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Management of Management of Breast CancerBreast Cancer

ByByHussein M. KhaledHussein M. Khaled

Prof. Medical OncologyProf. Medical OncologyVice President Vice President

Post graduate Studies and ResearchPost graduate Studies and ResearchCairo UniversityCairo University

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BREAST CANCERBREAST CANCERWorldwide incidence in females*Worldwide incidence in females*

*Incidence per 100,000 population.

Parkin DM, et al. CA Cancer J Clin. 1999;49:33-64.

67.4

36.0

28.6

71.7

21.2

25.0

31.5

25.5

86.3

Eastern Eastern EuropeEurope

JapanJapan

Australia/Australia/New ZealandNew Zealand

South CentralSouth CentralAsiaAsia

Northern Northern AfricaAfrica

Southern Southern AfricaAfrica

Central Central AmericaAmerica

WesternWestern Europe Europe

NorthNorthAmericaAmerica

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CANCER CONTROLCANCER CONTROL

EARLYEARLYDETECTIONDETECTION

DIAGNOSISDIAGNOSISPRIMARYPRIMARY

PREVENTIONPREVENTION

TREATMENTTREATMENT

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BREAST CANCERBREAST CANCERSigns and symptoms at Signs and symptoms at

presentationpresentation Mass or painMass or pain

in the axillain the axilla

Palpable massPalpable mass ThickeningThickening PainPain

Nipple dischargeNipple discharge Nipple retractionNipple retraction

Edema or erythemaEdema or erythema

of the skinof the skin

5

6

BREAST CANCERBREAST CANCERDiagnosis pathDiagnosis path

Evaluationfor

biopsy

Cystaspiration

Biopsy•Excisional biopsy•Core-cutting needle biopsy•Fine-needle aspiration

Palpable mass

Ductalcarcinoma

in situ

Invasivecancer

Lobularcarcinoma

in situBenign

Insufficientevaluation,rebiopsy

If persistent, short-term follow-up

with surgeon

Continuedappropriatescreening

Cyst Normal

Nonpalpable mass

Treatment Path

Needlelocalization

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Staging Classification of Breast Staging Classification of Breast TumourTumour

8

9

Early Breast CancerEarly Breast Cancer

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11

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NSABP B-06:NSABP B-06:Effect of Lumpectomy v. Mastectomy on SurvivalEffect of Lumpectomy v. Mastectomy on Survival

DIS

TA

NT

DIS

EA

SE

-FR

EE

SU

RV

IVA

L (

%) Cohort A Cohort B Cohort C

Total Mastectomy: 692/265 569/233 494/192

Lumpectomy: 699/302 634/282 520/236

No. of patients / No. of recurrences

YEAR

Lumpectomy + XRT: 714/278 628/253 515/204

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14

HT

15

16

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HER2 testing algorithmHER2 testing algorithm

Adapted from Bilous M, et al. Mod Pathol 2003;16:173–82Hanna W. Breast 2005;14(Suppl.1)S17 (Abstract 10)

+–

FISH/CISH

Patient tumoursample

IHC

2+ 3+1+0

+

FISH/CISH

+–

Herceptin®

therapy

Herceptin® therapy

Herceptin® therapy

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Locally Advanced Breast Locally Advanced Breast CancerCancer

19

20

21

22

23

24

25

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What elements drive therapy decision making ?

Prognosis

Treatmentefficacy

Treatmenttoxicity

Co morbidity

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ER +ER +

ER -ER -

ER +ER +

ER -ER -

T1a (0-5 mm)T1a (0-5 mm) T1b (6-10 mm)T1b (6-10 mm) T1c (11-20 mm)T1c (11-20 mm)

NCINCI

NCCNNCCN*)*)

St. GallenSt. Gallen

GUIDELINE RECOMMENDATIONFOR CHEMOTHERAPY FOR STAGE I BREAST CANCER

Not RecommendedNot Recommended OptionalOptional RecommendedRecommended

*) NCCN = National Comprehensive Cancer Network*) NCCN = National Comprehensive Cancer Network

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www/Adjuvant on line !www/Adjuvant on line !

