Breast Unit – University Malaya

Medical Centre

CH YipProfessor

Department of SurgeryUniversity Malaya Medical Centre

Jakarta

11th Nov 2009

Female Breast Cancer – NCR report 2003-2005

• 11 952 new cases over 3 years• Commonest cancer in Malaysia overall• Commonest cancer in Malaysian women • Crude rate 41.3 per 100,000• Age standardised rate (ASR) 46.4 per 100,000• Cumulative risk 5.0 ie a woman in Malaysia

have a 1 in 20 chance of developing breast cancer in her lifetime

Female Breast Cancer– NCR report 2003-5Race Incidence

Ethnic Group No % CR ASR CumR

Malay 4969 33.6 27.7 34.9 3.6Chinese 5051 30.3 66 59.8 6.3Indian 1265 31.2 47 54.1 6

Malay women 1 in 28 lifetime riskChinese women 1 in 16 lifetime riskIndian women 1 in 17 lifetime risk

Introduction

• The Breast Unit in UMMC was started in 1993

• The main activities of the Breast Unit are:

- Clinical services

- Education and training

- Research activities

Breast Unit in UMMC

Multidisciplinary clinical services• Surgery – breast surgery (mastectomy and lumpectomy, axillary

dissection) , immediate and delayed breast reconstruction

• Radiology – screening and diagnostic mammogram, ultrasound, MRI, guided biopsies

• Pathology – cytopathology and histopathology

• Oncology – chemotherapy, radiotherapy, targeted therapy (Oncology Unit started in 1999)

• Psycho-oncology (In 2007)

• Breast care nurse (In 2003)

• Palliative care (In 2007)

• Rehabilitative Medicine (2005)

Clinical Services

• Breast clinics – new cases clinic, follow-up clinic, results clinic, screening clinic, familial breast cancer clinic (risk assessment and risk management clinic)

• Multidisciplinary meeting ( radiology, patholgoy, surgery oncology) – once a week

• Main operating theatre – once a week• Daycare surgery – once a week• Breast cancer combined clinic (0ncology and surgery)

- once a week

Education and Training

• Undergraduate teaching - MBBS

• Postgraduate training – Master of Surgery programme, Mastectomy and axillary clearance is an index operation

• Breast Surgery Fellowship

Research

Collaboration• Cancer Research Initiatives Foundation (CARIF)

• Monash University

• University of Ohio Clinical Trials Centre

• Medical University of Vienna

• University of West of England

• Irish Cancer Registry

• Dharmais Cancer Centre, Jakarta

• UICC-ARO

• Within UM - Social and Preventive Medicine, Biostatistics, Molecular Biology, Institute of Mathematics, Faculty of Science

UMMC Breast Cancer Database

• Since the breast unit began in 1993, all new cases of breast cancer presenting to the UMMC was recorded

• The current database has nearly 4 000 patients registered

• This valuable database is the source of most of the clinical research eg stage, age, race, pathological features

• With the IC number, survival data is available

Breast Cancer in UMMCStage at presentation 1993-2008 (3689 cases)

Early Stage –Stage 1 and 2Late Stage – Stage 3 and 4

0%10%20%30%40%50%60%70%80%90%

100%

1993

1995

1997

1999

2001

2003

2005

2007

Stage 4Stage 3Stage 2Stage 1

Breast Cancer in UMMCStage at presentation and race 2008 (442 cases)

Early Stage –Stage 1 and 2Late Stage – Stage 3 and 4

0%10%20%30%40%50%60%70%80%90%

100%

Malays Chinese Indians

Stage 4Stage 3Stage 2Stage 1Stage 0

Malays 72

Chinese 313

Indians 57

Hormone receptor status at presentation

White Hispanic Blacks UMMC

ER+PR+ 58% 58% 44% 42.9%

ER+PR- 15% 12% 14% 11.1%

ER-PR+ 6% 8% 7% 8.8%

ER-PR- 20% 22% 35% 37.2%

13239 cases.

