BREAST

CANCER

Breast cancer is the most common cancer and the

second leading cause of cancer-related death for
women in USA

Jemal A., et al. CA Cancer J Clin

2008; 58:71-96

Five Year Relative Survival Rates for

Breast Cancer: 1973 - 2005

ncer survivors increased from 3 M to 9 M in the same period

CA, Jan 1973 and Jan 2005

Functional Anatomy

Blood Supply

(1) perforating branches of the internal mammary artery;

(2) lateral branches of the posterior intercostal arteries(3,4,5);
(3) branches from the axillary artery, including the highest thoracic,
lateral thoracic, and pectoral branches of the thoracoacromial artery

The lymphatic drainage of the

breast
Apical
group

75%
20-25%

The lymph node groups

1. level I LN(14-19). located lateral to or below the lower border of the pectoralis minor muscle: the axillary
vein 4-6): external mammary 5-6), scapular groups 5-7
2. Level II LN (5-8): located superficial or deep to the pectoralis minor muscle
the central(3-4), interpectoral groups (Rotters (1-4)
3. Level III LN : located medial to or above the upper border of the pectoralis minor muscle: the subclavicular
group 6-12)

Risk factors unchangeable

1. Being a woman
2. Age
3. Genetic factors - mutations in BRCA1 or BRCA2;
50-60% of women inheriting a BRCA1 mutation
from either parent will have breast cancer by age
70
4. Family history of breast cancer (not related to
BRCA mutations)
5. Personal history of hyperplastic breast disease

Risk factors - unchangeable

6. Personal history of breast cancer
7. Race: incidence is higher in Caucasian compared with
African-American, Hispanic or Asian women.
8. Radiation treatment: chest irradiation as a child/young
woman can significantly increase risk of developing breast
cancer.
9. Dense breast tissue.
10. Menstrual history: early menarche (<12 yr) or late
menopause (>50yr) has some association with increased
risk. Also nulliparous, or first childbirth at >30 yrs.

Risk factors associated with

lifestyle
1. Oral contraceptives - remains controversial
2. Hormone replacement therapy - >5 years of therapy
with combined estrogen and progesterone may
increase risk
3. Not breast feeding
4. Obesity, lack of physical activity
5. Alcohol - 2-5 drinks/day can increase risk x 1.5 over
non-drinkers.

Factors with uncertain, controversial or

unproven effects on risk of developing
breast cancer

1.
2.
3.
4.
5.
6.
7.

High fat diet

Induced abortions
Breast implants
Environmental chemical exposure (e.g.
pesticides)
Tobacco smoke
Night shift work
Human mammary tumor virus ?

Hereditary Breast
Cancer

Hereditary breast-ovarian cancer (HBOC)

syndrome Mutation in BRCA1, BRCA2 genes

Ataxia telangiectasia (A-T) : Mutation in ATM

gene

Li-Fraumeni syndrome: Mutation in p53 gene (?

CHEK2 gene).

Cowden syndrome: Mutation in PTEN gene

Peutz-Jeghers syndrome: Mutation in STK11 gene

Breast cancer risk assessment tool

(BCRAT)
BCRAT-

based on Gail model, using womans

personal medical history (previous breast biopsies,
ATH), reproductive history, whether first degree
relatives had breast cancer, to estimate risk of
invasive breast cancer over specific periods of time
(www.cancer.gov/bcrisktool)
CARE model gives more accurate estimates of
breast cancer risk for African-American women. Gail et
al, JNCI 99: 1782-1792, 2007.

Carcinoma In Situ

Invasive Breast Carcinoma

Paget's disease of the nipple

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%

3 Invasive lobular carcinoma 10%

4 Rare cancers (adenoid cystic, squamous cell,

apocrine)

Invasive ductal carcinoma

Infiltrating lobular carcinoma

 Blood

vessel invasion

Diagnosing breast cancer

Triple assessment

Clinical

Age
Examination

Imaging

Ultrasound

Pathology

Mammography

Fine needle aspiration

cytology

MRI

Core-cut biopsy

Clinical Presentation
New

lumps or a thickening in the

breast or under the arm
Nipple tenderness, discharge, or
physical changes
Skin irritation or changes
(puckers, dimples, scaliness, or
new creases)

Symptoms that may indicate breast

cancer

Lumps in the breast: single, hard and painless, irregular in shape

Lumps in the armpit

Breast pain: seldom (most the menstrual cycle, cyclic mastalgia)

Bleeding or discharge from the nipple (5%)

Involution or inversion of the nipple

Swelling of the arm (lymphedema)

Dimpling, ulceration of skin

Changes in size or shape of the breast

Symptoms of secondary tumors

Lump
A breast lump is most often the clinical problem that causes women to
seek treatment and remain the most common presentation of breast
carcinoma. 65% of breast cancer cases.
Other less frequent presenting signs and symptoms of breast cancer
include (1) breast enlargement or asymmetry; (2) nipple changes,
retraction, or discharge; (3) ulceration or erythema of the skin of the
breast; (4) an axillary mass; and (5) musculoskeletal discomfort.
However, some of women presenting with breast complaints have no
physical signs of breast pathology. Breast pain usually is associated
with benign disease.

