The document discusses the management of the axilla in breast cancer from a radiation oncologist's perspective. It covers how to stage the axilla through physical exam, imaging, or biopsy. For clinically node-negative patients, sentinel lymph node biopsy is standard, while clinically positive nodes may require lymph node dissection. Ongoing trials are exploring omitting further axillary treatment for some patients with positive nodes after neoadjuvant therapy. The conclusion emphasizes that axilla management remains controversial but aims for individualized treatment based on tumor characteristics and response to therapy.

1. Management of Axilla in Breast Cancer
A Radiation Oncologist’s Perspective
Dr. Sadia Sadiq
Consultant Oncologist
AECH,INMOL
CPC,SZH
03/06/2023

2. Contents
Why to address the Axilla
How to stage the Axilla
When not to stage Axilla
Management of cN0 Axilla
Management of cN1 Axilla
Management of the Axilla in setting of Post Neoadjuvant
systemic therapy
Ongoing trials
Conclusion
6/3/2023 2

3. Nodal Presentation
• Regardless of location of
primary tumor in the breast
Axilla is the most common
nodal site.
• Level III involvement
without level I or II is
unusual.
6/3/2023 3

4. Nodal Status 5 years OS
Node Negative BC 82.8%
1-3 positive nodes 73%
4-12 positive nodes 45.7%
>12 positive nodes 28.4%
Why to address the Axilla Cont.….
6/3/2023 4
Fisher et al

5. How to stage the Axilla
• Physical Examination
• Axillary Imaging
• Axillary Imaging plus FNAC/Trucut biopsy
• Sentinal Lymph Node Biopsy (SLNB)
• Axillary Lymph Noda Dissectin (ALND)
6/3/2023 5

6. When not to stage Axilla
1.Advanced age, serious comorbidities, or when it will not affect decisions
regarding adjuvant therapy
2. Pure DCIS undergoing breast-conserving surgery
3. ≥70 years of age with cT1-2N0 hormone receptor positive breast cancer
4. Prophylactic mastectomy
5. Primary breast sarcoma or phylloides tumor
6/3/2023 6

7. Management of clinically negative Axilla
cN0
• SLNB
• ALND
6/3/2023 7

8. SLNB…Background
The landmark NSABP B-04 trial (1971-1974)
questioned the necessity of ALND by comparing radical
mastectomy to total mastectomy.
The trial established that not all undissected nodal disease
resulted in disease recurrence
The NSABP B-04 trial and advent of SLNB paved way for the landmark Z0011 and
AMAROS trials, evaluating the role of ALND in patients with cT1-2N0 (≤5cm) breast
cancer and positive SLN.
6/3/2023 8

9. SLNB for cN0
• Accurate staging while minimizing morbidity.
• If upfront SLNB –ve, then no indication of further axillary
surgery or RT
• If upfront SLNB +ve ….again no further axillary surgery
6/3/2023 9

10. Important Trials of SLNB
To see accuracy
& morbidity of
SLNB
1.ALMANAC
2.Veronesi et al
3.NSABP-32
To identify
patients with
limited SN mets
who can be
spared axillary
Sx
1.Z0011
2.IBCSG 23-01
Optimal treatment
for higher risk
sentinal node +ve
patients
AMAROS study
6/3/2023 10

11. • Decreased incidence of lymphedema in the SLND arm (RR 0.37; 95% CI)
• Lower drain usage, hospital stay, and a shorter time to return to normal
activities with improved quality-of-life scores
6/3/2023 11

12. 6/3/2023 12

13. No difference in Local recurrence (3.6% vs 1.8 %),
Axillary recurrence(0.9 % vs 0.5 %),
disease free (82.4% vs 81.5%) or
overall survival (91.8% vs 90.3% ) rates at 8 years.
NSABP-B32
Sample size
5611
6/3/2023 13

14. ALLIANCE(Z0011)-
Limited SLN Positive disease – Omission of ALND
6/3/2023 14

15. The ACOSOG trial Z0011 (1999-2004) was a phase III non-inferiority trial
Approximately 97% of patients received adjuvant systemic therapy at the discretion
of the treating physicians.
The rate of wound infections, axillary seromas, and paresthesia
were higher for the ALND group than the SLNB-alone group (70% versus 25%,
p≤0.001)
While axillary radiotherapy was not explicit in the Z0011 trial, tangents for
whole breast irradiation likely would have included the low
axilla
ZOO11 TRIAL
6/3/2023 15

