The breast parenchyma consists of a branching duct system of 15 to

20 pyramidal shape lobes, bound together by the interlobular

connective tissue. The suspensory ligaments, extend from the
interlobular connective tissue to attach to the dermis.
Breast Tail = part of the mammary gland may extend along the
inferolateral edge of the pectoralis major toward the axilla (armpit),
forming an axillary tail (of Spence). This portion of breast tissue is in the
upper-outer quadrant of the breast which is important because 50% of
breast cancer is located in this quadrant and in the axillary tail
Each ductal system drains through a separate main duct, the lactiferous duct,
which terminates and exits the breast at the nipple via a secretory pore. the
large and intermediate (interlobular) ducts. The ducts are continuous with
the functional units of the breast, the terminal duct lobular units (TDLU). The
TDLU consists of the intralobular duct which end as ductules, which
differentiate into the secretory units or acini during lactation
Axillary nodes: from 20 to 30 and are organized in 5 groups based on their
position within the axilla: 1) pectoral nodes, along the lateral border of the
pectoralis major m.; 2) lateral nodes, located along the distal axillary v.; 3)
central nodes, centrally located along axillary v.; 4) subscapular nodes, located
along the subscapular v. and its tributaries; 5) apical nodes, located at the apex
of axilla
WHAT IS BREAST CANCER?
o BC occurs when cells in the breast tissue divide
and grow without control. In a healthy body, the
cell cycle is the natural mechanism that
regulates the creation, growth, and death of
cells. When the normal cell regulators
malfunction and cells do not die at the proper
rate, there is a failure of apoptosis
(programmed cell death) and cell growth goes
unchecked. As a result, cancer begins to
develop as cells divide without control,
accumulating into a mass of extra tissue called
a malignant tumor.
o As a tumor grows, it elicits new capillary growth
(angiogenesis) from the surrounding normal tissues
to feed itself. Unregulated angiogenesis can facilitate
the growth of cancer throughout the body.
o Cancer cells have the ability to leave the original tumor
site, travel to distant locations, and recolonize (process
is called metastasis). Although, these traveling cancer
cells do not always survive beyond the tumor, if they do
survive, the cancer cells will again begin to divide
abnormally and will create tumors in each new location.
The patient will eventually die of the disease when vital
organs such as the liver or lungs are invaded, overtaken,
and destroyed.
o Metastatic spread is not a random mechanical
phenomenon but requires systematic interaction among
breast cells, stroma, and surrounding normal tissue at
both primary and metastatic sites. Adhesion molecules,
local mediators, hormones, and growth factors must all
act for metastases to develop.
o Cancerous tumors in the breast usually grow
slowly. It is thought that by the time a tumor is
large enough to be felt as a lump, it may have
been growing for as long as 10 years. This has
lead to the belief that undetectable
micrometastasis may have already occurred
by the time of the diagnosis. Therefore,
preventative measures such as diet,
supplementation, and exercise are the primary
defensive tools against the development of
cancer.
o Early diagnosis is the single best way to lower
the risk of dying from BC → can be
accomplished with simple monthly self exams,
screening mammography, and clinical exams.
o BC is the most common malignancy in women.
o Rarely diagnosed in women younger than age 25 → a
peak around the age of menopause → older women are
still at increasing risk over time.
o About 1 in 8 women in the US and Canada will develop
BC. This incidence is similar for many European
countries → much less common in Asia.
o The incidence of BC has been rising steadily over the
past decade→ while mortality did not increase due to
early detection.
o Of the new patients diagnosed with invasive BC in 1990s,
75 to 80% will have early disease (clinical Stage I or II),
→ and ≈ 2/3 of them will have N (-)ve axilla.
o BC is more common in Lt > Rt.
Side.
o UO 39% > Central 29% > UI 14%
>LO 8% > LI 5% → amount of
breast tissue.
o BilateralBC → 1 - 2%
simultaneous; 5 - 8% Metachronus.
 .Risk Factors for BC
A specific cause has not been identified, → however, there
are risk factors that increase the likelihood of BC :
o Maternal relative with BC. (mother or sister or aunt),
particularly at a younger age.
o BRCA1 and BRCA2 genes. The incidence of the BRCA1
gene on chromosome 17 may be 1 in 800 women. The
BRCA2 gene on chromosome 13 is less frequent but
associated with early onset BC. The presence of these
genes may explain some of the familial cases, and may
be the etiology for about 1% of BC overall.
o Longer reproductive span (earlier menarche and/or a
later menopause) → increasing the length of
reproductive years.
o Obesity and increased dietary fat intake is a risk.
 Risk Factors for BC (2)
o Nulliparity.
o Later age at first pregnancy (first child over age 30).
o Atypical epithelial hyperplasia. Although fibrocystic
changes that produce benign breast "lumps" are not
premalignant, the presence of atypical changes in ductular
epithelium does increase the risk.
o Previous BC (opposite breast) and Previous endometrial
adenocarcinoma.
o Others : ionizing radiation, long-term postmenopausal
estrogen-replacement therapy (ERT), and alcohol
consumption.
o Familial BC syndromes, including the breast–
cancer syndrome, the Li–Fraumeni syndrome, and
ovarian
Cowden's disease
Aside from the genetic predisposition, the common factor
in many of these risks is increased endogenous estrogen
exposure over a long time.
 Biology
o The recent identification and cloning of BRCA1 and
BRCA2 has expanded our knowledge of familial BC.
Germ-line mutations in these two genes are associated
with a 50 - 85 % lifetime risk of BC, ovarian cancer, or
both →Tests for these mutations exist.
o All BC have somatic genetic abnormalities in several
genes (including p53, bcl-2, c-myc, and c-myb) and in
some cancers normal genes or gene products (HER-2/
neu and cyclin D1) are overexpressed. However, the
number and types of mutations necessary for the
development of sporadic BC are not known.
 Biology (2)
o Many factors that stimulate or inhibit growth influence
the growth and proliferation of BC cells. Gonadal steroid
hormones (estrogens, progestins, and androgens),
growth factors (epidermal growth factor, transforming
growth factors and , and insulin-like growth factors I and
II), and various cytokines and lymphokines influence
the behavior and phenotypic expression of breast cells.
For instance, production of parathyroid hormone–related
protein, prostaglandin E, or interleukin-6 by the tumor
leads to the development of osseous metastases.
 Pathology.

.Primary Metastatic.

Epithelial Lining Stroma.

Carcinomas Sarcomas

BCs are derived from the epithelial cells that line the
TDLU.
 Classification of invasive BC.
o The most commonly used classification of invasive BC
divides them into ductal and lobular types → based on the
belief that ductal Ca. arose from ducts and lobular Ca. from
lobules. We now know that invasive ductal and lobular
BC both arise from the TDLU, and this terminology is no
longer appropriate.
o Some tumors show distinct patterns of growth and cellular
morphology, and on this basis certain types of BC can be
identified → Invasive Ca. of Special Type, while the
remainder are considered to be of no special type. This
classification has clinical relevance in that certain special
type tumors have a much better prognosis than tumors that
are of no special type [in Node (-)ve Patients].
o The "NOS" categories contain Ca. not easily classified into
other histologic types or Ca. for which minimal tissue was
available for diagnosis.
90% Originate from Lactiferous Ducts.
10% Originate from Peripheral/Terminal Ducts.

