Uncertainties and Controversies in Axillary Management of Patientswith Breast Cancer
Phase 1 of the OPBC 2022/EUBREAST/Toolbox2 Project
Expert representatives
Walter P. Weber and Peter Dubsky, Jane Shaw, Ursula Ganz-Blättler, Joerg Heil, Florian
Fitzal, Zoltan Matrai, Jana de Boniface, Christoph Tausch, Thorsten Kuehn, Maggie BanysPaluchowski, Rosa di Micco, Nina Ditsch, Sherko Kuemmel, Orit Kaidar-Person, Philip
Poortmans, Oreste Gentilini, Michael Gnant

Staff
Martin Heidinger, Nadia Maggi

Aim
The aim of phase 1 of the OPBC 2022/EUBREAST/Toolbox2 project is to identify andprioritize uncertainties and controversies based on their importance in contemporary axillary
management of patients with breast cancer and to propose concrete strategies to address
them.
Definition of importanceImportance is defined as need for evidence-based expert consensus recommendations tostandardize international clinical practice.

Background
The OPBC was founded in March 2017 as a global non-profit organization. It became thelargest academic network of oncologic, oncoplastic and reconstructive breast surgeons,patient advocates and radiation oncologists from 86 countries with evident expertise in breast
cancer management with a practice primarily dedicated to breast cancer. The OPBC
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specialized in global phase III randomized controlled trials 1-3, as well as systematic
processes to identify knowledge gaps 4 and develop recommendations for clinical researchand practice. 5,6
The European Breast Cancer Research Association of Surgical Trialists (EUBREAST) is a
non-for-profit organization that was founded in 2018 with the goal to harmonize andcoordinate high level international research in the field of breast cancer surgery. Founding
members of EUBREAST have initiated and conducted highly ranked international trials on
lymph node surgery (BOOG, SENTINA, INSEMA, SOUND, SENOMAC, GANEA 1,2).7-16
EUBREAST runs currently the EUBREAST 1 and AXSANA (EUBREAST 3) studies. Morethan 220 sites from 30 countries are actively recruiting patients for EUBREAST studies.
Methods
Modified Delphi process performed by the OPBC and EUBREAST. OPBC coordinators andpanellists as well as EUBREAST scientific board members reflect permanent positions within
the OPBC and EUBREAST. They were selected and actively recruited based on evident
expertise in breast cancer management with a practice primarily dedicated to breast cancer.
The OPBC patient advocacy group consists of patients who underwent oncologic breast
surgery in the past and volunteered to support the mission of the OPBC. The OPBC radiation
oncologists were addressed by the national OPBC coordinators and responded to a call forparticipation in an OPBC newsletter. The rest of the OPBC membership consists of breast
surgeons from various backgrounds and with different levels of experience who decided tojoin the mission by self-registration on the OPBC website (www.oncoplasticbc.org).
Participants from EUBREAST are either effective members or associate members of one of
the network associations (EUBREAST e.V. Germany, EUBREAST ETS Italy)(www.eubreast.com).
For the Delphi process, given the complexity of identifying uncertainties and controversies inclinical practice in the field of axillary management, we a priori plan to recruit a minimum of
100 OPBC and/or EUBREAST members from around the world as key stakeholders,
representing a minimum of 90 clinical experts (i.e., surgeons, gynecologists and radiation
oncologists) who are responsible for axillary management and 10 patient advocates.
A questionnaire will be sent to all OPBC members assessing their role (surgeon vs radiation
oncologist vs patient advocate). Patients will be asked to provide information on theirpersonal history on a strictly volunteer basis (S/p no axillary surgery, sentinel lymph node
procedure, axillary lymph node dissection, breast conserving surgery, mastectomy without
reconstruction, mastectomy with implant-based reconstruction, mastectomy with autologous
reconstruction). Professionals will be asked about their discipline of origin (gynecologist vs2

surgeon vs radiation oncologist), years of experience, annual caseload, sex, and type ofbreast center (private vs public vs academic).
The modified Delphi process will consist of two rounds of electronic questionnaires followed
by a virtual (online) consensus meeting. The online consensus conference will involve agroup of expert panellists for discussion and voting with live attendance by the OPBC and
EUBREAST membership. Responses will be summarized using purely descriptive statistics.

