2. INTRODUCTION
Is a modified sweat gland.
Present in both sexes but rudimentary in males.
Is important accessory organ of the female
reproductive system.
Provides nutrition to the newborn in the form of
milk.
3. Anatomy
Lies in the superficial
fascia of the pectoral
region.
A small extension
called the axillary tail of
spence, pierces the deep
fascia and lies in the
axilla.
4. Extent of breast
2/3rd
rests on Pect.
Major while 1/3rd
on
serratus anterior.
Vertically, it extends
from the second rib to
the sixth rib.
Horizontally, it extends
from the lateral border
of sternum to the mid-
axillary line.
5. Deep relations of the breast
Lies on deep fascia/pectoral
fascia covering the pectoralis
major.
Is separated from pectoral fascia
by loose areolar tissue-
retromammary space.
Clinical importance;- if
retromammary space infiltrated.
Fixity of breast
6. Structure of the breast
Can be divided into-
Skin
The parenchyma
The stroma
7. Skin of the breast
It covers the gland
A conical projection called
nipple is present at the level
of fouth intercostal space.
Nipple is pierced by 15-20
lactiferous ducts.
Skin surrounding the base
of nipple is pigmented and
forms the circular area
called areola. Rich in
modified sebaceous glands
8. Parenchyma of breast
Is made up of glandular tissues
which secrete milk.
Gland consists of 15 to 20 lobes.
Each lobe is a cluster of
alveoli/acini, and is drained by
lactiferous duct.
Clinical importance;- Infiltration
of lactiferous ducts and their
consequent fibrosis can cause
retratction or puckering of the
skin
9. Stroma of the breast
It forms the supporting
framework of the gland.
It is partly fibrous and partly
fatty.
Fibrous stroma forms septa k/a
suspensory ligaments of cooper-
anchor skin and gland to the
pectoral fascia
Fatty stroma forms the main
bulk, is distirbuted all over
breast.
Clinical importance;- if infiltrates
suspensory ligaments breast becomes
fixed, contraction of ligaments can
10. Primary site
Nipple (areolar)
Central portion of breast (subareolar)
area extending 1 cm around areolar
complex
Upper inner quadrant (UIQ) of breast
Lower inner quadrant (LIQ) of breast
Upper outer quadrant (UOQ) of breast
Lower outer quadrant (LOQ) of breast
Axillary tail of breast
Overlapping lesion of breast
11. Most common site is
upper outer quadrant as
it has more glandular
tissue.
12. Multifocal and Multicentric primary sites
The presence of two or
more foci of cancer within
the same breast quadrant is
defined as multifocal, while
the presence of two or more
foci of cancer in different
quadrants of the same
breast is defined as
multicentric
13. Blood supply
Extremely vascular
Internal thoracic artery – perforating
branches
Axillary artery –
Lateral thoracic artery
Superior thoracic artery
Acromiothoracic artery
Posterior intercostal arteries – lateral
branches arteries are distributed in the
anterior surface.
Posterior surface is relatively avascular.
15. Venous drainage
Veins follow the arteries.
First converge around the nipple to
form an anastomotic venous circle
& then form 02 sets of veins.
Superficial veins: drain into Internal
thoracic vein & superficial veins of
the lower part of the neck
Deep veins: drain into Internal thoracic
, Axillary & Posterior intercostal
veins
Clinical importance;-They
communicate with vertebral venous
plexus- Spread to vertebrae and
brain
Axillary vein
Internal thoracic vein
Anastomotic
venous circle
16. Nerve supply of breast
Is supplied by the anterior and lateral cutaneous
branches of the intercostal nerves.
The nerves convey sensory fibres to the skin, and
autonomic fibres to smooth muscle and to blood
vessels.
The nerves do not control secretion of milk, which is
controlled by hormone prolactin.
17. Lymphatic drainage of breast
Drains by three major routes -
Axillary
Transpectoral
Internal mammary
18. Lymphatic vessels
The superficial lymphatics drain
the skin over the breast except
for nipple and areola.
Clinical importance:-
obstruction causes peau
d'orange
The deep lymphatics drain the
parenchyma of the breast, nipple
and areola.
Deep lymphatics communicate
with with sub diaphragmatic an
subperitoneal lymph plexuses
Clinical importance;- cancer may
spread to liver and pelvis
19.
