Overview on breast carcinoma. Includes - Risk factors Risk Assessment and Prevention Clinical Assessment Investigations TNM Staging Pathological Classification Molecular Classification Prognostic Factors Surgery Neoadjuvant Therapy Adjuvant therapy

1. BREAST
CARCINOMA
Presented by
Students of
Surgery Unit II

2. • Breast cancer is the most common cancer among Indian women
and 2nd leading cause of cancer deaths in women.
• Though it is more common in the western countries the incidence
of breast cancer is increasing due to urbanization, adoption of
western lifestyle.
• Yet there is more reason for optimism than ever before as in the
last 30 years doctors have made great strides in early diagnosis
and treatment and reducing breast cancer death.
INTRODUCTION

3. BREAST CARCINOMA :
RISK FACTORS,
RISK ASSESSMENT, AND
RISK PREVENTION
By
SAYAN MAHARATNA
Roll No.- 77

4. RISK FACTORS
OF
BREAST CARCINOMA

5. • Age
• Early menarche and late menopause
• Hormonal factors
• Parity
• Diet and obesity
• Family history
• Prior breast biopsy
• Socio economic status
RISK FACTORS

6. Factors Relative risk
Geography Varies in different areas
Age Increases after age 30
Family history
• First degree relative with breast ca
Premenopausal
Premenopausal and bilateral
Postmenopausal
Postmenopausal and bilateral
1.2-3.0
3.1
8.5-9.0
1.5
4.0-5.4
RELATIVE RISK OF
DIFFERENT FACTORS
(contd.)

7. Factors Relative Risk
Menstrual history
Age at menarche <12 years
Age at menopause >55 years
1.3
1.5-2.0
Pregnancy
1st live birth from ages 25-29 years
1st live birth after age 30 years
1st live birth after age 35 years
Nulliparous
1.5
1.9
2.0-3.0
3.0
Benign breast disease
Proliferative disease without atypia
Proliferative disease with atypical hyperplasia
Lobular carcinoma in situ
1.6
>2.0
6.9-12.0

8. RISK ASSESSMENT
OF
BREAST CARCINOMA

9. RISK ASSESSMENT MODELS
GAIL MODEL CLAUS MODEL
Data derived
from
Breast Cancer Detection
demonstration Project Study
Cancer and Steroid Hormone
Study
Family history
characteristic
FDR with breast cancer •FDR or SDR with breast cancer
•Age of onset in relatives
Other
characteristic
• Current age
• Age at menarche
• Age at first live birth
• Number of breast biopsies
• Race
Current age
(contd.)

10. GAIL MODEL CLAUS MODEL
Strength Incorporates –
Risk factors other than family
history
Incorporates –
•Paternal and maternal history
•Age of onset
•Familial history of ovarian
carcinoma
Limitations •Underestimates risk in
hereditary families
•Number of breast biopsies
without atypical hyperplasia
may cause inflated risk
estimates
Does not incorporate –
•Paternal family history of
breast cancer or family history
of ovarian cancer
•Age at onset of breast cancer
in relatives
•All known risk factors for
breast cancer
•May underestimates risk in
hereditary families
•May not be applicable to all
combination of affected
relatives
(contd.)

11. GAIL MODEL CLAUS MODEL
Best
application
•For individuals with no family history of
breast cancer or one FDR with breast
cancer, aged 50 or above.
•For determining eligibility of
chemoprevention studies.
For individuals with no
more than two FDR or
SDRs with breast
cancer.
 OTHER RISK ASSESSMENT MODELS:
• BRCAPRO
• Tyrer Cuzik’s Model

12. WEBSITE TO CALCULATE RELATIVE RISK

13. RISK PREVENTION
OF
BREAST CARCINOMA

14.  BREAST CANCER SCREENING
 RISK REDUCING SURGERY
 CHEMOPREVENTION
RISK PREVENTION

15. BREAST CANCER SCREENING
 MAMMOGRAPHY
• Routine use of mammography in women aged 50 years or above has
been reported to reduce mortality from breast cancer by 25%.
• Recommendation- Baseline mammography at age of 35 and from 40
years annually.
 MRI
Approved for screening of young high risk patients who have-
• Strong family history
• BRCA mutation carriers
• With a history of Li-Fraumeni syndrome and Cowden syndrome
 USG
It can be used in pregnant women.
RISK PREVENTION

16. CHEMOPREVENTION
 SERM Therapy by Tamoxifen, Raloxifen
• Should be given if relative risk >1.66
• After a mean follow up period of 4 years the incidence of breast
cancer was reduced by 49%
• Optimal duration of treatment is 5 years. (NSABP-1)
 Aromatase inhibitors- Exemestane, Anastrozol
• More suitable for reducing the incidence of contralateral breast
cancer in post menopausal women
RISK PREVENTION

17. RISK REDUCING SURGERY
 Prophylactic mastectomy
• Reduces risk >90%
• For women with an estimated life time risk of 40%, prophylactic
mastectomy adds 3 years of life where as for women with an
estimated life time risk of 85% prophylactic mastectomy adds >5
years
 Salpingo-oophorectomy
• Reduces the risk of both ovarian and breast carcinoma in BRCA
mutation carriers (hereditary breast and ovarian cancer
syndrome).
RISK PREVENTION

18. BREAST CARCINOMA:
CLINICAL ASSESSMENT,
INVESTIGATIONS AND
STAGING
By
SOAHAM TARAPHDAR
Roll No.- 83

19. CLINICAL ASSESSMENT
OF
BREAST CARCINOMA

20. CLINICAL ASSESSMENT
Clinical assessment
History Clinical Examination
General
Survey
Local Examination
of Breast
Systemic
Examination
• Inspection
• Palpation

