Transcript Document

How Do We Treat HR positive Breast
Cancer in Postmenopausal Women?
Oestrogen Receptors
Oestrogen Target Cell
Non-Target Cell
(e.g. Breast, Uterine lining,
Liver, etc.)
(contains no
oestrogen receptor)
Dominant Pathway
in Postmenopausal Women
Cholesterol
Adrenal
Pregnenolone
AROMATASE
Androstenedione
Adipose
Aromatase
Inhibitors
Oestrogen
Her2neu Positive Breast Cancer
and Herceptin (Trastuzumab)
Her2-normal
breast cancer cell
Her2+
breast cancer cell
Her2 receptors send
signals telling cells to
grow and divide
Too many Her2
receptors send more
signals, causing cells to
grow too quickly
Herceptin
Herceptin stops the
Her2 receptors from
signaling the cell to
grow
Subtypes of Breast Ca
• Luminal A
• Luminal B
• Erb-B2 Overexpression
• ‘Basal-like’
Normal mammary
development
Breast tumour
subtype
Signatures
Mesenchymal
Stem cell
Claudin-low
Bipotent progenitor
Basallike
Basal-like
Myoephithelial
progenitor
Luminal
progenitor
Late luminal
progenitor
Differentiated
myoephithelial
cells
Differentiated
luminal cells
HER2
-enriched
Luminal B
Luminal A
Luminal
Subtypes of Breast Ca
Intrinsic Subtype
Clinico-Pathological Definition
Treatment
Subtypes of Breast Ca
Intrinsic Subtype
Clinico-Pathological Definition
Luminal A
ER and/or PgR positive
HER2 negative
Ki-67 low
Treatment
Subtypes of Breast Ca
Intrinsic Subtype
Clinico-Pathological Definition
Treatment
Luminal A
HR positive
HER2 negative
Ki-67 low
ET
Subtypes of Breast Ca
Intrinsic Subtype
Clinico-Pathological Definition
Treatment
Luminal A
ER and/or PgR positive
HER2 negative Ki-6
Ki-67 low (<14%)
ET
Luminal B
ER and/or PgR positive
HER2 negative
Ki-67 high
ET +/- CT
ER and/or PgR positive
Any Ki-76
HER2 over-expressed or amplified
CT + anti-her2 + ET
Erb-B2
Overexpression
(non-Luminal)
HER2 over-expressed or amplified
ER and PgR absent
CT + anti-her2
Basal-like
Triple-negative (ductal)
ER and PgR absent
HER2 negative
CT
Special Hist Types
• We need Oncotype Dx to differentiate
between some types at least
Remarkably Similar Significant Interaction
between Chemotherapy Benefit and
Recurrence Score in B20 (N0) and S8814 (N+)
Variable / Study
Tamoxifen
Tamoxifen +
Chemotherapy
97 %
60 %
93 %
73 %
93 %
54 %
88 %
73 %
10 yr DRFS B20 N0*
Low Recurrence Score
High Recurrence Score
10 yr BCSS S8814 N+**
Low Recurrence Score
High Recurrence Score
Case Studies
Case Study 1
• 70
• Pleomorphic Lobular cancer - aggressive
subtype
• HR positive and her2 negative
• Stage 2 with no nodes involved
1. Nothing as she is elderly and early stage
2. ET alone
3. CT + ET
4. Don’t know
Subtypes of Breast Ca
Intrinsic Subtype
Clinico-Pathological Definition
Treatment
Luminal A
HR positive
HER2 negative
Ki-67 low
HR positive
HER2 negative
Ki-67 high
ET
Luminal B
ET +/- CT
HR positive
HER2 positive
Any Ki-76
ET + anti-her2 + CT
Erb-B2
Overexpression
(non-Luminal)
HR absent
HER 2 positive
CT + anti-her2
Basal-like
Triple-negative (ductal)
HR absent
HER2 negative
CT
Special Hist Types
ET or CT
• CT + ET
• ET alone
• Don’t know
• Suggestions?
21 Gene Recurrence
Score (RS)
70 Gene
Genomic Grade
Other Prognostic
Signatures…
Relative
Endocrine
“Resistance”
Relative
Chemo
“Sensitivity”
BUT… Only
RS tested in
Phase III
trials N0, N+
Very early tumours: Factors to
consider
Very early tumours: Factors to
consider
•
•
•
•
•
Age </=35
LVI
HER2 +
Triple negative subtype
Luminal with high risk genomic profile
• Comorbidities
Premenopausal Adjuvant Therapy
• 38
• RA and severe depression.