List of uncertainties and controversies
The expert representatives will be tasked with identifying key uncertainties and controversies
in contemporary axillary management of patients with breast cancer. We will purposefully
refrain from using a systematic literature search as basis for questionnaire development
because we want the OPBC and EUBREAST to identify open questions that are relevant inclinical practice based on either absence of conclusive evidence to inform treatment orabsence of expert consensus, or both. To identify published literature in the field that might
indicate whether an uncertainty or controversy has already been well addressed, two expert
representatives will perform a specific PubMed search (search terms will be defined). The
same expert representatives will search ClinicalTrials.gov (search terms will be defined) toobtain information on ongoing clinical trials indicating that uncertainties and controversies
might be sufficiently addressed in the near future. Their review of all abstracts and full textsof relevant articles will be used by the expert representatives to adjust the questionnaire,
which will be sent to all OPBC and EUBREAST members to give feedback and report
additional uncertainties and controversies. The expert representatives will finalize the list of
uncertainties and controversies according to these comments.

Delphi process
The modified Delphi method will include two rounds of surveys assessing t he importance of
uncertainties and controversies with anonymized feed-back of results. Importance is definedas need for evidence-based expert consensus recommendations to standardize international
clinical practice. The questionnaire will be sent to all patient advocates with explanations andglossary. After each round, two reminders will be sent by email in two-week intervals to
optimize response rates. The Delphi process will be coordinated by a facilitator from the
Department of Clinical Research at the University of Basel.
-Round 1:

The chairs will send out personalized access links to the electronic round 1 questionnaire to
all OPBC members and EUBREAST participants. They are asked to rank the importance ofevery knowledge gap on a 9-point Likert scale from 1 (not important) to 9 (extremely
important) within 2.5 weeks after receipt. A total of two reminders will be sent during that3

time. First-round non-responders will be considered to have declined study participation andwill not be contacted again for the second round.
-

Round 2:

All participants of round 1 will be sent a second personalized access link to the electronicround 2 questionnaire. The round 2 questionnaire will consist of the same list of uncertainties
and controversies as in round 1. In addition, the median rating of round 1 will be indicatedseparately for medical professionals and patient advocates. Participants will then be asked tocomplete the questionnaire again within two weeks to reprioritize the respective uncertainties
and controversies. A total of two reminders will be sent during that time. Feedback fromround 1 will be used for all participants that completed round 1 but did not complete round 2.
The median importance rating of each topic will be calculated separately for medical
professionals and patient advocates. The mean of the Likert ratings of the two groups willthen be used for the ranking of uncertainties and controversies. The ranking is determined bydescending median Likert rating.
Virtual OPBC and EUBREAST Consensus Conference (online)
Thursday, 1 Sept 2022, 1.00 p.m. - 4.00 p.m. CETCo-chairs: Walter P. Weber, Michael Gnant and Sherko Kümmel
An expert panel will meet online to discuss the best methods to address the most important
uncertainties and controversies. The 15 questions with the highest overall ranking, as well as
the top 5 ranked questions from each discipline will be selected for in-depth discussion at theconsensus conference. The panel will decide which uncertainties and controversies should
be addressed directly by consensus conferences to develop recommendations for clinicalpractice based on existing evidence or to bridge until conclusive evidence from ongoingstudies is expected to be available.5,6,17,18 In case of absence of ongoing or planned trials or
existing/expected conflicting evidence, the OPBC and EUBREAST will consider to add theseresearch priorities to their research agenda and develop specific clinical research projects togenerate conclusive evidence. For this purpose, a research question, which addresses theuncertainty/controversy at least in part, will be developed by the expert representatives in
PICO (population, intervention, comparison, outcome of interest) format together with aproposal for a trial design. Both PICO research question and proposed trial design will be
adjusted according to the discussion during the conference, followed by voting (y/n/abstain) if
panel and members consider them suitable to address the uncertainty and/or controversy.
Simple majority will be defined by agreement among 51–75% of the panellists andconsensus by agreement above 75%.