21.  MAJOR POINTS TO BE NOTED:
• Age
• Lump in breast: Mode of onset, duration, rate of growth
• Pain
• Breast or axillary changes
• Nipple: Retraction, Discharge
• Past history: H/O irradiation, cancers
• Personal history: Marital status, menstrual history
• Family history
HISTORY TAKING

22.  POSITIONS:
• Arms by her side
• Arms straight up in the air
• Hands on her hips (with
and without pectoral
muscle contraction)
• Arms extended forward
in a sitting position
leaning forward
• Semi recumbent position
with head raised by 45°
INSPECTION

23.  MAJOR POINTS TO BE NOTED:
• Breast: Symmetry, Size, Shape, Edema (peau d’ orange), Any
visible lump or fungation
• Skin: Retraction, Erythema, Ulceration
• Nipple: Retraction, Erythema, Ulceration, Discharge
INSPECTION

24. • In sitting, semi-recumbent and recumbent position
• Examination of all quadrants of the breast, along with the axillary tail
• Done with the pads of the middle 3 fingers; avoid grasping and
pinching motion
PALPATION OF BREAST

25.  POINTS TO BE NOTED IN CASE OF BREAST LUMP:
• Temperature
• Tenderness
• Number
• Situation
• Size
• Shape
• Surface
• Consistency
• Margin
• Mobility or fixity of lump
Fixity to skin, breast tissue, pectoral muscle and fascia, chest
wall
PALPATION OF BREAST

26. • Assessment of axillary lymphadenopathy
• Patient’s arm is supported on the non
examining arm of examiner to maintain
relaxation
• Examination with pads of middle 3 fingers in a
circular motion
PALPATION OF AXILLA

27. INVESTIGATION
OF
BREAST CARCINOMA

28. TO CONFIRM THE DIAGNOSIS:
 Imaging
• Mammography
• USG
• MRI
 Biopsy
• FNAC
• Trucut biopsy
INVESTIGATIONS

29. PROCEDURE
• Soft tissue radiographs are taken by placing the breast in
direct contact with an ultrasensitive film (selenium coated
plate) and exposing it to low-voltage, high-amperage X-rays.
• Radiation dose is 0.1 cGy.
• 2 views – (i) Mediolateral oblique and (ii) Craniocaudal
INDICATIONS
• Screening: Asymptomatic women of more than 40 years
• Diagnostic: Women with pain in the breast, mass, discharge,
family history of breast cancer
MAMMOGRAPY

30. FINDINGS
 Benign: Round, punctate, popcorn
like lesions
 Malignant:
• Solid mass with or without stellate
features
• Asymmetric thickening of breast
tissue
• Clustered microcalcifications
• Tentaculation
• Distortion of archtiectural pattern
of breast
MAMMOGRAPHY

31. MAMMOGRAPHY
Score Assessment Follow up
0 Incomplete assessment Needs additional imaging
1 Negative Continue regular screening (>40 yrs.)
2 Benign findings Same as above
3 Probably benign Follow up study after 6 month
4 Suspicious of carcinoma Core biopsy may be required
5 Highly suggestive of carcinoma Core biopsy is must
6 Known biopsy proven carcinoma Biopsy confirms presence of cancer before
treatment begins
BI-RADS scoring

32. ADVANTAGES
• Non-invasive procedure
• Minimum hazards of radiation
DISADVANTAGES
• 5% false positive cases
MAMMOGRAPHY

33. • Particularly useful in young women
with dense breasts in whom
mammograpy is difficult to interpret
• Can distinguish between solid and
cystic lesions
• Can be used to localise impalpable
areas of breast pathology
• USG guided aspiration of breast may
be done
• Cannot detect lesion less than 1mm
in diameter
ULTRASONOGRAPHY (USG)

34. • Can be useful to distinguish scar
from recurrence in women who
have had previous breast
conservation therapy for cancer
• Used in assessment of multifocality
and multicentricity of lobular
cancer
• Can be used to assess the extent of
DCIS
• Best imaging modality for the
breasts of women with implants
MRI

35. • Material is aspirated and collected
on slide with 23G needle, smear is
made, stained and examined
• More than 95% accuracy
• False negative 15%
• Invasiveness of cancer cannot be
determined
FNAC
FNAC Scoring
Co No epithelial cells
C1 Scanty epithelial cells , benign
C2 Benign cells
C3 Atypical cells
C4 Suspicious cells
C5 Malignant cells

36. • Also called Core cut biopsy or
Vacuum-assisted biopsy
• Lesion specimen is obtained with 11G
needle after proper antiseptic
dressing and local anesthesia
• Histological diagnosis of invasive or
non invasive carcinoma may be made
• Tumour grade and any
lymphovascular invasion may be
assessed
• ER/PR and Her2-neu status may also
be assessed
TRUCUT BIOPSY

37. OTHER INVESTIGATIONS
TO STAGE THE DISEASE – METASTATIC WORK UP
• CT scan chest
• X-ray
• Whole body bone scan
• Upper abdominal USG with LFT
• Sentinel node biopsy
TO KNOW THE GENERAL CONDITION
• Complete haemogram with ESR
• Serum albumin, sugar, urea, creatinine
• ECG,Echo and Pulmonary function test for elder patients

38. TRIPLE ASSESSMENT

39. STAGING
OF
BREAST CARCINOMA

40. 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
TNM STAGING
 PRIMARY TUMOUR (T)

41. 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
T2 Tumor >20 mm but ≤5 cm in greatest dimension
T3 Tumor >50 mm in greatest dimension
TNM STAGING
 PRIMARY TUMOUR (T)

