Board Review Q&A (2025): De-escalating Axillary Surgery in Breast Cancer

What was the pivotal shift from ALND to SLNB?
- Randomized trials:
  - Milan / Veronesi, NSABP B-32, ALMANAC
- This trials showed that SLNB achieves equivalent survival and regional control compared with ALND:
  - While markedly reducing arm morbidity and improving QoL:
    - Establishing SLNB as standard staging for cN0 disease
      - New England Journal of Medicine+2PubMed+2
NSABP B-32 – what did it prove?
- In > 5,600 cN0 patients:
  - SLNB alone (when SLN negative) yielded:
    - Equivalent OS and regional control to ALND:
      - With less lymphedema and sensory deficits
- This trial anchored SLNB as safe oncologically and better for function PubMed+1
ALMANAC – why do we still quote it?
- The UK multicenter RCT:
  - SLNB vs standard axillary treatment:
    - Showed substantially less arm morbidity, pain, and better QoL at 12 months with SLNB:
      - An early, practice-changing morbidity signal complementing efficacy trials OUP Academic+1
Milan (Veronesi) trial—what’s the take-home?
- Single-center RCT:
  - SLNB safely replaced routine ALND for cN0 with durable 10-year outcomes:
    - Cementing SLNB accuracy and safety in early breast cancer
Technique pearls that lower SLNB FNR in general?
- Use dual-tracer mapping and retrieve ≥ 2 to 3 SLNs when possible:
  - Dual mapping reduces FNR versus single dye, and more nodes improves accuracy
Positive SLN after upfront surgery (ALND omission)
- ACOSOG Z0011—who can safely avoid ALND?
  - Women with cT1 to cT2, cN0 undergoing BCS + whole-breast RT, with 1 to 2 positive SLNs:
    - Had no OS benefit from ALND:
      - 10-yr OS 86.3% SLNB-alone vs 83.6% ALND
  - Today, we omit ALND for Z0011-eligible patients JAMA Network
- Does ACOSOG Z0011 imply mandatory comprehensive RNI?
  - No:
    - Z0011 patients largely received tangential breast RT:
      - Comprehensive RNI wasn’t mandated
    - Decisions today are individualized by:
      - Tumor biology, nodal burden, and fields JAMA Network
IBCSG 23-01—what about micrometastases (≤ 2 mm)?
In patients with micrometastases:
- No ALND was noninferior to ALND for long-term outcomes (10-yr DFS noninferior):
  - Supporting omission of ALND in micrometastatic disease PubMed+1
AMAROS Trial – ART vs ALND after a positive SLN?
- Phase III trial:
  - Axillary RT produced similar control and survival as ALND:
    - But less lymphedema (11% vs 23% at 5 yr):
      - Making ART the preferred completion strategy when axillary treatment is needed PMC+2The Lancet+2
OTOASOR Trial – does it align with AMAROS Trial?
Yes:
- Single-center RCT with 8-yr follow-up:
  - RNI noninferior to ALND for control /survival after a positive SLN:
    - Reinforcing ART / RNI as an ALND alternative to limit morbidity PubMed
SENOMAC (2024 NEJM) – what’s new versus Z0011?
- Included mastectomy patients and broader indications:
  - Omission of completion ALND in patients with 1 to 2 SLN macrometastases:
    - Was noninferior for survival:
      - Most received RNI
  - Expands ALND omission beyond BCS PubMed
SENOMAC nuances – ECE, T3 tumors, men?
- SENOMAC enrolled some patients with ECE, cT3, and men
- Prespecified subgroup analyses did not show detriment with ALND omission:
  - Though numbers are smaller – supporting wider generalizability makadu.live
After mastectomy with 1 to 2 positive SLNs, do I need ALND?
- Not routinely – With planned comprehensive RNI, ALND can be omitted (AMAROS, SENOMAC) a position reflected in the 2025 ASTRO-ASCO-SSO PMRT guideline language emphasizing less invasive axillary management with nodal RT PubMed+2PubMed+2

Omission of any axillary surgery (SLNB-omission):
- SOUND (JAMA Oncol 2023) – who can skip SLNB entirely?