4

Amendments- Selection of most important uncertainties and controversies for in-depth discussion atconsensus conference: The 15 questions with the highest overall ranking, as well as the top
5 ranked question from each discipline will be transferred to the consensus conference.

24 July 2022

5

Figure 1. Timeline

6Figure 2. The modified Delphi process7

List of Uncertainties and Controversies in Contemporary Axillary Management ofPatients with Breast Cancer

Definition of importance during Delphi: Importance is defined as need for evidence-based
expert consensus recommendations to standardize international clinical practice.
Session I: Non-invasive staging of the clinically node-negative (cN0) axilla
Contrary to surgical staging (e.g., sentinel lymph node [SLN] procedure) and invasive sampling techniques (e.g.,
biopsies), non-invasive staging techniques comprise imaging-techniques (e.g., ultrasound [US] and magnetic
resonance imaging [MRI]). A clinically node-negative axilla is defined by an unremarkable clinical examination.

1. Should imaging-based staging of the axilla at initial diagnosis and/or after
neoadjuvant therapy be standard care and what is the best imaging modality?
Should all patients with breast cancer undergo imaging of the axilla at diagnosis? If a neoadjuvant therapy (atherapy given before the surgical procedure) is undertaken, should imaging of the axilla be standard of care?
Additionally, it remains unclear, which imaging modality is best.

2. Should there be development of baseline standards for axillary imaging (e.g., similar
to false-negative rates for sentinel lymph node [SLN] procedure)?
Should there be a development towards validation studies, comparing, e.g. different imaging modalities withsurgical staging?

3. What is the clinical implication of discordant axillary imaging before surgery (e.g.,
node suspicious on magnetic resonance imaging [MRI], but not seen on ultrasound[US]?
It remains unclear, how the differing results generated by the different imaging modalities (e.g., US vs. MRI)
should be integrated into clinical practice.

Session II: Omission of axillary surgery
Axillary surgery comprises (i) sentinel lumph node (SLN) procedure, (ii) targeted axillary dissection (TAD), which
includes SLN procedure and removal of clinically suspicious lymph nodes, and (iii) axillary lymph node dissection(ALND), which is defined as the removal of all lymphoid-tissue of the axilla.

4. Is there an optimal age, size or frailty threshold to omit the SLN p rocedure?
Are there optimal cut-offs in age, tumor size, and/or frailty (a state of increased vulnerability to stressors, following
declines in function and reserves across multiple physiologic systems) to omit the SLN procedure?

5. Should we omit the SLN procedure in a clinically node-negative (cN0) patient withtriple-negative (TNBC) or Her-2 positive breast cancer and a high likelihood of
pathologically negative nodes after neoadjuvant chemotherapy?
In patients with an overexpression of the human epidermal growth factor receptor 2 (Her-2), or with a triple
negative (estrogen receptor negative, progesterone receptor negative, Her -2 negative) breast cancer subtype, aclinically unremarkable examination of axillary lymph nodes, and a neoadjuvant chemotherapy with a high8likelihood of tumor-free lymph nodes in the histological examination (pathologically negative), the question
remains, whether we should omit the sentinel lymph node (SLN) procedure?

6. Should we evaluate omission of axillary surgery by delaying the SLN procedure after
evaluation of breast pathologic complete response during primary surgery?
Should we evaluate not conducting axillary surgery in patients who receive therapy before surgery by primarily
evaluating the therapy-response in surgically removed breast-tissue, and in a delayed second step conduct theSLN procedure, depending on a pathologic complete response in the breast or not?