42. T4 Tumor of any size with direct extension to the chest wall and/or to
the skin (ulceration or skin nodules)
T4a Extension to chest wall, not including only pectoralis muscle
adherence/invasion
T4b Ulceration and/or ipsilateral satellite nodules and/or edema
(including peaud’orange) of the skin, which do not meet the criteria
for inflammatory carcinoma
T4c Both T4a and T4b
T4d Inflammatory carcinoma
TNM STAGING
 PRIMARY TUMOUR (T)

43. 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 fixed or matted; or in clinically detected ipsilateral internal
mammary nodes in the absence of clinically evident axillary lymph
node metastases
N2a Metastases in ipsilateral level I, II axillary lymph nodes fixed to one
another (matted) or to other structures
N2b Metastases only in clinically detected* ipsilateral internal mammary
nodes and in the absence of clinically evident level I, II axillary lymph
node metastases
TNM STAGING
 REGIONAL LYMPH NODES – CLINICAL(N)

44. N3 Metastasis in ipsilateral infraclavicular (level III axillary) lymph node(s)
with or without level I, II axillary lymph node involvement; or in clinically
detected ipsilateral internal mammary lymph node(s) with clinically
evident level I, II axillary lymph node metastases; or metastases in
ipsilateral supraclavicular lymph node(s) with or without axillary or
internal mammary lymph node involvement
N3a Metastasis in ipsilateral infraclavicular lymph node(s)
N3b Metastasis in ipsilateral internal mammary lymph nodes(s) and axillary
lymph node(s)
N3c Metastasis in ipsilateral supraclavicular lymph node(s)
TNM STAGING
 REGIONAL LYMPH NODES – CLINICAL(N)

45. M0 No clinical or radiographic evidence of distant metastases
cM0(i+) No clinical or radiographic evidence of distant metastases, but
deposits of molecularly or microscopically detected tumor cells
in circulating blood, bone marrow, or other nonregional nodal
tissue that are no larger than 0.2 mm in a patient without
symptoms or signs of metastases
M1 Distant detectable metastases as determined by classic clinical
and radiographic means and/or histologically proven larger than
0.2 mm
TNM STAGING
 DISTANT METASTASIS (M)

46. Stage 0 Tis N0 M0
Stage IA T1 N0 M0
Stage IB T0 N1mi M0
T1 N1mi M0
Stage IIA T0 N1 M0
T1 N1 M0
T2 N0 M0
Stage IIB T2 N1 M0
T3 N0 M0
TNM STAGING
Stage IIIA T0 N2 M0
T1 N2 M0
T2 N2 M0
T3 N1 M0
T3 N2 M0
Stage IIIB T4 N0 M0
T4 N1 M0
T4 N2 M0
Stage IIIC Any T N3 M0
Stage IV Any T Any N M1
 TNM STAGE GROUPINGS

47. BREAST CARCINOMA:
PATHOLOGICAL
CLASSIFICATION
By
ASIF RAHAMAN
Roll No.- 86

48. Breast Carcinoma
Carcinoma in situ Invasive Carcinoma
1. Ductal Carcinoma in situ
2. Lobular Carcinoma in situ
1. Paget’s disease of the nipple
2. Invasive ductal carcinoma
3. Medullary carcinoma
4. Mucinous (colloid) carcinoma
5. Papillary carcinoma
6. Tubular carcinoma
7. Invasive lobular carcinoma
8. Rare cancers (adenoid cystic,
squamous cell, apocrine )

49. • Cancer cells are in situ or invasive depending on whether
or not they invade through the basement membrane.
• Broders’s original description of in situ breast cancer
stressed the absence of invasion of cells into the
surrounding stroma and their confinement within natural
ductal and alveolar boundaries.
CARCINOMA IN SITU

50. • Although DCIS is predominantly seen in the female breast, it
accounts for 5% of male breast cancers.
• Histologically, DCIS is characterized by a proliferation of the
epithelium that lines the minor ducts, resulting in papillary
growths within the duct lumina.
DUCTAL CARCINOMA IN SITU (DCIS)
(contd.)

51. • The papillary growths (papillary
growth pattern) eventually coalesce
and fill the duct lumina so that only
scattered, rounded spaces remain
between the clumps of atypical cancer
cells, which show hyperchromasia and
loss of polarity (cribriform growth
pattern).
• Eventually pleomorphic cancer cells
with frequent mitotic figures obliterate
the lumina and distend the ducts (solid
growth pattern).

52. TYPES OF DCIS
• Solid type, Ductal Carcinoma in situ:
The tumour cells completely fill the involved ducts.
• Cribriform type, Ductal Carcinoma in situ:
The tumour cells do not completely fill the ducts. The pattern has
little holes and slits, similar to a sieve.
• Papillary and micropapillary types, Ductal Carcinoma in situ:
These two types have fern-like projections of cells into the centre
of the duct. The micropapillary type projections are smaller than
those seen with the papillary type.
(contd.)

53. • Comedo type Ductal Carcinoma in situ:
 It tends to be slightly more aggressive than the other forms of
DCIS.
 Appearance under the microscope:
 The individual cells look more abnormal
 The centre of the duct is plugged up with dead cellular
debris, known as necrosis.
 Also seen very often in mammograms the areas of necrosis
are microcalcifications – small abnormal calcium deposits in
the areas of necrosis.

55. LOBULAR CARCINOMA IN SITU (LCIS)
• Originates from the terminal duct
lobular units and develops only in
the female breast.
• Characterized by distension and
distortion of the terminal duct
lobular units by cells
• Characterized by dyscohesive cells
lacking E-cadherin adhesion
protein.

