Professional Documents
Culture Documents
Reproduced with permission Ferlay J., Soerjomataram I., Ervik M., Dikshit R., Eser S., Mathers C., Rebelo M., Parkin D.M., Forman D., Bray, F.
GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide:IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for 8
Research on Cancer; 2013.Available from: http://globocan.iarc.fr, accessed on 02/06/2015.
Breast cancer is by far the most frequent cancer among women with an
estimated
1.6 million new cases diagnosed with more than 500,000 deaths
each year
(GLOBOCAN 2012)
Ferlay J, et al. Cancer incidence and mortality worldwide : source, methods and major pattern in globocan 2012. IJC. 2014. 136: E358-E386
Incidence and
mortality of breast
cancer is the biggest
among cancer in
Indonesia
11
MANAGEMENT of BREAST CANCER
1. DIAGNOSIS
2. STADIUM
3. PERFORMANCE STATUS
4. THERAPY PLANNING
5. THERAPY IMPLEMENTATION
6. EVALUATION
Diagnosis
TRIPLE DIAGNOSTIK
1. KLINIS
2. IMAGING/RADILOGI
3. HISTOPATOLOGI
13
KLINIS
ANAMNESIS
KELUHAN PAYUDARA DAN AXILLA
KELUHAN DITEMPAT LAIN
FAKTOR RESIKO
PEMERIKSAAN FISIK
STATUS GENERALIS
STATUS LOKALIS
PAYUDARA /IPSILATERAL dan KONTRALATERAL
MASA TUMOR : LOKASI,UKURAN,KONSISTENSI,PERMUKAAN,BENTUK
DAN BATAS TUMOR, JUMLAH TUMOR, FIKSASI TUMOR DI DINDING
DADA dan KULIT
PERUBAHAN KULIT
PAPILLA MAMA
KGB REGIONAL : AXILLA, INFRA CLAVICULA, SUPRA CLAVICULA
PEMERIKSAAN ORGAN LAIN (METASTASIS)
DIAGNOSA KLINIS : TUMOR PAYUDARA D SUSPECT
GANAS TNM
14
IMAGING/RADIOLOGI
USG
MAMOGRAFI
MRI
PET SCAN/PET CT
15
HISTOPATOLGI
16
STAGING/STADIUM
TNM (UICC,AJCC)
KLINIS (PEMERIKSAAN KLINIS)
RADIOLOGI : RO THORAX, USG LIVER
BONE SCANNING, BONE SURVEY,
CT SCAN,
MRI,PET SCAN/CT
17
PERFORMANCE STATUS
KARNOFSKY SCORE
WHO SCORE
ECOG SCORE
18
How is Breast Cancer Treated?
Treatment depends on stage of cancer
Surgery
Radiation therapy
Chemotherapy
Hormone therapy
Targeted therapy
Cancer Treatment: Adjuvant Therapy
HR+
65-75%
Triple
Neg 15%
HORMONAL TREATMENT
FOR POSTMENOPAUSAL BREAST
CANCER
26
Intrinsic subtype of breast cancer (St Gallen 2015) which is also
recommended by ESMO Clinical Practice Guidelines for making the
prognosis and treatment decision
Senkus E et al. Annals of Oncology. 2015. Downloaded from http://annonc.oxfordjournals.org/ at AZ Library on May 30,
2016 27
Treatment recommendation
for early breast cancer subtypes
Senkus E et al. Annals of Oncology. 2015. Downloaded from http://annonc.oxfordjournals.org/ at AZ Library on May 30, 2016
28
NCCN Guideline Version 2.2016
Adjuvant Endocrine Therapy For Postmenopausal Breast cancer
Aromatase inhibitors (AIs) and Tamoxifen are option for endocrine therapy for post
menopausal breast cancer patient.
NCCN Clinical practice guideline in oncology (NCCN Guidelines ). Version 2.2016. printed 6/2/2016 29
ARIMIDEX (anastrozole) :
Long term efficacy and tolerability
ATAC Trial Design
9366 postmenopausal women with localised
invasive breast cancer
Tamoxifen Arimidex
38
Comparison of lipid profile in
premenopausal and postmenopausal
women
Bade G et al. 2014. Downloaded free from http://www.cysonline.org on Tuesday, May 31, 2016.
A case-control study conducted in 2001-2003 in department of Surgical
Oncology in New Delhi.
