layers of
fascia comes into contact
with
each other.
Base : points downwards & laterally & it is
open
Surgical importance : Block dissection
of axillary lymph nodes should excise the
tentintact

& serratus ant muscle.

LYMPHATIC DRAINAGE OF THJE

BREAST

Lymphatic of the overlying skin:

These drains the integuments over the breast, but not the skin of the areola &
nipple.
They pass in a radial direction & end in the surrounding nodes.
Lymphatics from outer side- goes to axillary nodes
Skin of the upper part supraclavicular nodes & certain of the vessels may end
in cephalic nodes(which lies along with cephalic vein in deltopectoral groove)
Skin of the inner part of the breast- goes to internal mammary nodes.
Lymphatics of the skin over the breast communicates across midline & unilateral
disease may become bilateral by these roote.

LYMPHATIC DRAINAGE OF THJE

BREAST

Lymphatics of the parenchyma of the breast:

SURGERY FOR BREAST CANCER

Simple or total mastectomy:

removal of all breast tissue, nipple
areola complex,
& skin

SURGERY FOR BREAST CANCER

Extended simple mastectomy:

removal of all breast tissue, nipple areola

complex,
& skin + level 1 axillary
lymph node

SURGERY FOR BREAST CANCER

Modified radical mastectomy:

removal of all breast tissue, nipple areola

complex,
& skin + level 1 & level 2
axillary lymph nodes.

SURGERY FOR BREAST CANCER

Modified radical mastectomy:

removal of all breast tissue, nipple areola

complex,
& skin + level 1 & level 2
axillary lymph nodes.

Axillary Node Dissection

Typically Levels I and

II
10 30 lymph nodes
removed
15-20% incidence of
lymphedema

Sentinel node biopsy

SURGICAL TREATMENT

Two Aspects of surgery

Mastectomy
Conservative breast surgery

1:Mastectomy
INDICATIONS

Large tumor related to size of the breast

Central tumor beneath the areola or involving nipple
Multi focal disease
Local recurrence
Patients preference

Conservative breast surgery

Small tumor related to the size of breast
Availability of radiotherapy facility
Patient preference

IDInvolves
E LO
C AofLlumpEorXtumor
C I with
S Irim
OofN1cm normal
removal

breast tissue.
Term lumpectomy is reserved for operation in which benign tumour is
excised and large amount of normal breast is not resected

) Removing
Quad
a n segment
t e c tofothembreast
y which
therentire

contain the

tumor.
Radiotherapy to the remaining breast tissue
Quadrantectomy, axillary dissection & radiotherapy is known as
QUART

 Indications for Conservative

Surgery:
1. Small breast CA < 4cm
2. Clinically (-) axillary LN
3. Breast volume adequate size to allow
uniform dosage of irradiation
4. Radiation therapist experience to avoid
damage of retained breast

95

5. Subcutaneous Mastectomy:

Nipple is retained / for T1s

6. Quandrantectomy, axillary,
radiotherapy (QUART)

Quadrant of the breast that has the CA is

resected
(quadrant of breast tissue, skin and
superficial pectoralis fascia)
Unacceptable cosmetic result

96

5. Partial Mastectomy and Radiation:

Lumpectomy, segmental resection or

tylectomy
Histologically free margin of breast CA (1cm)
Advent of supervoltage radiotherapy with skin
sparing effect
Frozen section evaluation of margin
To determine adjuvant chemotherapy
adequate sampling of axillary LN (level I),
curvilinear incision should be done
If LN (+) ----> adjuvant chemotherapy

97

ICAL MASTECTOMY (HALSTE

It includes
Excision of whole breast
All axillary lymph nodes
All fat and fascia of the anterior chest wall
Excision of pectoralis major and minor muscles.

e d More
r acommonly
d i c aperformed
l (Patey mastectom

Excised Mass is composed of

Whole breast
Large portion of skin overlies the tumor and nipple
All fat, fascia, and lymph nodes of axilla
Pectoralis minor muscle divided or retracted
With preserving of axillary vein, nerve to serratus anterior &
lattissimus dorsi

Surgical Management:

4.

Modified Radical
Mastectomy:
1.
2.

5.

Patey preserved
pectoralis major
Madden / Auchincloss
preserved both the
pectoralis major and
minor

Total mastectomy w/ or
w/o radiation:
1.
2.

