Transcript How can I help you? (or frequently asked questions)

How can I help you? (or
frequently asked questions)
Adam Stacey-Clear
Consultant Breast and Endocrine Surgeon
Who gets breast cancer?
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Age
Sex
Where you live
Family history
Genetics
Social class and alcohol
How common?
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Incidence - 1 in 12
80% in women over 50
Very rare under 35
Are there different types?
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Ductal 85%
Lobular 15%
ER PR HER2 receptors
Basal, luminal phenotypes
Implications for rx
Screening
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50 years +
Every 3 years
Family history screening
Mammography
Ultrasound
MRI scans
Family history clinic/genetics
What treatments are available?
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Surgery
Primary chemotherapy/endocrine therapy
Radiotherapy
Extended endocrine therapy (Tamoxifen,
aromatase inhibitors)
Herceptin
Treatment side effects
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Bone marrow supression
Aching joints
Switch to tamoxifen
Reassurance, SFO, low dose progesterones,
venlafaxine ( flushes due to LHRH release)
Topical oestrogens
Menopausal status – blood tests (FSH)
How effective is treatment? Can it
be cured?
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CRC UK
85% 5 year survival
77% 10 year survival in England (2005-2009
data)
EBCTCG,
Lancet 2011
Hormone-Related Events that
Breast Cancer Risk
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Endogenous hormones
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Early menarche, late menopause
Oophorectomy, antiestrogens
High plasma estrogens, high bone density
Postmenopausal obesity
Protective effect of pregnancy
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Nulliparity, late first pregnancy
The history of endocrine
therapy
Mid 20th century – Standard endocrine therapy of
oopherectomy for young patients and oestrogenic drugs
for postmenopausal
 1962 – Tamoxifen (ICI 46,474) synthesised
 Late 1960’s – first clinical studies of tamoxifen in advanced
breast cancer patients at Christie Hospital, Manchester
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The history of endocrine
therapy
1973 - ICI launch tamoxifen in ABC
 1992 - Oxford Overview confirm benefit of adjuvant TAM
 1995 - Anastrozole launched in ABC as 2nd line Rx
 2000 – AIs show benefit over TAM in 1st line ABC
 2002 – ATAC shows DFS benefit for adjuvant AIs over Tam
 2004 – Sequential AIs after TAM improve DFS & Survival
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Estrogen Stimulation of Target Tissues
PRE-menopausal Women
POST-menopausal Women
Ovarlan
Steroidogenesis
Granulosa
A
R
O
M
A
T
A
S
E
ANDROSTENEDIONE
Corpus
Luteum
ESTRADIO
L
Adrenal Gland
Target Tissues
eg,
BREAST
BREAST TUMOR
A
R
O
M
A
T
A
SE
Adipose
Tissue
Liver
Breast
Breast
Tumor
ESTRADIO
L
ESTRONE
Estrogen Stimulation of Target Tissues
Aromatase Inhibitors
Anastrazole, Exemestane, Letrozole
POST-menopausal Women
Tamoxifen
Faslodex
ANDROSTENEDIONE
Adrenal Gland
AR
O
M
AT
AS
E
Adipose
Tissue
Liver
Breast
Breast
Tumor
Target Tissues
eg,
BREAST
BREAST TUMOR
ESTRADIOL
ESTRONE
Recommendations
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All post menopausal pts with node positive disease should be
offered Letrozole after completing 5 years of tamoxifen.
With no clear benefit appearing for different strategies then side
effects and costs are important considerations.
We recommend switching to an aromatase inhibitor after 2-3
years of tamoxifen or vice versa for all postmenopausal node
negative pts.
Skeletal health should be monitored as per recommendations.
Up front AIs should be considered for post menopausal pts who
are Her-2-neu positive? node+ve and those with
contraindications to tamoxifen.
Efficacy Endpoints
Favors Exemestane Favors Tamoxifen
HR (95% CI)
Disease Free Survival
0.76 (0.66, 0.88)
ITT (E=354, T=454)
ER+/UNK (E=339, T=438)
0.75 (0.65, 0.87)
Breast Cancer Free Survival
ITT (E=289, T=374)
0.76 (0.65, 0.88)
ER+/UNK (E=277, T=361)
0.75 (0.64, 0.87)
Time to Distant Recurrence
ITT (E=249, T=297)
0.83 (0.70, 0.98)
ER+/UNK (E=238, T=285)
0.82 (0.69, 0.98)
Time to Contralateral BC
ITT (E=20, T=35)
0.57 (0.33, 0.98)
ER+/UNK (E=20, T=35)
0.56 (0.33, 0.98)
0.4
0.6
Coombes RC, et al. Data presented at ASCO, June 2006
0.8
1.0
1.2
Hazard ratio (95% CI)
Pre-operative therapy?
