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Surg Cdr Chaminda Amarasekara
Maj D B Ayer
Maj Balachandra Menon
Guide Surg Capt R Shankaran
 Anatomy
 Epidemiology
 Risk factors & Causes of breast cancer
 Breast cancer pathology
10/8/2017 2
 From the level of 2nd/3rd rib to the
inframammary fold at 6th /7th rib.
 Transversely from the lateral border of the
sternum to the mid-axillary line.
 posterior surface of the breast rests on the
fascia of the
◦ pectorals major
◦ serrates anterior
◦ external oblique
◦ upper extent of the rectus sheath
 The axillary tail pierces the fascia and lies in the
axilla
310/8/2017
10/8/2017 4
10/8/2017 5
 The breast receives its principal blood
supply from:
◦ internal mammary artery
◦ posterior intercostal arteries
◦ axillary artery,
10/8/2017 6
 toward the axilla
◦ Perforating
branches of the
internal thoracic
vein
◦ Perforating
branches of the
posterior
intercostal veins
◦ Tributaries of the
axillary vein
10/8/2017 7
 Batson’s vertebral venous plexus
Route for breast cancer metastases to the
◦ Vertebrae
◦ Skull
◦ pelvic bones
◦ central nervous system.
810/8/2017
 Anterior (pectoral) group
 Posterior (subscapular)
group
 Lateral group:
 Central group
 Infraclavicular
(deltopectoral) group
 Apical group
Level1
Level II
Level iii
10/8/2017 9
 Lateral cutaneous branches of the third through
sixth inter- costal nerves provide sensory
innervation of the breast (lateral mammary
branches) and of the anterolateral chest wall.
1010/8/2017
 Most common site-specific cancer in
women
 Second leading cause of death from cancer
second to lung cancer
 More than 1 million cases diagnosed
worldwide annually
12Sabiston TEXT BOOK OF SURGERY 20TH Edition10/8/2017
 Incidence decreased from1999to 2006 2%
year
 2006-2010 breast cancer incidence rates
were stable.
 Survival rates in women with breast cancer
steadily improved over the last decades
5 year survival rate 90% during 1995-2005
10/8/2017 13Sabiston TEXT BOOK OF SURGERY 20TH Edition
 Risk Factors That Cannot be Modified
 Risk Factors That Can be Modified
 Histological Risk Factors*
Sabiston TEXT BOOK OF SURGERY 20TH Edition,831
10/8/2017 14
Factors That Cannot be
Modified
◦ Increasing age
◦ Female sex
◦ Menstrual factors
◦ Early age at
menarche
◦ Older age at
menopause
◦ Family history of
breast cancer
◦ Genetic
predisposition
◦ Personal history
of breast cancer
◦ Race, ethnicity
◦ History of
radiation
exposure
1510/8/2017Sabiston TEXT BOOK OF SURGERY 20TH Edition,831
 Risk Factors That Can Be Modified
◦ Reproductive factors
◦ Age at first live birth
◦ Parity
◦ Lack of breast feeding
◦ Obesity
10/8/2017 16Sabiston TEXT BOOK OF SURGERY 20TH Edition,831
 Risk Factors That Can Be Modified ctd…
10/8/2017 17
o Alcohol consumption
o Tobacco smoking
o HRT
o Decreased physical activity
o Shift work (night shift)
Sabiston TEXT BOOK OF SURGERY 20TH Edition,831
 Histological risk factors
◦ Proliferative breast disease
◦ Atypical ductal Hyperplasia
◦ Atypical lobular Hyperplasia
◦ Lobular Carcinoma in situ
10/8/2017 18
Sabiston TEXT BOOK OF SURGERY 20TH Edition,831
 Gail Model
◦ Age
◦ Race
◦ Age at menarche <12 yrs.
◦ Age at first live birth <18 yrs.