  - Women with small tumors and negative axillary ultrasound:
    - Had noninferior 5-yr distant DFS with no axillary surgery vs SLNB
  - If axillary pathology doesn’t change therapy:
    - Omission is safe
- INSEMA (NEJM 2024/2025) – does it reinforce SLNB omission?
  - Yes:
    - In cT1 to cT2 cN0 undergoing BCS + WBRT, omitting SLNB was noninferior for invasive DFS, with fewer arm morbidities:
      - Broadening omission beyond SOUND’s entry criteria
- Guideline impact – what does ASCO 2025 now recommend?
  - ASCO now supports SLNB omission for select postmenopausal ≥50, HR+/HER2-, G1–2, ≤2 cm tumors with negative AUS undergoing BCS + RT, when nodal status won’t alter adjuvant therapy
- How do I counsel a 65-year-old with 1.5 cm HR+/HER2–, AUS-negative tumor?
  - Discuss SLNB omission per ASCO 2025, referencing SOUND / INSEMA
  - Emphasize shared decision-making and document that nodal status won’t change systemic therapy / RNI plans
- Does negative AUS define cN0 reliably enough to omit surgery?
  - In SOUND / INSEMA, AUS was adequate for selection:
    - Axillary failures were rare with omission when systemic / RT plans were appropriat:
      - Still, ensure imaging quality and consider biology.
Pathology definitions and “what counts”
- Define ITCs vs micrometastases (AJCC 8e):
  - ITCs:
    - < 0.2 mm or < 200 cells (N0[i+])
  - Micrometastases:
    - 0.2 mm to 2 mm (N1mi)
- Management parallels the trials:
  - Micrometastases (IBCSG 23-01) often no ALND:
    - ITCs generally node-negative
- Do ITCs change indications for ALND or RNI
  - ITCs typically do not mandate ALND:
    - Decisions on RNI hinge on comprehensive risk assessment rather than ITCs alone (Use institutional protocols)
Neoadjuvant chemotherapy (NAC): SLNB and TAD
- ACOSOG Z1071 – what did we learn?
  - In biopsy-proven cN1→ycN0 after NAC:
    - SLNB had an FNR ≈ 12%:
      - Improved by dual tracer and retrieving ≥ 3 SLNs
      - Capturing the clipped node lowered the FNR further – ushering in targeted axillary dissection (TAD)
- SENTINA – why was FNR a concern?
  - Complex 4-arm RCT showed higher FNRs when SLNB was performed after NAC in initially node-positive patients, especially when only 1 to 2 SLNs were retrieved:
    - Driving optimization:
      - Dual mapping, ≥ 3 SLNs and TAD
- SN-FNAC (JCO 2015) – can SLNB be accurate post-NAC in cN+?
  - With mandatory IHC, ID rate 87.6% and FNR 8.4%:
    - When ≥ 2 SLNs were removed – evidence that optimized technique can make SLNB acceptable after NAC in prior cN+
- GANEA-2 (2019) – safety signal?
  - Prospective multicenter study supported feasibility and safety of post-NAC SLNB with low axillary failure when using optimized protocols; informs modern post-NAC algorithms
- What is TAD and why do it?
  - Targeted axillary dissection combines SLNB + removal of the pre-treatment clipped node:
    - To slash FNR vs SLNB alone and better mirror basin response – core idea from MD Anderson implementation work
- RISAS / TAD accuracy – what’s the FNR
  - Multicenter diagnostic study of radioactive iodine seed localization (RISAS):
    - FNR 3.5%, NPV 92.8% – strong diagnostic performance for restaging after NAC
- MARI protocol – how is it different?
  - Marking the positive node with a seed pre-NAC and excising it post-NAC; with PET-CT integration:
    - MARI can avoid ALND in ~80% of cN+ while keeping 3-yr axillary recurrence-free interval ~98%
- TAD outcomes – can we safely omit ALND in responders?