• Infiltrating Duct Ca (NOS) 52.0%

• Medullary 6.0%
• Lobular 5.0%
• Mucinous 2.5%
• Tubular 1.2%
• Adenocystic 0.4%
• Papillary 0.3%
• Carcinosarcoma 0.2
• Combination with IDC %
• Other Combinations 28.0
• (Very rarely → Sq. C. Ca; Metaplastc; Apocrine & %
Giant C. Ca.)
3.0
• %
• Paget’s Dis. (Alone/in Comb) 4.6%
DCIS
The irregular mass lesion seen here is an IDC of breast.
The center is very firm (scirrhous) and white because of
the desmoplasia. There are areas of yellowish necrosis in
the portions of neoplasm infiltrating into the surrounding
breast. Such tumors appear very firm and non-mobile on
physical exam.
IDC → Note the infiltration of ill-defined glands into the
surrounding collagenous stroma. There is also a small
microcalcification, a finding that could be seen by
mammography. About 65-80% of BC are of
this type
Lobular CIS consists of a neoplastic proliferation
of cells in the terminal breast ducts and acini. The
cells are small and round. Though these lesions
are low grade, there is a 30% risk for
development of invasive carcinoma in the same or
the opposite breast.
Medullary Type (lymphoid stroma is present)
.
Infiltrating Lobular Type
Arises in the terminal ductules. About 5 to 10% of BCs
are of this type. There is about a 20% chance that the
opposite breast will also be involved, and many of
them arise multicentrically in the same breast. At high
magnification, the characteristic "Indian file" strands
of ILC cells are seen in the fibrous stroma.
Pleomorphism is not great.
 Mucinous Type
colloid, Note the abundant bluish mucin. The Ca cells =
appear to be floating in the mucin. → tends to occur in
older women and is slower growing, and if it is the
predominant histologic pattern present, then the
.prognosis is
Tubular Type
Ciribriform Type
Histologic Type Frequency (%) 5-year Survival (%)
IDC 63.6 79

ILC 5.9 84

IDC & ILC 1.6 85

Medullary 2.8 82

Mucinous 2.1 95

Comedocarcinoma 1.4 87

Paget's Disease 1.0 79

Papillary 0.8 96

Tubular 0.6 96

Adenocarcinoma, NOS 7.5 65

Carcinoma, NOS 3.5 62

Tumor differentiation
Among the cancers of no special type, prognostic
information can be gainedby grading the degree of
differentiation of the tumor. Degrees of glandular
formation, nuclear pleomorphism, and frequency of
mitoses are scored from 1 to 3. For example, a tumor with
many glands would score 1 whereas a tumor with no
glands would score 3. These values are combined and
converted into three groups: grade I (score 3-5), grade II
(scores 6 and 7), and grade III (scores 8 and 9). This
derived histological grade (often known as the Scarff,
Bloom, and Richardson grade) → is an important predictor
of both disease free and overall survival.
Gr. I = 10%; Gr II. = 50%; Gr. III = 40%.
Tubular Formation* Score.
> 75% 1
10 – 75% 2
< 10% 3
Nuclear Pleomorphism. Score.
Small Uniform Cells. 1
Moderate Increase in Size & Variation. 2
Marked Variation. 3
Mitotic Count/ 10 HPF. Score.
7≥ 1
8 - 14 2
≥ 15 3
*% of BC Composed of Tubular
Structure.
 Tumor Spread:
❑ Direct.
❑ Lymphatic Channels.
❑ Blood-borne Metastatses : →
Skin; Bone; Liver; Lung and Brain.
Lymph Node Metastases:
o Detected in 55-70% of Cases at Diagnosis.
o Clinically Non-palpable Axillary LNs → 40% (+)ve
at histologic Exam.
o % of (+)ve LN → Increases with Tumor Size;
Fast Growing Tumors & High Histologic Gr.
o Int. Mammary LNs → (+)ve in 25% of Inner
Quad. Lesions & 15% in Outer Quad. Lesions
And Rarely Involved in (-)ve Axilla.
Patient Evaluation.
➢ 1- Local Symptoms : (Onset & Course).
➢ Breast : Mass (90% of Cases); Pain.
➢ Skin : Changes.
➢ Nipple : Discharge or
Retraction. : Mass & Pain.
➢ Axilla : Swelling.
➢ ➢ Arm
2- Symptoms of Dissemination.
➢ 3- Medical History : Breast Diseases & Prior
Biopsies.
Patient Evaluation (2).
➢ 4- Reproductive History :
➢ Menses : Age of menarche; Regularity;
Frequency; Duration and Age of Menopause.
➢ Pregnancies : Age of 1st Preg.; No. of
Preg. (full term & abortions) and No. of
Children.
➢ Breast Feeding.
➢ Hormonal Use : Including C.C.P.
➢ 5- Family History :
Degree; No.; Age of Diagnosis & Deaths due to
BC.
 .Physical Examination
□ Breast
Mass :
Size (cm).
Site (Clock
position &
distance
from areola).
Consistency.
Fixation
(Skin;
Pectoralis
Muscle &
Chest wall).
□ Skin Changes : (1-3 =
T4a).
1)Edema (including peau d’orange).
2)Ulceration. 3) Satellite Nodules.
4) Erythema. 5) Dimpling.
□ Nipple
Changes : 2) Erosion. 3)
1) Retraction.
4) Discharge : Color & Location.
□ Discoloration.
Nodes :
1) Axillary : Number; size & Fixation.
2) Supraclavicular. 3)
Infraclavicular.
Dimpling of Skin
Provocated Dimpling of Skin
Nipple Retraction (Rt.
)
En
Nipple Discharge :
Is the second most common sign in Breast Ca. It
is a manifestation of benign breast disease in
approximately 90% of cases, however, in females
>50 years, it is more likely representing a
cancerous condition.
Types : * Milky * Purulent * Multicolored &
Sticky → almost Benign. *Serous 5%
* Serosanguineous 15% * Bloody
* Watery 50% (chance of Ca.). 20%
Pretreatment Staging Procedures:

o Laboratory : CBC; Renal; Liver Functions.