Changes in the skin of the breast

(DPUSE)
Dimpling: skin retraction, tumors
deep within the substance of the
breast that involves the Coopers
ligaments)
Peau dorange: edema of the breast.
Usually obstruction of the dermal
lymphatics with tumor, extensive
axillary LN involvement related
met tumor, primary disease of the
axillary nodes, axillary dissection.
(also after irradiation of the
breast).

Ulceration: in advanced case, the tumor may involve

the skin, leading to it.
Satellite change: tumor cells enter the lymphatic
vessels and form masses around the primary site.

Erythema inflammatory breast cancer, usually

involves the entire breast and is distinguished from
the inflammation due to infection by the absence of
breast tenderness and fever.

The nipple change

Nipple retraction tumor involves the tissue beneath
the nipple.
Bleeding:
Eczematous change: Paget's
Changes in the character of the skin.

Lymph nodes

Breast self-examination

Encourage
Adverse

effect: a lifetime of
uncertainty and anxiety for the
patient (of proven harm!)
Controversy

Mammography

Annual

screening mammography beginning

at age 40 years is recommended in the
United States
Mammography is shown to reduce mortality
from breast cancer by as much as 44%
American Cancer Society (ACS) 1997

Aged > 40 Annual mammogram

Screening Mammography (cont.)

Invasive cancer (4 mm)

Malignant microcalcifications

Ultrasonography
Ultrasonography

is an important
method of resolving equivocal
mammography findings, defining cystic
masses, and demonstrating the
echogenic qualities of specific solid
abnormalities.
Breast cysts are well circumscribed,
with smooth margins and an echo-free
center
Benign breast masses usually show
smooth contours, round or oval shapes,
weak internal echoes, and well-defined
anterior and posterior margins
Breast cancer characteristically has

MRI
High

sensitivity (94 100%)

Low specificity (37 97%)
Better screening tool than
mammography in high-risk
populations
Expensive, invasive and more
time consuming

Breast Biopsy
1. Fine-needle aspiration (FNA) biopsy
Sensitivity: 65 98%
Specificity: 34 100%
False-positive Rate: 0.17%
2. Core-needle biopsy
Automated biopsy gun (14-guage, 5 core samples for mass
and 5-10 for microcalcification)
Directional vacuum-assisted biopsy (Mammotome, EnCore)
Stereotactic Core Biopsy
Nonpalpable Lesion
Sensitivity: 92 100%
Nonpalpable Lesion
Imaging-guide Needle Localization
3. Incisional or Excisional Biopsy

Biomarkers and Circulatory

tumor cells

Carcinoembryonic antigen (CEA): positive rate 20%70%.

The MUC -1 gene product (CA15-3: positive 33-60%;

CA27.29).(Ch 1q21-24).

The HER-2/neuextrocellular domain (Ch 17q11-12).

20-30% overexpression.

New serum tumor markers (uPA urokinase

plasminogen activator; PAI-1, plasminogen
activator inhibitor-1).

Circulatory tumor cells (CTC), 5 or more CTC cells in

the blood of patients with MBC.

Comparative frequency of fibrocystic

changes, fibroadenomas, and carcinomas
by age groups

Staging
TNM
Histologic

type (DCIS. LDIS, IBC)

Hormone receptors (ER,PR)
Oncogenes (Her-2)
Staging procedures

TNM staging

TNM 'Staging' takes into account

the size of the tumour (T);
whether the lymph nodes (N) are affected and;
whether the tumor has matastasized (M) anywhere
else.

The TNM system for staging is a frequently used

staging system used all over the world.

More likely to use this staging system because it

describes stage more accurately than others.

Treat breast cancer according to the staging and

grade.

The T0 and Tis Stage

Tx: primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis: Carcinoma in situ
Tis (DCIS), Ductal carcinoma in situ
Tis (LCIS), lobular carcinoma in situ
Tis (Pagets), pagets disease of the
nipple with
no tumor.
Modified from American Joint Committee on Cancer: AJCC
Cancer Staging Manual, 6th ed. New York: Springer, 2002,
pp 227228.

