Management of axilla in breast cancer has evolved over period of time and in many instances now we can use RT with caution

1. Management of Axilla in Ca Breast:
Axillary RT v/s Axillary Dissection
Dr Ajeet Kumar Gandhi
MD (AIIMS), DNB (Gold Medalist),
ECMO
UICCF (MSKCC,USA)
Assistant professor, Radiation oncology
Dr RMLIMS, Lucknow

3. Axillary RT : Rationale
• Regional nodal metastasis is effectively treated with RT
in many epithelial tumours
• IMN and SCF are not surgically addressed: RT is
effective in managing these nodal sites
• Axillary failure rates are very low in recent series
• Incidental doses to axilla in tangential planned RT
• Advancement in RT (IMRT/IGRT/VMAT) has made it
safe with minimal morbidity

4. Axillary node +vity rate
• Clinically node –ve : Microscopic disease in up
to 30-40% of patients
• T1-2 breast cancers: 10-40%
• Sentinel node –ve cases: 3-12% [NSABP-32:
9.7%]
• Sentinel node +ve cases: up to 33%

5. Assessment of Axilla
• Clinical examination unreliable (50 - 75%)
• PET/MRI – low sensitivity (75%)
• Ultrasound – High sensitivity (97%)
• Sentinel Lymph node biopsy
• Axillary nodal sampling (ANS)/Blue dye
augmented ANS (BDANS): Popular in UK
• ALND – ‘Gold standard’

6. Evolution of Loco-regional treatment
in breast cancer
• Radical mastectomy  MRM+/- RT BCS + RT [1960s-
2000s] Radical RT with SLNB
• No role of PMRT In selected individuals In most cases
(expanding with RT for 1-3 lymph node/ T 1-2 high risk)
• Axillary dissection (I-III) Limited dissection  SLNB 
Axillary RT
• Systemic therapy & endocrine therapy: Important role in
loco-regional control as well !!

7. Evolution of Axillary management
• Sentinel node biopsy (SLNB) replaced axillary lymph
node dissection (ALND) in clinically negative axilla.
• Several randomized trails showed : No ALND in SLNB
–ve cases.
– No difference in survival
– Significantly better morbidity profiles
• In SLNB +ve cases: (??)ALND is the standard of care
What was the need of this evolution:
Morbidity, Morbidity, Morbidity!!!

8. Arm swelling 15 – 40%
Decreased shoulder mobility 10 – 30%
Shoulder weakness 10 - 40%
Numbness 50 – 80%
Arm pain 30 – 70%
ALND

9. • Appox 21% develop arm lymphedema
• Increase up to 24 months of time and beyond
• Roughly, 1/5 women suffer from lymphedema
• High rate of lymphedema roughly 4 times more with
ALND than SLNB
• Lymphedema risk, multi-factorial:
– Axillary lymph node dissection and extent
– BMI/ Co-morbidities
– Axillary radiation

10. • 299 patients [63% stage I & II]
• 67% Patients received Adjuvant RT and 79 % of them
received axillary nodal irradiation
• Level I-III dissection was done in all patients
• Overall, clinically significant edema was 33.5% and
severe edema was 17.2%
• 13.4% with surgery alone and 42.4% if combined
with radiotherapy

11. Lymphedema risk: Extent of Axillary
dissection
• A 50 year old lady with no h/o infusion of CT in I/L arm; No
seroma within 6 months of surgery; no arm edema within
6 months of surgery. Predicted 5 year lymphedema
probability [www.lymphedemarisk.com; Cleveland clinic]
– Level I & II dissection without axillary RT: 10.8%
– Level I, II & III dissection without axillary RT: 15.4%

12. Lymphedema: Axillary dissection or
RT
• Results from NSABP-B32:
Intervention Clinical
Lymphedema
Bothersome
Symptoms
SLNB only 4.5% 4.8%
SLNB+RT 7.4% 3.2%
SLNB+ALND 16.7% 8.8%
SLNB + ALND+
AxRT
12.4% 7.4%