o Radiologic : Mammography; CXR; Liver
Scan (US or CT)
o Isotopic Bone Scan : CS ≥ II (In Stage I if
signs or biochemical tests are abnormal) →
Plain X-ray Correlation.
o BM Aspiration : Unexplained cytopenia or
leukoerythroblastic blood smear.
 .Mammography
o The most sensitive and specific method to detect BC
(75% Sensitivity & 90% Specificity).
o It is performed by compressing each breast between
metal plates and producing an image of the breast on a
radiographic film.
o Current mammographic methods employ very small
amounts of radiation, which cumulatively are not enough
to be a hazard even with yearly mammographic
examinations.
o Mammography can detect masses that are not palpable,
because they have a density greater than the
surrounding breast tissue. The presence of breast
implants makes it difficult to see lesions in the breast
mammographically.
 Mammographic Features of
.Malignancy
Indications of Malignancy are :
• Soft Tissue masses : A speculated soft tissue
mass is the most specific mamm. feature of malig.
with an almost 99% chance of representing
cancer (1/3 of noncalcified cancers).Less
commonly, irregularly outlined masses (25%),
round, oval or lobulated masses with indistinct
borders (25%), well defined solid masses (10%) or
areas of architectural distortion of dense tissue
(5%).
3 signs of suspected malignancy are described: an abnormal opacity
with an hyperdense center; ill-delimited outline, as well as an
irregular, even speculated aspect of its contour.
This mammogram demonstrates a mass lesion with
tiny peripheral calcifications that was a carcinoma
• Clustered Microcalcifications : Approx. seen in
60% of cancers. Calcium particles of various size
and shape measuring 100 microns to 1 mm in
diameter and numbering > 4-5/cm3. They
represent intraductal calcifications in areas of
necrosis. Microcalcifications could be Linear
branching e.g. in Comedoca. (higher predictive
value for malignancy), or Granular in shape.
Additional Magnification Views of the tumor site
are needed if breast-conserving treatment is to be
considered.
NB: (-)ve Mammogram in the presence of a suspicious
lesion is not a justification to avoid biopsy.
 Indications of Mammography :
❖ Screening : * Age 40-50ys → Every 1-2 years.
*Age > 50 ys. → yearly.
❖ Symptomatic Women with Breast Mass :
Should precede a diagnostic procedure (Extent &
Multicent.).
❖ Patient with Proven Cancer (Follow-up) :
Evaluate Contralat. Breast → at least yearly.
Evaluate Ipsilat. Breast for other
suspicious areas.
Evaluate Tumor Bed for clearance of all
microcalc. following conservative ttt. and follow-up.
Any New or Previously Unevaluated
Breast Mass in any female of any age
that has a Dominant Characters → Must
be biopsied without delay.
 TYPES OF BIOPSIES
Two general categories of biopsies are used
to diagnose BC These are:
• Needle biopsies: which include core
needle biopsy and fine needle aspiration.
• Open biopsies: which include excisional
biopsy (including wire localization) and
incisional biopsy.
• FNA. : 87% Sensitivity, Fast, Painless
Efficient, Outpatient, No Scar. However, will
not distinguish CIS from Invasive Ca., No
Hist. Details, False (-)ve in 4-10% (Fibrotic
Tu.; ILCa; Tubular & Cribriform types). And
Requires Expert Cytopathologist.
• Core Biopsy : Advantages are the
same as FNA + More Hist. Details and can
be read by any Pathologist.
 A Core Needle Biopsy using:
• Stereotactic Mammography (using Biopsy Gun) entails
first placing a woman on her stomach on a mammography
table with the affected breast fitted through a hole in the
table. Then, as in a diagnostic mammogram, the breast is
compressed so it will remain in place and the equipment
can record an accurate image. Calculations are made
based on this image, and a biopsy device containing a
needle automatically takes a number of tissue samples
from the affected area in the breast. Multiple samples
increase the chances of an accurate diagnosis. This
procedure involves little pain because the device inserts
and removes the needle very quickly.
• US Guided entails a women lying on her back and the
doctor holding an ultrasound transducer against the breast.
The transducer makes an image of the area to be sampled,
allowing the doctor to follow the needle as it enters the
breast and reaches the abnormal area. The needle is then
inserted by hand and a sample of tissue is removed.
Excisional Biopsy.
An excisional biopsy is the most accurate method
for diagnosing BC. It is also referred to as
"lumpectomy" or "partial mastectomy." An
excisional biopsy is generally done under a local
anesthetic. During the procedure, the surgeon
makes an incision in the breast and removes the
entire suspicious area and a small amount of
surrounding normal tissue. Most women are
able to have a biopsy and return home the same
day.
 Excisional Biopsy as a Surgical Treatment
o To diagnose cancer. However, it can also serve as
definitive surgery by removing the entire tumor plus a
surrounding amount of normal tissue (a margin) and
possibly the axillary lymph nodes.
o Advantages: It provides a larger sample size, ensuring far
fewer false negative results, and provides accurate
information on factors such as tumor size, tumor grade,
and the presence of estrogen receptors, all of which are
key factors in deciding on a treatment plan.
o Disadvantages: It is a far more extensive procedure than
a needle biopsy. If a large amount of tissue is removed,
the appearance and feel of the breast may also be
changed. An excisional biopsy is also expensive and has a
longer, more painful recovery period.
Wire Localization for Nonpalpable
Lesions.
o Is difficult to locate during an excisional biopsy.
Therefore, → use a mamm. or US image for direction
and a surgeon inserts a very thin wire into the breast as
a guide to identify the breast tissue that requires
removal. The surgeon then removes the abnormal area.

o Once the nonpalpable mass is removed, the tissue is x-

rayed immediately. This allows matching the suspicious
areas on a mamm. with those in the biopsy tissue. If
the areas do not match, → two options. 1- to make an
additional attempt to remove the correct tissue. 2- to
wait and rebiopsy at another time.
Stereotactic automated surgical biopsy
 Frozen Sections:
o Immediately after the tumor is removed → a frozen
section is usually performed. This process entails
freezing a portion of the biopsied tissue and then quickly
cutting a thin slice for the pathologist to analyze under
the microscope. In the past, if a biopsy came back as
positive for cancer, surgical treatment was performed
immediately. Currently, biopsies are prior to and separate
from the definitive surgery. However, immediate results
using frozen sections can help alleviate a woman's
anxiety.
o A high % of false negatives may be produced with frozen
sections. Therefore, frozen section results are only
preliminary and need to be confirmed by a routine fixed
sample, which takes about 2 working days to analyze.
Incisional Biopsy.
Is a surgical procedure done most often on
women with advanced-stage cancer whose
tumors are too large to be removed as an
initial treatment. Only a portion of the tumor
is removed, providing a sufficient amount of
tissue to procure information essential for
developing a treatment plan.
Paget's Disease of the Nipple.
Paget's disease is a rare, slowly growing cancer of the
nipple. → is usually associated with in situ or invasive
cancer. One of the biggest problems with Paget's disease
of the nipple is that its symptoms appear to be harmless. It
is frequently thought to be a skin inflammation or infection,
leading to unfortunate delays in detection and care.
Symptoms of Paget's disease include persistent redness,
itching, oozing, crusting, and fluid discharge of nipple or a
sore on the nipple that will not heal. Typically only one
nipple is affected. Treatment and prognosis for the disease
are directly related to the type and extent of the underlying
cancer.
This photo shows breast cancer cells invading the stratified
squamous epithelium of the nipple. This situation is called
"Paget's disease of the breast." Any "rash" on the nipple is
suspicious for an underlying BC.
T Carcinoma in situ. Tis (DCIS) =Ductal carcinoma in
i situ. Tis (LCIS) = Lobular carcinoma in situ. Tis
(Paget) = Poget's disease of the nipple with no
s tumor.
T Tumor ≤ 2 cm in greatest dimension. T1mic
=
1 Microinvasion ≤ 0.1 cm . T1a = Tumor > 0.1 cm
but not > 0.5 cm. T1b =Tumor > 0.5 cm but not > 1

T2 cm. T1c= Tumor > 1 cm but not > 2 cm.