7. What is the role of axillary surgery in ipsilateral in-breast recurrence after previous
breast-conserving surgery and SLN procedure?
What is the role of axillary surgery in patients, who experience an in-breast recurrence in the same breast, whichhas previously been operated by breast-conserving surgery and SLN procedure?

8. What is standard care in case of aberrant drainage with internal mammary or
contralateral axillary SLNs on lymphoscintigraphy in ipsilateral in -breast recurrence
after previous breast-conserving surgery and SLN procedure?
How should we proceed in patients, who experience an in-breast recurrence in the same breast, which has
previously been operated by breast-conserving surgery and SLN procedure, and show atypical lymphoid drainage
to the internal mammary lymph nodes, or the contralateral axillary lymph nodes detected by a special type ofimaging known as lymphoscintigraphy?

Session III: Omission of axillary lymph node dissection (ALND) in cN0 SLN+ patients
Axillary lymph node dissection (ALND) is defined as the removal of all lymphoid-tissue of the axilla, including
three anatomically defined levels, namely (i) Level I below and lateral the pectoralis minor muscle, (ii) Level II
underneath/posterior the pectoralis minor muscle, and (iii) Level III above/medial the pectoralis minor muscle,
whereas removal of Level III lymph nodes is only performed upon gross nodal disease with palpation during
surgery. Questions remains, in which patients with an unremarkable clinical examination, yet a tumor infiltrated(positive) sentinel lymph node ALND can be omitted.

9. Should the ACOSOG Z0011 protocol considered to be standard care around theworld?
In the ACOSOG Z0011 study, patients with a breast cancer up to 5 cm (≤T2) and a clinically node-negative axilla
yet 1 or 2 positive sentinel lymph nodes were randomized to receive ALND or no ALND, with all patients receiving
lumpectomy of the breast, adjuvant whole-breast radiotherapy and adjuvant systemic therapy. 10-year follow-up
results showed no difference in overall survival, disease-free survival, and regional recurrences. Therefore, thequestion is, whether treatment according to this study-protocol should be standard of care?

10. Should we offer choice between observation (Z0011), axillary radiation (AMAROS)
and ALND, or set hard thresholds and if we offer choice should we explore research
into shared decision making and informational provision for this choice to support
women?
Whilst no further axillary intervention after the SLN procedure was undertaken in the ACOSOG Z0011 study,
patients with a breast cancer up to 5 cm and a clinically node-negative axilla yet ≥1 positive sentinel lymph node9

were randomized to receive ALND or axillary irradiation in the AMAROS trial. 10-year follow-up results showed nodifference in overall survival, regional recurrences and distant metastasis -free survival. Hence, the question
remains, whether clinicians should offer patients the choice between those three axillary treatment options, orwhether hard thresholds for the respective practice should be set. Furthermore, should we explore research in toshared decision making and informational provision for this choice to support women?

11. What is standard care for non-palpable ultrasound-detected lymph node metastases
in a Z0011-eligible patient?
In patients with an ultrasound (US) detected positive lymph node, who are therefore clinically node positive but
otherwise fulfill all inclusion criteria of the ACOSOG Z0011 study, it remains unclear, what should be standard ofcare.

12. What is the role of imaging-guided localization and selective removal of non-palpablebiopsy-positive or suspicious nodes in the upfront surgery setting?
In breast cancer patients undergoing upfront surgery, what is the role of imaging-guided (e.g., US-guided)
localization and selective removal of lymph nodes, which are non-palpable but are either biopsy proven to containtumor, or which look suspicious on imaging?

