CARCINOMA OF BREAST

DR. SAURAV
Normal Breast
Breast profile
A ducts
B lobules
C dilated section of duct to hold milk
D nipple
E fat
F pectoralis major mu...
Female Breast Anatomy
• Breasts consist
mainly of fatty tissue
interspersed with
connective tissue
• There are also less
c...
Breast Gland
• Each breast has 15 to 20
sections (lobes)
• Inside each lobe are many
smaller structures called
lobules

• ...
Breast Cancer
• The most common form of cancer among
women
• The second most common cause of cancer
related mortality
• 1 ...
Epidemiology
 Incidence rates are highest in North

America, Australia and Western
Europe; intermediate in South
America,...
Risk factors
 Age
 Incidence of breast cancer increases

with age. More than 80 % of breast cancer cases
occur in women ...
 Family History
 Approx 10% of breast cancer is due to

inherited genetic predisposition
 A woman whose mother or siste...
 Family History
 At least two genes that predispose to

breast cancer have been identified—
BRCA 1 and BRCA 2
 Mutation...
 Benign Breast Disease
 Certain types of benign breast disease like
– Hyperplasia - 1.5 to 2 fold
– Atypical hyperplasia...
 Hormonal Factors
 levels of estrogen risk:
 Early age at menarche
 Late age at menopause
 Nulliparity
 Late age at ...
Environmental Factors
 High fat intake
 Excess alcohol consumption
 Ionizing radiation
Etiology
The etiology of breast cancer in most women
is unknown.
 Most likely due to a combination of risk
factors i.e. g...
Hereditary breast cancer
• Genes are as follows;
-BRCA1 or BRCA2 are now believed to be responsible
for 30% to 50% of here...
• Other defective genes that contribute to breast
cancer include:
BRCA3
p53 ( Li-Fraumeni syndrome)
CHEK2 (Variant of Li-f...
Sporadic breast cancer
• Over-exposure to estrogen
Because growth of breast tissue is highly
sensitive to estrogens, the m...
• Hormone exposure increases the number of
potential target cells by stimulating breast
growth. It also drives cycles of p...
Signs and Symptoms
Most common:
lump or
thickening in
breast. Often
painless

Discharge
or
bleeding
Change in size
or cont...
Classification of carcinoma of breast
– 95% of breast malignancies are adenocarcinomas
which are divided into in situ and ...
Histological types
• In situ
– Ductal carcinoma in situ (DCIS)
– Lobular carcinoma in situ (LCIS)

• Invasive
– Infiltrati...
Relative risk of developing invasive
cancer
v

No Increased Risk (1%)

 Mastitis
 Fat necrosis
 Mammary duct ectasia
 ...
v Slightly

=

Risk
Risk 1.5-2 Times

 Moderate/florid hyperplasia
 Sclerosing adenosis
 Fibroadenoma (complex)
 Duct ...
v Moderately Risk

= Risk 4-5 Times
 Atypical ductal hyperplasia
 Atypical lobular hyperplasia
Carcinoma in situ = 8-10%
lobular carcinoma in situ
ductal carcinoma in situ
Invasive ductal carcinomas, No special
type(NST)
• Clinical presentation Hard, irregular palpable lump

 Peau d’orange (...
 Tethering of the skin
 Retraction of the nipple
 Axillary mass (spread to regional

lymph nodes)
 Distant mets (lung,...
morphology
• Gross examination
Characterised by a irregular , hard to firm
mass. Produces a grating sound while cutting.
S...
• Histology
 well differentiated carcinomas show
prominent tubule formation and small round
nuclei.
moderately different...
Invasive ductal carcinoma(IDC)
•
•
•
•
•
•
•

A. Breast Duct System
B. Lobules
C. Breast Duct System
D. Nipple
E. Fat
F. C...
Cancer Can also Invade Lymph or
Blood Vessels