.cm 5 – 2>

T3 5cm
>

Tumor of any size with direct extension to chest

T4 wall(T4a) or skin (T4b), Both (T4c), Inflamm. Ca
(T4d).
Regional Lymph Nodes (CN).
o N1 = Metastasis in movable ipsilateral axillary lymph node(s)
o N2 = Metastases in ipsilateral axillary lymph nodes fixed or matted,
or in clinically apparent' ipsilateral internal mammary nodes in the
absence of clinically evident axillary lymph node metastasis.

* N2a = Metastasis in ipsilateral axillary lymph nodes fixed to one

another (matted) or to other structures.
* N2b = Metastasis only in clinically apparent' ipsilateral internal
mammary nodes and in the absence of clinically evident axillary
lymph node metastasis.
o N3 = Metastasis in ipsilateral infraclavicular lymph node(s), or in
clinically apparent' ipsilateral internal mammary lymph node(s) and
in the presence of clinically evident axillary lymph node metastasis;
or metastasis in ipsilateral supraclavicular lymph node(s) with or
without axillary or internal mammary lymph node involvement.
* N3a =Metastasis in ipsilateral infraclavicular lymph
* N3b = Metastasis in ipsilateral internal mammary lymph node(s)
and axillary lymph node(s).
* N3c = Metastasis in ipsilateral supraclavicular lymph node(s)
 Stage Grouping
Stage year Survival- year Survival-
5 (%) 7 (%)
0 Tis N0 0’ 99> 99>
I T1 N0 M0 96 92
IIA T0 N1 M0

T1 N1 81 71

T2 N0
IIB T N M0
2 1
T N
3 0
Rules for Use of TNM.

o cT : Physical or Mammographic .
o pT : Measurement of Invasive component (Not In Situ).
o Multiple Simultaneous Ipsilat. Ca. → use the largest
lesion & specify that this is a case of multiple lesions.
o Any Skin Changes other than edema, ulceration &
satellite nodules (Dimpling; Nipple Retraction..etc) →
don’t change T staging.
o Chest Wall includes Ribs, Intercostal Ms. and Serratus
Ant. Ms. (not Pectoral Ms.).
.Rules for Use of TNM (2)
o If there is Doubt concerning the correct T, N, or M
category → the lower (less advanced) one should be
chosen.
o Paget’s dis. of the nipple without an associated tumor
mass → Tis. Lesions with a demonstrable mass
(clinically or pathologically) → T according to the size of
the mass.
o Inflammatory Carcinoma → is a clinicopathologic entity
characterized by Diffuse, Brawny Induration of the skin
of the breast with an Erysipeloid edge, usually without
an underlying palpable mass → due to Embolization of
Dermal Lymphatics.
 Prognostic and Predictive Factors
o Intensive efforts to define an individual
patient's risk of recurrence → have
produced a plethora of potential prognostic
factors, from patient characteristics to
histologic, biochemical, and molecular
characteristics of the tumor.
o The importance of these various prognostic
factors has been the subject of controversy.
▪ Prognostic factors are those that predict
the risk of recurrence or death from BC after
primary surgery.

▪Predictive factors are those that distinguish

between patients who are more or less likely to
have disease response from a given therapy.
Judicious use of prognostic and
predictive factors can help
select most likely to relapse and
those factors can help select
those most likely to benefit from
specific therapies.
 Axillary Lymph Nodes

The most established prognostic factor is

the number of positive axillary L.Ns. based
on at least a level I or II axillary
dissection and a detailed histologic
evaluation. Patients are often grouped as
having negative nodes or positive nodes (1-
3; 4-9 & ≥ 10).
Axillary Lymph Nodes (2):
o The emerging data on the clinical significance of
micrometastases to axillary L.Ns. has provided
the driving force for revisions to the new AJCC
Staging Manual for the staging of breast cancer
pathologic nodal (pN) stage.
o The AJCC Staging Manual (2003) divides ALN
metastasis into * those detected by reverse
transcriptase PCR only, * those with isolated
tumor cells only, * those with micrometastasis
only (size >0.2 mm but not >2 mm), and * those
with other nodal metastases.
☞ Tumor Size
o In many studies the size of the tumor at the
time of surgery has been found to be an
important predictor of recurrence and survival
in patients with BC (level III evidence).
o The influence of size on prognosis appears
to be a continuum, with tumors < 1 cm in
diameter having very low risk, which
a
gradually increases as the size of tumor
the
increases to ≥3 cm.
 Tumor Size
(2):
o Although no precise size can be
identified that differentiates high risk
from low risk of recurrence or death,
→ many studies have used a diameter
of 2 cm as a cutoff point.
☞ Histopathological and Nuclear Grade:
o Multivariate analyses show histopathological grade
to be an important independent predictor on
outcome.
o However, histologic grade was not incorporated
into the modified TNM staging system for BC
(2002).
.Gr Score (%)year Survival-5 year Survival-7
(%)
1 to 5 3 95 90
2 or 7 6 75 65
3 or 8 9 50 45
☞ Histopathologic Subtype:

o Excellent prognosis tumor types include:

Tubular, Cribriform, Medullary,
Mucinous Adenoid cystic
and carcinomas.
o On the other hand, Micropapillary
invasive and Duct carcinomas with
extensive central necrosis or fibrosis,
both are examples of tumor entities with
dismal prognosis.
↳ The St. Gallen Consensus
Conferences (2001) have indicated
tumor type and grade as currently
accepted prognostic and predictive
parameters, clinically useful to guide the
choice of adjuvant therapy.
 :Hormone Receptor (HR) Status
o BC in which the cells express ER in their nuclei
will have a better prognosis → because such
positive neoplastic cells are better differentiated,
and they can respond to hormonal manipulation.

o Almost 75% of ER (+)ve BC will respond to

hormonal therapy, whereas < 5% of ER (-)ve
respond.
o The significance of PR positivity in a BC is less
well understood. In general, cancers that are ER
positive will also be PR positive. However,
carcinomas that are PR (+)ve, but ER (-)ve, may
have a worse prognosis.
☞ Hormone Receptor (HR) Status:
o The influence of HR status on outcome is weaker
than that of tumor size or grade and has been
demonstrated less consistently. However, the ER
status based on IHC techniques is now accepted as
a prognostic factor.
o Hormone receptor status is also the most important
predictive factor for response to systemic endocrine
therapy.
o PR status should be taken into account when
discussing relative risk reductions expected from
endocrine treatment with individual patients.
☞
Age
o Patients < 35 years of age appear to have,
on average, a poorer prognosis than older
patients, → used as a prognostic
indicator. However, the relationship is
poorly defined and difficult
to from the influence of
distinguish
menopausal status and other tumor
features.
o At present, there is insufficient evidence to
justify the incorporation of age as an
independent prognostic factor.
Lymphatic and Vascular Invasion (LVI)
o In several studies of patients with Node
-ve disease, a relationship has been
found between invasion of lymphatic and
blood vessels and ↑ recurrence or
reduced survival.
o However, not all studies have found such
an association, and its practical value as
a prognostic factor is diminished by the
fact that it can be difficult to evaluate and
may have poor reproducibility.
The skin overlying the breast has prominent lymphatic
spaces filled with small metastases from BC. Carcinomas
often metastasize to lymphatics → to the axillary lymph
nodes.
☞ Bone Marrow Involvement
o Is the first site of distant relapse in a high
percentage of women with BC.
o In the last St. Gallen conference (2003),
implementation of BM evaluation into current tumor
risk classification systems was discussed. This is
important especially for Node -ve patients who have
very high rates of DFS & OS. The absence of
detectable tumor cells in the L.Ns. and BM of these
women may indicate a cancer that is truly confined
to the breast or, may reflect host factors that clear
circulating tumor cells effectively.
o Recently, at least 5 matured clinical studies
(3500 pts) → provide evidence for the
independent prognostic value of the presence of
tumor cells in the BM.
o At present, BM evaluation is considered a
diagnostic tool for improved identification of the
individual risk of distant relapse and death
among potentially curable breast cancer
patients.
o However, due to the lack of consensus for a
benchmark technology for tumor cell detection,
the implementation into tumor classifications is
pending, and awaits confirmatory studies.
☞ Biological and Molecular Markers
o Many recent studies have focused on the
potential prognostic and/or predictive role of
newer biological and molecular markers, such
as growth factors and their receptors,
oncogenes and tumor suppressor genes and
their products, proteolytic enzymes,
adhesion molecules, and markers of cellular
proliferation and angiogenesis, among others.