Communicates with the superficial lymphatics of breast across the
midline
Clinical importance;- spread to contralateral breast
About 75% drain axillary nodes, 20% in internal mammary nodes, 5%
in posterior intercostal nodes
20. Axillary lymph nodes
Clinically divided into 5 groups
Anterior, central, posterior,
lateral and apical
Lymphatics mostly end in
anterior group and posterior
group and through them to
apical finally to supraclavicular
clinical importance;- sentinel
lymph node is anterior group of
axillary lymph nodes mostly and
if cancer has not spread that
means it has not spread beyond.
21.
Level I- lymph nodes
lateral to lateral border of
pectoralis minor
Level II- lymph nodes
between medial and lateral
borders of pectoralis minor
and interpectoral lymph
nodes.
Lymph III- nodes medial to
medial margin of pectoralis
minor
22. Other groups of lymph nodes
Internal mammary lymph
nodes- in the intercostal
spaces along the edge of
the sternum.
Supraclavicular lymph
nodes- in the
supraclavicular fossa
Intramammary lymph
nodes- within the breast are
considered as axillary LNs
for staging.
23. CA Breast
Is the most commonly diagnosed malignancy in women in the
Western countries, and accounts for more than 25% of cancers
diagnosed in women worldwide
Is 2nd
most common cancer to be diagnosed overall (11.9%)
Is now the most common cancer among women in most cities in India,
and 2nd most common in the rural areas, accounts for 25% to 32% of
all female cancers in all cities
It is most common cause cancer related death in females
24. Risk factors of CA Breast
Established risk factors other reported risk factors possible risk
Age alcohol consumption high density breast
Germline mutation birth pills high socioeconomic pos
Family history breast-feeding physical activity
Benign breast disease BMI dietary factors
Radiation exposure
Long menstrual history
obesity
25.
Female gender- at the age of 50- 1 in 400 women per year, 1% are male
breast cancer.
Age – Annual increase in developing breast cancer is approximately
0.07% per yer at 30 yr of age .This increases to 0.44% per year for
women in their late 70s.At 40-59 yr age =4% and 60-79 yr of age=
6.9%.
Family history of breast cancer – Ist degree relative risk is 1.7-2.5, 2nd
degree relative risk is 1.5. It may be explained in part by inheritance of
genetic condition that predisposes an individual to breast cancer
development ( e.g., mutaion in BRCA1 and BRCA2); shared lifestyle;
and inheritance of genes that affect risk factors, such as body habitus
and age at menarche.
26. Breast Cancer Susceptibility Genes
BRCA1 Hereditary breast/ovarian cancer 60%-85% (lifetime); 15-40% risk of
ovarian cancer
BRCA2 Hereditary breast/ovarian cancer 60-80%, (lifetime), 15%-40% risk of
ovarian cancer
P53 Li-Fraumeni syndrome 50% (by age 50)
PTEN1 Cowden syndrome 25% (lifetime)
other common genes that can slightly increase a woman's risk of developing
breast cancer CASP8, FGFR2, TNRCP, MAP3K1, rs4973768, LSP1
Rare genes that can also increase breast cancer risk slightly include CHEK2,
ATM (ataxia telangiectasia mutated), BRIP1, PALB2
27.
Child Bearing/Parity/Breastfeeding- linear relation between relative
risk of breast cancer and age at first birth, with women age 20 to 25
having nearly a 50 % reduction in relative risk compared to
nulliparous.
Ovarian Function- With long menstrual history increases breast cancer
risk. In observational studies, removal of ovaries reduces the risk of
breast cancer. Women with surgically induced menopause shown to
have significantly reduced risk of breast cancer compared to women
who has menopause naturally.
Benign Breast Disease- The relative risk of breast cancer developing
in women with non proliferative benign breast disease was1.27, for
proliferative changes without atypia is 1.88, and for women with
proliferative changes with atypia is 4.24
28.
Radiation Exposure- It increases approximately linearly with with
increasing dose and was heavily dependent on age at exposure.
Multiple flouroscopic examinations for tuberculosis, and multiple
examinations for mastitis, radiation therapy at young age for
Hodgkin's disease.