◦ No of previous breast biopsies
◦ Presence of proliferative disease with atypia
◦ No of 1st degree relative
◦ Underestimate BRCA1 & BRCA 2
10/8/2017 19
 Genetic
 Hormonal
 Environmental
10/8/2017 20
 10% breast cancers are familial (90%
sporadic)
 Positive Family History, especially in 1st
degree relatives (mother, daughter, sister)
confers increased risk for breast cancer
 Tumor suppressor genes (BRCA1, BRCA2)
 Risk is greatest with:
 Relative with BILATERAL disease
 Relative affected at a YOUNG AGE
10/8/2017 21
 Responsible for up to 1/2 of “inherited”
breast cancers (5% of cancers)
 Increased risk of ovarian and colon
cancers (“Breast-Ovarian” cancer gene)
 Breast cancer develops in >50% of
these women by age 50 (“Early onset”
breast cancer gene)
10/8/2017 22
 Responsible for up to 30% of inherited
breast cancer
 Characterized by increased risk of
breast cancer in women and MALE
breast cancer (“Male Breast Cancer”
gene)
10/8/2017 23
 Due to Inherited p53 Tumor Suppressor
Gene Mutation (cell cycle checkpoint)
 Family cancer syndrome characterized
by increased risk of breast cancer,
osteosarcoma, soft tissue sarcomas,
brain tumors, leukemia, other
 Accounts for approximately 1% of
breast cancers detected before age 40
10/8/2017 24
 Early menarche, late menopause, null
parity, late age at first term pregnancy
 Oophorectomy before age 35 DECREASES
the risk of breast cancer.
 Oral contraceptive use and hormone
replacement therapy may be associated
with a increased risk
10/8/2017 25
 4-5 fold greater incidence in
industrialized countries
 Increased risk may be related to:
◦ Higher fat diet
◦ Earlier menarche
◦ Less physical activity
◦ Decreased parity
◦ Later age at parity
10/8/2017 26
◦ Radiation therapy for Hodgkin’s Disease in
young women
◦ Survivors of atomic bomb blasts
 Increased risk when exposure is at a young
age, little increase in risk after age 40
◦ Indicates that the risk is GREATEST to the
developing and hormonally cycling breast
10/8/2017 27
 Presence of a history of breast pathology
increases risk of breast cancer
10/8/2017 28
HISTOLOGICAL
DIAGNOSIS
ESTIMATES,RR
 Non proliferative
disease
 Proliferative disease
with out atypia
 Proliferative disease
with atypia
◦ And strong family history
 LCIS
 1.0
 1.3-1.9
 3.7-4.2
 4-9
 >7
Sabiston TEXT BOOK OF SURGERY 20TH Edition,83210/8/2017 29
 Multicentricity refers to the occurrence of a
second breast cancer outside the breast
quadrant of the primary cancer (or at least 4
cm away)
 Multifocality refers to the occurrence of a
second cancer within the same breast
quadrant as the primary cancer (or within 4
cm of it).
3010/8/2017
 Non Invasive Epithelial Cancers
 Invasive Epithelial Cancers
 Mixed Connective Epithelial Tumors
10/8/2017 31
 Lobular Carcinoma in situ
 Ductal Carcinoma in situ or Intra ductal
Carcinoma
◦ Papillary
◦ Cribriform
◦ Solid
◦ comedo
10/8/2017 32
 Invasive Lobular Carcinoma (10%)
 Invasive Ductal Carcinoma
◦ Invasive Ductal Carcinoma NOS (50-70%)
◦ Tubular Carcinoma (2%-3%)
◦ Mucinous or Colloid Carcinoma(2%-3%)
◦ Medullary Carcinoma(5%)
◦ Invasive Cribriform Carcinoma (1%-3%)
◦ Invasive Papillary Carcinoma (1%-2%)
◦ Adenoid Cystic Carcinoma(1%)
◦ Metaplastic Carcinoma(1%)
10/8/2017 33
 Phyllodes tumors benign & malignant
 Carcinosarcoma
 Angiosarcoma
 Adenocarcinoma
10/8/2017 34
 LCIS recognized risk factor development of
Ca
 Pleomorphic LCIS is more aggressive
histopathologic sub type
 If pleomorphic LCIS is associated with
calcification can be detected
mamographically
 DCIS are usually mixed morphologic types
 The solid and comedo type are generally
higher grade lesions
10/8/2017 35
 Invasive breast cancers have been described
as lobular or ductal in origin.
 Current histologic classifications recognize
special types of breast cancers (10% of total
cases), which are defined by specific
histologic features.
3610/8/2017
 To qualify as a special-type cancer, at least
90% of the cancer must contain the defining
histologic features.
 About 50-70% of invasive breast cancers are
described as invasive ductal carcinoma of no
special type (NST).
 These cancers generally have a worse
prognosis than special-type cancers.