• ‘FA’ excised: T2 (23mm) N – HR strongly
positive + Her2negative cancer. G1 Ki 67
High
• Very worried about developing suicidal
depression again
Subtypes of Breast Ca
Intrinsic Subtype
Clinico-Pathological Definition
Treatment
Luminal A
ER and/or PgR positive
HER2 negative
Ki-67 low (<14%)
ET
Luminal B
ER and/or PgR positive
HER2 negative
Ki-67 high
ET +/- CT
ER and/or PgR positive
Any Ki-76
HER2 over-expressed or amplified
ET + anti-her2 + CT
Erb-B2
Overexpression
(non-Luminal)
HER2 over-expressed or amplified
ER and PgR absent
CT + anti-her2
Basal-like
Triple-negative (ductal)
ER and PgR absent
HER2 negative
CT
Special Hist Types
ET or CT
• CT + ET
• ET alone
• Don’t know
• Suggestions?
Adjuvant Online – S D
Age: 38
ER: Positive Grade: 1
Size: 2.1 - 3.0 cm Nodes : 0
CT: AC x 4 → T x 4
Decision: No Additional Therapy
87/100 women alive
09/100 women died - cancer
04/100 women died - other
Decision: Hormonal Therapy
03/100 women alive because of therapy
Decision: Chemotherapy
04/100 women alive because of therapy
Decision: Combined Therapy
05/100 women alive because of therapy
Node Negative, ER-Positive Breast Ca
Chemotherapy Benefit
Which hormonal therapy?
Oestrogen Receptors
Oestrogen Target Cell
Non-Target Cell
(e.g. Breast, Uterine lining,
Liver, etc.)
(contains no
oestrogen receptor)
Pathway in Premenopausal Women
Oophorectomy
FSH
LH
Hypothalamus
LHRH
Agonist
Pituitary
Ovaries
Oestrogen
Post-mastectomy RT
• No benefit proven if stage 4
• Reduces LR recurrence by 2/3
Oxford Overview
Oxford Overview
Oxford Overview NO
Indications for Post-Mx RT
• Nodes Positive
• T 3 or 4 or muscle invasion
• Margins
Treatment of
Advanced Breast Cancer
• Relapsed
• Late Stage 3
• Stage 4
Treatment of Advanced Breast Cancer
•
•
•
•
•
•
Hormones
Chemotherapy
Biologicals
Radiotherapy
Surgery
Bisphosphanates for bone
secondaries
Treatment of Advanced Disease
Rx = ET
Elderly &
unfit
HR+
Rx = CT
Young & fit
HR-
Long DFI
Short DFI /
Rapid progress
Bones &
Soft Tissue
Visceral /
Life-threatening
Case 3
• 46 Premenopausal
• Mx Lt 2009 for T2 ca
with micromet in node
• HR positive and her2 negative :
CT x 3 (poorly tolerated )then Tam
• Now presented severe RUQ pain
• CXR mass in lung and ultrasound 3 liver
lesions = mets
Case 3 cont’d
• Liver and lung secondaries
• PS: 3
• Hospitalised for symptom control
• Reluctant to see counsellor or St Lukes
1. Symptomatic care
2. Chemotherapy
3. Endocrine therapy
Case 3 cont’d
• Liver and lung secondaries
• PS: 3
• Hospitalised for symptom control
• Reluctant to see counsellor or St Lukes
• CT – patient choice
Performance Status
0 Symptom-free
1 Symptomatic, fully active
2 Resting < 50% of day
3 Resting > 50% of day
4 Bedridden
Case 4
• Painful Rib metastasis 7 years after primary
treatment
• HR positive
• Her2 negative
1. CT
2. ET
3. Other
4. Combination
Case 4
• Painful Rib metastasis
• Rx ET + RT with control of symptoms
Case 5
• Obese Looked after her about 10 years
with bone secondaries
• HR positive
• Her2 negative
How would you try to control this long
term?
Case 5 cont’d
• 2 -3 operations to spine
+ RT + BP + CT + ET
• Lifestyle
• Still works