Download Her-2/neu over-expression (about 40% of breast cancers)

SYSTEMIC MANAGEMENT OF
BREAST CANCER
Dr Alice Musibi
Medical Oncologist
KENYATTA NATIONAL HOSPITAL
BREAST CANCER
INTRODUCTION
• Is one of the deadliest and most common
cancers ailing women all over the world
• In Australia 1 in 13 women will develop ca
breast at sometime in her life
• In USA 215,990 women will be found to have
invasive ca breast in 2004
• More common in older than younger women
with average age of diagnosis of 64 years
CANCER IN NAIROBI (KENYA)
• A total of 2,716 cases were registered,
comprising of 1246 men and 1470 women
between 2000-2003
• Breast cancer was leading with 22.9%
followed by cervical cancer with 19.3%
• The mean age of diagnosis was 45 years
Most C ommon C ance rs for all C ase s Re giste re d (2000 - 2002)
Male
IC D-10
C 00-C 14,C 30-C 32 & C 73 He a d & ne c k
Female
14.8
C 15 Oe s o pha gus
7.2
10.0
C 16 S to m a c h
4.4
7.1
3.3
3.4
C 18 C o lo n
C 22 Live r
2.0
5.7
C 44 Othe r S kin
2.1
3.7
C 46 Ka po s i s a rc o m a
2.6
6.9
2.4
C 50 B re a s t
0.9
23.3
C 53 C e rvix Ute ri
20.0
C 56 Ova ry
3.3
C 61 P ro s ta te
9.4
C 69 Eye
3.0
C 82-C 85;C 96 No n-Ho dgkin lym pho m a
2.1
4.2
20.0
15.0
10.0
5.0
2.4
0.0
5.0
10.0
15.0
Pe rce ntage (%) of All C ase s
20.0
25.0
30.0
BREAST CANCER TREND IN
NAIROBI
60
50
No of cases
40
Breast
30
Cervix uteri
20
10
0
4
0-
5
to
9
10
to
14
9
4
9
4
9
4
9
4
9
4
9
4
9
5
-1 0 -2 5 -2 0 -3 5 -3 0 -4 5 -4 0 -5 5 -5 0 -6 5 -6 0 -7 5 -7 0 -8
5
1
2
2
3
3
4
4
5
5
6
6
7
7
8
Age-group
Treatment
• Local management
– 18th century – Louis Petit
of France - total
mastectomy and excision
of axillary's lymph nodes
– 1895 - William Halstead popularized radical
mastectomy
– Harvey Cushing - extended
radical - internal mammary
chain excised after splitting
the mediastinum
– 1923-1937 - local excision
and radium needles.
– Conventional radiotherapy
Out-come
• Poor overall results of survival
• Frequent local recurrence and distant
metastases
• Treatment worse than disease
• Concept of quality life
• Women’s insistence for breast
preservation
Treatment
• Multidisciplinary
– Surgery
– Chemotherapy,
hormonal therapy,
immunotherapy
– Radiation therapy
– Palliative therapy
– Occupational/physioth
erapy
• Lymph edema therapy
– etc
Systemic therapy
• Types
– Primary
induction
therapy
– Neo-adjuvant
chemotherapy
– Adjuvant
chemotherapy
– Palliative
• Associated with
– a decrease in the
death rate
– prolonged relapsefree survivals
• Acute and chronic
side effects
Systemic therapy- combination
– Maximum cell kill
– Tolerable range of
toxicity for each drug
– Broader range of
interaction between
drugs and tumor cells
– Less chance of
developing cellular
drug resistance
Adjuvant systemic therapy
• For patients at risk of disease
•
•
•
•
recurrence after treatment of
primary tumior
Known tumor or maximum
bulk should be removed
Chemotherapy started as soon
as possible post op
Effective chemotherapy must
be used at maximally tolerated
doses
Usually for a period (6-8
cycles)
• Milan CMF trial
(overview)-
– CMF vs. surgery alone
• Relapse free survivalmedian 19.4
– benefits in pre-menopausal
patients
(Bonnadona G et al N Engl. J Med
1995;332;901)
Neo-adjuvant chemotherapy
• Systemic therapy given
preoperatively
– Advantage
• Early exposure to micro-
•
•
metastasis
Tumor response
measurable
Reduce tumor bulk so less
extensive surgery
– Disadvantage
• May delay surgery in
•
tumors which may turn
out to be chemo-resistant
May obscure real extent of
disease
Choice of treatment regime
• Depends on prognostic factors
for
–
–
–
–
–
–
recurrence/survival
Age
tumour size,
nodal status
histologic grade,
hormone receptors,
??Her-2/neu overexpression (about 40%
of breast cancers)
– ?Lymphatic/vascular
invasion)
– Estimated benefit of
therapy in terms of
absolute risk reduction of
relapse and death.
