KIRTI DIXIT IV TERM BGS GIMS GUIDE- Dr. DHARANI

CA BREAST GRADING, STAGING &

PROGNOSTIC FACTORS

OVERVIEW

Introduction

Grading

Staging

Prognostic factors

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.

STATISTICAL FACTS

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

Obesity

Breastfeeding & Exercise

Environmental toxins

AETIOPATHOGENESIS – 12% FAMILIAL

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

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

GRADING– WHY ….?

For treatment and prognosis

Lower grade better prognosis

Higher grade worse prognosis

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

NUCLEAR PLEOMORPHISM

NUCLEAR PLEOMORPHISM

,

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

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%

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.

Distant Metastasis (M) MX - Distant metastasis cannot be evaluated M0 - No distant metastasis M1 - Distant metastasis

Tumour not involving skin or chest wall

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

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

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

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

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%,

5 ) Locally advanced disease :

Carcinomas invading into skin or skeletal muscles

Poor prognosis

Ususally large , difficult to treat surgically

6 ) Inflammatory Ca - Peau d’ orange :

Obstruction of dermal lymphatics

Breast swelling and skin thickening

Poor prognosis

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 %

BETTER PROGNOSIS (>60%)

RELATIVELY POOR PROGNOSIS (<20%)

•Mucinous • Micropapillary

• Medullary • Metastatic

• Papillary

•Tubular

• Lobar

• Cystic

2 ) Histologic subtypes

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

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

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

5) Lymphovascular Invasion –

Presence of tumor cells within lymphatics or small capillaries.

Leads to inflammatory breast carcinoma

Associated with lymph node metastasis

Poor prognosis

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

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.

8) Response to Neoadjuvant Therapy

Systemic treatment before surgery

Doesn’t improve survival

Treated tumor responds better to chemotherapy

good prognosis

9) Gene Expression Profiling –

Determines - metastatic potetial, -type of chemotherapy required for

treatment

Formalin fixed paraffin embeded tissues used

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