T1 Stage

T1mic:

<0.1 cm
T1a:>0.1- 0.5 cm
T1b: >0.5- 1.0 cm
T1c: >1.0- 2.0 cm

T2 Stage
T2:

> 2.0 - 5.0

T3 Stage
T3:

cm

>5.0

T4 Stage
Tumor of any size with direct extension to (a)
chest wall or (b) skin, only as described
below
T4a: The tumor is fixed to the chest wall
T4b: The tumor is fixed to the skin
T4c: T4a+T4b
T4d: inflammatory carcinoma (red,
swollen,and painful to the touch)

The N stage (clinical regional LN

Nx Regional lymph nodes cannot be assessed (e.g., previously

removed) .

N0: No cancer cells found in any LN.

N1: Metastasis to movable ipsilateral axillary LN.

N2:
N2a:Met in ipsilateral axillary LN fixed or matted or to other
structures,
N2b:Met only in clinically apparenta ipsilateral internal mammary
LN and in the absence of clinically evident axillary LN met.

N3:
N3a:Met in ipsilateral infraclavicular LN.
N3b: Met in ipsilateral internal mammary LN and axillary LN.
N3c: Metastasis in ipsilateral supraclavicular LN.

The N stage (pathologic regional LN

pNx Regional LN cannot be assessed (e.g.,

previously removed)
pN0: No regional LN met histologically.
pN1: Met in 1 to 3 axillary LN
pN2: Met in 4 to 9 axillary LN
pN3: Met in 10 or more axillary LN

The M stage (distant

metastasis)
Mx:

Distant metastasis cannot be assessed

M0: No distant metastasis
M1 Distant metastasis.

Stage and Grade

The stage of breast cancer means how far it

has grown and whether it has spread.

The grade means what the cancer cells look

like under the microscope. Breast cancers
can be
grade 1 (Low grade or slow growing)
grade 2( Intermediate grade )
grade 3 (High grade or fast growing)

Stage 0. Tis, N0, M0.

Stage I. T1 N0, M0.
When the cancer has spread beyond a milk duct or
lobe, but not outside the breast. The tumor size for
this stage is equal to or less than 2 cm.
The tumour is no more than 2 cm across (T1)
The LNin the armpit are not affected
The cancer has not spread

Stage II

This is divided into two groups

Stage IIA : T0,N1,M0; T1,N1,M0; T2,N0,M0;

T1,N1,M0 : The tumour is less than 2 cm, the LN under the arm
contain cancer but are not stuck to each other and the cancer has
not spread.
T0,N1,M0: Although no tumour is seen in the breast, the LN under
the arm contain cancer cells but are not stuck together, and there is
no sign of spread to other parts of the body.
T2,N0,M0: The tumour is less than 5 cm, there are no cancer cells
in LN in the armpit and the cancer has not spread.

Stage IIB: T2,N1,M0; T3,N0,M0

T2,N1,M0 : The tumour is less than 5 cm and the LN under the arm
contain cancer cells but are not stuck to each other, and the cancer
has not spread or
T3,N0,M0 : The tumour is bigger than 5 cm across, there are no
cancer cells in the lymph nodes in the armpit and the cancer has not
spread

Stage III
Stage IIIA: T0,N2,M0; T1,N2,M0; T2,N2,M0;T3,N1,M0;T3,N2,M0.
Although no tumour is seen in the breast, the lymph nodes
under the arm contain cancer cells and are stuck together,
but there is no sign of cancer spread or
The tumour is 5 cm or less, the lymph nodes in the armpit
contain cancer cells and are stuck to each other, but the
cancer has not spread elsewhereor
The tumour is more than 5 cm, the lymph nodes in the
armpit contain cancer cells and may be stuck together, but
there is no further spread.
Stage IIIB: T4,N0,M0; T4,N1,M0; T4,N2,M0.
The tumour is fixed to the skin or chest wall, the lymph
nodes may or may not contain cancer cells, but there is no
further spread.
Stage IIIC: Ant T, N3, M0.
The tumour can be any size and has spread to lymph nodes
in the armpit and under the breast bone, or to nodes above

Stage IV

Stage IV. Ant T, any N, M1.

Metastatic cancer, which is cancer that has spread to other
more distantorgans of the body.
Frequent metastatic sites for breast cancer are the bones,
lungs, liver or brain. Stage IV is also the classification given
to inflammatory breast cancer or breast cancer that has
spread to the lymph nodes in the neck near the collarbone.