Cancer cells
invade
lymph duct
Cancer cells
invade
blood vessel
30

Illustr...
Gross specimen of ductal carcinoma.
Infiltrating ductal carcinoma NST
Patterns of gene expression in NST
1. Luminal A – 40 to 50% of NST cancers
ER positive and HER2/neu negative.
2. Luminal B...
4. Basal-like – 13 to 25% of NST cancers
ER, PR, HER2/neu Negative
expression of myoepithelial cell markers
like basal ker...
Invasive lobular carcinoma
 Much less common than IDC
 Can present with similar features like palpable

mass or mammogra...
morphology
• Hallmark is presence of dyscohesive
inflitrating tumor cells.
• Arranged in single file or in loose clusters ...
Invasive lobular carcinoma, signet ring variant
• Gradingwell differentiated and moderately
differentiated lobular carcinomas are usually
diploid, ER positive and associa...
• Lobular carcinomas are characterised by loss
of E-cadherin, a cell adhesion molecule that
functions as a tumor suppresso...
Invasive lobular carcinoma(ILC)
•
•
•
•
•
•
•

A. Breast Duct System
B. Lobules
C. Breast Duct System
D. Nipple
E. Fat
F. ...
Infiltrating lobular carcinoma
Medullary carcinomas
• Most common in women in 6th decade presenting
as a well- circumsribed mass with rapid growth.
• 4%
...
Morphology
• Tumor is soft , fleshy and well- circumscibed mass.
• Histologically –
 Solid syncytium like sheets of large...
Medullary carcinoma.
• Diagnosis of this lesion denotes a better 5year survival than pure invasive ductal or
lobular carcinoma.
• They have a b...
Mucinous (colloid) carcinomas
• This adenocarcinoma of ductal origin
constitutes approximately 2% of all breast
cancers
• ...
morphology
• Tumor is soft or rubbery
• Borders are circumscribed
• Tumor cells are arranged in clusters and small
islands...
Mucinous carcinoma.
• Mucinous cancers are usually diploid, well to
moderately differentiated and ER positive.
• Lymph node metastasis rare
• ...
Tubular carcinoma
• This lesion is a well-differantiated variant of
breast carcinoma with an incidence of
approximately 2 ...
morphology
• Tumor consists of well formed tubules.
• Myoepithelial cell layer is absent placing cells
in direct contact w...
Tubular carcinoma
• Majority of tubular carcinomas are diploid, ER
positive and HER2/neu negative.
• Excellent prognosis.
Invasive Papillary carcinoma
• Papillary cacinoma and micropapillary
accounts for less than 1% of all invasive
carcinomas
...
Invasive micropapillary carcinoma
Metaplastic carcinomas
• Rare tumors- less than 1% of all cases.
• Typesmatrix producing carcinomas
squamous cell carcinom...
Metaplastic carcinoma
Inflammatory carcinoma
• 1.5 to 3% of all cancers
• Clincal features : erythema, peau d’orange, and skin
thickening due to...
Diagnosis
• Early detection of breast cancer significantly
reduces the risk of death
• 20-49 ages
physical examination by ...
imaging techniques
• Breast sonography
– Superior in dense breast, young age

• Mammography
– Superior in loose(fatty) bre...
Biopsy
• A definitive diagnosis of breast cancer can be
made only by a biopsy.
• When a lump can be felt and is suspicious...
Staging of Breast Cancer
• The American Joint Committee on Cancer
(AJCC) has designated staging by TNM
• T= tumor size
• N...
TNM
•
•
•
•
•
•
•

Tx
No evidence of primary tumor
Tis
Carcinoma in situ
T1
Tumor 2cm or <
T2
2 to 5 cm
T3
T> 5cm
T4a
exte...
Regional lymph nodes
• N0
• N1
• N2

• N3

no regional lymph node met.
Movable ipsilateral axillary lymph node.
Fixed ipsi...
Distant metastasis
• M0 - no distant metastasis
• M1 - distant metastasis
Stage 1
• Tumor < 2.0 cm in
greatest dimension
• No nodal
involvement (N0)
• No metastases (M0)
• 5-year survival- 87%
Stage II
• Tumor > 2.0 < 5 cm
or
• Ipsilateral axillary
• lymph node (N1)
• No Metastasis (M0)
• 5-year survival- 75%
Stage III
• Tumor > 5 cm (T3)
• or ipsilateral axillary lymph nodes fixed to
each other or other structures (N2)
• involve...
Stage IV (Metastatic breast cancer)
•
•
•
•