16. • Designed for HIGHER risk sentinel node positive patients who
DO NOT fit into ACOSOG Z0011 criteria. ( e.g. mastectomy
candidates)
• First trial to COMPARE prospectively axillary LN dissection vs
axillary RT in such patients.
6/3/2023 16

17. Results of AMAROS Trial
• Lymphedema noted to be significantly higher after
axillary LN dissection than after axillary RT
6/3/2023 17

18. • In both trials, about 1/3 of the ALND group (27.3% in Z0011
and 33% in AMAROS) had additional +ve LNs after the SLNB
• It is likely that a similar portion of patients receiving SLNB
without ALND had residual un-dissected axillary metastases
• It is unclear if the adjuvant systemic therapy, axillary
radiotherapy, or combination of both treated the residual
nodal disease not removed during surgery.
6/3/2023 18

19. The evidence regarding the omission of ALND
did not include patients :
 With history of another cancer
 Multicentric breast cancer
 Prior ipsilateral breast cancer
surgery
 Prior ipsilateral axillary surgery
 Age < 18 or > 80 years
 Pregnant or lactating
 Allergic to blue dye or radioisotope
 Evidence of metastatic disease
 Tumors > 5cm
 Chronic life-threatening diseases
possibly preventing the use of
adjuvant therapy
 Stage T0 tumors (ie, ductal
carcinoma in situ)
 Multifocal tumors
 Received previous NAC
6/3/2023 19

20. 6/3/2023 20

21. In Elderly Patients Think differently and wisely
• In 2016, the Society of Surgical Oncology joined the
American Board of Internal Medicine Foundation in
their Choosing Wisely campaign.
• One of the recommendations included omitting the
routine use of SLND in women > 70 years old with
clinically node-negative, hormone receptor positive
breast cancer.
6/3/2023 21

22. Management Of Clinically Positive Axilla
cN1
6/3/2023 22

23. Why Axillary nodal dissection?
• Allows proper staging
• Yields diagnostic information
• Guides subsequent treatment
• Removes tumor for potential therapeutic gain
• Diminishes risk of axillary recurrence
6/3/2023 23

24. Regional Nodal Irradiation
• Clinical trials evaluating RNI (MA.20, EORTC 22922-10925, and
the EBCTG meta-analysis ) demonstrated that even patients
with 1-3 lymph nodes could be considered for RNI
• Conclusions drawn from these studies potentially increased
the use of comprehensive RNI..increased risks of lymphedema
and cardiopulmonary toxicity
6/3/2023 24

25. 6/3/2023 25

26. Management Of Axilla In Setting Of
Neoadjuvant Systemic Therapy
6/3/2023 26

27. Nodal assessment prior to NAC
• For initial cN1 Disease USG combined with US guided
FNAC of suspicious node will give a sensitivity of
almost 90 % and specificity of 100 %
• Prior to systemic therapy in cN0 Axilla. Only
radiological assessment.
6/3/2023 27

28. Post-neoadjuvant Chemotherapy
SLNB Accuracy
• Data from M.D. Anderson Cancer Centre have shown that
comparable FNR (5.9% vs. 4.1% in neoadjuvant and in
surgery first group respectively, p=0.39) with no significant
differences in OS or DFS.
• Dual tracer method with removal of ≥2 sentinel nodes are
recommended to reduce the false negative rates.
6/3/2023 28

29. 6/3/2023 29
• Results from three prospective studies (ACOSOG Z1071, SENTINA
and SN FAC ) support SLNB after NAC in patients with initial cN1
disease if
1)dual mapping with 99m-technetium and a blue dye is used
2)more than two SLN are removed
3)a clip is placed in the positive node with successful retrieval on SLNB

30. • Primary objective was to check the FNR of SLNB after
NAC in patients presenting with initial cN1
• The secondary objective was to study nodal conversion
rate from cN1 to cN0.
• 663 pts with cN1 received NAC f/b SLNB f/b ALND.
6/3/2023 30

31. ACOSOG Z1071 (Cont..)
• Targeted axillary dissection
• removes both the sentinel nodes and the clipped node
• help minimize morbidity of ALND while maintaining an acceptable
low FNR
• Usefulness of placing a nodal clips
• In 75.9% patients with >2 SLNs retrieved, the clip was found to be inside
the retrieved SLN with a FNR of 6.8% (95% CI=1.9%–16.5%).
• Higher FNRs if clip was not used or when the clip could not be retrieved
during surgery (13.4% and 14.3%, respectively
6/3/2023 31