Tamoxifen Alone v Surgery + Tamoxifen:
‘Golden Oldies’
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CRC UK trial tamoxifen alone v surgery and
tamoxifen
451 women 70 years or over
34 months FU
no significant early differences in survival or quality
of life follow-up
significantly higher loco-regional relapse rate with
tamoxifen alone [23% v 8%]
Bates et al Br J Surg 78:591-594, 1991
Maintaining Bone Health
Provisional Recommendations
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Routine calcium and vitamin D supplements
“Baseline” DXA in all patients beginning 5 years of an AI
If osteoporosis - give approved bisphosphonate
 If osteopaenia - monitor annually
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If normal - monitor every 2-3 years
“Baseline” DXA in over 65s receiving TAM - AI sequential therapy
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Treat if confirmed bone loss of >5% per year
Monitor and treat as above
“Baseline” DXA in all patients with premature (<45) menopause
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Monitor and treat as above
UK Management Algorithm for Breast Cancer - NOS/NCRI
Post-menopausal women >age 45
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Baseline DEXA scan and risk assessment if for AI therapy
Risk adapted strategy
Lifestyle advice and adequate calcium and vitamin D
 1 g calcium and 800iu vitamin D
Reassure if T score > -1 and no risk factors
 No monitoring required
Monitor BMD of osteopaenic patients every 2 years
 Baseline T score <-1
Intervention with bisphosphonates
 > age 75 and > 1 risk factor for osteoporotic fracture
 T score < -2 either at baseline or on follow-up
 T score < -1 at baseline and annual bone loss >4%
Issues-Costs
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5 years tamoxifen= £136
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5 years AI =£5400
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2yrs Tamoxifen 3yrs AI=£3294
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3yrs Tamoxifen 2yrs AI=£2241
The HER-2 Gene
Encodes a 185kd protein that is a member of the
type I
receptor tyrosine kinase family which also contains
EGFR,
HER-3 and HER-4
Functions When Altered
 Growth and proliferation increased
 Differentiation decreased
 Cell survival increased
 Motility increased
 Neoangiogenesis increased
 Reduced dependency on estrogen and
insensitivity to hormonal blockade
Combined Analysis for DFS of
NSABP B-31 / NCCTG – N9831
AC TH
87%
85%
AC T
75%
%
67%
AC T
AC TH
N
1679
1672
Events
261
134
HR=0.48,
2P=3x10-12
Years From Randomization
Combined Analysis for DDFS of
NSABP B-31 / NCCTG – N9831
AC
TH
AC->T+H
90%
90%
90%
AC
T
AC->T
90%
90%
90%
81%
81%
81%
%
N
74%
74%
74%
Events
N Events
AC TH 1672 96
AC->T
1679 194
AC
T 1679
194 96
AC->T+H
1672
HR=0.47, 2P=8x10-10 HR=0.47, 2P=8x10-10
0
1
2
3
Years From Randomization
4
5
Annual Hazard of Distant Recurrence
120
100
AC T
80
60
40
AC TH
20
0
0
1
2
Years From Randomization
3
4
Summary
Dramatic improvements in DFS
 Early overall survival benefit
 Optimal duration Unknown (HERA 1
vs. 2y pending). Current data supports
one year (9weeks?)
 ? Concurrent better efficacy but assoc
with xs cardiac events
 Assessment of cardiac ftn. remains
important
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‘Evolution’ of Chemotherapy
)
100
Dose Dense
FEC -D
TAC
AC -T
Adriamycin
CMF
Surgery
83%
78%
75%
67%
50
35,9%
5,9%
32,4%
26%
0
1
3
5
7
9
Time (years)
11
13
15
Early Results Do Not Always Reflect
Late Results In Adjuvant Therapy
Poly Chemotherapy
50
Tamoxifen (5 yrs)
70
60
40
50
30
40
20
30
20
10
10
0
0
0- 2
2- 5
5 - 10
Time Periods (yrs)
Recurrence
0-2
2-5
5 - 10
Time Periods (yrs)
Breast Cancer Specific Mortality
Breast conserving surgery + RT v. BCS
alone - Ipsilateral breast recurrences
Breast conservation + RT v. mastectomy
- breast cancer deaths
Adjuvant radiotherapy following
mastectomy – benefit additive to
chemotherapy
Overgaard et al. NEJM 1997
Follow up
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Bone density scans every 2 years if on
aromatase inhibitor
Mammography
Ultrasound
Local recurrence – 72% between clinic visits
Thyroid cancer
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V rare – less than 1% of all malignancies
Women more than men
Solid lump in male more worrying
Nuclear medicine scan
Ultrasound guided FNA
Blood tests
Thyroid types
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Follicular
Papillary
Medullary
Anaplastic
Total thyroidectomy or partial thyroidectomy?
Nuclear medicine imaging
Auto antibodies
Thy 1 – Thy 5
CT scans
Thyroid cancer prognosis
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Very good even with lymph node metastasis
97% 10 year survival
Thyroglobulin measurements
Long term follow up
Thyroid surgery
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Recurrent laryngeal nerve injury
Hypocalcaemia
Hypothyroidism
Length of stay
Follow up – annual blood tests
Pregnancy
Thyrotoxicosis
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60% relapse on medical treatment eg
carbimazole or propylthiouracyl
Antibodies
Radioiodine ablation – age, exophthalmos,
local preferences
Surgery – usually curative
Lifelong thyroxine