13. Should we apply the Z0011 protocol to cN- patients with pathologically positive SLNs
who were not eligible for Z0011 (e.g., mastectomy, cT3 cancer, >2 positive SLNs,
gross extranodal disease, partial breast or intraoperative radiotherapy)?
The question remains, whether patients, who were not eligible for participation in the ACOSOG Z0011 study (e.g.,
because they underwent mastectomy, or their primary tumor had a diameter of >5cm, or more than 2 lymph
nodes were positive, or tumor cells were detected outside the lymph node in the peri -lymphoid tissue, or who
underwent partial breast radiotherapy or intraoperative irradiation), should also be treated according to the
ACOSOG Z0011 study protocol?

14. Should we apply the Z0011 protocol to cN- patients with microscopic extranodal
extension in SLN metastases?
The question remains, whether patients, who show microscopic tumor cell spread outside of the lymph node i nthe peri-lymphoid tissue should also be treated according to the ACOSOG Z0011 study protocol?

15. Should the ratio of positive to negative sentinel nodes have an impact on eligibility ofthe Z0011 protocol (e.g., 2 of 2 versus 2 of 5 removed SLNs are positive )?
It remains unclear, whether the ratio of positive to negative SLN should have an impact on the eligibility of the
ACOSOG Z0011 protocol (e.g., should it have an impact if 2 out of 2 SLN are positive, compared to the situationin which 2 out of 5 SLN are positive)?

16. Should tumor biology have an impact on eligibility of the Z0011 protocol?
Should it have an impact on the ACOSOG Z0011 protocol, whether a breast cancer patient has a e.g. hormone receptor positive breast cancer, compared to a Her-2 positive breast cancer, or a triple-negative breast cancer<?

17. Should invasive lobular breast cancer be managed equally to invasive ductal
carcinoma regarding omission of ALND?
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Should criteria for the omission of ALND be equally applied in patients with an invasive lobular cancer, comparedto patients with an invasive ductal carcinoma?

18. In which non-Z0011 eligible patients should intraoperative frozen section analysis of
the SLN be standard care?
In which patients, who do not fulfill eligibility criteria for the ACOSOG Z0011, should a frozen section taken during
the primary operation on the SLN be standard of care?

19. What should be standard care in case of nodal disease left behind after axillary
surgery and detected by imaging before the end of adjuvant therapy (e.g., PET -CT orplanning CT for radiation): biopsy, resect, irradiate as special field or boost, observe,
ignore?
The question remains, how to proceed in patients, who underwent axillary surgery, and in which secondary
cancers are detected by imaging that takes place during post-operative therapy. Should we take a biopsy,
remove, irradiate as special field or boost (i.e. extra radiotherapy on the area of the metastasis), observe or ignore
them?

20. What is the contemporary morbidity of the SLN procedure versus ALND and SLN
procedure versus no axillary surgery and its impact on quality of life?
What is the disease burden, and impact on the quality of life in patients undergoing the SLN procedure comparedto ALND or no axillary surgery?

21. What is the impact of the lack of knowledge of the exact number of positive andnegative nodes on use of molecular tests (e.g., Oncotype DX®, Mammaprint®) andadjuvant therapy decisions?
Regarding omission of axillary surgery, the question remains what the impact of our lack of knowledge on theexact number of positive and negative lymph nodes is regarding molecular test and adjuvant treatment decisions?

Session IV: Omission of ALND in patients with clinically node-positive (cN+) breast
cancer
22. When will we be able to banish most of the remaining routine indications for radical
ALND from clinical practice to improve patient-reported quality of life without
jeopardizing survival and oncologic safety (e.g., palpable disease in the adjuvant
setting or residual disease in the neoadjuvant setting)?
In, for example, patients showing palpable lymph nodes in the adjuvant setting, or residual disease after
neoadjuvant treatment, what needs to be true for us to be able to banish the remaining routine indications forradical Axillary lymph node dissection (ALND) from clinical practice to improve patient-reported quality of life
without jeopardizing survival and oncologic safety?