Any T
Any N
Metastasis (M1)
5-year survival- 13%
Prognosis of breast carcinomas
• Major prognostic factors
 Tumor Size
 lymph nodes status
Nuclear grade
Age
The locat...
• Minor prognostic factors
 Histologic Subtypes
 Tumour Grade
 Hormone Receptors: ER, PR
 HER2/neu
 Lymphovascular in...
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Carcinoma of breast

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  • This is structure of normal breast showing….
  • These are present in only about 0.1 of the population.
  • Slightly  Risk =  Risk 1.5-2 Times
  • Commonest cancer of breast( 70 to 80%)…Peau d orange is thickening/dimpling of the skin caused by lymphatic obstruction..Pagetsds is ulceration/inflammation due to intraductal spread to cancer ofthe nipple
  • Mets-metastasis of lung,brain,bone
  • Poorly diff---They show high proliferation rates and areas of tumor necrosis…
  • This is a figure showing IDC in which cancer cells arising frm the ducts are seen breaking through basement membrane..
  • An irregular white dense white mass is present within yellow adipose tissue.
  • The carcinoma grows in tubules and solid trabeculae. The nuclei show relatively little pleomorphism, and the rate of mitotic activity is low.
  • No special type(NST)
  • The cells contain vacuole-like spaces, which stain for mucus.
  • Lcis—lobular carcinoma in situ..
  • this is a figure showing ILC in which cancer cells arising frm the lobules are seen breaking through basement membrane..
  • The cells invade singly and as single files of cells and lack cohesion.
  • 4% of breast cancer
  • poorly differentiated tumor cells show a syncytial growth pattern.
  • Clumps of tumor cells lie within pools of mucin, without apparent fibrous reaction.
  • may be multifocal or bilateral also.
  • Tubular carcinoma composed of open tubules with angulated outlines. These are lined by a single layer of well-differentiated cells having luminal protrusions (apical snouts)
  • Clusters of neoplastic cells are present within clear spaces separated by fibrovascular tissue.
  • This tumor is composed of interlacing bundles of spindle-shaped cells having the pattern of a spindle cell sarcoma NOS.
  • Women have a better prognosis if their tumors are receptor-positive. The presence of HER-2 may suggest aggressive cancer and poorer prognosis.
  • Carcinoma of breast