– Estimation of the toxicity
associated with therapy
– [COST]
Prognosis
• Five year relative survival is dependent on the
stage of breast cancer at diagnosis
Stage
Survival rate
0
100%
I
98%
IIA
88%
IIB
76%
IIIA
56%
IIIB
49%
IV
16%
*(Overview American Cancer Society –2003)*
Post-surgical Mx of breast cancer
(KNH) [1989-2000]
• Surgery 374 patients
• Chemotherapy
– Adjuvant – Metastatic
22 (5.8%)
-21
– Adjuvant
– Palliation
-
• Radiotherapy
46 (12.4%)
53
• Hormone therapy (tamoxifen)
(33.7%)
-
126
• East African Medical Journal: 2002 79(3): 156-162
Metastatic breast cancer (MBC)
• MBC is considered an incurable disease.
• majority of patients with MBC do not
survive beyond 5 years after diagnosis.
• Treatment usually is palliative with
systemic therapy including
– chemotherapy
– hormonal treatment
– biologic therapy (e.g. Trastuzumab)
• Pain control
MBC -2
• The surgery of breast tumors with distant
metastases has been indicated to
– prevent local complications (toilet surgery)
– Removal of the metastatic lesions in selected patients
(single brain, liver, bone or pulmonary lesions).
• Surgery of the primary tumor can actually
improve survival of metastatic breast cancer.
– especially in patients with only bone metastases
• (JCO, Vol 24, No 18 (June 20), 2006: pp. 2743-2749)
Many of our women are presenting
like this!!
Language
Lack of
medical
insurance
Poverty
Fears
False beliefs
Fatalism
Lack of information
Knowledge
Attitude
Behavior
Risk factors
• Normal lifetime risk of developing breast
cancer in white women is 1 in 8 or 9
• There is no family history in over 75% of
patients
• Most women with breast cancer do not
have any identifiable risk factors
Risk factors
• Age
• Ethnicity – more cancer in white
•
•
•
•
women but more mortality in blacks
Family history of breast cancer
Previous history of personal breast
cancer gives 1-2% risk of contralateral
breast cancer/year
Previous history of ovarian or
endometrial cancers
Prolonged estrogen exposure
–
–
–
Early menarche (under age 12)/late
menopause (after age 50)
Late first pregnancy/nulliparous/no fullterm pregnancy (1.5 times higher
incidence)
Hormone replacement therapy
especially high estrogen based pills but
more so the combined pills
• Genetic predisposition
• BRCA1 (85%)
• BRCA2
• p53 gene – 1% in women with cancer
of breast below 40 years
• Lifestyle factors
–
–
–
–
–
Dietary factors – particularly increased
fat consumption
Obesity
Lack of exercise
Alcohol consumption
Smoking (???)
• Prior Radiation therapy
• Atypical epithelial hyperplasia of the
•
•
breast
Fibrocystic disease with proliferative
changes
Lobular carcinoma in situ (LCIS)
Recommendations
GovernmentAcknowledge
the volcano in cancer
Policy
National guidelines
Clinical practice
guidelines
Recommendations
• Clinical breast
•
•
•
•
examination
U/S
Mammography
MRI scans of breast
Genetic mapping
Recommendations
• Facilities
– Cancer centres – 1 (KNH)
– Laboratories
• ordinary histopathology
• immunohistochemical
studies
– KEMRI mainly research
purposes
– Private hosp (Nbi, AKUH)
– all send the specimens
to SA or Italy
– Radiotherapy units – 2
MEDICAL
ONCOLOGY
RADIOTHERAPY
PATHOLOGY
RADIOLOGY
SURGEONS AND ORGAN
SPECIALISTS