Gapstur etal Cancer 1996

15 year review of ER status in UMMC

Year ER positive ER negative Total

1994-1998 150 (54.3%) 126 276

1999-2003 588 (56.6%) 451 1039

2004-2008 1019 (58.3%) 728 1747

Total 1757 (57.4%) 1305 3062

P=0.406

15 year review of ER status in UMMC

Race ER positive ER negative Total

Malay 318 (52%) 293 611

Chinese 1218 (59.4%) 832 2050

Indian 221(55.1%) 180 401

Total 1757 1305 3062

P=0.003

15 year review of ER status in UMMC

Age ER positive ER negative Total

Less than 40 192 (51.1%) 185 377

40 and above 1565 (58.3%) 1120 2685

Total 1757 1305 3062

P=0.007

Ongoing analysis of breast cancer database

Master of Surgery projects – funding from the Clinical Masters research grant

• A Review of Pathological Subtypes of Breast Cancer in UMMC. • The association between estrogen, progesterone and HER2

receptors with patient characteristics and prognosis in breast cancer.

• Early Breast Cancer Survival and the Nottingham Prognostic Index

Data management

• Improving breast cancer management delivery through the development of a comprehensive data management system and survival analysis

(Funded by MOSTI)

Breast Cancer Survival in Malaysia

• Mortality statistics inaccurate• Only 40% of deaths are medically certified• Hospital data – UMMC database on breast cancer

1993-2002. Exclude DCIS and patients who absconded. Total of over 800 patients

• Patient’s IC checked with the Registry Dept (JPN) to see if they are alive or dead

• Study of survival in 2 cohorts – 1993-1997 and 1998-2002

Yip etal APJCP 2006

0 20 40 60 80 100

Survival times

0.0

0.2

0.4

0.6

0.8

1.0

Estim

ated

sur

viva

l pro

babi

litie

sOverall survival plot

0.584

Median follow-up : 55 months(1 month to 107 months)

Overall Survival Breast Cancer Patients in UMMC- 1993-1997 (n=423)

0 20 40 60 80 100

Survival times

0.0

0.2

0.4

0.6

0.8

1.0

Estim

ated

sur

viva

l pro

babi

litie

s

Stage 1Stage 2Stage 3Stage 4

Survival Plot by Stage

Stage 1

Stage 2

Stage 3

Stage 4p < 0.05

Survival by Stage in UMMC

1993-1997 (n=423)

Mohd Taib NA, Yip CH, Mohamed I. Survival analysis of Malaysian women with breast cancer: results from the University Malaya Medical Centre. Asian Pac J Cancer Prev 2008 Apr-Jun;9(2):197-202

0 20 40 60 80 100

Survival times

0.0

0.2

0.4

0.6

0.8

1.0

Estim

ated

sur

viva

l pro

babi

litie

s

ChineseIndianMalay

Survival Plot by Race

p = 0.0025

Survival by Race in UMMC-1993-1997 (n=423)

Survival analysis

• The Cox regression model by stepwise selection showed stage, nodal status and grade of tumour to be independent prognostic factors, whereas ethnicity, age and ER status were not.

• Survival analysis ongoing – comparing survival in 5-year cohorts

5-year Overall Survival

0 20 40 60 80 100

0.0

0.2

0.4

0.6

0.8

1.0

Months

Sur

viva

l Pro

babi

lity

patients 93 - 97patients 98 - 02

93-97 Median follow-up : 56 months98-02 Median follow-up : 53 months

76.2%

59.1%

Ethnic Group

0 20 40 60 80 100

0.0

0.2

0.4

0.6

0.8

1.0

OthersMalayIndianChinese

Months

Sur

viva

l Pro

babi

lity

p= 2.85e-010

0 20 40 60 80 100

0.0

0.2

0.4

0.6

0.8

1.0

ChineseIndianMalay

Months

Sur

viva

l

p-value0.00631

5-year survival probability

1993-1997 1998-2002

Chinese 63.5% 81.6%

Indian 57.4% 80.4%

Malay 47.5% 58.9%

Other NA 92.9%

p=0

1993-97 1998-2002

Stage

0 20 40 60 80 100

0.0

0.2

0.4

0.6

0.8

1.0

stg IVstg IIIstg IIstg Istg 0

p= 0

Sur

viva

l Pro

babi

lity

Months

0 20 40 60 80 100

0.0

0.2

0.4

0.6

0.8

1.0

Months

Sur

viva

lIIIIIIIV

p-value=0 1993-1997 1998-2002

Stage 0 NA 100%

Stage 1 82.6% 95%

Stage II 72.8% 87.1%

Stage III 39.8% 56.3%

Stage IV 13.2% 20.7%

p=0.