3710/8/2017
 Microarray- based expression profiling
 Microarray is a chip containing spots
arranged in orderly fashion
 Contains unique DNA fragments which
match to specific gene(ER,HER2 etc)
 5 main molecular subgroups were identified
which defer in there insintric gene list
10/8/2017 38
 3 ER positive
◦ Luminal A (ER+(high levels), Ki 67 low
grade,
excellent prognosis
Luminal B (ER+ HER2+,high Ki
67expression,high grade :Poor prognosis
Normal-like (ER+, good prognosis),but
poorly characterized, may be the result of
sample contamination with normal tissue
10/8/2017 39
 2ER negative
◦ HER2 positive (ER-,Bad Prognosis)
◦ Basal –like( ER -, bad prognosis, Good
response to chemotherapy
10/8/2017 40
 There may be 3 more, recently described, ER
negative types
◦ Apocrine group
◦ Interferon groupClaudin-low group( s/o cancer
stem cell like phenotype
10/8/2017 41
 Defined as invasive carcinoma involving
superficial dermal lymphatic spaces
 Poor prognosis (T3 disease)
 Erythema and induration of the skin, so
called “inflammatory changes”
10/8/2017 42
Inflammatory carcinoma
10/8/2017 43
 Invasion of the SKIN of the nipple or
areola by malignant cells, singly or in
small nests
 Associated with an underlying cancer:
either IN SITU OR INVASIVE carcinoma
 Clinically-erythema, scaling, ulceration
10/8/2017 44
10/8/2017 45
Paget’s
disease: nipple
ulceration

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Breast Cancer Pathology and Risk Factors

  • 1. Surg Cdr Chaminda Amarasekara Maj D B Ayer Maj Balachandra Menon Guide Surg Capt R Shankaran
  • 2.  Anatomy  Epidemiology  Risk factors & Causes of breast cancer  Breast cancer pathology 10/8/2017 2
  • 3.  From the level of 2nd/3rd rib to the inframammary fold at 6th /7th rib.  Transversely from the lateral border of the sternum to the mid-axillary line.  posterior surface of the breast rests on the fascia of the ◦ pectorals major ◦ serrates anterior ◦ external oblique ◦ upper extent of the rectus sheath  The axillary tail pierces the fascia and lies in the axilla 310/8/2017
  • 6.  The breast receives its principal blood supply from: ◦ internal mammary artery ◦ posterior intercostal arteries ◦ axillary artery, 10/8/2017 6
  • 7.  toward the axilla ◦ Perforating branches of the internal thoracic vein ◦ Perforating branches of the posterior intercostal veins ◦ Tributaries of the axillary vein 10/8/2017 7
  • 8.  Batson’s vertebral venous plexus Route for breast cancer metastases to the ◦ Vertebrae ◦ Skull ◦ pelvic bones ◦ central nervous system. 810/8/2017
  • 9.  Anterior (pectoral) group  Posterior (subscapular) group  Lateral group:  Central group  Infraclavicular (deltopectoral) group  Apical group Level1 Level II Level iii 10/8/2017 9
  • 10.  Lateral cutaneous branches of the third through sixth inter- costal nerves provide sensory innervation of the breast (lateral mammary branches) and of the anterolateral chest wall. 1010/8/2017
  • 11.
  • 12.  Most common site-specific cancer in women  Second leading cause of death from cancer second to lung cancer  More than 1 million cases diagnosed worldwide annually 12Sabiston TEXT BOOK OF SURGERY 20TH Edition10/8/2017
  • 13.  Incidence decreased from1999to 2006 2% year  2006-2010 breast cancer incidence rates were stable.  Survival rates in women with breast cancer steadily improved over the last decades 5 year survival rate 90% during 1995-2005 10/8/2017 13Sabiston TEXT BOOK OF SURGERY 20TH Edition
  • 14.  Risk Factors That Cannot be Modified  Risk Factors That Can be Modified  Histological Risk Factors* Sabiston TEXT BOOK OF SURGERY 20TH Edition,831 10/8/2017 14
  • 15. Factors That Cannot be Modified ◦ Increasing age ◦ Female sex ◦ Menstrual factors ◦ Early age at menarche ◦ Older age at menopause ◦ Family history of breast cancer ◦ Genetic predisposition ◦ Personal history of breast cancer ◦ Race, ethnicity ◦ History of radiation exposure 1510/8/2017Sabiston TEXT BOOK OF SURGERY 20TH Edition,831
  • 16.  Risk Factors That Can Be Modified ◦ Reproductive factors ◦ Age at first live birth ◦ Parity ◦ Lack of breast feeding ◦ Obesity 10/8/2017 16Sabiston TEXT BOOK OF SURGERY 20TH Edition,831
