1. Jayant S Vaidya What is the best way to treat the axilla? 19th century
21st century
The background picture won a prize among 180 contestants at UCL for ‘research image as art’
Jayant S Vaidya
MBBS MS DNB FRCSGlag PhD FRCS(Gen Surg)

2. of axillary sampling procedures
For
Axillary Sampling …with a choice of flavours…
Clearance
4-node Sample
Blue dye guided Sample
Sentinel Node biopsy
for…
A CHOICE
of axillary sampling procedures

3. Once upon a time…..
Tata Memorial Cancer Centre
Axillary Clearance

4. Middlesex Hospital, University College London
Axillary Clearance
Sentinel Node Biopsy

5. Axillary Clearance Axillary Sample – Sentinel Node Biopsy
Ninewells Hospital, University of Dundee
Axillary Clearance
Sunshine in Oct
Axillary
Sample –
best of both worlds
Sentinel Node Biopsy
Snowshine in Feb

6. False negative rate The chance of missing a positive axilla
Could cause harm by
Axillary relapse
Missed opportunity to institute systemic adjuvant therapy

7. How Much?

8. Mathematical
Model

9. Mathematical
Model

10. The mathematical model - the known facts
(NSABP B-32) trial False negative rate (FNR)
SEER dataset Estimated node positivity (ENP)
Benefit from chemotherapy in ER negative women
This would be similar to additional benefit of chemotherapy in ER positive women on top of hormone therapy

11. The mathematical model - the known facts
NSABP B-04
(Fisher, 2002) 50% of involved nodes cause local recurrence
Overview
(Peto R, 2004) 20% of local recurrence translates into mortality
(for example,
if LR increases by 10%
the mortality increases by 2%)
Thus, if 10% of patients have untreated axillary disease,
5% will have local recurrence
1% more will die as a consequence.

13. Mathematical Model
Age 60 years
Grade 1
0.5cm
ER negative
Estimated Node Positivity
(ENP) = 10%

14. The 10-Year mortality risk 1 to 3 - Node positive women
Node negative women 3%
1 to 3 - Node positive women
13%

15. The Benefit from adjuvant chemotherapy
(reduction in 10 year mortality)
If Node negative
(adjuvantonline.com)
0.8%
If (1 to 3) Node positive
3.4%

16. Difference in benefit “if NN” vs. “if NP”is
3.4% minus 0.8% = 2.6%

17. Let us assume the False Negative Rate of SNB is
9.7%

18. Mathematical Model
Actual (chance of )False Negative axilla in this patient undergoing SNB is =
AFN = FNR x ENP
e.g., if FNR =9.7% and ENP is 10%
AFN= 1%

19. Increased mortality due to axillary recurrence
Mathematical Model
Actual chance of missing a positive axilla in this patient is (AFN=ENP x FNR) 1%
Increased mortality due to axillary recurrence
1/10th of 1%
= 0.1%

20. Mathematical Model
Actual chance of missing a positive axilla in this patient is (AFN=ENP x FNR) 1%
Increased mortality due to “no chemotherapy”
= 2.4% times D (diff. in benefit in NN and NP)
= 1% x 2.6%
= 0.02%

21. Unsuspected harm in this SNB-negative woman (60yrs, 1
Unsuspected harm in this SNB-negative woman (60yrs, 1.5cm, Grade I, ER-ve)
because of omitting chemotherapy on assumption that she is node negative
Increased Mortality due to axillary recurrence +
Increased mortality due to “no chemotherapy”
0.1% %
= 0.12%

22. Tweak…
Increase False Negative Rate to
20%
100%

23. Unsuspected harm in this SNB-negative woman (60yrs, 0
Unsuspected harm in this SNB-negative woman (60yrs, 0.5cm, Grade i, ER-ve)
because of omitting chemotherapy on assumption that she is node negative
(FNR=20%)
Increased Mortality due to axillary recurrence +
Increased mortality due to “no chemotherapy”
0.2% %
= 0.25%

24. Unsuspected harm in this SNB-negative woman (60yrs, 0
Unsuspected harm in this SNB-negative woman (60yrs, 0.5cm, Grade i, ER-ve)
because of omitting chemotherapy on assumption that she is node negative
(FNR=100%)
Increased Mortality due to axillary recurrence +
Increased mortality due to “no chemotherapy”
1% %
= 1.26%

25. False negative rate does not matter…

26. But…

27. More Tweaks…
Increase tumour size and grade
Size 2cm
Grade 2

29. Unsuspected harm in this SNB-negative woman (60yrs, 2 cm, Grade ii, ER-ve)
because of omitting chemotherapy on assumption that she is node negative
(FNR=9.7%)
Increased Mortality due to axillary recurrence +
Increased mortality due to “no chemotherapy”
0.29% %
= 0.4%

30. Unsuspected harm in this SNB-negative woman (60yrs, 2 cm, Grade ii, ER-ve)
because of omitting chemotherapy on assumption that she is node negative
(FNR=20%)
Increased Mortality due to axillary recurrence +
Increased mortality due to “no chemotherapy”
0.6% %
= 0.82%