13. Lymphedema: Axillary dissection or RT
Study No. of patients Median
follow up
Outcome Comment
Deutsch et al.
IJROBP 2008; 70 (4):
1020-1024
NSABP-04
1665 Patients
[RM, TM+RT,
TM]
No
chemotherapy/
large tumor size
25 Years Arm edema: RM,
TM+RT, TM;
58.1%, 38.2%,
39.1%
respectively [p
<0.001]
cN0 patients,
axillary failure
was <4% (surgery
or with RT vs. 19%
in TM alone arm)
No difference in
OS
Lymphedema: AMAROS

14. Intervention Relative Risk
Axillary dissection compared
with no axillary dissection
RR = 3.47; 95% CI 2.34-5.15
Axillary dissection compared
with sentinel node biopsy
RR = 3.07; 95% CI 2.20-4.29
Radiation therapy RR = 1.92; 95% CI 1.61-2.28

15. Lymphedema: Axillary dissection or RT
Shah C et al. IJROBP 2011; 81 (4): 907-914

16. Advancement in Radiation Technology

17. Conclusion I
• Lymphedema and other morbidities are a significant
deterrent for patients after treatment.
• Though lymphedema is multi-factorial, axillary dissection has
a prime role to play in causation
• Axillary RT alone without dissection has minimal risk of
axillary complications
• In combination, however, has supra-additive effect (??)
• Solutions:
– Avoid axillary dissection
– Avoid combination of dissection and radiotherapy

18. But Wait..
There is more to ALND than Lymphedema!!
 Major prognostic determinant
 Therapeutic value of ALND (??)
 Planning adjuvant treatment (??)
 Survival impact of ALND (??)

19. ALND: Present status
• SLNB –ve 10% False negative
• SLNB +ve  Further axillary lymph node
dissection:
– 1-3 lymph node: Supraclavicular Lymph node [Also
would add to lymphedema*#]
– ≥ 4 Node: Axillary + Supraclavicular Lymph node
[Increased Lymphedema risk]
* Kim M et al. IJROBP 2013; 86 (3):498-503
# Warren LE et al. IROBP 2014; 88 (3):565-71

20. ALND: Present status
• Any further or no further Lymph node: Unlikely to change
systemic therapy/Endocrine therapy [Except few patients]
• Molecular profiling and primary tumor factors guide
systemic adjuvant therapy: Oncotype DX etc.
• 5.4% survival advantage [Orr RK; Ann Surg Oncol 1999; 6
(1):109-16]
– No patient in included six RCTs received systemic
chemotherapy
– Present era: (??) Survival advantage of ALND

21. • The point now is:
– SLNB to be preferred over ALND
– What to do with SLNB+ ve patients?
– Can patients with SLNB +ve be spared of ALND?
– Can Axillary RT be an alternative to ALND in these
cases?

22. Further nodal involvement in ALND
specimens [AMAROS Trial]
• SLNB was +ve in 647 patients (34%)
– Macro-metastases : 409 (63%)41%
– Micro-metastases: 161 (25%) 18%
– Isolated tumor cells : 77 (12%) 18%
Macro
(n= 200)
Micro
(n=84)
ITC
(n=33)
Combined
(317)
No further
Involvement
117 69 27 213
1-3 nodes 65 10 5 80 (25%)
4-9 nodes 10 3 1 14 (5%)
>9 nodes 8 2 0 10 (3%)
8% ≥ 4 nodes
33% ≥ 1 nodes

25. ASCO Guideline update on SLNB

26. Incidental dose to axilla
• Standard tangents: cover around 50-60% of axillary level I & II
• Mean dose to level I & II has been estimated to be around 40
Gray
• Better coverage could be achieved with high tangents/modern
techniques without increasing morbidities

28. Axillary dissection versus RT: Pre-SLNB era
Study Design No. of patients Median
follow up
Outcome Comment
Pejavar S et al.
IJROBP 2006; 66
(5): 1320-1327
Retrospecti
ve
Stage I & II
1920; 1330
(ALND) & 590
(AXRT)
13 Years Nodal control
rate 98%
versus 97.9 %
ALND not a
significant
factor for
nodal
recurrence
Hafty BG et al.
IJROBP 1990;
19:859-865
Retrospecti
ve
Stage I & II
187 (ALND) &
245 (AXRT)
7.5 Years Nodal control
rate 96-97%
-
Wazer DE et al.
Cancer 1994; 74
(3):878-83
Prospective Stage I & II, Age
=>65 Years; 73
Years
8 Years Regional
nodal control
rate: 100%
Tumor
excision +
Breast +
Regional RT
Galper S et al.
IJROBP 2000; 48
(1):125-32
Retrospecti
ve
418 patients;
AXRT in
absence of
dissection
8 Years Regional
nodal failure:
1.4%
126 had
limited
dissection (<=
5 Lymph
node)