23. What is the exact definition of clinical complete response (ycN0), thus allowing limited
axillary surgery (i.e., SLN or TAD) with the aim of omitting ALND?

11

It remains unclear, how exactly a clinical complete response of the axillary lymph nodes after neoadjuvant
treatment (ycN0) should be defined, thus allowing a limited axillary surgery (i.e., SLN or targeted axillary
dissection [TAD], which comprises the removal of sentinel lymph nodes as well as pre-neoadjuvant treatment
marked positive lymph nodes) and omitting ALND.

24. Should measures to decrease the false-negative rate of the SLN procedure in initiallycN+ converting to ycN0 be standard care, such as use of dual tracer or removal of aminimum of 3 negative SLNs?
In patients with breast cancer, who initially present with lymph node metastases, receive neoadjuvant treatment,
and clinically do not show tumor cells in the lymph nodes thereafter (ycN0), the question remains, whether
measures to decrease the false-negative rate of the SLN procedure, such as dual tracer, or the removal of aminimum of 3 sentinel lymph nodes should be applied?

25. Should targeted axillary dissection (TAD versus SLN only or ALND) be standard carein initially cN+ converting to ycN0 and is TAD oncologically safe compared to ALND?
In patients with breast cancer, who initially present with lymph node metastases, receive neoadjuvant tr eatment,
and clinically do not show tumor cells in the lymph nodes thereafter (ycN0), the question remains, whether
targeted axillary dissection (TAD), should be standard of care (compared to sentinel lymph node procedure or
Axillary lymph node dissection (ALND), and whether it is oncologically safe?

26. Should use of the SLN or TAD procedures with the aim of omitting ALND in patientswith cN+ converting to ycN0 depend on the initial clinical tumor load (e.g., large
number of initially suspicious lymph nodes, cN2/3, cT4)?
In patients with breast cancer, who initially present with l ymph node metastases, receive neoadjuvant treatment,
and clinically do not show tumor cells in the lymph nodes thereafter (ycN0), the question remains, whether TAD or
the SLN procedure with the aim of omitting ALND should depend on the initial tumor stage?

27. Should the finding of nodal pCR by use of the SLN or TAD procedure with the aim ofomitting ALND in patients with cN+ converting to ycN0 depend on the documentationof regressive changes in the lymph node by the pathologist?
In patients with breast cancer, who initially present with lymph node metastases, receive neoadjuvant treatment,
and clinically do not show tumor cells in the lymph nodes thereafter (ycN0), the question remains, whether thedefinition of a pathologic complete response (pCR) after TAD or the SLN procedure should depend on thevisualization of regressive changes in the removed lymph nodes?

28. How many suspicious nodes on imaging should be marked (e.g., clipped) in a patientundergoing neoadjuvant chemotherapy (NACT)?
In patients with breast cancer, who initially present with lymph node metastases, and are planned to receive
neoadjuvant treatment, the question remains, how many suspicious l ymph nodes should be marked before
treatment initiation?

29. Is there a volume threshold of residual nodal disease after neoadjuvant
chemotherapy (NACT) when radiation can replace ALND (ITC versus
12micrometastatic versus macrometastatic residual disease in one or more lymph
nodes)?
In patients with breast cancer, who initially present with lymph node metastases and receive neoadjuvant
chemotherapy, the question remains, whether we can define a volume threshold of residual nodal disease after
surgical lymph node removal in which radiation can replace Axillary lymph node dissection ALND (i.e. isolated
tumor cells [ITC], micrometastasis, (Micrometastasisstases are microscopic cancer cells that have escaped fromthe original tumor and are defined by size. They should be less than or equal to 2mm in largest dimension),
macrometastasis (Metastases larger than 2mm), residual disease in one or more lymph nodes)?