o However, studies of such factors have frequently

yielded conflicting results and clinical confusion.
↳ Tissue Microarray (TMA) is a
procedure whereby a 0.6-mm plug of
paraffin-embedded tissue is extracted.
The core may be sectioned, and multiple
sections can be analyzed by standard
IHC, thereby facilitating studying a panel
of markers on a single specimen. The use
of TMA allowed the investigators to study
a panel of prognostic factors reported to
be of value in previous studies.
 Measures of proliferation
o The amount of DNA contained in the nuclei of BC cells will
provide an indication of their malignant potential. Flow
cytometry is a means for measuring the amount of DNA.
Normal cells → tend to have a single homogenous
population of cells with a "euploid" DNA content. Malignant
cells are less differentiated and have abnormal expression
of DNA content. This is measurable as the degree of
"aneuploidy" by flow cytometry. The prognosis is worse for
Ca. with a greater degree of cellular aneuploidy.
o The most thoroughly evaluated measure of proliferation
has been DNA flow cytometry → measure the DNA ploidy
and the distribution of cells in the cell cycle.
o The p53 oncosuppressor gene has a negative
influence on cell proliferation. Expression of
mutant p53 is frequently seen in breast tumors
and has been significantly related with clinical
outcome. Its prognostic role is currently
not included in decision
making in breast
therapy about cancer. adjuvant
o Studies using antibodies to Ki-67 and
proliferating cell nuclear antigen have shown
encouraging early results but are not
established.
 Growth Factors
o Of these growth factors, the greatest interest has been in
C-erb B2 (HER-2/neu).
o The HER2-neu is identified by staining around the
cytoplasmic membrane of the cells. There is a correlation
between HER2 positivity and high nuclear grade and
aneuploidy, → a specific drug (trastuzumab) is available
as a therapeutic option with HER2 (+)ve BC.
o The overexpression is associated with a higher risk of
recurrence of BC.
o There is evidence that HER-2/neu may be a useful
predictive factor. Several studies suggest that only
patients whose tumors have little or no detectable levels
of HER-2/neu derive considerable benefit from CMF
regimen, and, patients whose tumors have high levels of
HER-2/neu derive greater benefit from dose-intensive
CAF regimen.
o It has also been suggested that HER-2/neu
status may predict response to endocrine
therapy.
o Among patients treated with adjuvant TAM,
those with HER-2/neu +ve tumors tend to
have shorter DF & OS times compared with
patients with low HER-2/neu levels. However,
the data supporting an interaction between
HER-2/neu expression and adjuvant TAM
therapy is not conclusive and patients with
ER(+)ve and HER-2/neu(+)ve cancers
should still receive adjuvant hormonal
therapy
BRCA1 and BRCA2 Mutations

BRCA1 and BRCA2 are familial (inherited) gene mutations that have
been linked to BC. BRCA1 is a tumor suppressor gene located on the
long arm of chromosome 17, and BRCA2 is located on chromosome
13. → play a role in regulating cell growth. When one copy of BRCA1
is inherited in a defective (mutant) form, a woman is predisposed to
breast and ovarian cancer. However, BRCA1 mutations do not appear
critical for the development of the majority of breast and ovarian
cancers. Development of cancer in either organ involves a number of
additional mutations, at least one of which involves the other copy
(allele) of BRCA1. A woman who inherits one mutant allele of BRCA1
from either her mother or father has a greater than 80% risk of
developing breast cancer during her life. While it appears that a high
number of currently identified high-risk families have mutations in
either the BRCA1 or BRCA2 genes, hereditary breast cancer accounts
for only about 5% of all cases of breast cancer.
 Carcinoma In Situ
(CIS).

Ductal. (Precancerous) *Lobular.