29. Axillary dissection vs. RT: Randomized trial
Study No. of patients Median
follow up
Outcome Comment
Deutsch et al.
IJROBP 2008; 70 (4):
1020-1024
NSABP-04
1665 Patients
[RM, TM+RT,
TM]
No
chemotherapy/
large tumor size
25 Yrs cN0 patients,
axillary failure was
<4% (surgery or
with RT vs. 19% in
TM alone arm)
Arm edema: RM,
TM+RT, TM;
58.1%, 38.2%,
39.1%
respectively [p
<0.001]
No difference in
OS
Sylvestre-LC et al.
JCO 2004; 22
658 pts. [ALND
vs. AxRT]
15 Years Isolated recurrence
rates in ALND vs.
RT group (1 vs. 3%;
p=0.04
<10% had any
form of systemic
therapy
OS [73.8% versus
75.5%]
Veronesi U et al.
Annals of Oncology
2005;16:383-88
435 patients
[Age =>45 years;
1.2 cm; No
Axillary t/t vs.
AxRT]
5.5 Years Axillary failure
rate: 1.5 % vs. 0.5%
5 Year DFS: 96%

30. • Multicentric trial; 4806 patients; 34 Centres; 2001-2010
• 1425 patients (30%) with +ve sentinel node: 744 to
ALND and 681 to AxRT
• T 1-2 primary, no palpable lymphadenopathy, unifocal
(multifocal)
• Axillary RT used if ≥ 4 nodes are involved
• Lymphedema and shoulder mobility at 1,3,5,10 years
measured
• Primary endpoint: 5 year axillary recurrence
• Secondary endpoint: Axillary recurrence free survival,
DFS, OS, shoulder mobility, lymphedema, and QOL
Landmark EORTC 10981-22023 AMAROS
Trial

31. Results
• Median follow up: 6.1 years
• Median of 2 SLN removed in both arm
• Median lymph nodes removed in ALND arm : 15
ALND Group Axillary RT Group
5-year axillary
recurrence
0.43% 1.19%
5-year DFS 86.9% 82.7%
5-year OS 93.3% 92.5%

32. Lymphedema: AMAROS

33. Implications of these studies
• Axillary dissection does not add to survival
advantage.
• Axillary dissection is not therapeutic and needs
adjuvant radiotherapy
• Combination treatment of surgery plus
radiotherapy adds to increased morbidity
• Axillary radiotherapy is effective, therapeutic and
associated with minimal morbidity
– In non-dissected axilla
– In SLNB micro-metastatic
– In SLNB Macro-metastatic

34. Where is the problem then?
• No difference in QOL overall in AMAROSS:
– QOL questionnaire not sensitive for lymphedema
– Patient`s adaptation to their symptoms over time
• Under powering of primary test hypothesis:
– Fewer recurrences as expected (<2% at 5 years): Reflective
of better systemic treatment & EBC
– Similar issue with ACOSOG Z011
• Short term follow up:
– Axillary recurrence early event (15-30 months)*
*Fischer B et al. NSABP-B 04. N Engl J Med 2002; 347: 567–75
* Greco M et al. Ann Surg 2000; 232: 1–7.

36. Where is the problem then?
• Not for all patients: Agreed [We need to select patients
carefully]
– ALND still remains the standard in Node +ve patients
• What if we use APBI: Patients in the category we discuss,
might fit in [What about tangential RT then??]
– Not a problem right now, Cavity and or axilla can be easily
treated with modern RT techniques
• What if patients received NACT?
– Well, please wait for ACOSOG Z1071

38. Conclusion
• Axillary failure rates in early breast cancer (I & II) is
very low
• Clinically negative patients with SLNB+ ve can either
safely receive:
– No further dissection with tangential field RT/Axillary RT
– Axillary RT and no further dissection

39. Axillary RT vs. dissection

40. Thanks !!!!