30. What is the maximum volume of residual nodal disease after neoadjuvant hormonal
therapy (NET) that radiation can control (ITC versus micrometastatic versus
macrometastatic residual disease in one or more lymph nodes), thus allowing
omission of ALND?
In patients with breast cancer, who initially present with lymph node metastases and receive neoadj uvant
hormonal therapy, the question remains, whether we can define a volume threshold of residual nodal disease
after surgical lymph node removal in which radiation can replace ALND (isolated tumor cells [ITC],
micrometastasis, macrometastasis, residual disease in one or more lymph nodes)?

31. What is standard care for suspicious findings in internal mammary or supraclavicularlymph nodes on imaging?
How should we proceed, if suspicious findings are seen in lymph nodes of the internal mammary or
supraclavicular region?

32. What is the best axillary surgery procedure after neoadjuvant radiation therapy?
Session V: Axillary radiation and extended regional nodal irradiation (ERNI)
Axillary radiotherapy is defined as the irradiation of the axilla. Extended regional nodal irradiation (ERNI) includes
radiotherapy of the axilla, the supra- and infraclavicular lymph nodes and/or the internal mammary lymph nodes.

33. What is the best nodal irradiation technique?
34. Are there subgroups of Z0011-eligible patients that should receive axillary radiation,and should axillary radiation in Z0011-eligible patients –if indicated- be combined withERNI (e.g., levels 1-4, levels 3-4, internal mammary nodes, and combinations)?
Should certain Z0011-eligible patients receive axillary irradiation, and should axillary irradiation be combined with
ERNI?

35. What is the optimal patient selection for ERNI in general and for specific ERNI
protocols in particular (e.g., levels 1-4, levels 3-4, internal mammary nodes, andcombinations)?
The question remains, which selection criteria are optimal to select patients for ERNI in general and for specific
ERNI protocols.

36. What are the side effects of axillary radiation using modern techniques?
1337. What is the risk of lymphedema in a patient who develops recurrence in the axilla
after radiation of the axilla and undergoes ALND?
38. In what situations can axillary radiotherapy be de-escalated?
It remains unclear, in which patients/situations axillary radiotherapy can be omitted.

Session VI: Conceptual and technical questions
39. Should intercostobrachial nerves be preserved during ALND?
Intercostobrachial nerves are nerves, which run from the intercostal space to the upper -arm, transmitting
sensation and pain, which is why damage to these nerves can cause sensation losses as well as pain.

40. How can we prevent axillary web syndrome?
Axillary web syndrome comprises the formation of postoperative fibrotic cords or bands underneath the armpit ,which may also involve the arm.

41. Should lymphatic vessels be preserved during ALND, e.g. by using axillary reverse
mapping or stepwise limited ALND?
Axillary reverse mapping (ARM) is a technique where blue dye is injected into the upper arm at surgery, allowing
direct visualization of arm lymphatics and nodes during either SLN or ALND.

42. Should level II be included in standard ALND?
The question remains, whether level II lymph nodes (i.e., lymph nodes underneath/posterior the pectoralis minor
muscle) should be included in standard ALND?

43. When should level III be included in ALND?
The question remains, whether level III lymph nodes (i.e., lymph nodes above/medial the pectoralis minor muscle)
should be included in standard ALND?

44. What is the best tracer to mark sentinel nodes and when should we use dual tracer?
It remains unclear, which tracer is best for the SLN procedure, and when dual tracer (i.e., using two tracing
methods as for example Technetium and blue-dye) should be used?

45. What is the best method to mark the sampled node and the best imaging modality tolocalize it?
It remains unclear, which method is best to mark the sampled lymph node (e.g., clip), and which imaging modality
is best to localize it?

46. Should the biopsied lymph node be marked (e.g., clipped) immediately or after
histologic confirmation of metastasis?
47. What is the best pathology assessment of the SLN and should it be standardized?
48. Is there a role for nomograms that predict the likelihood of nodal metastases basedon patient, tumor and treatment variables in contemporary axillary management?

