Jakarta

11th Nov 2009

Breast Unit
– University Malaya
Medical Centre

CH Yip
Professor
Department of Surgery
University Malaya Medical Centre
 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 2003-5
Race Incidence

Ethnic Group No % CR ASR CumR

Malay 4969 33.6 27.7 34.9 3.6

Chinese 5051 30.3 66 59.8 6.3
Indian 1265 31.2 47 54.1 6

Malay women 1 in 28 lifetime risk

Chinese women 1 in 16 lifetime risk
Indian 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 UMMC
Stage at presentation 1993-2008 (3689 cases)

Early Stage –Stage 1 and 2

Late Stage – Stage 3 and 4
100%
90%
80%
70% Stage 4
60% Stage 3
50% Stage 2
40% Stage 1
30%
20%
10%
0%
95

97

99

07
93

01

03

05
19

19

19

20
19

20

20

20
 Breast Cancer in UMMC
Stage at presentation and race 2008 (442 cases)

Malays 72
Chinese 313
Early Stage –Stage 1 and 2 Indians 57
Late Stage – Stage 3 and 4
100%
90% Stage 4
80% Stage 3
70% Stage 2
60% Stage 1
50% Stage 0
40%
30%
20%
10%
0%
Malays Chinese Indians
 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

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

Overall survival plot

1.0
Estimated survival probabilities

0.8

0.584
0.6
0.4
0.2
0.0

0 20 40 60 80 100
Survival times

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

 Survival by Stage in UMMC
1993-1997 (n=423)
Survival Plot by Stage
1.0 Stage 1
Stage 2
Stage 3
Stage 1 Stage 4
Estimated survival probabilities
0.8

Stage 2
0.6

Stage 3
0.4
0.2

Stage 4
p < 0.05
0.0

0 20 40 60 80 100

Survival times

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

Chinese
Indian
Malay
0.8
Estimated survival probabilities

p = 0.0025
0.6
0.4
0.2
0.0

0 20 40 60 80 100

Survival times
 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
1.0

76.2%
0.8
Survival Probability
0.6
0.4

59.1%
0.2

patients 93 - 97
patients 98 - 02
0.0

0 20 40 60 80 100
Months

93-97 Median follow-up : 56 months

98-02 Median follow-up : 53 months
 Ethnic Group
1993-97 1998-2002
1.0

1.0
Chinese
Indian
Malay

0.8
0.8

Survival Probability
0.6
0.6
Survival

0.4
0.4

Others
Malay

0.2
Indian
Chinese
0.2

p= 2.85e-010

0.0
p-value0.00631 0 20 40 60 80 100
0.0

Months

0 20 40 60 80 100
Months

5-year survival 1993-1997 1998-2002

probability

p=0 Chinese 63.5% 81.6%

Indian 57.4% 80.4%
Malay 47.5% 58.9%
Other NA 92.9%
 Stage
1998-2002

1.0
0.8
Survival Probability
0.6
1993-97
1.0
I

0.4
II
III
IV stg IV
0.8

stg III

0.2
stg II
stg I
stg 0
0.6

p= 0
Survival

0.0
0 20 40 60 80 100
0.4

Months
0.2

p-value=0 1993-1997 1998-2002

0.0

0 20 40 60 80 100
Months

Stage 0 NA 100%
Stage 1 82.6% 95%
p=0.
Stage II 72.8% 87.1%
Stage III 39.8% 56.3%
Stage IV 13.2% 20.7%
 History of Breast Services
Breast Clinic database - non-dedicated service-
1993-1996 General Surgeons performing surgery and
chemotherapy

1998
In-house radiotherapy services

1996
Dedicated Breast Unit
with surgical
chemotherapy service

1999
Daycare Oncology
chemotherapy service
 History of Breast Services
1993 to present
1993 Radiologist services

2000 Reconstruction
2003 Combined pathology meeting
 Support Services

1993- Survivor Support-BCWA

2003- Breast Care Nurse sanctioned

2005-Breast Cancer Resource Centre

2007- Free basic prosthesis kit

2007-Psychooncology services

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 standard
chemotherapy 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)

 Research Methodology
Recruitment into
CARIF-UMMC research study
n = 901

Cohort selection
for BRCA1 / 2 screening
n = 282

Patients with
deleterious Patients with Patients with
mutations unclassified variants no mutations
n = 41 n = 63 n = 183

Patients approached
for genetic Patients approached
Other genetic studies
counseling genetic counseling
& family studies
 Uptake of BRCA status results
Patients with
deleterious mutations
n = 41

Patients who are Patients who do not

Patients who want
deceased / cannot want genetic
genetic counseling
be contacted counseling
n = 33
n=3 n=5
• 28 (85%)decided after 1st intake • 3 - do not want the burden of
• 2 (6%) decided after 2 intakes carrier status
• 3 (9%) decided after 3 intakes • 1 - do not want to relive treatment
trauma
• 1 - spouse did not want patient
to have further information about
her genes.
 Informing relatives

Index patients with deleterious mutations counseled

n = 33

Yes, I want to I am considering No, I don’t want to

inform my relatives informing my relatives inform my relatives
n = 25 n=1 n=7

• Have poor relationships

Families who Families Families who with family members
want considering declined • Do not want to burden
counseling counseling counseling family with carrier
n = 15 n=4 n=6 information

• Worried about
insurance
• Doesn’t think that
Information will be useful
• Doesn’t think they can cope
with the knowledge
 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