56. LOBULAR CARCINOMA IN SITU (LCIS)
• Malignant proliferation of cells
in lobules with no invasion of
the basement membrane.
• Does not produce a mass or
calcifications; usually
discovered incidentally on
biopsy.
• Often multifocal and bilateral.

57. PAGET’S DISEASE OF THE NIPPLE
• Frequently presents as a chronic,
eczematous eruption of the nipple,
which may be subtle but may
progress to an ulcerated, weeping
lesion.
• Usually is associated with extensive
DCIS, may be associated with an
invasive cancer.

58. PAGET’S DISEASE OF THE NIPPLE
• Nipple biopsy specimen shows
a population of cells that are
identical to the underlying
DCIS cells (pagetoid features
or pagetoid change).
• Pathognomonic of this cancer
is the presence of large, pale,
vacuolated cells (Paget cells)
in the rete pegs of the
epithelium.

59. INVASIVE DUCTAL CARCINOMA
• Occurs most frequently in
perimenopausal or
postmenopausal women in the
fifth to sixth decades of life.
• Presents as a solitary, firm mass
with poorly defined margins.
• Broad spectrum of histologic
types with variable cellular and
nuclear grades.

60. INVASIVE DUCTAL CARCINOMA
• Cut surfaces show a central
stellate configuration with
chalky white or yellow
streaks extending into
surrounding breast tissues.

61. MEDULLARY CARCINOMA
• 4% of all invasive breast cancers.
• Frequent phenotype of BRCA1
hereditary breast cancer.
• Gross characteristics:
 Soft and haemorrhagic
 A rapid increase in size may
occur secondary to necrosis
and haemorrhage.

62. MEDULLARY CARCINOMA
• Microscopic characteristics:
 Dense lymphoreticular infiltrate
composed predominantly of
lymphocytes and plasma cells
 Large pleomorphic nuclei that
are poorly differentiated and
show active mitosis
 Sheet-like growth pattern with
minimal or absent ductal or
alveolar differentiation

63. MUCINOUS (COLLOID) CARCINOMA
• 2% of all invasive breast cancers.
• Typically presents in the elderly
population as a bulky tumour.
• Cut surface is glistening and
gelatinous.
• Fibrosis is variable, and when
abundant, imparts a firm
consistency to the cancer.

64. MUCINOUS CARCINOMA
• Microscopically defined by
extracellular pools of mucin
surrounding aggregates of low-
grade cancer cells.

65. • Generally presents in the seventh
decade of life.
• Occurs in a disproportionate number
of non-white women.
• Typically small, rarely attain a size of 3
cm in diameter.
• Defined by papillae with fibrovascular
stalks and multilayered epithelium.
PAPILLARY CARCINOMA

66. • 2% of all invasive breast cancers.
• Diagnosed in the perimenopausal or
early menopausal periods.
• Under low-power magnification, a
haphazard array of small, randomly
arranged tubular elements are seen.
• Distant metastases are rare.
• Long-term survival approaches 100%.
TUBULAR CARCINOMA

67. • 10% of breast cancers.
• Presentation: Varies from clinically
inapparent carcinomas to those that
replace the entire breast with a
poorly defined mass.
• Frequently multifocal, multicentric,
and bilateral.
LOBULAR CARCINOMA

68. LOBULAR CARCINOMA
• Histopathological features:
 Small cells with rounded nuclei,
inconspicuous nucleoli, and
scant cytoplasm.
 Special stains may confirm the
presence of intracytoplasmic
mucin, which may displace the
nucleus (signet-ring cell
carcinoma).

69. BREAST CARCINOMA:
MOLECULAR CLASSIFICATION,
BIOMARKERS AND
PROGNOSTIC FACTORS
By
MAYUKH MUKHERJEE
Roll No.- 84

70. MOLECULAR CLASSIFICATION
OF
BREAST CARCINOMA

71. Subtype These tumours tend to be
(Characteristics)
Prevalence
(approximate)
Luminal A
• ER-positive and/or PR-positive
• HER2-negative
• Low Ki67
40-55%
Luminal B
• ER-positive and/or PR-positive
• HER2-positive (or HER2-negative with
high Ki67)
15-20%
Basal-like
(Triple –ve)
• ER-negative
• PR-negative
• HER2-negative
13-25%
HER2 type
• ER-negative
• PR-negative
• HER2-positive
7-12%
Normal
breast-like
• ER-positive
• HER2-negative
6-10%

72. • Express ER
• Most common
• Posses a higher ER and oestrogen associated gene ESR1, GATA3,
and FOXA1
• Do not express HER-2/neu
• Ki-67 proliferation index is low
• Luminal A tumours are associated with better prognosis
LUMINAL A

73. Association of osteopontin, cyclooxygenase 2, oestrogen receptor,
progesterone receptor & human epidermal growth factor receptor 2
LUMINAL A

74. • Express ER
• Variable HER-2/neu expression
• Increased frequency of TP53 mutations
• Ki-67 proliferation index is high
• Luminal B tumours are associated with worse prognosis than
Luminal A
LUMINAL B

75. LUMINAL B
Association of osteopontin, cyclooxygenase 2, oestrogen receptor,
progesterone receptor & human epidermal growth factor receptor 2

76. • Hormone receptor (ER and PR) and HER-2/neu receptor negative
• Expression of genes associated with myoepithelial cells: KRT5
(keratin 5), KRT17 (keratin 17), CNN1 (calponin 1), CAV1 (caveolin)
and LAMB1 (laminin)
• Aggressive with a poorer disease free and overall survival than
other breast cancer subtypes.
BASAL LIKE (TRIPLE NEGATIVE)
SUBTYPE