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The The Breast Health Global Breast Health Global Initiative (BHGI)Initiative (BHGI)

Guideline Publication 2003Guideline Publication 2003

CONSENSUS STATEMENTSCONSENSUS STATEMENTS

Early Detection PanelEarly Detection Panel

Diagnosis PanelDiagnosis Panel

Treatment PanelTreatment Panel

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BHGI GLOBAL SUMMIT BHGI GLOBAL SUMMIT 2005:2005:

Guideline StratificationGuideline Stratification

Breast J 2006;12 Suppl 1:S117-120

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History

Physical examination

Clinical breast examination

Surgical biopsy

Fine-needle aspiration biopsy

Diagnostic breast ultrasound +/- diagnostic mammography

Plain chest radiography

Liver ultrasound

Blood chemistry profile / complete blood count (CBC)

Maximal

Stereotactic biopsy HER-2/neu status

CT scanning, PET scan, MIBI scan, breast MRI

Sentinel node biopsyIHC staining of sentinel nodes

for cytokeratin to detect micrometastases

Enhanced

Diagnostic mammography

Bone scan

On-site cytopathologistPreoperative needle localization

under mammographic or ultrasound guidance

Basic

Interpretation of biopsies

Cytology and/or pathology report describing tumor size, lymph node status, histologic

type, tumor grade

Limited

Determination and reporting of ER and PR status

Determination and reporting of margin status

Core needle biopsy

Image guided sampling (ultrasounographic +/-

mammographic)

Level of resources

Clinical Pathology Imaging and lab testsDiagnoDiagnosissis

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Controversial Issues :Controversial Issues :

FNAC or Frozen SectionsFNAC or Frozen Sections 5 or 10 years of HT5 or 10 years of HT T and AIT and AI Type of CTType of CT Herceptin and othersHerceptin and others Pre or post op CTPre or post op CT Ov ablationOv ablation Cases who do not need systemic Cases who do not need systemic

treatmenttreatment

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Cancer Treatment Cancer Treatment

S

Chemo. Radio.

Types of cancer treatment

Application of cancer treatment

Cost of cancer treatment

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Situation AnalysisSituation Analysis Egypt Egypt

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EGYPT

Gharbia Population–based registryGharbia Population–based registry

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Rate per 100 000 pop.

Incidence Rates of Common Sites of CancerPopulation Data: Females

37.8

8.14.1 3.7 3.7 3.4 3 2.3 2.4

49.6

10.7

6 5.2 5 5.33.5 3 3.6

0

10

20

30

40

50

60

Breast NHL Liver Colon-Rectum

Ovary Bladder Brain&CNS Thyroid Lung

Crude Rate ASIR

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GLOBAL STATISTICS:GLOBAL STATISTICS:Age-Specific Rates / 100,000 Females Age-Specific Rates / 100,000 Females

(all ages)(all ages)

Globocan 2002 (IARC)

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The National Cancer The National Cancer InstituteInstitute

  Cairo UniversityCairo Universitywww.nci.cu.edu.egwww.nci.cu.edu.eg

Cairo University National Cancer Institute

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NCI Most Common Sites in Males NCI Most Common Sites in Males and femalesand females

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National Cancer RegistryNational Cancer Registry

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ProportionProportion Cumm. %Cumm. %

<35<35

35-35-

40- 40-

45-45-

50-50-

55-55-

60- 60-

65-65-

70+70+

7.77.7

12.612.6

14.814.8

17.617.6

16.216.2

10.410.4

11.211.2

5.05.0

4.54.5

7.77.7

20.320.3

35.135.1

52.752.7

68.968.9

79.379.3

90.590.5

95.595.5

100.0100.0

Age structure of Age structure of

Female breast cancer patients.Female breast cancer patients.

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EgyptEgypt US SEERUS SEER

20-2420-24

25-2925-29

30-3430-34

35-3935-39

40-4440-44

45-4945-49

50-5450-54

…………

1.41.4

9.89.8

28.928.9

63.663.6

96.796.7

171.5171.5

181.2181.2

1.31.3

7.17.1

25.225.2

61.761.7

117.5117.5

192.1192.1

253.1253.1

Age-specific Incidence Rates of Breast cancerAge-specific Incidence Rates of Breast cancerin younger age groups: Egypt and US SEERin younger age groups: Egypt and US SEER