Both are Different in Clinical Presentation & Biologic

.Potentials
 DCIS.
o A Proliferation of Malignant Epithelial Cells
Confined to Mammary Ducts & Lobules
the
Without Evidence of Invasion through the
Basement Membrane into Surrounding Stroma.
o Increasing Detection Rate due to Screening
Mammography → from 1-2% up to 15% of
newly diagnosed BC.
o Progression to Invasive Ca. → Uncertain,
approx. 30% progress to Invasive Ca. At 10
years (If Not Treated).
o Clinically : Lump.
Discharge/nipple ± mass.
Paget’s Dis. of the nipple.
Incidental finding (e.g. Biopsy).
o Abnormal Mammogram (mostcommon
presentation now → Clustered Microcalcific.).
o Types : Classified according to
Histopathology; Extent & Biologic Behavior into :
* Comedo.
* Non-Comedo : Cribriform.
Micropapillary
Clining.
Comedocarcinoma pattern, which is characterized by the
presence of rapidly proliferating, high-grade malignant
cells. The cells in the center of the ducts with are often
necrotic and calcify, as shown here. This central necrosis
leads to the gross characteristic of extrusion of cheesy
material from the ducts with pressure (comedone-like).
o Cytologically :
C Type →More Malignant; Higher Proliferation
Rate & more likely to be associated with areas
of Microinvasion.
o Mammography :
* Microcalcifications are linear or coarse
granular in C vs. Fine granular in Non-C.
* Size of the tumor → approximate hist.
Size in
C vs. Smaller size in Non-C types.
o Biologically :
C Type is more associated with Biologic
Markers e.g. Aneuploidy; Overexpression of
Management of DCIS :
o Mastectomy → 98% curative treatment.
o Conserving Therapy → Why ?
Acceptance of CTT in invasive. Ca.
Multicentericity is rare in DCIS.
Identification of very early lesions
using mamm.
a) Excision Alone :
Not recommended & needs further studies with long
term results → L.R in 20% of cases & is associated with
50% invas. & L.R is higher with Comedo > Non-Com.
b) Excision + RT (50 Gy) : → RT appear to decrease L.
However,
R from 10.4 -longer
7.5% & follow-up
Invasive L.Risfrom 10.5 - 2.9%.Also,
needed. →
development in Molecular Biology will
allow prediction of progression to invasive better
o cancer.
The role of Tamoxifen→ not yet established →
needs further clinical trials.
 LCIS.
o A risk factor but Not a precursor lesion.
o Microscopic finding → Solid
proliferation of small cells with small
oval nuclei withlow proliferation
uniformround/ rate;
typically ER (+)ve and
overexpression of HER-2/neu. rarely
o Multicentric in 60-80% of
cases.
o Frequently Bilateral.
o Epidemiology :
* ? incidence. * Whites > Blacks.
* More common in young females (45 ys mean age) →
Due to regression following menopause and Benign
conditions that need biopsy are more common among
premenopausing females.
o Lack both clinical and Mammographic signs → Almost
always an Incidental Diagnosis made on tissue that
was obtained for another purpose).
o LCIS is associated with 7 folds increase in Breast Ca.
Development in both biopsed side & contralateral side
→ most Ca. Are IDCa. And ILCa. in minority of cases,
No path. Factors predictive for the subsequent
development of Invasive Ca. Have been identified.
Management of LCI:
o Bilateral Mastectomies + Immediate
Reconstruction → Option decreasing over
time in USA.
o Careful Observation following biopsy
→Lifetime as the risk
persists
indefinitely→ Exam. Every 4-6 months +
annual mammogram → No need for (-)ve
margins and No role for RT.
Local and Regional
.Treatment of BC
Biologically : it was found that
although there is a Subgroup of
tumors
women that can be Cured
who have by Local
Treatment Alone. Yet BC
Systemic at the time of are that
Diagnosis and
Most
Surgery’s Effect is Limited to Local Control
at Best. → On the basis of this approach,
treatment consisted of Systemic Adjuvant
Therapy coupled with Local Control.
Local treatment was considered the domain of the
surgeon for many years, however,
1- Changes in understanding of the Biology of
the disease.
2- The Detection of Smaller Tumors over
time.
3- Increasing emphasis on Systemic
Therapy.
4- Greater Patient Participation in the Decision-
Making Process.
→ Have radically changed the approach to the
Local Treatment of BC over the last 20 years→
Conservative versus more Radical treatment.
The traditional role of the surgeon in the treatment
of BC has changed. The days when a suspicious
lump meant an immediate trip to the operating
room, Frozen Section Biopsy, and immediate
Radical Mastectomy are Gone. Today, Local
Treatment involves a collaborative effort between
Surgeons, Radiologists, Pathologists, Radiation
Oncologist, and Medical Oncologists all working
with the patient.
 Local Control Principles :
o It is important to remove the tumor with a
rim of normal tissue.
o RT works best ona limited amountof
disease.
o Optimize cosmetic results without
sacrificing survival.
Stage I, and II, breast cancer often
requires a multimodality approach to
treatment. Irrespective of the eventual
procedure selected, the diagnostic biopsy
and surgical procedure that will be used as
1ry treatment should be performed as 2
separate procedures.
o After the presence of a malignancy is
confirmed and histology is determined,
options should be
with the patient
treatment discussed
procedure is selected.
before a therapeutic
o ER and PR protein status should be
determined for the primary tumor
Additional characteristics,
.
pathologicgrade, proliferative activity,
including
and HER2/neu status, are of value.
Surgical Management of
Primary BC.
Radical Mastectomy :
First described in 1894, it includes excision of wide
margin of skin around the tumor → Dissection of
thin flaps → En bloc removal of the breast; Axillary
LNs and Pectoralis Muscles (Major & Minor). It was
the surgical procedure of choice till 1970s
Modified Radical Mastectomy :
= Simple Mastectomy + Removal of Pectoralis Fascia +
Axillary Dissection, preserving the Pectoralis Major ms, the
Pectoralis Minor may be excised, divided or left intact.
Axillary dissection may vary in extent from sampling to
complete dissection. It has superior cosmetic and
functional (Upper Limb) results& easier to reconstruct. Is
not suitable for patients with tumors fixed to Pect. Major or
with bulky axillary LN involvement → Rad. Mast.
 Extended Radical Mastectomy :
= Rad. Mast + resection of IMN en bloc → very extensive
with no survival benefit.

Total (Simple) Mastectomy :

= Removal of the Entire Breast including Nipple-Areolar
complex but without Ax. Dissection or removal of Pect. Ms.
It is indicated in :
o CIS. (<1% incidence of LN involv.).
o Prophylactic : (often of contralateral breast).
o Salvage : Recurrence after CTT (Metast. Free).
o Palliative : patients with bulky breast tumors ±
metastases → to facilitate LC of the breast.
:Total (Simple) Mastectomy
Subcutaneous Mastectomy :
Proposed as Prophylactic & Cosmetic procedure
→ Spares the Nipple-Areolar Complex & leaves
10-20% of breast tissue behind. Disadvantages
include : development of Ca. In remaining portion
and unsatisfactory cosmetic results → very little, if
any, indications for this procedure.
Breast Preservation Procedures :
• The extent of both Breast & Ax. surgery varies.
For Breast Tumors they include
• Lumpectomy (Tumerectomy) :- Removal of the
tumor grossly without attention to margins.
• Wide Excision (Partial Mastectomy/
Tylectomy) :- Excision of the tumor + grossly
normal clean margins.
• Quadrentectomy :- En bloc excision of the
tumor within a quadrant of breast tissue along
with the Pectoralis Fascia & Overlying Skin →
probably more tissue than is necessary in many
cases → worse cosmetic results.
 Trials Revealed :
o Treatment Failure after Surgery is usually due to Systemic
Dissemination of Ca. Cells Before Surgery rather than an
inadequate operative procedures.
o No difference in Survival between Radical & Mod.
Radical Mastectomy.
o No difference in Survival between Radical vs. Simple
Mastectomy + RT.
o Moderate Dose RT was effective in eliminating subclinical
foci of BC after Mastectomy.
These Observations led to Conservative Surgery (CS) i.e.
removal of the tumor bulk surgically followed by → Use
Moderate Doses RT to Eradicate Residual Ca.
 Objections (Local Control):
o Multifocality → Evidence of cancer in
the Vicinity of and in Continuity with the
o tumor.
Multicentericity → IndependentFoci of
Ca. NOT in relation to the primary Tumor.