77. BASAL LIKE (TRIPLE NEGATIVE)
SUBTYPE
Association of osteopontin, cyclooxygenase 2, oestrogen receptor,
progesterone receptor & human epidermal growth factor receptor 2

78. • Increased expression of genes located in the same region of
chromosome 17q: human epidermal growth receptor factor 2, and
growth factor receptor bound protein 7
• Associated with high histological grade, low expression of ER and
PR
• Poor clinical outcome.
HER-2/NEU OVER EXPRESSING
SUBTYPE

79. HER-2/NEU OVER EXPRESSING
SUBTYPE
Association of osteopontin, cyclooxygenase 2, oestrogen receptor,
progesterone receptor & human epidermal growth factor receptor 2

80. BIOMARKERS IN
BREAST CARCINOMA

81. TYPES OF BIOMARKERS
 Endpoint biomarkers
Used as endpoints in short term chemoprophylaxis trials.
 Prognostic biomarkers
For info regarding cancer outcome irrespective of therapy.
 Predictive biomarkers
For info regarding response to therapy.

82.  Risk factor biomarkers:
• Familial clustering and inherited germ line abnormality
• Proliferative breast disease with atypia
• Mammographic densities
 Exposure biomarkers:
e.g. DNA adducts
 Surrogate endpoint biomarkers:
Markers of biologic alterations in tissues that occur between
cancer initiation and development
ENDPOINT BIOMARKERS

83. a. Indices of proliferation
• PNCA (Proliferating cell nuclear antigen)
• Ki 67
b. Indices of apoptosis and apoptosis modulators
• bcl-2
• bax:bcl-2 ratio
c. Indices of angiogenesis
• VEGF
• AI (Angiogenesis index)
PROGNOSTIC AND PREDICTIVE
BIOMARKERS
(contd.)

84. d. Growth factor and growth factor receptor
• HER-2/neu (Human epidermal growth factor receptor 2)
• EGFr (Epidermal growth factor receptor)
• Transforming growth factor
• PDGF (Platelet derived growth factor)
• IDGF (Insulin derived growth factor)
e. Steroid hormone receptor pathway
• Estrogen receptor
 ER alpha
 ER beta
• Progesterone receptor
 PR alpha
 PR beta
(contd.)

85. f. Cell cycles, cyclines, cell dependent kinase S
g. Proteasome
h. COX-2 enzyme
i. PPARs (Peroxisome proliferator activated receptors)
j. Tumour suppressor genes: p53
k. mTOR (Mammalian target of rapamycin) signalling pathway

86. PROGNOSTIC FACTORS
OF
BREAST CARCINOMA

87. Tumour Factors Host Factors
Nodal Status Age
Tumour size Menopausal status
Histologic/Nuclear grade Family history
Lymphatic/Vascular invasion Previous breast cancer
Pathologic stage Immunosuppresion
Hormone receptor status Nutrition
DNA content (Ploidy, S phase
fraction)
Prior chemotherapy
Extent of intraductal component Prior radiation therapy
HER-2/ neu expression

88. A FEW POINTS ABOUT
PROGNOSTIC FACTORS
• Spread to the axillary nodes is the most important prognostic
indicator.
 Lymph node as prognostic factor
 Number of nodes: >2 carries poor prognosis
 Location of nodes
 Capsular invasion
 Size of nodes: >2.5cm ha poor prognosis
 More than 4 nodes/level III (apical nodes) involvement
has worst prognosis
(contd.)

89. • Younger age has worse prognosis
• CA male breast has worse prognosis than CA female breast
• Stage 1 & 2 of carcinoma of breast has better prognosis than
stage 3 & 4
• ER +ve & PR +ve tumours have better prognosis
• HER-2/neu +ve tumours have poor prognosis
• p53 tumour suppressor gene shows bad prognosis
• Inflammatory carcinoma has worst prognosis
• Tumour size less than 1cm has better prognosis

90. BREAST CARCINOMA:
TREATMENT OPTIONS
AND SURGERY
By
SHRONA BANDOPADHYAY
Roll No.- 82

91. SURGERY
CHEMOTHERAPY
RADIOTHERAPY
HORMONAL THERAPY
TREATMENT MODALITIES

92. CHOICE OF TREATMENT
ACCORDING TO STAGING
WITH EMPHASIS ON
SURGICAL METHODS

93. IN SITU (STAGE 0)
LOBULAR CARCINOMA IN
SITU (LCIS):
• Observation
or
• Chemoprevention
or
• B/L Total Mastectomy
DUCTAL CARCINOMA IN
SITU (DCIS):
• Limited disease :
Lumpectomy with
radiation.
• Extensive disease :
Modified radical
mastectomy (MRM).

94. Breast Conservation Surgery (BCS): Lumpectomy with
Radiation.
Modified Radical Mastectomy (MRM).
 Whether BCS or MRM assessment of Lymph node status is done.
Clinically negative axillary LN status has to be detected by sentinel
LN biopsy.
 When clinically palpable or sentinel LN biopsy is positive then
axillary clearance is to be performed by dissecting the level I and II
LN.
(contd.)
EARLY INVASIVE BREAST CARCINOMA
(STAGE I, IIA, OR IIB)

95.  Unless contraindicated, here Lumpectomy with Radiation
therapy is preferred over MRM because :
• Equivalent in terms of oncologic safety
• Better quality of life & aesthetics post surgically.
• Preservation of breast shape and skin as well as
sensation.