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Magnitude of Breast Cancer in Magnitude of Breast Cancer in Egypt: 2025Egypt: 2025

Population size: 51 million females Population size: 51 million females Crude incidence rate: 55.1./100,000 femalesCrude incidence rate: 55.1./100,000 females Incidence: 14,000 Incidence: 14,000 28,000 breast cancer cases 28,000 breast cancer cases

Prevalence: 42,000 Prevalence: 42,000 84,000 breast cancer cases84,000 breast cancer cases

Magnitude of Breast Cancer in Magnitude of Breast Cancer in Egypt: 2050Egypt: 2050

Population size: 64 million females Population size: 64 million females Crude incidence rate: 68.8./100,000 femalesCrude incidence rate: 68.8./100,000 females Incidence: 14,000 Incidence: 14,000 44,000 breast cancer cases 44,000 breast cancer cases

Prevalence: 42,000 Prevalence: 42,000 132,000 breast cancer cases132,000 breast cancer cases

Projection of Magnitude of Breast CancerProjection of Magnitude of Breast Cancer in Egypt: 2025, 2050 in Egypt: 2025, 2050

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Breast cancer T stage 1984 - 2006, Port Said, Breast cancer T stage 1984 - 2006, Port Said, EgyptEgypt

0

10

20

30

40

50

60

70

80

84-1985 86-1988 94-1999 2004 2005 2006

T1 T2 T3 T4

SOURCE: Prof. Dr. Ahmed Elzawawy

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Cancer Control in Cancer Control in EgyptEgypt

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Inflammatory Breast Cancer (IBC)Inflammatory Breast Cancer (IBC)

Swollen

Erythema

Peau d’Orange

Frequently Mistaken for Mastitis

Swollen

Erythema

Peau d’Orange

Frequently Mistaken for Mastitis

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Clinico–Pathological Clinico–Pathological CorrelationCorrelation

in Breast Cancer Cases in Breast Cancer Cases (2002)(2002)

Revision of the slides of 212 patients.Revision of the slides of 212 patients. Only 16 patients had both clinical and Only 16 patients had both clinical and

pathological features of IBC (8%)pathological features of IBC (8%) Age distributionAge distribution

4 patients4 patients 35 yrs or less35 yrs or less

8 patients8 patients 45 yrs or less45 yrs or less

8 patients8 patients More than 45 yrsMore than 45 yrs

The youngest The youngest 25 yrs25 yrs

The oldest The oldest 76 yrs76 yrs

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More than 90% of IBC showed positive axillary nodes.

IBC’s are characterized by:

High histologic grade tumors with high Nuclear grade, necrosis and high PCNA and MIB-1(Ki-67) labeling indices.

ER & PgR are frequently negative.

p53 > 70% positivity.

HER-2/Neu > 60%.

Biologic profile“ Immunphenotypic signature”

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Tumor emboli and LYVE-1 and RhoC expression in IBC Tumor emboli and LYVE-1 and RhoC expression in IBC tumors from Egypt and the United Statestumors from Egypt and the United States

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RhoC Scoring and Tumor Emboli for Egyptian patients with IBC and non-IBC

IBC (N=IBC (N=46)46)

No. (%)No. (%)

Non-IBC Non-IBC (N=(N=64)64)

No. (%)No. (%) PP-value-value

RhoC ScoreRhoC Score

11

22

33

4 4

1 (2)1 (2)

5 (10)5 (10)

2020 (44)(44)

20 (44) 20 (44)

24 (38)24 (38)

29 (45)29 (45)

7 (10)7 (10)

4 (6) 4 (6) <<0.00010.0001

RhoC CategoriesRhoC Categories

1-21-2

3-43-4 6 (13)6 (13)

40 (87)40 (87)53 (83)53 (83)

11 (17)11 (17) <0.0001<0.0001

Tumor EmboliTumor Emboli

Mean ± SDMean ± SD

0-10-1

2-82-8

9+ 9+

14.1 ± 14.014.1 ± 14.0

1 (2)1 (2)

1919 (41)(41)

26 (57) 26 (57)

7.0 ± 12.97.0 ± 12.9

32 (50)32 (50)

18 (28)18 (28)

14 (22 14 (22

<0.0001<0.0001

<0.0001<0.0001

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Cairo University National Cancer Institute

Thank you