It was found that BC is Very Commonly Multifocal

and Rarely Multicentric → LR Occurs at or Near
the 1ry Tumor Site in Most Cases.
Risk Factors for LR :
o Young Patient Age (<35 years): By itself & Due to
association with various adverse path. Features (Gr. III
histology; Lymph. Ves. Invasion; ER(-)ve and EIDC).
Although it is a prognostic factor, yet the available data
suggests that it does not seem helpful in selecting the
best form of local treatment. Also the use of adjuvant
systemic CT →Decreased LR after RT.
o Extensive Intraductal Component (EIDC): Defined as
Intraductal Carcinoma Present (>25%) both Within &
Adjacent to the Primary Invasive Tumor. Increases LR
Rate at or Near Primary Tumor Site (Not elsewhere in
Ipsilat. Or Contralat. Breast). Careful attention to
Excising this Histopath. Entity with NEGATIVE Surgical
Margins Should be Employed.
o Lymph.Vessels Invasion & LN Involvement :
Decreases Prognosis & Increases LR → May be
more useful in assessing the Overall Prognosis
rather than selecting local treatment. There is no
reason to believe that LN (+)ve patients should
more often be treated with mastectomy than
with CTT → Most of them will receive Adjuvant
Systemic Treatment
o ILC = IDC. : But ILC due to its diffuse and
apparently discontinuous infiltration → a wide
resection with clearly (-)ve microscopic margins
is advised.
o Microscopic Margins of Resection :
Is of great importance in predicting LR.
Negative Margins = Absence of Ca. Cells directly at an
inked surface (India Ink) → Low LRR & Surviv.
Comparable to Mastectomy, Also with (-)ve Margins →
EIDC was not found to influence LR.
Positive Margins = Tu. Present at inked margin.
Close Margins = Tu. Within 1 mm of inked margin.
Focally (+)ve Margins = Tu. at the margin in < 3 LPF.
Results indicated that low rates of LR for patients with (-
)ve margins whether close or not & whether an EIDC is
present or not. So the presence of EIDC per se should
not be a contraindication to breast CTT. Patients with
EIDC & (+)ve margins → Reexcision of the primary
tumor site in an attempt to obtain (-)ve margins. Also,
patients with No EIDC & only focal margins → CTT +
Boost RT.
 An attempt should be made to remove the tumor
with a Rim of Normal Tissue as Determined by :
o Pathology (e.g.. in Classic Sclerotic IDC → tumor
can be removed with a small rim of 1 cm; in IDC +
EIDC & ILC → more Generous Margin is needed).
o Margins : Examined →Clean; Close or Dirty.
o Post-biopsy Mammography to detect any
residual lesions.

If the Margins & Post-biopsy Mammogram are Clear

→ this Limited Surgery is then Combined with RT
(CTT). If Not Clear or Surgery (Reexcision)
Cannot be done Cosmetically → a Mastectomy
may be Necessary.
The Optimal Operation
is determined by the size of the tumor and the size of the
breast.
o 4 cm was arbitrarily chosen by the NSABP as the
maximum tumor size that could be approached
conservatively because it was considered difficult to
achieve an adequate cosmetic result with larger tumors.
o Some authors found no problem with Breast
Conservation for 4 - 5 cm tumors if the surgery can be
cosmetically performed.
o > 5 cm, the tumor is characterized as T3 and subject to
Neoadjuvant CTh. Bonadonna has shown that many
women can be converted to candidates for breast
conservation with Neoadjuvant CTh.
Reexcision in :
o Mammogram → Residual Microcalc. after Initial
Excision.
o Unknown Margin Status → Failure to perform
Evaluation or (+)ve Margins, especially if the
tumor is >2 cm.
o EIC-positive Tumors unless 1ry excision had
widely (-)ve Margins.
o Tumors which have been grossly incompletely
excised.
 :Patient Selection For CTT
We have to assess :
o Removal of Primary Tumor with
Acceptable Cosmetic Results.
o LR. Following CTT vs. Mastectomy.
o Patient’s Desires and Expectations.
Evaluation of these factors requires a Medical
History; Physical Examination; a detailed
Mammographic Evaluation prior to surgical biopsy
and careful Pathologic Evaluation of the resected
breast specimen.
Absolute Contraindications :
o Pregnancy [1st & 2nd trimesters].
o Diffuse Microcalcifications.
o Two or more gross tumors in separate quadrants.
o Previous RT to the breast.
Relative Contraindications :
o Ratio (Large tumor/Breast ratio)→ depends on the
quadrant involved (inf. Lesions) & depth of the tu. within
the breast.
o Retroareolar Location (patient desires breast
sensation).
o Large Breast → Technical difficulties (immobilization &
dose homogeneity).
o Collagen Vasc. Dis.→ Extensive Fibrosis following RT.
Breast CTT. Consists of :
o Tumor Excision.
o Axillary Dissection.
o Breast Irradiation.

Randomized Trials revealed :

o Equivalent Survival between Mast. Vs. CS + RT.
o LR occurs after prolonged time course in some patients
following CTT vs. most LR tend to occur within the first 3
years after more Radical treatment → May represent
another primary & Needs life long FU.
o Treatment Related Changes tend to stabilize by 3
years following CTT.
o The Amount of Breast Tissue Resected → a major factor
in Cosmetic Results.
The Acceptable Risk of Local Recurrence (LR):
o Will vary from individual to individual. Among all
factors influencing LR, if all gross tumor has
been excised (Resection Margins), the
predictive value of the other factors is low.
Because even a high rate of recurrence in the
breast has not been shown to alter breast
cancer mortality → caution must be exercised in
excluding patients from BCT on the basis of a
small increase in the risk of LR.
o In patients with (+)ve axillary LNs esp.>4, the risk
of distant metastases frequently outweighs the
risk of recurrence in the breast, and they are
also at high risk for chest wall recurrence after
mastectomy.
 The Patient Desire :
o Is a critical in the selection of
therapy in Early BC. local
factor
o Surgical Treatment is Not an Emergency and a
Delay of Several Weeks to Consider Carefully
the Risks and Benefits of the Various Options is
Reasonable.
o For patients who elect or require Mastectomy →
Breast Reconstruction should be discussed
routinely with the patient before definite surgery.
Reconstruction should be offered either
immediately or as a second procedure.
Cosmetic Results :
o The cosmetic results after CTT (CS + RT) are usually
good to excellent. Overall cosmetic results decline
during the first 3 years after treatment but then remain
stable. Measured Features Include : Breast Edema;
Arm Edema; Breast Retraction; Telangiectasia & Overall
Cosmetic Appearance as Judged by the Physician.
Factors associated with a poor outcome are :
o Large Breast Size.
o Large Tumor Size.
o Extensive Surgical Resection.
o RT : 3 field technique; use of Large RT
Fraction Size and the use of Iridium-192 Implant.
o Use of CT especially when given Concomitant. with RT.
Surgery
o Options include BCS + RT, mastectomy plus
reconstruction, and mastectomy alone. Surgical
staging of the axilla should also be performed.
→ Survival is equivalent with any of these options.
o MRM continues to be appropriate for some
patients, BCT has become the preferred method
of treatment for many patients.
o Selection of a local therapeutic approach
depends on the location and size of the lesion,
analysis of the mammogram, breast size, and
the patient's attitude.
o All histologic types of invasive BC may be
treated with BCT → There is debate as to
whether completely clear microscopic margins
are necessary.
o ALND is still considered to be a standard part of
the management because of the significant
prognostic information it imparts and the
increasing refinement in the use of adjuvant
therapies. The standard evaluation usually
involves only a level I and II dissection, thereby
removing a satisfactory number of nodes for
evaluation (at a minimum 6-10) while reducing
morbidity from the procedure.
Types of Axillary Dissection :
o Sampling = Removal of ≥ 1 LNs from the lower axilla
without definition of precise anatomic boundaries.
o Low Axillary Dissection = En bloc excision of Level I of
the axilla (From Latismus Dorsi Ms. Laterally to the lat.
Border of Pect. Minor Ms. medially + Clearing of Axillary
Vein Superiorly).
o Level I & II Dissection = From Latis. Dorsi Lat. To the
Med. Border of Pect. Minor Medially with clearing of
Axillary Vein Superiorly.
o Full Axillary Dissection = Removal of the Entire Axillary
Contents from Latis. Dorsi Lat. To the Subclavious Ms.
Medially + Clearing of Axillary Vein ± Excision of Pect.
Minor → Was for many years the Standard Treatment in
patients with Invas. Breast Ca.
 :The Optimal Extent of ALND
Trials Revealed :
o Overall Survival : In Patients with (-)ve Axilla
→ No Statist. Sig. difference in 10-y
Surviv. between :
Rad. Mastectomy.
Total Mast. + RT to Ax.
Total Mast.
+