1993-97

1998-2002

History of Breast ServicesBreast Clinic database - non-dedicated service-General Surgeons performing surgery and chemotherapy

1993-1996

Dedicated Breast Unit with surgical chemotherapy service

In-house radiotherapy services

Daycare Oncology chemotherapy service

1996

1998

1999

History of Breast Services1993 to present

2000 Reconstruction

2003 Combined pathology meeting

1993 Radiologist services

Support Services

2003- Breast Care Nurse sanctioned

2005-Breast Cancer Resource Centre

1993- Survivor Support-BCWA

2007-Psychooncology services

2007- Free basic prosthesis kit

2007- Palliative care consultancy

Psycho-social research

• Qualitative study on why women with breast cancer come late. (MD research project ongoing)

• Husband Support during adjuvant chemotherapy after different modalities of breast cancer treatment (PhD completed 2008)

• The self-management intervention of Malaysian women with breast cancer – enabling participation and quality of life (PhD completed 2009)

• Measuring Disability using ICF core sets in Breast Cancer Survivors. WHO Collaboration (Rehab Medicine Dept)

• Information Needs of Breast Cancer Patients on Chemotherapy from the patients and nurses perspective. (M Med Sc completed 2008)

Why do women present late?

• Small pilot study in UMMC on 25 women presenting with late disease

• 60% had tried alternative therapy as the first choice of treatment; the rest ignored the symptoms or prayed, hoping that it would go away

• One had spent over USD10 000 of alternative therapy

• Main reasons was fear of surgery and belief in traditional treatment, others were financial, family problems, did not know that cancer could spread….

• Most had been diagnosed early but did not agree to conventional treatment

Taib NA, Yip CH etal APJCP 2007

32 year old woman, diagnosed with early breast cancer, refused treatment, went for traditional medicine, returned after a year with locally advanced breast cancer

Traditional medicine

• Scars on the breast from traditional medicine

Traditional Medicine

• 33 yr old diagnosed with breast cancer when 36 weeks pregnant

• After delivery defaulted surgery

• Presented 5 months later with a large right breast mass

• Alternative therapy with joss sticks

Clinical trials

• Phase 3 Randomized Study of Luteal Phase vs Follicular Phase Surgical Oophorectomy and Tamoxifen in premenopausal women with metastatic hormone-receptor positive breast cancer – Multicentric international study in collaboration with the Professor Richard Love, University of Ohio Clinical Trials Centre.

• A multi-national, multicentre randomized, double-blind, parallel group, placebo-controlled clinical trial to investigate safety and efficacy of tibolone (Org OD14) in women with climacteric symptoms and a history of breast cancer Organon

• Randomised Phase 2 trial of Gemcitabine combined with a Taxane for metastatic breast cancer Eli Lilly

• Phase II, open label study of SB-715992 in subjects with advanced or metastatic breast cancer. GSK

• A Phase III trial of novel Epothilone BMS-247550 plus capecitabine versus capecitabine alone in patients with advanced breast cancer previously treated with or resistant to an anthracycline and who are taxane resistant. BMS

Clinical trials

• A Phase II, Open-label, Randomised, Multicenter Trial of GW786034 (Pazopanib) in combination with Lapatinib (GW 572016) compared to Lapatinib alone as first line therapy in subjects with advanced or metastatic breast cancer with erb-B2 FISH positive tumours. GSK

• A phase 3 multicentre, randomised, placebo-controlled trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy regimens in subjects with previously treated metastatic breast cancer. Roche

• BEATRICE studyPhase 3 adjuvant standard chemotherapy vs standardchemotherapy plus bevacizumab for triple negative breast cancer. Roche