The study involved 160 patients diagnosed with breast cancer which have not
received any treatment specific for breast cancer
Asia : Rates in Singapore, particularly among the Chinese, are also relatively high
for the region
Bray F et al. Breast Cancer Research. 2004; 6:229-239
Recovery from Chemotherapy-induced Amenorrhea: According
to Age
Proportion patient with Amenorrhea decreasing for Age < 40
Kim HA et al. The Incidence of Chemotherapy-induced Amenorrhea and Recovery in Young (<45-year-old) Breast Cancer Patients.
J Breast Cancer. 2009 Mar;12(1):20-26 (South Korea)
Chemotherapy-Induced Amenorrhea (CIA) for
Hormone Receptor Positive (HR +) & Prognosis
DFS OS
Patient no CIA showed poor Disease Free Survival (DFS) and Over all Survival (OS)
Jung M et al. The clinical outcome of chemotherapy-induced amenorrhea in premenopausal young patients with breast cancer with
long-term follow-up. Ann Surg Oncol. 2010 Dec;17(12):3259-68. (South Korea)
ZOLADEX in the management
of breast cancer
St Gallen 2013
It suggests that adjuvant tamoxifen alone may not be very effective in very young HR(+) patients
Early breast cancer can be treated with ovarian suppression using the GnRH analogue
(goserelin)2
Adjuvant or after adjuvant chemotherapy in pre-/peri-menopausal women
Note :
HR: hormone receptor
GnRH: Gonadotropin hormone-releasing hormone
Pituitary gland
LHRH
(hypothalamus)
Breast
Gonadotrophins
(FSH + LH)
Ovary
Pituitary Pituitary
Cell LH Cell LH
Adapted from :
Kovacs M. PNAS. 2001; 98(21):1219712202
Emons et al. Trend in Endocrinology and metabolism. 1997. Vol.8,No.9 LH : luteinizing hormone.
ZOLADEX 3.6 mg suppresses serum oestradiol to
postmenopausal level by the eighth day.
Matta WH, et al. Endocrinologic and clinical evaluation following a single administration of a GnRH agonist (ZOLADEX),in a depot formulation to premenopausal
women.Fertil Steril. 1988;49:163-165
IBCSG VIII: Trial Design
Objective
To examine the role of adjuvant treatment using chemotherapy, ovarian suppression with
goserelin, or the sequential combination of both modalities in pre- and peri-menopausal
patients with lymph nodenegative breast cancer
Pre-/Peri-menopausal
Stratification R
a
n
ZOLADEX 3.6 mg/28 days for 2 years
d
ER+ or ER or ER o
unknown m 1:1:1
Surgery i CMF* x 6 cycles
Planned
z (N=1063)
radiotherapy
a
(Yes/No)
t
CMF* x 6 cycles followed by ZOLADEX
Institution i
o
3.6 mg/28 days for 18 months
n
Primary Outcome:
*CMF: Cyclophosphamide 100 mg/m2 oral on
Disease-free survival days 1-14; Methotrexate 40 mg/m2 IV on days
1, 8; 5-Fluorouracil 600 mg/m2 IV on days 1, 8
Castiglione-Gertsch M et al. J Natl Cancer Inst. 2003;95:18331846.