  - Cohorts show low 3-yr axillary recurrence with TAD alone in good responders (and no survival decrement vs TAD + ALND in selected patients):
    - Supporting ALND omission after accurate TAD
- Practical NAC pearls to minimize FNR:
  - Always clip the biopsied positive node pre-NAC
  - Use dual / multi-tracers
  - Aim to remove clipped node + ≥ 2 to 3 SLNs
  - Consider seed / mag / wire techniques to ensure clipped-node retrieval
- What if the clipped node is not a sentinel node?
  - Happens in ~ 20% to 25% – hence TAD’s value:
  - Explicitly localize and remove the clipped node in addition to SLNs to mitigate mapping discordance
- “Lost marker” after NAC – how common and what to do?
  - About 6% markers cannot be retrieved:
    - Have contingency plans:
      - Intra-op imaging
      - Secondary localization
      - Proceed to ALND if residual disease risk is high and target cannot be verified
- After NAC, who still needs ALND?
  - Persistent palpable / yrcN+ disease
  - Inadequate TAD / SLN retrieval
  - Gross ECE / bulky residual nodal disease
  - Tailor with imaging, pathology, and MDT input
Radiotherapy interplay and guidelines:
- When you omit ALND after positive SLN, what about RT?
  - Trials (AMAROS, OTOASOR):
    - Delivered axillary / RNI with excellent control and less lymphedema than ALND
  - For mastectomy with 1 to 2 SLN macrometastases:
    - RNI without ALND is supported (now reflected in 2025 PMRT guidance)
- 2025 ASTRO-ASCO-SSO PMRT update – what changed?
  - Reaffirms PMRT in most node-positive after mastectomy
  - Clarifies post-NAC ypN0 and scope of RNI:
    - Emphasizes integration with less invasive axillary surgery to limit morbidity
- Does RNI obviate ALND in all scenarios?
  - No:
    - Use patient selection akin to AMAROS /SENOMAC (limited macrometastases burden)
    - Bulky residual disease or inadequate mapping still tips to ALND
Special populations and situations:
- Age ≥ 70, small HR+ / HER2- tumors – do I need SLNB?
  - SSO Choosing Wisely and ASBrS support omitting axillary staging when it won’t change adjuvant therapy:
    - Aligns with ASCO 2025 omission framework
- DCIS – when is SLNB indicated?
  - Not for BCS without invasion suspicion
  - Do SLNB for mastectomy or if imaging / biopsy suggests invasion risk
- Re-SLNB after prior surgery?
  - Feasible after prior BCS / SLNB:
    - But results may not alter systemic therapy in local recurrences:
      - Individualize
- Pregnancy – map with what tracer?
  - Avoid radiocolloid if possible depending on local policy
  - Many centers use blue dye cautiously (risk of anaphylaxis)
    - Institutional / obstetric MDT policy applies; outside trial scope
- Male breast cancer – apply same axillary principles?
  - Generally yes:
    - SENOMAC included men without a signal of harm from ALND omission in selected cases
Minimum SLNs to retrieve?
- Strive for ≥ 2
- ≥ 3 post-NAC if possible – associated with lower FNR in SENTINA / ACOSOG Z1071:
  - Ensure robust mapping
Mapping – dye alone acceptable?
- Dual tracer is preferred for lowest FNR
- Dye-only can work but increases FNR / variability – reserve for exceptional logistics Does extracapsular extension (ECE) mandate ALND?
Does extracapsular extension (ECE) mandate ALND?
- Not categorically:
  - SENOMAC included some ECE without harming noninferiority
  - Consider extent (gross vs microscopic) and planned RNI
Two vs three positive SLNs in BCS – Z0011 boundary?
- >2 positive SLNs (or Z0011-ineligible features):
  - Generally push toward further axillary therapy:
    - Often ART / RNI rather than routine ALND
Mastectomy, 1 to 2 macrometastases SLNs – can I do SLNB alone + RNI?
- Yes – supported by AMAROS and SENOMAC:
  - Many centers omit ALND and deliver comprehensive RNI
Micrometastases (≤ 2 mm) after SLNB – ALND needed?
- No:
  - IBCSG 23-01 provides level-1 evidence to omit ALND:
    - Manage with breast / RT decisions as appropriate
ITCs only – how to code / manage?