Body Mass Index, Physical Activity, and Dietary Factors- the risk of
breast cancer to be 30% higher in postmenopausal women with a BMI
over 31 kg/m2 compared to women with a BMI of 20 kg/m2 , annual
average of at least 1.3 hours of exercise per week from age 10 years
onward was associated with a 20% reduction in breast cancer risk .
It is apparent that maintaing sound, varied diet, limiting alcohol
intake, avoiding obesity, an getting moderate physical activity are
modifiable behaviours that can impact breast cancer risk.
29. High risk female for breast cancer
>35 yr of age
Family history
Received therapeutic radiation
LCIS
Genetic predisposition
31. Presenting symptoms of breast cancer
The majority of women presents with a lump- hard, painless, immobile, and
demonstrates a degree of fixity to surrounding tissues, overlying skin, or the
underlying pectoral muscle
Not all cancers are painless may have symptoms of increased discomfort in the lump
prior to menstruation. It is, therefore, advisable to undertake histological and
cytological examination of any discrete lump in a woman over the age of 25. A
diagnosis of a fibroadenoma or 'cystic change' without such confirmation is
extremely dangerous.
Up to 15 per cent of women with breast cancer present with a more diffuse process
within the breast, in which a lump is not necessarily the presenting feature in lobular
carcinoma.
Changes in the skin may be the sole presenting symptom or present with other
features of the cancer Puckering maybe present
32.
Peu d'orange is a feature of advanced cancer. The cause of this characteristic clinical
sign is oedema of the skin: this is not due to direct infiltration of the skin by tumour
but represents lymphatic obstruction of the breast as a result of axillary metastasis
In advanced, untreated cases the skin may be broken, and tumor ulcerates through
the skin, with associated haemorrhage and odour
Presentations with changes at the nipple are not uncommon, but these primary
tumors may be difficult to diagnose as they are often small and may be easily missed
by mammography.
A unifocal or bloodstained nipple discharge is often an intraductal carcinoma
developing within the major duct system beneath the nipple. The discharge
associated characteristically watery and bloodstained, in contrast to the milk
discharge of galactorrhoea and multifocal, tenacious, and coloured discharge of duct
ectasia.
It usually represents an underlying intraductal carcinoma that may be quite
extensive in the breast and which may also exhibit an invasive component.
33. Screening of CA Breast
Has resulted in shift in both incidence and stage of
patients presenting with breast cancer
Early detection by mammography, followed by
appropriate local, regional and systemic treatment is
associated with reduced breast cancer mortality
rates.
Screening can be Mammogram, Ultrasound of
breast, MRI screening, self breast examination.
34. Mammography Screening
Using low-energy X-rays
(usually around 30 kVp) to
examine the human breast.
Overall senstivity 75%
Two images taken, craniocaudal
and mediolateral oblique
35.
National Cancer Institute recommends baseline mammogram at the
age of 35 years , for high risk group it is 30 yrs.
Repeat examination should be carried out every 2 years beginning at
40 yrs of age.
In women older than 50 yrs, mammogram should be performed
annually.
Breast imaging reporting and data system has been developed by
American College of Radiology to study mammogram
37. Ultrasound screening
It is useful tool to supplement mammography in
diagnosis of breast cancer
However use in routine screening of general
population has not been established.
It may have role in young patients and high risk
patients.
38. MRI Screening
Role of MRI screening is rapidly evolving however
it is unlikely to replace mammography for screening
general population.
As it is expensive, not available everywhere and has
high false positive rate
It is more sensitive test and there is no risk of
radiation exposure
Therefore, can be used for screening high risk
patients
39. Self Breast examination
The estimated overall
senstivity is 26%
compared with 75% for
the combination of
clinical breast
examination and
mammography.
Can be done at home,
cost effective.
41. Initial work-up
History with emphasis on presenting symptoms, menstrual
status, parity, family history of cancer, other risk factors
should be done
To clinically rule out metastasis history about bony pain,
jaundice, haemoptysis and altered sensorium/ seizures
should be asked.
Physical examination with emphasis on breast, axilla,
supraclavicular area, abdomen should be done.
43. Fine-Needle Aspiration (FNA)
This technique usually is performed when a palpable mass is evident.
The combination of physical examination, mammography, and FNA
provides a diagnostic accuracy that approaches 100 percent.