  • 17.  Risk Factors That Can Be Modified ctd… 10/8/2017 17 o Alcohol consumption o Tobacco smoking o HRT o Decreased physical activity o Shift work (night shift) Sabiston TEXT BOOK OF SURGERY 20TH Edition,831
  • 18.  Histological risk factors ◦ Proliferative breast disease ◦ Atypical ductal Hyperplasia ◦ Atypical lobular Hyperplasia ◦ Lobular Carcinoma in situ 10/8/2017 18 Sabiston TEXT BOOK OF SURGERY 20TH Edition,831
  • 19.  Gail Model ◦ Age ◦ Race ◦ Age at menarche <12 yrs. ◦ Age at first live birth <18 yrs. ◦ No of previous breast biopsies ◦ Presence of proliferative disease with atypia ◦ No of 1st degree relative ◦ Underestimate BRCA1 & BRCA 2 10/8/2017 19
  • 20.  Genetic  Hormonal  Environmental 10/8/2017 20
  • 21.  10% breast cancers are familial (90% sporadic)  Positive Family History, especially in 1st degree relatives (mother, daughter, sister) confers increased risk for breast cancer  Tumor suppressor genes (BRCA1, BRCA2)  Risk is greatest with:  Relative with BILATERAL disease  Relative affected at a YOUNG AGE 10/8/2017 21
  • 22.  Responsible for up to 1/2 of “inherited” breast cancers (5% of cancers)  Increased risk of ovarian and colon cancers (“Breast-Ovarian” cancer gene)  Breast cancer develops in >50% of these women by age 50 (“Early onset” breast cancer gene) 10/8/2017 22
  • 23.  Responsible for up to 30% of inherited breast cancer  Characterized by increased risk of breast cancer in women and MALE breast cancer (“Male Breast Cancer” gene) 10/8/2017 23
  • 24.  Due to Inherited p53 Tumor Suppressor Gene Mutation (cell cycle checkpoint)  Family cancer syndrome characterized by increased risk of breast cancer, osteosarcoma, soft tissue sarcomas, brain tumors, leukemia, other  Accounts for approximately 1% of breast cancers detected before age 40 10/8/2017 24
  • 25.  Early menarche, late menopause, null parity, late age at first term pregnancy  Oophorectomy before age 35 DECREASES the risk of breast cancer.  Oral contraceptive use and hormone replacement therapy may be associated with a increased risk 10/8/2017 25
  • 26.  4-5 fold greater incidence in industrialized countries  Increased risk may be related to: ◦ Higher fat diet ◦ Earlier menarche ◦ Less physical activity ◦ Decreased parity ◦ Later age at parity 10/8/2017 26
  • 27. ◦ Radiation therapy for Hodgkin’s Disease in young women ◦ Survivors of atomic bomb blasts  Increased risk when exposure is at a young age, little increase in risk after age 40 ◦ Indicates that the risk is GREATEST to the developing and hormonally cycling breast 10/8/2017 27
  • 28.  Presence of a history of breast pathology increases risk of breast cancer 10/8/2017 28
  • 29. HISTOLOGICAL DIAGNOSIS ESTIMATES,RR  Non proliferative disease  Proliferative disease with out atypia  Proliferative disease with atypia ◦ And strong family history  LCIS  1.0  1.3-1.9  3.7-4.2  4-9  >7 Sabiston TEXT BOOK OF SURGERY 20TH Edition,83210/8/2017 29
  • 30.  Multicentricity refers to the occurrence of a second breast cancer outside the breast quadrant of the primary cancer (or at least 4 cm away)  Multifocality refers to the occurrence of a second cancer within the same breast quadrant as the primary cancer (or within 4 cm of it). 3010/8/2017
  • 31.  Non Invasive Epithelial Cancers  Invasive Epithelial Cancers  Mixed Connective Epithelial Tumors 10/8/2017 31
  • 32.  Lobular Carcinoma in situ  Ductal Carcinoma in situ or Intra ductal Carcinoma ◦ Papillary ◦ Cribriform ◦ Solid ◦ comedo 10/8/2017 32
  • 33.  Invasive Lobular Carcinoma (10%)  Invasive Ductal Carcinoma ◦ Invasive Ductal Carcinoma NOS (50-70%) ◦ Tubular Carcinoma (2%-3%) ◦ Mucinous or Colloid Carcinoma(2%-3%) ◦ Medullary Carcinoma(5%) ◦ Invasive Cribriform Carcinoma (1%-3%) ◦ Invasive Papillary Carcinoma (1%-2%) ◦ Adenoid Cystic Carcinoma(1%) ◦ Metaplastic Carcinoma(1%) 10/8/2017 33
  • 34.  Phyllodes tumors benign & malignant  Carcinosarcoma  Angiosarcoma  Adenocarcinoma 10/8/2017 34
  • 35.  LCIS recognized risk factor development of Ca  Pleomorphic LCIS is more aggressive histopathologic sub type  If pleomorphic LCIS is associated with calcification can be detected mamographically  DCIS are usually mixed morphologic types  The solid and comedo type are generally higher grade lesions 10/8/2017 35
