ca breast final
TRANSCRIPT
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KIRTI DIXIT IV TERM BGS GIMS GUIDE- Dr. DHARANI
CA BREAST GRADING, STAGING &
PROGNOSTIC FACTORS
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OVERVIEW
Introduction
Grading
Staging
Prognostic factors
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CACINOMA OFTHE BREAST Worldwide – most common primary cancer
In India Second to cervical cancer
25% to 31% of all cancers amongst women in Indian cities.
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STATISTICAL FACTS
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PREDISPOSING FACTORS Gender and age Age of menarche and menopause Age at first live birth First degree relatives with breast ca Atypical Hyperplasia Race/Ethnicity Estrogen exposure Breast radiodensity Radiation exposure Carcinoma of contralateral breast or endometrium
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Obesity
Breastfeeding & Exercise
Environmental toxins
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AETIOPATHOGENESIS – 12% FAMILIAL
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CLASSIFICATION OF CA BREAST
NON- INVASIVE
INVASIVE
MORPHOLOGIAL AND HISTOLOGICAL BASIS
MOLECULAR SUBTYPES
DUCTAL CARCINOMA IN-SITU
MUCINOUS CARCINOMA LUMINAL-AER + , HER2 -
LOBAR CARCINOMA IN SITU
MEDULLARY CARCINOMA LUMINAL-BER + , HER2 +
PAGETS DISEASE PAPILLARY CARCINOMA HER2 POSISTIVEER - , HER2 +
LOBULAR CARCINOMA TRIPLE NEGATIVEER - , HER2 -
TUBULAR CARCINOMA
MICROPAPILLARY CARCINOMA
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GRADING Degree of maturity or differentiation of tumor cells under the microscope
1. Histologic grade - resemblance between tumor and normal cells
2. Nuclear grade - size and shape of nucleus regularity, compactness.
3. Abnormal mitotic figures and their numbers
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GRADING– WHY ….?
For treatment and prognosis
Lower grade better prognosis
Higher grade worse prognosis
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HISTOLOGICAL TYPE OF TUMOR
GRADE 1 (LOW GRADE) – NON METASTASISING Intraductal & lobar carcinoma in situ
GRADE 2 (INTERMEDIATE GRADE) – LESS COMMONLY METASTASISING medullary, papillary, tubular, colloid, Adenoid cystic & secretory carcinomas
GRADE 3 (HIGH GRADE) –COMMONLY METASTASISING infiltrating duct, invasive lobar & inflammatory carcinomas
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NUCLEAR PLEOMORPHISM
NUCLEAR PLEOMORPHISM
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,
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STAGING Extent of the primary tumor and extent of spread in the body
Importance - Allows the health professional to determine appropriate treatment
( primary, adjuvant) -Allows assessment of prognosis and outcomes -Enables the reliable evaluation of treatment results -Results in quality cancer care
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CA BREAST AJCC STAGING
STAGE
T: PRIMARY TUMOUR N: LYMPH NODE M: METASTASIS
5 YR SURVIVAL
0 DCIS / LCIS NO absent 92%
I Invasive ca =/<02 cm
NO absent 87%
II Invasive Ca >02 cm
Invasive Ca <5cm
No LN
1-3 LN positive
absent 75%
III Invasive Ca >5 cm
Any size Invassive ca
INLAMMATORY CA
1-3LN pos
>4LNposive
LN posi/neg
absent 46%
IV Any size LN posi/neg present 13%
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TNM STAGING Primary Tumor (T) TX - Primary tumor cannot be evaluated T0 - No evidence of primary tumor Tis - Carcinoma in situ (has not spread) T1 - = /< 2 Cm T2 - 2 Cm to 5 Cm across T3 - > 5 Cm across T4 - Any size with direct extesion to the chest and / or to the skin
Regional Lymph Nodes (N) NX - Regional lymph nodes cannot be evaluated N0 - No regional lymph node involvement N1 - Metastases to movable ipsilateral axillary lymph nodes. N2 - Metastases in ipsilateral axillary lymph nodes that are clinically fixed or matted. N3 - Metastases in ipsilateral infraclavicular lymph nodes with or without axillary lymph node involvement.