    1. 1. CARCINOMA OF BREAST DR. SAURAV
    2. 2. Normal Breast Breast profile A ducts B lobules C dilated section of duct to hold milk D nipple E fat F pectoralis major muscle G chest wall/rib cage Enlargement A normal duct cells B basement membrane (duct wall) C lumen (center of duct) Illustration © Mary K. Bryson 2
    3. 3. Female Breast Anatomy • Breasts consist mainly of fatty tissue interspersed with connective tissue • There are also less conspicuous parts – lobes – ducts – lymph nodes 3
    4. 4. Breast Gland • Each breast has 15 to 20 sections (lobes) • Inside each lobe are many smaller structures called lobules • At the end of each lobule are tiny sacs (bulbs) that can produce milk 4
    5. 5. Breast Cancer • The most common form of cancer among women • The second most common cause of cancer related mortality • 1 of 8 women (12.2%) • One third of women with breast cancer die from breast cancer
    6. 6. Epidemiology  Incidence rates are highest in North America, Australia and Western Europe; intermediate in South America, the Caribbean and Eastern Europe and lowest in China, Japan and India.  Over the years there has been decline in breast cancer mortality rates due to early detection by screening and more effective treatment modalities.
    7. 7. Risk factors  Age  Incidence of breast cancer increases with age. More than 80 % of breast cancer cases occur in women over 50 .  Uncommon before age 25 years; incidence increases to the time of menopause and then slows
    8. 8.  Family History  Approx 10% of breast cancer is due to inherited genetic predisposition  A woman whose mother or sister has had breast cancer is at relative risk 2 to 3 times compared to other women
    9. 9.  Family History  At least two genes that predispose to breast cancer have been identified— BRCA 1 and BRCA 2  Mutations in these tumour-suppressor genes also predispose affected women to ovarian cancer
    10. 10.  Benign Breast Disease  Certain types of benign breast disease like – Hyperplasia - 1.5 to 2 fold – Atypical hyperplasia- 4 to 5 fold  History of Other Cancer  A history of cancer in the other breast or a history of ovarian or endometrial cancer
    11. 11.  Hormonal Factors  levels of estrogen risk:  Early age at menarche  Late age at menopause  Nulliparity  Late age at first child-birth  Obesity
    12. 12. Environmental Factors  High fat intake  Excess alcohol consumption  Ionizing radiation
    13. 13. Etiology The etiology of breast cancer in most women is unknown.  Most likely due to a combination of risk factors i.e. genetic, hormonal and environmental factors . 
    14. 14. Hereditary breast cancer • Genes are as follows; -BRCA1 or BRCA2 are now believed to be responsible for 30% to 50% of hereditary breast cancer, ovarian cancer or both in families with a history of these cancers. - About 90% of BRCA1 carriers will develop breast cancer in whole lifetime. -These mutations can be passed down to the daughter by either mother or the father.
    15. 15. • Other defective genes that contribute to breast cancer include: BRCA3 p53 ( Li-Fraumeni syndrome) CHEK2 (Variant of Li-fraumeni) PTEN ( Cowden syndrome) LKBI/STK11 (Peutz-Jeghers syndrome) ATM ( ataxia telengiectasia)
    16. 16. Sporadic breast cancer • Over-exposure to estrogen Because growth of breast tissue is highly sensitive to estrogens, the more a women is exposed to estrogen over her lifetime,the higher the risk for breast cancer.
    17. 17. • Hormone exposure increases the number of potential target cells by stimulating breast growth. It also drives cycles of proliferation that can cause DNA damage. • Majority occur in post menopausal women and are ER positive.
    18. 18. Signs and Symptoms Most common: lump or thickening in breast. Often painless Discharge or bleeding Change in size or contours of breast 18 Redness or pitting of skin over the breast, like the skin of an orange Change in color or appearance of areola
    19. 19. Classification of carcinoma of breast – 95% of breast malignancies are adenocarcinomas which are divided into in situ and invasive carcinomas. – Carcinoma in situ- it is a neoplastic proliferation that is limited to ducts and lobules by the basement membrane. – Invasive carcinoma- infiltrating cancer that has penetrated through the basement membrane into stroma.
    20. 20. Histological types • In situ – Ductal carcinoma in situ (DCIS) – Lobular carcinoma in situ (LCIS) • Invasive – Infiltrating ductal carcinoma – Tubular/ cribriform carcinoma – Medullary carcinoma – Mucinous/ colloid carcinoma – Papillary carcinoma – Metaplasic carcinoma
    21. 21. Relative risk of developing invasive cancer v No Increased Risk (1%)  Mastitis  Fat necrosis  Mammary duct ectasia  Non-proliferative (“fibrocystic”) disease  Fibroadenoma without complex features