Crile Total mastectomy

Mc Whirter Total
mastectomy and radiation
(Axilla,
supraclavicular and
internal mammary nodes)
100

Radiotherapy
INDICATION

After mastectomy
High grade tumour
Large nodal involvement
Multifocal disease
Extensive lymphovascular invasion

DJUVANT
SYSTEMIC THERAPY
AIM:
To delay the relapse
To prolong the survival

Indications:
Lymph node positive women
Poor prognosis
Hormonal receptor positive women
Old patient

Radiotherapy:

Local control
Pre-operative / post-operative radiation

Breast irradiation
positioning

Acute effects of
breast irradiation

106

External Beam Therapy

107

Brachytherapy

108

HORMONAL THERAPY

Tamoxifen is widely used hormonal treatment

If pat is premenopausal get benefit from 2omg daily of tamoxifen
New aromatase inhibitors i.e.anastrozole,letrozole etc are used if
pat is post menopausal
It reduces risk of cancer in contra lateral breast
Other hormonal agents are being developed i.e. LHRH

CHEMOTHERAPY

The aim of this Rx is to shrink tumor to enable breast preserving

surgery.
6 months cycles of cyclophosphamide, methotrexate and 5-FU
achieve 25% reduction in risk of relapse
Chemotherapy may be considered in node ve pts if there is hi
risk of recurrence
This Rx is confined to premenopausal women.

Chemotherapy:

CMF, CAF, CA, AV, doxorubicin

Side effect: nausea, vomiting, myelosuppression,
alopecia, thrombocytopenia, exercise intolerance

Hormonal Therapy:

Receptor Assay (ER/PR):

1 gm of fresh tissue obtained by using cold scalpel and should be

determined w/in 20-30 min.

ER (-) < 10% respond to endocrine ablation or exogenous

estrogen

ER (+) > 60% responds

premenopausal 30% (only due to masking effect of endogenous

estrogen)

Menopausal 60%

PR (+) 15% of premenopausal benefit from 15%

110

Hormonal Therapy:
2. Anti-estrogen:
a. Tamoxifen a non-steroidal antiestrogenic compound that compete w/
estrogen at receptor site.
Estrogen receptor assay should be
determined; if negative chance of
success is very low

111

NEOADJUVANT SYSTEMIC THERAPY

FOR OPERABLE BREAST CANCER

Administration of systemic chemotherapy or hormonal

therapy result in reduction of tumor size in 50 to 80% of
the patients with locally advanced breast carcinoma
Preoperative or neoadjuvant therapy
can convert

Inoperable
Tumor

Operable one

tumor that require

mastectomy

to eligible for
lumpectomy

can shrink
large
tumor
to allow more
cosmetic
lumpectomy

CHEMOTHERAPUTIC REGIMEN
OF ADVANCED BREAST CANCER

C M F regimen
C cyclophosphamide
M methotrexate
F 5 flurouracil
FAC regimen
F 5 flurouracil
A adriamycin(doxorubicin)
C cyclophosphamide
AC regimen
A adriamycin
C - cyclophosphamide

NEWER AGENTS

Trastuzumab : is a humanized murine

(Herceptin)
monoclonal antibody raised
against erb B2, HER 2
surface receptor
Laptinib : a dual inhibitor of both
- EGFR
- HER 2

ENDOCRINE- AGENTS USED IN TREATMENT

OF
BREAST CANCER
Class
Common examples
Clinical use
Selective estrogen
receptor
modulator(SERMS)

Tamoxifen,
Raloxifen,
Toremifen

Adjuvant therapy for

metasttic disease

Aromatase
inhibitors(AIs)

Anastrazole
Letrozole
Exemestane

Adjuvant therapy for

metasttic disease

Pure antiestrogen
Lutinizing hormonereleasing
hormone(LHRH)

Fluvistrant
Goserelin
Leuprolide

-2nd line therapy for

metastatic disease
-Adjuvant therapy
for metasttic disease

Progestational
agents

Megestrol

2nd line therapy for

metastatic disease

Androgens

Fluoxymesterone

3rd line therapy for

metastatic disease

High dose estrogens

Diethylstilbestrol

3rd line therapy for

metastatic disease