• Real-Life Extended Adjuvant Surveillance Study Upon registration (REASSURE) Trial: Observational study on the use of LETROZOLE In the Extended Adjuvant Treatment of patients with hormone-receptor-positive early breast cancer. Novartis

Molecular Medicine and Pathology• A Study of Hormonal Receptors and Topoisomerase II Alpha as Prognostic

Markers in Asian Breast Cancer Patients. Collaboration with Monash University and UM Dept of Pathology

• Analysis of genetic factors that contribute to increased risk o breast cancer in Malaysia’s multi-ethnic population- Role of TP 53. Collaboration with CARIF

• The clinical predictors, spectrum and frequency of BRCA1 and BRCA2 mutations in an ethnically diverse high risk clinic population and to evaluate the performance of various risk prediction models (BRCAPRO, BOADICEA, MYriad statistical models) and the Manchester scoring system in predicting the likelihood of a mutation. Collaboration with CARIF.

• Association between Low Penetrance Gene(s) and Risk to Breast Cancer in Malaysian High-Risk Breast Cancer Patients. Collaboration with CARIF.

• Gene Analysis of Selected Oncogenes in Breast Cancers and Correlation with Patient Survival. Collaboration with Monash University.

• Gene Analysis of Selected Oncogenes in Breast Cancers and Correlation with Patient Survival. Collaboration with Monash University.

• Role of immunohistochemistry in the diagnosis of proliferative breast lesions. Collaboration with Dept of Pathology

CARIF-UM Familial Breast Cancer Study

• Objectives of the CARIF-UM breast cancer study :

– To determine the prevalence of BRCA1 & 2 mutations

To determine risk assessment model in an Asian population

– To determine impact of genetic testing in this multi -ethnic population

• 282 breast cancer patients were screened

(Thirthagiri et al, Breast Cancer Research August 2008)

Patients with unclassified variants

n = 63

Recruitment intoCARIF-UMMC research study

n = 901

Research Methodology

Cohort selectionfor BRCA1 / 2 screening

n = 282

Patients withno mutations

n = 183

Patients withdeleterious mutations

n = 41

Patients approachedfor genetic counseling

Patients approached genetic counseling

& family studies

Other genetic studies

Patients with deleterious mutations

n = 41

Uptake of BRCA status results

Patients who are deceased / cannot

be contactedn = 3

Patients who do notwant geneticcounseling

n = 5

Patients who want genetic counseling

n = 33

• 28 (85%)decided after 1st intake• 2 (6%) decided after 2 intakes• 3 (9%) decided after 3 intakes

• 3 - do not want the burden ofcarrier status• 1 - do not want to relive treatmenttrauma• 1 - spouse did not want patientto have further information about her genes.

Index patients with deleterious mutations counseledn = 33

Yes, I want to inform my relatives

n = 25

Informing relatives

No, I don’t want to inform my relatives

n = 7

Families who want

counselingn = 15

Families who declined

counselingn = 6

Familiesconsidering counseling

n = 4

• Have poor relationshipswith family members• Do not want to burdenfamily with carrier information

• Worried aboutinsurance• Doesn’t think thatInformation will be useful• Doesn’t think they can copewith the knowledge

I am consideringinforming my relatives

n = 1

Lessons learnt from pilot study

• Risk assessment challenges• Organisational challenges• Counseling challenges / Issues raised

Translation of research project into clinical practice

• Genetic counseling under auspice of research serve as a basis for planning of a familial cancer service

• Pilot study revealed counseling issues which can expected in future clinics

Translating research into clinical practice –Other examples

• Self management research – translate into setting up a clinical service for patients

• Results from the qualitative study on why women present late will translate into overcoming barriers to early detection

Future research plans

• Genetics – applying for ERI grant for collaborative studies with Hong Kong and Singapore

• Collaborative research with University of West of England to compare breast cancer in Asians and Caucasians

• Clinical Epidemiology - research project with Indonesia to compare presentation of breast cancer in two neighbouring countries

The success of a breast unit depends on collaboration between all the members of the unit – surgeon,radiologist, pathologist, breast

care nurse, oncologist, basic scientist, biostatisticians etc

AND most important of all,

THE PATIENTS……

Thank you