- N0(i+):
  - Do not count as node-positive for N category:
    - Decisions about RT / systemic therapy rely on whole-patient risk
Post-NAC, cN1→ycN0 with TAD negative – omit ALND?
- Yes for many:
  - With robust TAD (clipped node retrieved + SLNs) showing pCR / low burden:
    - ALND can be omitted:
      - Early outcomes show low axillary failure
Post-NAC, ypN1mi – what’s the move?
- Case-by-case:
  - Limited data
  - Many MDTs favor RNI and omit ALND if TAD robust and burden minimal:
    - Document rationale (biology, response, fields):
      - See ASBrS resource guide framing individualized decisions
When is pre-NAC SLNB appropriate?
- Avoid:
  - Image-guided needle biopsy / clip suspicious nodes before NAC and stage after NAC with SLNB / TAD
Does adding axillary RT after TAD-negative improve outcomes?
- Uncertain; trials ongoing:
  - Observational data suggest very low axillary recurrence with accurate TAD even without ALND:
    - RT decisions are individualized
Acceptable axillary failure rates with de-escalation?
- Across ACOSOG Z0011 / AMAROS / OTOASOR /SOUND / INSEMA:
  - Axillary recurrences are ~ 1% to 2% range at mid-term, with no survival penalty – key benchmark when counseling
Documentation when omitting SLNB in 2025
- Record AUS quality / negative, eligibility per ASCO 2025 & SOUND / INSEMA:
  - That nodal status won’t alter systemic / RT plan, and shared decision-making
How do European trials generalize to a diverse US population?
- Biology and systemic therapy drive outcomes; de-escalation trials show consistency across subgroups
- Apply trial entry criteria, use high-quality AUS, and partner with RNI where trials did:
  - Guideline-concordant practice mitigates external validity concerns
What’s on the horizon (TAXIS)?
- TAXIS tests tailored axillary surgery (remove clipped + sentinel nodes; omit ALND) with RNI in cN+:
  - Continuing the move away from full ALND where disease control is maintained
- Blue dye vs radiocolloid vs ICG – does tracer choice change outcomes?
  - Dual tracer (radiocolloid + blue) remains the most validated for lowest FNR
  - ICG is promising, especially post-NAC, but data are heterogeneous
  - Choose the approach that maximizes node yield in your OR
What lymphedema differences matter in clinic?
- Expect lowest rates with no axillary surgery (SOUND / INSEMA) or SLNB alone
- Intermediate with ART / RNI
- Highest with ALND (AMAROS quantified 11% vs 23% at 5 yr)
  - Use this in counseling
After prophylactic mastectomy, should we stage the axilla?
- No:
  - SLNB is not recommended during prophylactic mastectomy given the very low chance of invasive cancer / nodal disease
Relevance of ACOSOG Z0011 to mastectomy patients?
- Z0011 enrolled BCS + whole-breast RT
- For mastectomy, lean on AMAROS and SENOMAC to omit ALND with planned RNI for 1 to 2 macrometastases
One-slide algorithm to operationalize (2025):
- Upfront cN0, AUS negative, small HR+ / HER2 negative:
  - Consider omit SLNB (ASCO 2025):
    - Else SLNB
- 1 to 2 SLN macrometastases:
  - Omit ALND
  - BCS → usually radiation tangents ± RNI
- Mastectomy → RNI (AMAROS/SENOMAC)
- NAC cN1→ycN0 → TAD (clip+SLNs):
  - If negative / low burden:
    - Omit ALND; tailor RNI
  - Persistent cN+, bulky / ECE, mapping failure:
    - ALND
Quick source keys (selected):
- SLNB vs ALND:
  - NSABP B-32, ALMANAC, Milan
- No ALND (positive SLN):
  - ACOSOG Z0011; IBCSG 23-01 (micrometastases); AMAROS; OTOASOR
- No SLNB:
  - SOUND; INSEMA; ASCO 2025
- Post-NAC:
  - ACOSG Z1071; SENTINA; SN-FNAC; GANEA-2; TAD / RISAS / MARI
- Guidelines (2024–2025):
  - ASCO 2025 SLNB update; ASTRO-ASCO-SSO 2025 PMRT; ASBrS resource guide