    22. 22. v Slightly = Risk Risk 1.5-2 Times  Moderate/florid hyperplasia  Sclerosing adenosis  Fibroadenoma (complex)  Duct papilloma
    23. 23. v Moderately Risk = Risk 4-5 Times  Atypical ductal hyperplasia  Atypical lobular hyperplasia
    24. 24. Carcinoma in situ = 8-10% lobular carcinoma in situ ductal carcinoma in situ
    25. 25. Invasive ductal carcinomas, No special type(NST) • Clinical presentation Hard, irregular palpable lump  Peau d’orange (lymphatic obstruction + thickening/dimpling of the skin)  Paget’s disease of the nipple (ulceration/inflammation due to intraductal spread to the nipple)
    26. 26.  Tethering of the skin  Retraction of the nipple  Axillary mass (spread to regional lymph nodes)  Distant mets (lung, brain, bone)
    27. 27. morphology • Gross examination Characterised by a irregular , hard to firm mass. Produces a grating sound while cutting. Small, central foci of chalky- white elastotic stroma and occasionally small foci of calcification can be seen.
    28. 28. • Histology  well differentiated carcinomas show prominent tubule formation and small round nuclei. moderately differentiated carcinomas may have tubules but solid clusters or single infiltrating cells may also be seen. poorly differentiated cancers often invade as ragged nests or solid sheets of cells with enlarged irregular nuclei.
    29. 29. Invasive ductal carcinoma(IDC) • • • • • • • A. Breast Duct System B. Lobules C. Breast Duct System D. Nipple E. Fat F. Chest Muscle G. Ribs • A. Cells lining duct • B. Cancer cells, breaking through the basement membrane • C. Basement membrane
    30. 30. Cancer Can also Invade Lymph or Blood Vessels Cancer cells invade lymph duct Cancer cells invade blood vessel 30 Illustration © Mary K. Bryson
    31. 31. Gross specimen of ductal carcinoma.
    32. 32. Infiltrating ductal carcinoma NST
    33. 33. Patterns of gene expression in NST 1. Luminal A – 40 to 50% of NST cancers ER positive and HER2/neu negative. 2. Luminal B – 15 to 20% of NST ER positive , higher proliferation rate and HER2/neu expression. Referred as triple positive. 3. Normal breast like - 6 to 10% of NST well differentiated ER positive , HER2/neu negative cancers
    34. 34. 4. Basal-like – 13 to 25% of NST cancers ER, PR, HER2/neu Negative expression of myoepithelial cell markers like basal keratins, P-cadherin or laminin 5. HER2/neu Positive- 7 to 12% ER negative but overexpression of HER2/neu protein.
    35. 35. Invasive lobular carcinoma  Much less common than IDC  Can present with similar features like palpable mass or mammographic density with irregular borders.  More likely to be bilateral and/or multicentric (multiple lesions within the same breast
    36. 36. morphology • Hallmark is presence of dyscohesive inflitrating tumor cells. • Arranged in single file or in loose clusters or sheets . Tubule formation is absent. • Signet-ring cells containing intracytoplasmic mucin droplet are seen.
    37. 37. Invasive lobular carcinoma, signet ring variant
    38. 38. • Gradingwell differentiated and moderately differentiated lobular carcinomas are usually diploid, ER positive and associated with LCIS Poorly differentiated cancers are generally aneuploid , lack hormone receptors and may overexpress HER2/neu.
    39. 39. • Lobular carcinomas are characterised by loss of E-cadherin, a cell adhesion molecule that functions as a tumor suppressor. • Metastasize more frequently to CSF, serosal surfaces and pelvic organs
    40. 40. Invasive lobular carcinoma(ILC) • • • • • • • A. Breast Duct System B. Lobules C. Breast Duct System D. Nipple E. Fat F. Chest Muscle G. Ribs • A. Cells lining lobule • B. Cancer cells, breaking through the basement membrane. • C. Basement membrane
    41. 41. Infiltrating lobular carcinoma
    42. 42. Medullary carcinomas • Most common in women in 6th decade presenting as a well- circumsribed mass with rapid growth. • 4% • Originates in large ducts. • Commonly, the lesion is positioned deep within the breast and mobile.
    43. 43. Morphology • Tumor is soft , fleshy and well- circumscibed mass. • Histologically –  Solid syncytium like sheets of large cells with pleomorphic nuclei and prominent nucleoi.  Frequent mitotic figures  Moderate to marked lymphoplasmacytic infiltrate in and around the tumor
    44. 44. Medullary carcinoma.
    45. 45. • Diagnosis of this lesion denotes a better 5year survival than pure invasive ductal or lobular carcinoma. • They have a basal-like gene expression profile
    46. 46. Mucinous (colloid) carcinomas • This adenocarcinoma of ductal origin constitutes approximately 2% of all breast cancers • Typically presents as a bulky, mucinous (colloid) tumor that is largely confined to the elderly population. • Tends to grow slowly over years.
    47. 47. morphology • Tumor is soft or rubbery • Borders are circumscribed • Tumor cells are arranged in clusters and small islands of cells within large lakes of mucin.