  • 36.  Invasive breast cancers have been described as lobular or ductal in origin.  Current histologic classifications recognize special types of breast cancers (10% of total cases), which are defined by specific histologic features. 3610/8/2017
  • 37.  To qualify as a special-type cancer, at least 90% of the cancer must contain the defining histologic features.  About 50-70% of invasive breast cancers are described as invasive ductal carcinoma of no special type (NST).  These cancers generally have a worse prognosis than special-type cancers. 3710/8/2017
  • 38.  Microarray- based expression profiling  Microarray is a chip containing spots arranged in orderly fashion  Contains unique DNA fragments which match to specific gene(ER,HER2 etc)  5 main molecular subgroups were identified which defer in there insintric gene list 10/8/2017 38
  • 39.  3 ER positive ◦ Luminal A (ER+(high levels), Ki 67 low grade, excellent prognosis Luminal B (ER+ HER2+,high Ki 67expression,high grade :Poor prognosis Normal-like (ER+, good prognosis),but poorly characterized, may be the result of sample contamination with normal tissue 10/8/2017 39
  • 40.  2ER negative ◦ HER2 positive (ER-,Bad Prognosis) ◦ Basal –like( ER -, bad prognosis, Good response to chemotherapy 10/8/2017 40
  • 41.  There may be 3 more, recently described, ER negative types ◦ Apocrine group ◦ Interferon groupClaudin-low group( s/o cancer stem cell like phenotype 10/8/2017 41
  • 42.  Defined as invasive carcinoma involving superficial dermal lymphatic spaces  Poor prognosis (T3 disease)  Erythema and induration of the skin, so called “inflammatory changes” 10/8/2017 42
  • 44.  Invasion of the SKIN of the nipple or areola by malignant cells, singly or in small nests  Associated with an underlying cancer: either IN SITU OR INVASIVE carcinoma  Clinically-erythema, scaling, ulceration 10/8/2017 44

Editor's Notes

  1. (a) perforating branches of the , (b) lateral branches of the , (c) branches from the including the highest thoracic, lateral thoracic, and pectoral branches of the thoraco-acromial artery
  2. which invests the vertebrae and extends from the base of the skull to the sacrum, may provide a
  3. Lying along the lower border of the pectoralis minor behind the pectoralis major, these nodes receive lymph vessels from the lateral quadrants of the breast and superficial vessels from the anterolateral abdominal wall above the level of the umbilicus. Lying in front of the subscapularis muscle, these nodes receive superficial lymph vessels from the back, down as far as the level of the iliac crests. Lying along the medial side of the axillary vein, these nodes receive most of the lymph vessels of the upper limb (except those superficial vessels draining the lateral side). 4.Lying in the center of the axilla in the axillary fat, these nodes receive lymph from the above three groups. 5.These nodes are not strictly axillary nodes because they are located outside the axilla. They lie in the groove between the deltoid and pectoralis major muscles and receive superficial lymph vessels from the lateral side of the hand, forearm, and arm 6.Lying at the apex of the axilla at the lateral border of the 1st rib, these nodes receive the efferent lymph vessels from all the other axillary nodes LN Lvel Lymph nodes located lateral to or below the lower border of the pectoralis minor muscle are referred to as level 1, which include the anterior, posterior, and lateral groups Lymph nodes located superficial or deep to the pectoralis minor muscle are referred to as level 2, which include the central and interpectoral groups. 3. Lymph nodes located medial to or above the upper border of the pectoralis minor muscle are referred to as level 3, which consist of the apical group
  4. These branches exit the intercostal spaces between slips of the serratus anterior muscle. Cutaneous branches that arise from the cervical plexus, specifically the anterior branches of the supraclavicular nerve, supply a limited area of skin over the upper portion of the breast