Observ. to
Ax.
→
If
o Staging and Skip Metastases :
1. Studies to assess the extent of ALND needed to determine whether
LNs are (-) or (+)ve revealed :
2. Involv. of Level III in absence of Level I&II is Rare.
3. Involv. of Level II in absence of Level I is Variable (Not Definite ).
4. Some authors concluded that Level I Dissect. Provides accurate
Staging Information. However, Most authors concluded that
removal of at least All Level I and some of Level II is required, this
is best defined anatomically rather than by the No. of LNs removed.

5. Local Control :
Also a Level I-II Dissect. Is Effective at providing LC in the Ax.→
<3% LR. More Limited Ax. Sampling → the likelihood of
LR is related to the No. of LNs removed :
No LN removed → 20% 5-y LR. 1-
2 LNs →
10% 5-y LR.
6-10 LNs. → Need to be Removed to Avoid
Misclassification & Optimize LC in the Ax.
Advantages to ALND :
o Accurate Staging : The Number of Involved Ax. LNs
Remains the Single Most Reliable Indicator of
Prognosis → helps to determine Further Treatment.
o A Reliable Treatment of the Axilla (LC) : Few LR. in
patients with dissected histologically (+)ve Ax. LNs.→
RT to the Ax. Is unnecessary following Complete
Dissection.
o Palliation : If Bulky Ax. LNs can be excised → Sparing
the patient to develop a painful edema of UL (due to
invasion of the neurovascular bundle).
Complications :
o Major (Infrequent) : Ax. Vein Thrombosis/Injury & Injury
to Motor Nerves of Ax.
o Minor (More Common) : Seroma; Loss of Sens. In
intercostobrachial n; Shoulder Dysfunction and Edema
of Arm & Breast.
 Recently in view of Increased use of Adjuvant Systemic Therapy.
BCTT; Increased No. of patients with Small Mammographically
Detected Breast Ca. :
ALND. Can be used in only a proportion of patients:
o Will Undergo Mastectomy.
o Clinically Palpable Ax. LNs.
o To obtain Prog. Information in patients with
Favorable Hist. Features
→ (+)ve LNs → Adj. Syst. Therapy.
o Clinical Trials.

ALND. Can be Omitted in patients with very low risk of Ax.

Involvement :
o DCIS./ DCIS with Microinvasion.
o Pure Tubular Ca. < 1 cm in Diameter.
o ± Most patients with tumors > 1-2 cm in diameter who undergo CTT
→ will receive Adj. Syst. Therapy Regardless of Histologic
Nodal Status.

As the value of Biologic Prognostic Factors are established & the use
Sentinel Lymph Node (SLN) Biopsy
o Is defined as the first node in the lymphatic basin
that receives primary lymphatic flow. Studies
have shown that the identification of the SLN is
possible in 92% to 98% of patients. Preliminary
reports demonstrate a 97.5% to 100%
concordance between SNB and complete
ALND.
o Trials on SNB in BC are still ongoing, the
technique has been widely adopted by
surgeons. The development of SNB and the
increasing use of adjuvant systemic therapy
provide a rationale for omission of ALND, but it
has not yet been proven that these approaches
result in equivalent survival and axillary control.
 To Locate the SLN→ a colored dye and/or
radioactive-labeled tracer is injected into
the breast near the tumor. A device called a
scintillation counter determines which LN
is the first node to take up the dye or
tracer.
This LN is then surgically removed and
sent
for pathologic examination.
o Advantages: it is accurate, less traumatic,
and it allows axillary dissections to be done
on only those women whose sentinel nodes
o Disadvantages: fairly new, not widely
available, and its accuracy depends in
large part on the training of the surgeon
doing the procedure. Several ongoing
clinical trials will ultimately determine
whether sentinel node biopsy becomes
part of the standard diagnostic procedure
for breast cancer.
o If the SN is cancer free, it's likely that the
other ALN are cancer free as well.
However, if the SN is positive for cancer,
there is a strong likelihood that other
nodes may also be involved, and a
standard ALND may be required.
:The NIH (2001), Surgical Recommendations
o The diagnosis should be established by FNAC, limited incisional
biopsy or definitive wide local excision.
o The type and placement of incisions can influence greatly the quality
of cosmesis.
o It is appropriate to excise the primary lesion with a normal tissue
margin of approximately 1 cm → to achieve a surgical margin that
is grossly and microscopically uninvolved with tumor. Mark the
specimen for proper orientation and to ink the resection margins.
When margins are grossly involved → further resection is indicated.
Available data are inadequate to determine whether focal
microscopic involvement of a margin $s the risk of local failure after
optimal RT. Because cosmetic result is related to the amount of
tissue excised, unnecessarily wide margins (> 2 cm) should be
avoided.
o A Level I-II ALND should be routine for staging and for prevention of
axillary recurrence → separate incisions → enhance functional and
cosmetic results.
 .Breast
Reconstruction
Mastectomy causes significant Functional and Emotional
Problems → Reconstruction is an important option &
should routinely be discussed before definitive surgery.
o The Goal is to provide a Lasting Mound of Tissue with an
Acceptable Shape, Form and Consistency that is
Reasonably Symmetric with that of the Opposite Breast.
o Absolute Contraindication : Only in Comorbid
Conditions.
o Timing : Immediate (at time of mastectomy) or Delayed
3-6 ms. later (longer delay is possible up to many years).
o Radical Mastectomy Is more difficult to Reconstruct →
Loss of tissue; and tight skin.
Techniques
o Implants : the simplest technique and involves the use of available
tissue and placement of an implant (Inorganic material). Best for
small/median size breast with minimal ptosis → ±Tissue
Expander → if insufficient skin is available to achieve symmetry
with the contralat. Breast to cover the implant. Silicon Gel filled
implants → FDA declared not to be used since 1992
(Contractures, Leak & Connective tissue dis.). Now Saline filled
Implants are used. If Chest Wall RT is desired→ Avoid implants
(high risk of implant loss).
o Autologus Tissue (Flaps) : 1- Myocutaneous Flaps →
Serratus Ant.; Transverse Rectus Abdominus (TRAM) ± Implants.
2- Free Flaps → mainly for delayed reconstruction & need skilled
surgeons.
o Nipple Areola reconstruction : Another secondary procedure
→ Done by tattooing; local flap techniques or full thickness skin
grafts. Avoid the patients own nipple/areola → 2ry Ca. & also
contralat. nipple/areola → Transfer breast tissue to reconstruction
site.
Implants and Tissue Expander
Transverse Rectus Abdominus (TRAM)
THANK YOU