The tumour can be any size

The lymph nodes may or may not contain cancer cells

The cancer has spread or metastasised to other parts of the

body such as the lungs, liver or bones

Survival rate and prognosis

factors
Stage
year(%)
Stage
Stage
Stage
Stage

Survival rate at 8
90
70
40
10

Stage Classifications for

Early Stage Disease
Stage 0 Tis N0 M0
Stage I
T1 N0 M0
Stage IIA
T0 N1 M0
T1 N1 M0
T2 N0 M0
Stage IIB
T2 N1 M0

Singletary SE, et al. J Clin Oncol. 2002;20:3576-3577.

Locally Advanced Breast Cancer

LABC
This means the cancer has not spread to
another part of the body but may be:
Bigger

than 5 cm across
Growing into the skin or muscle of the
chest
Present in the lymph nodes in the armpit,
and these lymph nodes are either stuck to
each other, or other structures ( N2)

Prognostic Factors that

Influence Survival

Younger age at diagnosis

Tumor size at diagnosis
Number of nodes with metastasis
Histologic grade of primary tumor
Hormone and HER2 receptor
status

merican Cancer Society. Breast Cancer Facts and Figures 2003-2004.

Surgical options in breast cancer

Breast-Conserving Surgery (BCS): an operation to remove the

cancer but not the breast itself. some of the lymph nodes that may
be removed. and radiation therapy is usually given after surgery for
six to eight weeks.
Segmental mastectomy: also called a partial mastectomy or
quadrantectomy. to remove more breast tissue than with a
lumpectomy. The cancerous area and a surrounding margin of
normal tissue are removed.

Surgical options in breast cancer

(cont.)

Total mastectomy: also called a simple

mastectomy.
to remove the whole breast that has cancer .

Modified radical mastectomy: to remove the

whole breast that has cancer, many of the
lymph nodes under the arm, the lining over
the chest muscles, and sometimes, part of
the chest muscles. Auchincloss (left the
pectoral muscle behind) and Patey (1848)
(remove the pectoralis minor muscles).

Radical mastectomy (rarely done): Halsted

and Meyer reported (1894) . to remove the
breast that has cancer, chest wall muscles
under the breast, and complete dissection of
axillary LD levels I to III, the long thoracic n.
and the thoracodosal neurovascular bundle.

Surgical options in breast cancer

Prophylactic mastectomy: is preventive removal of the

breast to lower the risk of breast cancer in high-risk people.

Prophylactic ovary removal. is a preventive surgery that

lowers the amount of estrogen in the body, making it harder
for estrogen to stimulate the development of breast cancer.

Breast reconstruction. is the rebuilding of the breast after

mastectomy and sometimes lumpectomy. Reconstruction
can take place at the same time as cancer-removing surgery,
or months to years later. Some women decide not to have
reconstruction and opt for a prosthesis instead.

Axillary Lymph Node

Dissection
Goals

Accurate staging
Regional control
Survival advantage?
No

benefit in removing healthy

lymph nodes

Is

complete node dissection

necessary for staging?

Sentinel node

The sentinel nodes are the first nodes through which

lymphatic fluid flows from a tumor. In other words, the
sentinel nodes are like the gatekeepers to the rest of
the lymph nodes.

Sentinel Lymph Node Biopsy as a Substitute

for Axillary Lymph Node Dissection

Standard

practice in U.S.A. and Europe

Proven accurate method for detection of clinically
occult node metastases
Can be used to detect lymph node metastases in
patients with a clinically negative axilla
Technique requires multidisciplinary participation
and validation

Sentinel Node Biopsy

isosulfan blue dye

(Lymphazurin) is
injected in a similar
fashion

Breast cancers suitable for conservation

surgery
Single

clinical and mammographic

lesion
Tumor 4 cm
No local advancement (T1, T2 < 4
cm), extensive nodal involvement
(No, N1), or metastases (M0)
Tumor > 4 cm in a large breast

Radiation Therapy

is mandatory following breast-conserving surgery.

Whole-breast radiation following breast-conserving
surgery reduces chance of local recurrence by about
two-thirds.

Is considered appropriate for patients at high risk of

recurrence after mastectomy such as (T 5 cm, N(+)
4, involvement of the pectoralis muscle)

Systemic Adjuvant Therapy

Aim to prevent or delay distant metastases.

1.

Chemotherapy

2.

Hormonal therapy

3.

Targeted therapy

. Is

based on two principles: Fisrt there is a burst of mitotic

activity in met sites after a primary tumor is removed; secondly,
breast cancer is a systemic disease characterized by widespread
early occult met, which usually antedates diagnosis.

. Tamoxifen
. The

is beneficial for ER-positive breast cancer.

benefit of tamoxifen and chemotherapy is additive, but must

be given sequentially