A negative FNA cytology in the presence of a palpable mass,
however, does not conclusively exclude carcinoma.
When the mass is clinically and mammographically suspicious, the
sensitivity (true-positive) of FNA is 80 to 98 percent. The false-
negative rate of FNA is 2 to 10 percent.
The specificity and predictive value of FNA approach 100 percent
because false-positive results are rare.
44. Core Biopsy
False-positive diagnostic rates are lower with tissue procured by cutting needles
than with FNA specimens because more tissue is submitted for analysis.
But a core biopsy specimen without malignant tissue cannot conclusively be
considered a “negative” biopsy, as it might reflect a sampling error.
Excisional Biopsies
Implies removal of the entire lesion and generally a margin of normal breast
parenchyma surrounding the suspicious lesion.
False negative cases rare
Complete histology before treatment decision
May be unnecessary surgery if the condition is benign.
46. In Situ Breast Carcinoma
Ductal carcinoma in situ (DCIS)
- Number of cases have increased (5% -15% to 30%) due to screening mammogram.
- It consists of malignant population of cells limited to ducts and lobules by the
basement membrane
- Many cases of low grade DCIS and most cases of high grade and extensive DCIS
progress to invasive cancer.
Lobular carcinoma in situ (LCIS)
- It is an incidental finding in biopsy performed for another reason as it is not
associated with calcification or stromal reaction that would form a density.
- It is bilateral in 20 to 40% of women and more common in young.
47. Invasive(Infiltrating) Breast Cancer
Invasive Ductal carcinoma
- It includes majority of carcinoma that cannot be identified as any other
sub type
Invasive lobular carcinoma
- Have been reported to have a greater incidence of bilaterality
- Incidence is increasing among post menopausal women due to
increased use of HRT
- Has different pattern of metastases compared to other breast cancer.
Metastases to peritoneum, retroperitoneum, leptomeninges, GIT and
the ovaries and uterus are more frequently observed
- Less likely to have metastasis to lungs
48. Tumor Grade
Scarff Bloom Richardson grading
Combines nuclear grade, tubule formation, and
mitotic rate
85% if grade I, 60% of grade II, 15% of grade III of
early breast cancer survive for 10 years
49. Biomarkers for breast cancer
In addition to the classical clinical prognostic factors of breast cancer,
established molecular biomarkers such as estrogen receptor and
progesterone receptor have played a significant role in the selection of
patients benefiting from endocrine therapy for many years.
The human epidermal growth factor receptor 2 (HER2) has been
validated to be not only a prognostic factor, but also a predictor of
response to HER2 targeting therapy.
The marker of proliferation Ki67 has recently emerged as an
important marker due to several applications in neoadjuvant therapy
in addition to its moderate prognostic value
About 15 biomarkers have been studied like uPA, PAI and TF, h-
MAM, osteopontin, snail, twist, zeb-1, FGFR, PTEN and sirtuins and
it has been found that combination of all these could be utilized for
diagnostic and prognosis.
50. Immunohistochemistry Status
For assessing hormone responsive receptor status
ER/PR/Her2 status
Microarray studies have identified subtypes by
morphology (e.g., lobular carcinomas), by protein
expression (e.g., ER+ve and Her2 +ve) and by
germline mutations (e.g., BRCA1 and BRCA2)
New subtype identified (e.g., Basal like)
51.
ER +ve carcinomas- 70 to 80% breast carcinomas are positive,
are usually well to moderately differentiated. Are usually lobular type
which infiltrates as single cell.
ER -ve carcinomas- are major 2 types
1. Her 2 +ve carcinomas- tend to be poorly differentiated
2. Basal like- poorly diff, lacking ER/PR/her2, expressing basal like
keratins.
52. Molecular Staging
Type ER PR Her2 neu CK 5/6 EGFR Ki67
Luminal A + + - avg avg low
Luminal B + + + avg avg high
Luminal Her 2 + + + avg avg avg
Her2 Enriched - - + avg avg avg
Basal like - - - + + avg
53. Metastatic Work Up
Indicated for N2/N3 patients
and T3 orT4 primary lesions
Approximately 6-10% of new
breast cancer cases are initially
Stage IV or metastatic. This is
sometimes called "de novo"
metastatic disease
Bone (41.1%)>lung (22.4%)>
liver (7.3%)>brain (7.3%).