96. ADVANCED LOCAL-REGIONAL BREAST
CARCINOMA (STAGE IIIA OR IIIB)
Neoadjuvant Chemotherapy
Reassessment of stage
MRM with axillary LN level I, II, III dissection
Adjuvant Radiation Therapy

97. Systemic Chemotherapy
 Hormonal Therapy
 Radiation Therapy
 Palliative Surgery
DISTANT METASTASES (STAGE IV)

98. BREAST CONSERVATION
SURGERY

99. BREAST CONSERVATION SURGERY
(BCS)
Principle: Breast tissue, nipple-areolar complex and skin
are preserved. BCS is always associated with
Radiation Therapy.
QUART: Quadrantectomy + axillary LN clearance
(Level I, II, III) + post operative radiation therapy.
Lumpectomy: Lump with 1cm normal surrounding
breast tissue is excised.

100. INDICATIONS:
• Early breast carcinoma with tumour size < 4cm.
• Radiation is not contraindicated.
• Facility of radiation is present.
 CONTRAINDICATIONS:
• Multicentric tumour.
• History of previous breast irradiation.
• Pregnancy.
• Persistent positive margins after reasonable surgical attempts.
• Collagen vascular disease.
LUMPECTOMY

101.  DISADVANTAGES :
• Higher rate of local recurrence, more common in
younger women and tumours with high grades.
• Needs radiotherapy after surgery.
LUMPECTOMY

102. MASTECTOMY

103. TYPES OF MASTECTOMY
Simple or total
mastectomy
Removal of breast tissue, nipple-areola complex, skin.
Extended simple
mastectomy
Removal of breast tissue, nipple-areola complex, skin &
level I axillary nodes.
Modified radical
mastectomy
Removal of breast tissue, nipple-areola complex, skin &
level I, II axillary LNs.
Halstead’s radical
mastectomy
Removal of breast tissue, nipple-areola complex, skin,
pectoralis major & minor &level I, II, III axillary LNs.
Extended radical
mastectomy
Radical mastectomy + removal of internal mammary
LNs.
Super radical
mastectomy
Radical mastectomy + removal of internal mammary
LNs, mediastinal & supraclavicular LNs.

104.  Most acceptable and most widely practised surgery.
Advantages over radical mastectomy:
• Good postoperative cosmetic appearance
• Maintain motor activity in the arm
• Low rate of postoperative arm oedema
• Easy postoperative breast reconstruction
MODIFIED RADICAL MASTECTOMY

105. TYPES:
It is of 3 types:
1. Patey’s Modified Radical Mastectomy: Pectoralis major
muscle is preserved and Pectoralis minor removed.
2. Scanlon’s Modified Radical Mastectomy: Pectoralis minor
muscle is divided but not removed.
3. Auchincloss’ Modified Radical Mastectomy: Pectoralis
minor is retraced but not divided.
Auchincloss’ Modified Radical Mastectomy is widely practiced
nowadays.
MODIFIED RADICAL MASTECTOMY

106. INDICATIONS:
• Large tumour size > 5cm.
• Multicentric tumour.
• Surgical lines after lumpectomy are not free of tumour.
• Poorly differentiated tumour.
MODIFIED RADICAL MASTECTOMY

107. INCISION
Transverse elliptical incisions, including the nipple areola complex
and skin overlying the tumour together with skin margins that lie
1-2 cm from the cephalic and caudal extents of the tumour.
MODIFIED RADICAL MASTECTOMY

108. Anatomical boundaries of MRM:
• Lateral: Anterior margin of latissimus dorsi muscle
• Medial: Sternal border
• Superior: Clavicle
• Inferior: Up to upper ¼ th of rectus sheath.
Raising skin flaps:
The upper skin flap is raised upto the clavicle and the lower
skin flap is raised upto the upper quadrant of the rectus
sheath.
MODIFIED RADICAL MASTECTOMY

109.  The fascia of the
pectoralis major
muscle and the
overlying breast
tissue are elevated
off the underlying
musculature.
MODIFIED RADICAL MASTECTOMY

110. Three important structures should be preserved:
1. Axillary vein
2. Bell’s nerve(long thoracic nerve)
3. Cephalic vein
MODIFIED RADICAL MASTECTOMY

111. COMPLICATIONS
1. Seroma/ lymph collection
2. Secondary infection
3. Flap necrosis
4. Haemorrhage
5. Pain and numbness in axilla, medial side of the arm
6. Shoulder dysfunction
7. Injury/thrombosis of axillary vein
8. Winging of scapula
9. Lymphedema of arm(few month later)
MODIFIED RADICAL MASTECTOMY

112. The goals of reconstructive surgery after mastectomy are
wound closure & breast reconstruction.
COMMON OPTIONS:
• Implant(silicon gel).
• Latissimus dorsi flap (LD flap).
• Transverse Rectus Abdominis Myocutaneous flap (TRAM
flap).
RECONSTRUCTION OF THE BREAST
AND CHEST WALL

113. • Role of axillary surgery in CA breast is debated, but it is
accepted that presence of metastatic disease within
axillary lymph nodes is still the best single marker for
prognosis.
• In early breast carcinoma, if there is no clinically apparent
nodes and the disease is not multicentric, then sentinel
node biopsy is considered.
• Otherwise Complete Axillary Dissection is done.
AXILLARY SURGERY

114. A sentinel lymph node is defined as the first lymph node
to which cancer cells are most likely to spread from
a primary tumour.
INDICATION:
Early breast cancer with clinically node negative axilla.
SENTINEL LYMPH NODE BIOPSY

115. • SLN can be detected either by radioactive Tc-99m labelled sulphur
colloid or Isosulfan blue dye.However combination of both gives
better results.
Radioactive colloid is injected in subareolar region or near the primary
tumour 2-24 hours before the surgery.
Isosulfan blue dye is injected at the time of surgery in the same region.
A hand held gamma camera is used to identify the location of SLN.
PROCEDURE OF
SENTINEL LYMPH NODE BIOPSY
(contd.)