IBCSG VIII Result : DFS in ER+ Patients by Age
ZOLADEX 3.6 mg demonstrated similar efficacy to CMF with respect to DFS in
pre-/peri-menopausal women with hormone-sensitive, node-negative disease
80 80
60 60
R
a ZOLADEX 3.6mg/28 days for
n 2 years
Tumor recurrence
d
o
m
1:1
Surgery
i Death
radiotherapy
z
Eligibility criteria: a
Pre- or peri-menopausal t
Age: 50 years i CMF* x 6 cycles (each cycle
Node-positive Stage II o of 28 days)
early breast cancer n
80 80
60 60
R
a ZOLADEX 3.6mg/28 days for
n 2 years
Tumor recurrence
d
o
m
1:1
Surgery
i Death
radiotherapy
z
Eligibility criteria: a
Pre- or peri-menopausal t
Age: 50 years i CMF* x 6 cycles (each cycle
Node-positive Stage II o of 28 days)
early breast cancer n
(A) Kaplan-Meier curve of OS in the ER-positive (B) Kaplan-Meier curve of OS in the ER-negative
patient subgroup patient subgroup
A 1.0
Goserelin B 1.0
Goserelin
CMF CMF
0.9 0.9
0.8 0.8
0.7 0.7
Proportion alive
Proportion alive
0.6 0.6
0.5 0.5
HR=0.94:95% CI:0.75-1.18 HR=1.64:96% CI:1.13-2.39
0.4 0.4
0.3 0.3
0.2 Patients at risk at the start of each year 0.2 Patients at risk at the start of each year
0.1 591 573 554 521 487 450 374 262 174 83 Goserelin 0.1 144 136 125 107 95 81 64 53 33 16 Goserelin
598 584 555 535 512 455 377 261 166 89 CMF 160 154 140 124 119 108 97 74 51 22 CMF
0 0
0 1 2 3 4 5 6 7 8 9 10 0 1 2 3 4 5 6 7 8 9 10
Time (years) Time (years)
1.0
ZOLADEX 3.6 mg
0.9
Proportion alive and free
CMF
0.8
0.7
of disease
0.6
0.5
0.4
0.3
0.2
HR=1.05, 95% CI 0.881.24; p=0.597
0.1
0
0 1 2 3 4 5 6 7 8 9 10
Time (years)
R
a CAF
n
6 x 28-day cycles
d
o
Multicenter, US m
comparative trial
1:1:1 CAF x 6 cycles followed by
i
Surgery ZOLADEX 3.6mg/28 days for 5 years
z
radiotherapy
a
t CAF x 6 cycles followed by ZOLADEX
i
3.6mg/28 days for 5 years + tamoxifen
o
n
10 mg p.o bid for 5 years
0.6
9-yr DFS
0.4
CAF 57%
0.8
Probability
0.6
9yr DFS
0.4
CAF 48%
0.2 CAFZ 55%
CAFZT 64%
0
0 1 2 3 5 6 7 8 9 10
Disease Free Survival (years)
For women < 40 years seemed to benefit from the addition of ZOLADEX to CAF
R
a ZOLADEX 3.6 mg/28 days
n for 3 years +
d Tamoxifen 20 mg/day
Pre-menopausal women with o for 5 years
ER+ and/or PgR+ breast cancer m
Node +ve or node ve i
z
a
t
i CMF x 6 cycles
o
1034 assessable patient
Stage I & II n
CMF = Cyclophosphamide 600 mg/m2 ,Methotrexate 40 mg/m2
and Fluorouracil 600 mg/m2
Jakesz R et al. J Clin Oncol. 2002;20:46214627. ABCSG5 : Austrian Breast and Colorectal Cancer Study Group
Trial 5
ABCSG5: Outcomes
ZOLADEX +Tamoxifen is more effective than chemotherapy in the adjuvant
treatment of HR+ pre-menopausal patients with stage I and II breast cancer
90
RFS (%)
80
0 12 24 36 48 60
Months
Tamoxifen 2040mg/day
Standard randomise for 2 years
Surgery
. + 1:1:1:1
therapy
Zoladex 3.6mg/28 days +
tamoxifen 2040mg/day for 2 years
No further treatment
Baum et al. Eur J Cancer. 2006; 42:895-904 ZIPP : Zoladex in Pre-menopausal Patients
ZIPP: Outcomes
ZOLADEX combined with standard therapy is more effective than standard
therapy alone in pre-menopausal women with early breast cancer1,2
Kaplan-Meier curve of event-free survival in patients Kaplan-Meier curve of overall survival in patients receiving
receiving goserelin or no goserelin in addition to standard goserelin or no goserelin in addition to standard adjuvant
adjuvant therapy. therapy.
Goserelin Goserelin
1.0 1.0
Control Control
0.8 0.8
Proportion alive and
Proportion alive
0.6 0.6
event-free
0.4 0.4
HR 0.81;95%, CI 0.67-0.99,
HR 0.80;95%, CI 0.69-0.92,
P=0.038
0.2 P=0.002 0.2
0.0 0.0
0 2 4 6 8 10 12 0 2 4 6 8 10 12
Time since randomisation (years) Time since randomisation (years)
Number at risk: Number at risk:
No goserelin 1356 1062 702 381 134 22 0 No goserelin 1356 1216 877 486 178 33 0
Goserelin 1354 1108 772 418 156 31 0
Goserelin 1354 1214 893 501 198 37 0