Bone- scan
Computed tomography of chest,
abdomen and pelvis
CECT brain
54. CA breast staging
TNM staging by AJCC latest updated in 2010, given in 7th
edition of
AJCC cancer staging manual.
Various changes have been made from previous 6th
edition reflect
advances in both management options and in prognostic information
and clarifications in definitions used in the 6th edition.
The changes can be divided into 4 areas:
ƒ Tumor size definition
ƒ Node classification
ƒ Metastasis classification
ƒ Special issues in patients who received neoadjuvant chemotherapy.
55. Tumor size definition
Invasive tumors should be recorded to the nearest millimeter
Small invasive tumors should be defined by microscopic measurement
and larger tumors by gross measurement however, acknowledges that
gross measurement may be inaccurate for the following reasons-
1.) the gross appearance of invasive versus non-invasive tumor may not
always be distinctive.
2.) invasive tumor may extend microscopically further than is grossly
visible .
Multiple cancers as those that are grossly or macroscopically distinct.
AJCC defines 0.5 cm as the minimum distance required between two
macroscopic cancer foci to call them multiple cancers, anything closer
than 0.5 cm likely represents a single cancer .
56. Primary Tumor (T)
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 (Paget’s) Paget’s disease of the nipple NOT associated with invasive carcinoma
and/or carcinoma in situ (DCIS and/or LCIS) in the underlying breast parenchyma.
Carcinomas in the breast parenchyma associated with Paget’s disease are
categorized based on the size and characteristics of the parenchymal disease,
although the presence of Paget’s disease should still be noted
57. Primary Tumor (T) cont
T1 Tumor ≤ 20 mm in greatest dimension
T1mi Tumor ≤ 1 mm in greatest dimension
T1a Tumor > 1 mm but ≤ 5 mm in greatest dimension
T1b Tumor > 5 mm but ≤ 10 mm in greatest dimension
T1c Tumor > 10 mm but ≤ 20 mm in greatest dimension
58. Primary Tumor (T) cont
T2 Tumor > 20 mm but ≤ 50 mm in greatest dimension
T3 Tumor > 50 mm in greatest dimension
59. Primary Tumor (T) cont
T4 Tumor of any size with direct extension to the chest wall and/or to the skin
(ulceration or skin nodules)
Note: Invasion of the dermis alone does not qualify as T4
T4a Extension to the chest wall, not including only pectoralis muscle
adherence/invasion
(Chest wall includes intercostal muscles and serratus
anterior muscle, but not the pectoral muscles.
Therefore, involvement of the pectoral muscle does
not constitute chest wall invasion)
60. Primary Tumor (T) cont
T4b Ulceration and/or ipsilateral satellite nodules and/or edema
(including peau d’orange) of the skin, which do not meet the criteria
for inflammatory carcinoma
Peau d'orange represents lymphatic obstruction of the breast as a
result of axillary metastasis
T4c Both T4a and T4b
61.
T4d Inflammatory carcinoma
Inflammatory carcinoma is a
clinical-pathologic entity characterized by
diffuse erythema and edema
involving a third or more of the skin of the
Breast.
- Microscopically, dermal lymphatic invasion
is typically seen in this setting, however dermal
lymphatic invasion alone is NOT sufficient
(nor necessary) to diagnose
62. Controversy
Does not take tumor burden into account as multiple synchronus
tumor has more tumor load as compared to single tumor of same size
Does not take immunohistochemistry into account
Does not mention how lymphatic invasion should be
handled in terms of tumor size.
63. Node classification
Classification of isolated tumor cell clusters and single cells is more
stringent.
Clusters of cells not greater than 0.2 mm, or non confluent or nearly
confluent clusters of cells not exceeding 200 cells in a single
histologic lymph node cross section .
When six or more sentinel nodes are identified on gross examination
of pathology specimens the (sn) modifier should be omitted.
The separation of pN1mic from pN1 in the overall staging.