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Distant Metastasis (M) MX - Distant metastasis cannot be evaluated M0 - No distant metastasis M1 - Distant metastasis
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Tumour not involving skin or chest wall
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PROGNOSTIC FACTORS
Major MinorInvasive v/s in situ Histologic subtypesDistant Metastasis Histologic GradeLymphnode Metastasis Estrogen Progesterone
Receptors Tumor size HER2 OverexpressinLocally Advanced Disease Lymphovascular InvasionInflammatory Carcinoma Proliferative Rate
DNA Content Response to Neoadjuvant Therapy Gene Expression Profiling
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MAJOR PROGNOSTIC FACTORS 1 ) Invasive v/s In situ :
In situ better prognosis
Ductal carcinoma in situ – if detected on time and treated can be cured
Invasive carcinoma metastasizes and leads to poor prognosis
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2) DISTANT METASTASIS Poor prognosis
Lymphatic route – Internal Mammary, Mediastinal,
supraclavicular and pleural lymphnodes & pleural
lymphatics
Hematogenous – lungs, liver, bone, brain, ovaries
Unlikely to cure
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3) Lymph Node Metastasis
Axillary lymphnode status – most important prognostic factor in the absence of distant
metastasis. 10 year survival rate - No nodes- 70-80% - 1 to 3 nodes- 35-40 % - >10 nodes- 10-15%
Macrometastasis (>0.2cm) – proven prognostic importance Micrometastasis (<0.2cm)– immunohistochemistry for keratins PCR based detection of tumor specific mRNA
Sentinal lymphnode – biopsy restricted to sentinal nodes negative for metastasis distant nodes not involved
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4) TUMOR SIZE
2ND most important prognostic factor of invasive carcinoma
10 year survival rate in node negative cases <1 cm – 90%, > 2 cm – 77%,
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5 ) Locally advanced disease :
Carcinomas invading into skin or skeletal muscles
Poor prognosis
Ususally large , difficult to treat surgically
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6 ) Inflammatory Ca - Peau d’ orange :
Obstruction of dermal lymphatics
Breast swelling and skin thickening
Poor prognosis
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MINOR PROGNOSTIC FACTORS
1)Histological Grades –
Nottingham histological grade correlates with survival rates.
Long Term survival rate - GRADE 1 70 % - GRADE 2 slightly better than grade 3 - GRADE 3 45 %
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BETTER PROGNOSIS (>60%)
RELATIVELY POOR PROGNOSIS (<20%)
•Mucinous • Micropapillary
• Medullary • Metastatic
• Papillary
•Tubular
• Lobar
• Cystic
2 ) Histologic subtypes
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3) Estrogen and Progesterone Receptors ER / PR positive – 40% respond to hormonal
therapy ER + PR positive –80 % respond to hormonal
therapy ER & PR negative – only 10 % to hormonal but
more to chemotherapy.
Nuclear hormone receptors – detected by
immunohistochemistry
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4) HER2 Overexpression – indicates poor prognosis but treatment with
agents (trastuzumab) to target the receptor
is very effective.
Member of family of epidermal growth factors
Transmembrane protein with tyrosine kinase activity
Detected by – immunohistochemistry - fluorescence in situ therapy
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Triple negative carcinomas/Basal like carcinomas
Absence of ER,PR & HER2/neu
Absence of expression of markers typical of
myoepithelial cells –basal keratins, P cadherin, p63
Very poor response to hormone therapy
Chemotherapy used for treatment
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5) Lymphovascular Invasion –
Presence of tumor cells within lymphatics or small capillaries.
Leads to inflammatory breast carcinoma
Associated with lymph node metastasis
Poor prognosis
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6) Proliferative rate –
judged by abnormal mitotic figures
higher the rate poorer the prognosis
Measured by - immunohistochemical detection of cellular proteins (Ki-67) produced during cell cycle - flow cytometry - thymidine labelling index
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7) DNA Content–
Determination of Amount of DNA per tumor cell
– flowcytometry - image analysis of tissue
section Tumor cell with DNA index 1
Same total amount of DNA as normal diploid cell
Aneuploid tumors with abnormal indices have worse prognosis than tumor cells with DNA index 1.
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8) Response to Neoadjuvant Therapy
Systemic treatment before surgery
Doesn’t improve survival
Treated tumor responds better to chemotherapy
good prognosis
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9) Gene Expression Profiling –
Determines - metastatic potetial, -type of chemotherapy required for
treatment
Formalin fixed paraffin embeded tissues used
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CONCLUSION
Grading staging and evaluation of prognostic
factors of breast carcinoma are extremely important modalities which help
the clinician to - devise an effective plan of treatment - counsel the patients better - provide quality cancer care
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