116. 3-4cm transverse incision is given just below the hairline of axilla.
Blunt dissection is done to visualise the dye containing lymphatics
which are traced to locate the SLN.
The SLN is removed and send for histopathological examination.

117. INTERPRETATION:
1. If –ve: No axillary block dissection
is required.
2.If +ve: Axillary block dissection is
done.
SENTINEL LYMPH NODE BIOPSY

118. BREAST CARCINOMA:
NEOADJUVANT AND
ADJUVANT THERAPIES
By
SOHAM SEN
Roll No.- 81

119. NEOADJUVANT
THERAPY

120. Neoadjuvant therapy refers to the administration of drugs –
chemotherapy or hormonal therapy
 Prior to surgery
 For a large operable tumour
 With the aim to reduce the loco regional tumour burden
to make it better amendable for surgical resection.
NEOADJUVANT THERAPY

121. 1. T3,T4 tumours
2. Inflammatory breast CA
3. Ipsilateral supra or infraclavicular lymph node involvement
INDICATIONS

122. CLASSIFICATION
Neoadjuvant therapy
Chemotherapy Hormonal therapy

123. • 4 cycles of Anthracyclin followed by 4 cycles of Pacitaxel followed
by surgery.
• Full course chemotherapy should be completed whether or not the
growth has completely resolved, before or after surgery.
• Patients who have received full course neoadjuvant chemotherapy
before surgery need not receive adjuvant chemotherapy.
NEOADJUVANT CHEMOTHERAPY

124. • Drugs –
 Trastuzumab
 Pertuzumab
• If one gets neoadjuvant Trastuzumab, she will likely also receive
adjuvant Trastuzumab.
• Trastuzumab is not usually given at the same time as Anthracycline
based chemotherapy, neither in the neoadjuvant nor the adjuvant
setting.
• Pertuzumab is only used as a neoadjuvant therapy and not given
after surgery.
NEOADJUVANT CHEMOTHERAPY
FOR HER-2 POSITIVE PATIENTS

125. INDICATIONS
• Women who are not candidates for chemotherapy due
to other health problems or advanced age
• ER/PR-positive tumours
• Low grade tumours
• Invasive lobular breast cancer
 Most young women with large tumours are treated with
chemotherapy rather than hormone therapy, even if their
tumours are ER-positive.
NEOADJUVANT HORMONAL
THERAPY

126. DRUGS
• Tamoxifen
• Letrozole
• Anastrozole
 Duration of treatment should be up to achievement of maximal
response.
NEOADJUVANT HORMONAL
THERAPY

127. To check the response to neoadjuvant therapy, several tests are done,
including –
• a clinical breast exam,
• a mammogram,
• a breast MRI , and/or
• an ultrasound.
Then, surgery is planned much in the same way as if there was no
neoadjuvant therapy
AFTER NEOADJUVANT THERAPY

128. • When a person has neoadjuvant therapy, a pathologist
checks the breast tissue removed during surgery for a
pathologic response.
• Pathologic response describes how much of the tumour is
left in the breast and lymph nodes after neoadjuvant
therapy.
PATHOLOGIC RESPONSE

129. • Here neoadjuvant therapy shrinks the tumour so much that the
pathologist cannot find any remaining cancer in the tissue removed
during surgery.
• Gives some information about prognosis, but it does not change the
treatment plan.
• pCR rates to neoadjuvant chemotherapy are highest among women
with –
 High grade tumours
 Hormone receptor-negative (ER & PR -ve) tumours
 HER2-positive tumours (when the neoadjuvant treatment plan
includes Trastuzumab and Pertuzumab)
PATHOLOGICAL COMPLETE
RESPONSE (pCR)

130. • Downstages the disease
• Increases chances of breast conservation
• Inoperable tumours may become operable
• Systemic treatment (chemotherapy) starts early
• Assesses response in vivo
• Inhibits a potential postsurgical growth spurt
• Chemotherapy is delivered through an intact vasculature
ADVANTAGES OF NEOADJUVANT
THERAPY

131. ADJUVANT
THERAPY

132. ADJUVANT THERAPY
Adjuvant therapy for breast cancer is any treatment given
after primary therapy to increase the chance of long-
term disease free survival.

133. TYPES OF ADJUVANT THERAPY
Adjuvant therapy
Radiotherapy Systemic therapy
Chemotherapy Hormonal therapy

134. INDICATIONS:
ADJUVANT RADIOTHERAPY
To the Chest Wall To the Axilla
• T3,T4 tumour >5cm
• Residual disease-LABC
• Positive margin
• After conservative surgery
• High risk group
• Inflammatory carcinoma
• 4 or more nodes positive
• Extranodal spread
• Axillary status not known

135. 1. ACCELERATED PARTIAL BREAST
IRRADIATION (APBI)
• APBI is generally defined as radiation
therapy that uses daily fraction doses
greater than 2 cGy delivered in less
than 5 weeks.
• By increasing the radiation fraction
size and decreasing the target
volume in a shorter period.
• Given only to the lumpectomy bed.
TYPES OF ADJUVANT
RADIOTHERAPY

136. 2. BRACHYTHERAPY
• Also called Internal Radiation Therapy.
• Involves placing a radioactive material inside or next to the
tumour.
• Higher dose of radiation can be used to treat a smaller area
and in lesser time.
TYPES OF ADJUVANT
RADIOTHERAPY