64. Regional Lymph Nodes (N)
Clinical
NX Regional lymph nodes cannot be assessed (e.g.,previously removed)
N0 No regional lymph node metastases
N1 Metastases to movable ipsilateral level I, II axillary lymph node(s)
N2 Metastases in ipsilateral level I, II axillary lymph nodes that are clinically fi xed or matted;
or in clinically detected * ipsilateral internal mammary nodesin theabsence of clinically
evident axillary lymph node metastases
N2a Metastases in ipsilateral level I, II axillary lymph nodes fi xed to one another (matted) or to
other structures
N2b Metastases only in clinically detected * ipsilateral internal mammary nodesand in the
absence of clinically evident level I, II axillary lymph node metastases
65. N3
N3a Metastases in ipsilateral infraclavicular lymph node(s) with or
without level I, II axillary lymph node involvement
N3b Metastases in ipsilateral internal mammary lymph node(s) and
axillary lymph node(s) with clinically evident level I, II axillary
lymph node metastases
N3c Metastases in ipsilateral supraclavicular lymph
node(s)
Controversy- Internal mammary lymph nodes are not clinically
palpable.
66.
67. Regional Lymph Nodes (N)
Pathologic (pN)
-Level I/II clearance
-Level III if gross nodes in level II
-Atleast 10 LN should be removed
By size of the metastasis
0.2 mm (or >200 cells) up to 2 mm is a
micrometastasis: pN1mic
>2 mm is a macrometastasis: pN1, pN2,
pN3, depending on total number of positive
nodes
68. By total number of positive nodes
Total of 1-3 positive nodes is pN1a
Total of 4-9 positive nodes is pN2a
Total of >9 positive nodes is pN3a
69. Regional Lymph Nodes (N)
Pathologic (pN)
By specific anatomic node
Positive internal mammary sentinel affects
pN depending on status of other nodes.
pN1b- clinically not detectable but sentinel lymph
node biopsy shows micro or macrometastases
pN2b- clinically detectable in absence of axillary
lymph nodes
pN3b- 1 or more axillary LN + clinically detectable
IMLN or >3 axillary LN + IMLN positive in SLN biopsy
Positive infraclavicular axillary node is pN3a
Positive supraclavicular axillary node is pN3c
70. Metastasis classification
Now separates out incidentally detected cancer cells (<0.2 millimeter)
in distant, non-regional nodal tissue if there is no clinical or radiologic
evidence of metastasis.
example raised by AJCC is incidental metastasis <0.2 mm found in a
prophylactic oophorectomy; in the absence of any clinical/radiologic
evidence of ovarian involvement, this finding should not be staged as
pM1 distant metastasis but as pM0i+.
Controversy- Does not differntiate between oligometastasis and
multiple metastasis
71. Staging Patients After Neoadjuvant Therapy
ypT is based on the largest single focus of residual invasive cancer;
Stromal fibrosis in the residual tumor bed should not be used to increase the size beyond that
of actual invasive tumor cells
If the residual tumor consists of microscopic nests in fibrotic stroma, ypT should be based
on the largest contiguous area of invasive carcinoma
Controversy- may shrink in one of two patterns following
Scenario 1.) concentric shrinkage, resulting in a single residual focus smaller
Scenario 2.) patchy, non-concentric shrinkage, resulting in multifocal residual tumor that
may span the same size as the pre-treatment tumor size (but with reduced cellularity) or that
may span a smaller size than the pre-treatment tumor size.
Does not provide a definition of what constitutes separate multiple foci or of whether the
definition applies to macroscopic tumor or microscopic tumor.
Post-treatment ypN is same as pretreatment.
The M category remains same as pretreatment Identifi cation of distant metastases after the
start of therapy is considered progression of disease.
72. Anatomic Stage
Can be classified as Early breast
cancer, Locally invasive breast
cancer, Metastatic breast cancer
Early breast cancer- Any T1 0r
T2 with N0 or N1 ( IA to IIB)
Locally invasive breast cancer-
T3 or T4 , N2 or N3 (IIIA to
IIIC)
Metastatic breast cancer- with
distant metastasis (IV)
73. Conclusion
Ca breast is the most common cancer among women and is
the leading cause of death among cancers in women.
Breast has good lymphatic drainage which results in fast
progression of disease
Most of the risk factors are non modifiable some can be
modified
Screening for ca breast has resulted in early detection of
cancer
AJCC classification needs to take into account immuno
histochemistry status, nuclear grade, LVI invasion.