    48. 48. Mucinous carcinoma.
    49. 49. • Mucinous cancers are usually diploid, well to moderately differentiated and ER positive. • Lymph node metastasis rare • Overall prognosis is slightly better than NST carcinomas.
    50. 50. Tubular carcinoma • This lesion is a well-differantiated variant of breast carcinoma with an incidence of approximately 2 percent. • Most commonly, is diagnosed in the perimenapousal or early menopausal population.
    51. 51. morphology • Tumor consists of well formed tubules. • Myoepithelial cell layer is absent placing cells in direct contact with the stroma • Typical apocrine snouts and calcification may be present. • Frequently associated with atypical lobular hyperplasia or LCIS.
    52. 52. Tubular carcinoma
    53. 53. • Majority of tubular carcinomas are diploid, ER positive and HER2/neu negative. • Excellent prognosis.
    54. 54. Invasive Papillary carcinoma • Papillary cacinoma and micropapillary accounts for less than 1% of all invasive carcinomas • generally presents in the 7th decade. • Typically, papillary or micropapillary cancer is small and commonly seen in DCIS. • Invasive papillary are ER positive with favourable prognosis while micropapillary are ER +ve and HER2/neu –ve. • Lymph node metastasis very common and prognosis is poor.
    55. 55. Invasive micropapillary carcinoma
    56. 56. Metaplastic carcinomas • Rare tumors- less than 1% of all cases. • Typesmatrix producing carcinomas squamous cell carcinomas They are triple negative but often express myoepithelial proteins. Poor prognosis.
    57. 57. Metaplastic carcinoma
    58. 58. Inflammatory carcinoma • 1.5 to 3% of all cancers • Clincal features : erythema, peau d’orange, and skin thickening due to dermal lymphatic involvement with or without the presence of a palpable mass • Typically the skin over the lesion is warm, diffusely scaly, and indurated with ridging • It may present with the characteristics of a cellulits. • Diagnosis : biosy of skin, subcutaneous tissue, and parenchyma • This disease progresses rapidly and prognosis is poor.
    59. 59. Diagnosis • Early detection of breast cancer significantly reduces the risk of death • 20-49 ages physical examination by a health professional every 1 to 2 years. • 50 and over should be examined annualy • Women should perform self examination every month.
    60. 60. imaging techniques • Breast sonography – Superior in dense breast, young age • Mammography – Superior in loose(fatty) breast, elder. Others • Schintomammography • Doppler ultrasonography • Breast MR
    61. 61. Biopsy • A definitive diagnosis of breast cancer can be made only by a biopsy. • When a lump can be felt and is suspicious for cancer on mammography: FNAC Excisional biopsy İncisional biopsy Core biopsy Radioguided biopsy (for occult lumps)
    62. 62. Staging of Breast Cancer • The American Joint Committee on Cancer (AJCC) has designated staging by TNM • T= tumor size • N = lymph node involvement • M = metastasis
    63. 63. TNM • • • • • • • Tx No evidence of primary tumor Tis Carcinoma in situ T1 Tumor 2cm or < T2 2 to 5 cm T3 T> 5cm T4a extension to chest wall T4b edema (including peau d’orange), ulceration of skin, satellite nodules • T4c T4a + T4b • T4d Inflammatory carcinoma
    64. 64. Regional lymph nodes • N0 • N1 • N2 • N3 no regional lymph node met. Movable ipsilateral axillary lymph node. Fixed ipsilateral axillary lymph n. or internal mammary lymph nodes -ipsilateral supraclavicular lymph node. -Fixed ipsilateral axillary lymph n. and İnternal mammary lymph nodes -İpsilateral infraclavicular lymph node.
    65. 65. Distant metastasis • M0 - no distant metastasis • M1 - distant metastasis
    66. 66. Stage 1 • Tumor < 2.0 cm in greatest dimension • No nodal involvement (N0) • No metastases (M0) • 5-year survival- 87%
    67. 67. Stage II • Tumor > 2.0 < 5 cm or • Ipsilateral axillary • lymph node (N1) • No Metastasis (M0) • 5-year survival- 75%
    68. 68. Stage III • Tumor > 5 cm (T3) • or ipsilateral axillary lymph nodes fixed to each other or other structures (N2) • involvement of ipsilateral internal mammary nodes (N3) • Inflammatory carcinoma (T4d) • 5-year survival- 46%
    69. 69. Stage IV (Metastatic breast cancer) • • • • Any T Any N Metastasis (M1) 5-year survival- 13%
    70. 70. Prognosis of breast carcinomas • Major prognostic factors  Tumor Size  lymph nodes status Nuclear grade Age The location of the tumor its spread
    71. 71. • Minor prognostic factors  Histologic Subtypes  Tumour Grade  Hormone Receptors: ER, PR  HER2/neu  Lymphovascular invasion  Proliferative rate  DNA content  Response to neoadjuvant therapy  Gene expression profiling  Molecular Markers Includes c-erb-B2, c-myc and p53
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