137. 3. EXTERNAL RADIOTHERAPY
• Sites:
 Breast area
 Axilla (in selected patients
like if axillary dissection is
not done or more than 4
positive axillary nodes)
 Internal mammary
 Supraclavicular area
• Total dosage 5000 cGY units
• 200-cGY units daily 5 days a week
for 6 weeks.
TYPES OF ADJUVANT
RADIOTHERAPY

138. 4. INTRAOPERATIVE RADIOTHERAPY
• Administration of low energy, high dose radiation directly to the
tumour bed with minimal exposure of surrounding tissues in the
operating room, right after the tumour is removed.
• Leser dose of radiation is given unlike standard radiotherapy.
• Duration: 30 mins
• Effects:
 Immediate sterilization of residual tumour cells.
 Inhibits stimulating effects of wound fluid.
TYPES OF ADJUVANT
RADIOTHERAPY
(contd.)

139.  INDICATIONS:
• Age >50 years
• Early stage of breast cancer (not spread)
 ADVANTAGES:
• All radiation in single dose.
• Less dose.
• Adjacent structures receive less radiation.
• Less costly.
 SIDE EFFECTS:
• Bruising.
• Increased fluid accumulation in breast tissues.
INTRAOPERATIVE RADIOTHERAPY

140. • Skin-
May become red, dry, tender, and itchy
• Breast-
May feel heavy and tight.
SIDE EFFECTS OF
ADJUVANT RADIOTHERAPY

141. Adjuvant Chemotherapy refers to administration of cytotoxic
drugs to women after breast cancer surgery to eliminate
undetectable distant spread.
INDICATIONS:
• Tumour size >1cm
• Tumour size <1cm with ER negative
HER-2 Positive
High grade
ADJUVANT CHEMOTHERAPY

142. 1st LINE DRUGS:
2nd LINE DRUGS:
Taxanes- Paclitaxel
Docetaxel
3rd LINE DRUGS:
Gemiticabine
DRUGS USED IN
ADJUVANT CHEMOTHERAPY
CMF regime CAF regime MMM regime
Cyclophosphamide Cyclophosphamide Methotrexate
Methotrexate Adriamycin Mitomycin-C
5-Fluorouracil 5-Fluorouracil Mitozantrone

143. REGIMES OF ADJUVANT
CHEMOTHERAPY

144. • Given orally or by i.v. injection.
• Given in cycles, consisting of a treatment period followed
by a recovery period. The number of cycles depends on
the types of drugs used.
• Usually does not last for much more than 6 months.
ADMINISTRATION OF
ADJUVANT CHEMOTHERAPY

145. ADJUVANT TRASTUZUMAB THERAPY:
• Trastuzumab: A monoclonal antibody against tyrosine kinase
receptor(HER-2) is administrated in patients with HER-2 +ve
Patients to improve Disease Free Survival(DFS)
• Dose: Loading: 4mg/kg
Maintenance: 2mg/kg for 9 weeks
• Administration: i.v. infusion every 1 to 3 weeks for a year.
ADJUVANT CHEMOTHERAPY FOR
HER-2/NEU POSITIVE PATIENTS

146. • Infections and bruise or bleed easily, less energy loss of
appetite, nausea, vomiting, diarrhoea, or mouth sores.
• Anthracyclines can increase the risk of heart problems.
• Trastuzumab can induce nausea, vomiting, hot flashes,
and joint pain. It can also increase the risk of heart
problems.
SIDE EFFECTS OF
ADJUVANT CHEMOTHERAPY

147. PRINCIPLES:
• It is used in ER/PR positive patient in all age groups
• It gives prophylaxis against carcinoma of opposite breast
• It is not used in ER negative Patients
ADJUVANT HORMONAL THERAPY

148. 1st LINE:
Anti oestrogen: Tamoxifen
2nd LINE:
Aromatase inhibitor: Prevent the synthesis of oestrogen by
blocking aromatase inhibitor enzyme which converts androstenedione
to oestradiol on adrenals.
• 1st generation: Aminoglutathemide
• 2nd generation: Anastrozole, Letrozole
3rd LINE:
Progestogens: Megestrol acetate
4th LINE:
Androgen: Fluoxymesterone
DRUGS USED IN
ADJUVANT HORMONAL THERAPY

149. • Oestrogen Receptor Antagonist
• Dose: 20mg once daily for 5 years
• Half life: 7 days
• Used commonly in Premenopausal women
• Adverse Effects:
Flushing, tachycardia, Sweating, vaginal atrophy, itching, bone pain
• Advantages:
 Reduces recurrence rate by 25%
 Equally effective in male breast carcinoma
 Cheap, easily available, less toxic
ADJUVANT HORMONAL THERAPY:
TAMOXIFEN

150. • Usually given orally, as a pill.
• Most women who undergo hormonal therapy take Tamoxifen every
day for 5 years.
• Some women may take an Aromatase inhibitor every day for 5 years
instead of Tamoxifen.
• Some women may receive additional treatment with an Aromatase
inhibitor after 5 years of Tamoxifen.
ADMINISTRATION OF ADJUVANT
HORMONAL THERAPY

151. ADVANTAGES:
• Relatively safe, easy to administer
• Used in metastatic carcinoma of breast
SIDE EFFECTS:
• Hot flushes, vaginal discharge, and nausea.
• Tamoxifen also increases the risk of cataract development .
• Aromatase inhibitors: Hot flushes, vaginal dryness, and other
symptoms of menopause joint pain (arthralgia) or muscle
pain (myalgia) during treatment.
ADJUVANT HORMONAL THERAPY

152. THANK
YOU