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A nomogram is a predictive tool. These tools are based on information from hundreds or even thousands ofpeople with cancer. The tools can be used to predict cancer outcomes or assess risk based on specificcharacteristics of a patient and their disease.

Session VII: Follow up
49. What is the optimal follow-up interval and imaging modality for patients after axillary
surgery?
How often should we see patients for follow-up, and which imaging modality is optimal for patients after axill ary
surgery (e.g., sonography, MRI)?

50. How should we address lack of sensitivity of axillary imaging during follow-up?
51. What are the clinically most relevant endpoints in axillary management (survival,
recurrence, lymphedema, morbidity, patient-reported outcomes)?

15

Appendix 1: Questionnaires to assess characteristics of OPBC panelists

2022 Consensus Conference
PERSONAL INFORMATION FORM

PATIENT ADVOCATES
Name (optional): _________________________________________________________________
Middle Name (optional): __________________________________________________________
Surname (optional): ______________________________________________________________
Affiliation (if applicable): __________________________________________________________
Gender: Female 

Male 

Year of diagnosis: ________________________________________________________

Surgical procedure (zero, one or more than one response possible): No axillary surgery
 S entinel lymph node procedure Axillary lymph node dissection
 Breast conserving surgery
 Mastectomy without reconstruction
 Mastectomy with implant-based reconstruction
 Mastectomy with reconstruction using your own body tissue
 No surgical treatment
 I prefer not to disclose this information16

2022 Consensus Conference
PERSONAL INFORMATION FORM

SURGEONS
Name: __________________________________________________________________________
Middle Name: ____________________________________________________________________
Surname: ________________________________________________________________________
Affiliation: _________________________________________________________________________________________________________________________________________________________________________________________________________________________________________
Board Certificate: General Surgery 

Gynecology 

Plastic Surgery Years of Experience: ______________________________________________________________
Estimated Number of Breast Surgery Procedures Performed or Assisted in 2020:
0-20 

20-50 Gender: Female 

50-100 

100+ 

Male 

Type of Breast Center: Academic  Public  Private 17

2022 Consensus Conference
PERSONAL INFORMATION FORM

Radiation Oncologists
Name: __________________________________________________________________________
Middle Name: ____________________________________________________________________
Surname: ________________________________________________________________________
Affiliation: _________________________________________________________________________________________________________________________________________________________________________________________________________________________________________
Years of Experience: ______________________________________________________________
Estimated number of patients with breast cancer treated in 2020:
0-20 

20-50 Gender: Female 

50-100 

100+ 

Male 

Type of Breast Center: Academic  Public  Private  Not applicable 18

References1.
Weber WP, Matrai Z, Hayoz S, et al: Tailored axillary surgery in patients with clinicallynode-positive breast cancer: Pre-planned feasibility substudy of TAXIS (OPBC-03, SAKK 23/16, IBCSG
57-18, ABCSG-53, GBG 101). Breast 60:98-110, 2021
2.
Henke G, Knauer M, Ribi K, et al: Tailored axillary surgery with or without axillary
lymph node dissection followed by radiotherapy in patients with clinically node-positive breast
cancer (TAXIS): study protocol for a multicenter, randomized phase-III trial. Trials 19:667, 2018
3.
Kappos EA, Schulz A, Regan MM, et al: Prepectoral versus subpectoral implant-basedbreast reconstruction after skin-sparing mastectomy or nipple-sparing mastectomy (OPBC-02/
PREPEC): a pragmatic, multicentre, randomised, superiority trial. BMJ Open 11:e045239, 2021
4.
Weber WP, Morrow M, Boniface J, et al: Knowledge gaps in oncoplastic breast
surgery. Lancet Oncol 21:e375-e385, 2020
5.
Weber WP, Soysal SD, El-Tamer M, et al: First international consensus conference on
standardization of oncoplastic breast conserving surgery. Breast Cancer Res Treat 165:139-149, 20176.
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