31. Unsuspected harm in this SNB-negative woman (60yrs, 1
Unsuspected harm in this SNB-negative woman (60yrs, 1.5cm, Grade I, ER-ve)
because of omitting chemotherapy on assumption that she is node negative
(FNR=100%)
Increased Mortality due to axillary recurrence +
Increased mortality due to “no chemotherapy”
3% %
= 4.11%

32. Tweaks… Increase tumour size, grade and reduce age Size 2cm Grade 3

34. Unsuspected harm in this SNB-negative woman (40yrs, 2 cm, Grade iii, ER-ve)
because of omitting chemotherapy on assumption that she is node negative
(FNR=9.7%)
Increased Mortality due to axillary recurrence +
Increased mortality due to “no chemotherapy”
0.34% %
= 0.56%

35. Unsuspected harm in this SNB-negative woman (40yrs, 2 cm, Grade iii, ER-ve)
because of omitting chemotherapy on assumption that she is node negative
(FNR=9.7%)
Increased Mortality due to axillary recurrence +
Increased mortality due to “no chemotherapy”
0.34% %
= 0.56%

36. Unsuspected harm in this SNB-negative woman (40yrs, 2 cm, Grade iii, ER-ve)
because of omitting chemotherapy on assumption that she is node negative
(FNR=20%)
Increased Mortality due to axillary recurrence +
Increased mortality due to “no chemotherapy” %
= 1.16%

37. Unsuspected harm in this SNB-negative woman (60yrs, 1
Unsuspected harm in this SNB-negative woman (60yrs, 1.5cm, Grade I, ER-ve)
because of omitting chemotherapy on assumption that she is node negative
(FNR=100%)
Increased Mortality due to axillary recurrence +
Increased mortality due to “no chemotherapy”
3.5% %
= 5.81%

38. We need to inform our patients and take a shared decision about using Sentinel Node Biopsy?

39. p < 0.0001 p = 0.30 NSABP B-32 Smoothed Technical Failure Rates15 10
p <
Percentage Technical Failure 5 50
100
150
Surgeon Case Number
NSABP B-32 Smoothed False Negative Rates 60 40
p = 0.30
Percentage False Negative 20 50
100
150
Surgeon Case Number

40. We need to accept that this 10% false negative rate is not a correctable technical error
It is an indicator of the biological behaviour of breast cancer

41. “barking dogs do not bite” but the dog doesn’t know that

42. SNB is appealing because it is precise and logical But
breast cancer doesn’t know the rules!

43. In 10% of cases tumour skips the sentinel lymph node

44. Is there
an alternative?

45. There is
an alternative

46. Replace “dogma”
with
“informed choice”

47. Breast conservation (466)
Edinburgh Studies
Prof Bob Steele, Mr Udi Chetty, Sir Patrick Forrest and colleagues
Mastectomy (417)
Breast conservation (466)
4- node sample
RANDOMISATION
Axillary clearance
Outcome- local relapse, survival and morbidity

49. Technical Success Sample Clearance (202) (199) Mean Number 4.8 20.6
(202) (199)
Mean Number
Positive 85(42%) (40%)
Failure

50. False negative rate
In 135 patients, randomisation was done after sampling
N Positive Additional Positive
Sample only (38%) -
Sample
+Clearance (39%) 0

51. Overall Survival

52. Axillary Recurrence

53. Arm Oedema

54. the Edinburgh technique
4-node sample
the Edinburgh technique
Near 100% detection rate
Near 0% false negative rate
Low morbidity
Survival and local relapse equivalent

55. 4-node sample - Other benefits
No need of costly equipment
No need of Nuclear medicine and ARSAC
No need of radiation protection
Needs proper surgical training

56. Study of biology of
Biological tissues are NOT contaminated with radiation
So can be stored in tissue bank for further study – e.g., gene microarray analysis.
RADIATION HAZARD

57. Applying the Mathematical model to 4 node sampl e
FNR = 0%
Effect of mortality = 0
Effect of local recurrence = 0

58. Node positivity in trials of SNB
26%
On average,
1 in 4 patients have a second operation

59. Patient Choice
A. ¾ chance of an unnecessary axillary procedure, but the full treatment is completed in one operation (AC)
B. ¼ chance of 2nd operation + 1/10 chance of a missed positive node (SNB)
C. ¼ chance of a 2nd procedure + 0 chance of a missed positive node (AS)

60. What is the right way? INFORMED CHOICE AND PATIENT SELECTION
Those with high risk of nodal metastasis= Axillary clearance
Those with medium risk of nodal metastasis = Axillary sample
Those with low risk of nodal metastasis =
Sentinel node biopsy (don’t bother about FNR)

61. REMEMBER WHEN YOU VOTE
If you Vote for the action then you are voting for a choice – surgeon choice and patient choice- in different ways of sampling the axilla – Clearance-Sample-SNB
If you Vote against the action then you are voting against such an informed and wise choice – and NOT for Sentinel node biopsy.

62. Remember
VOTING AGAINST this action is NOT the same as to VOTING FOR SNB
So if you believe that SNB is
A right way
then you should vote FOR the action

63. Vote for choice
If you wish to just replace the dogma of Axillary clearance to the dogma of Sentinel node biopsy
Vote against
the action
If you believe that Surgeons and Patients should be allowed to make an informed choice
Vote for
the action