32. SLNB after NACT in initial cN1 – Nodal
conversion
• Pts with clinically +ve node, NACT can eradicate nodal
disease in 40% of patients (1). This de-escalates axillary
surgery and morbidity.
• Nodal conversion rates depending on the receptor status
of the tumor (2)
–21.1% for ER/PR positive, HER-2 negative tumors
–49.4% for triple negative tumors
–64.7% for HER-2 positive tumors.
6/3/2023 32

33. • The goal of this study was to determine the effect of Z 1071 on surgical
practices.
• In pre-Z1071 cohort 99 % of initial cN1 patients had ALND.
• Only 27% of cN1 patients had an ALND as first intervention post-Z1071.
• These are meaningful practice changes.
6/3/2023 33

34. Final Recommendation
6/3/2023 34

35. Radiation Decisions Based On Post NACT
SLNB Histopathology Results
6/3/2023 35

36. T1 and T2-RT after NAC
• cN0-NAC-SLNB-ypN0-BCS-WBRT+Boost.
cN0-NAC-SLNB-ypN0-Mastectomy- No RT.
• cN1-NAC-ycN0-SLNB-
• cN1-NAC-ycN1-ALND-
• Strongly consider RT whole
breast/chest wall and RNI with
inclusion of any un-dissected
axilla at risk.
6/3/2023 36

37. Ongoing Clinical Trials
Benefit of RNI after complete nodal response to NAC NSABP – B51
Omission of ALND in Post NAC SLNB+ve patients Alliance A11202
No axillary Rx in SLNB + patients(Post mastectomy/ENE+) POSNOC
Axillary RT decision based on Genomic Profiling TAILOR RT
6/3/2023 37

38. NSABP- B51 Trial
• The trial randomizes patients with cT1-3N1, ypN0 breast
cancer to no RNI or RNI.
• This bold omission of radiation is based on analysis from
NSABP B-18 and B-27 trials (NAC trials) which showed low
nodal recurrence in patients with initial cN+ disease and
ypN0 responses (range 0-2.4% in the post-BCS population
and 0-8.1% in the post-mastectomy patients)
6/3/2023 38

39. Alliance A11202 Trial
(ClinicalTrials.gov identifier: NCT01901094)
• Looking for an option for patients with residual positive
SLNs after NAC. cN1- ypN1
• Patients are randomized to ALND versus no further
axillary surgery and all patients receive regional nodal
irradiation.
6/3/2023 39

40. POSNOC Trial
• Multicentre, non-inferiority, international trial
• T1/T2, unifocal or multifocal IBC
• 1 or 2 macrometastasis at sentinel node biopsy, with or
without ENE
• Randomized to adjuvant therapy alone VS ANC or axillary RT.
6/3/2023 40

41. TAILOR RT TRIAL
(CCTG MA.39)
• Compares RNI to no RNI in patients with
• ER+ breast cancer
• 1-3 positive axillary lymph nodes
• Oncotype DX scores less than 18
• The trial is a major milestone for radiation oncology in using
personalized breast cancer biology in decision-making
6/3/2023 41

42. 6/3/2023 42

43. Conclusion
• Management of axilla has always remained controversial
• For initial cN0 patients,upfront SLNB is standard intervention
• For cN1 patients converting to ycN0 after NAC,SLNB should be
considered
• Results of ongoing trials will guide if further axillary treatment
is needed in cN1- ypN1 patients after SLNB
6/3/2023 43

44. HOW DO WE ADDRESS AXILLA
6/3/2023 44

45. • RT APPOINTMENT
• CT SIMULATION
• CONTOURING
• RT PLANNING
• PLAN EVALUATION
• RT DELIVERY
• FOLLOW-UP
6/3/2023 45

46. CT SIMULATION
6/3/2023 46

47. VOLUMETRIC CONTOURING
CHEST WALL CTV
6/3/2023 47

48. INTACT BREAST CTV
6/3/2023 48

49. NODAL CTV
6/3/2023 49

50. Organs at Risk (0ARS)
6/3/2023 50

51. RT FIELDS
2 FEILDS
6/3/2023 51

52. 3 FIELDS RT
6/3/2023 52

53. 4TH FIELD
6/3/2023 53

54. PLAN EVALUATION
‘Dose Volume Histograms
6/3/2023 54

55. DOSE FRACTIONATION
• Conventional 50 Gy/25 #
• Hypofractionation
40 Gy/15 #
35 Gy/10 #
Boost
12 Gy/4 #,9 Gy/3 #
6/3/2023 55

56. RT DELIVERY
6/3/2023 56

57. 6/3/2023 57

58. ThankYou
6/3/2023 58