doing less in….the axilla · • evaluation axillary lymph node status important for staging,...

DOING LESS IN….THE AXILLA

Dr Fleur Kilburn-Toppin MA MB BChir FRCR

Consultant Breast Radiologist

Cambridge University Hospital, UK

IMAGING THE AXILLA: WHY WE DO IT

• Evaluation axillary lymph node status important for staging, treatment planning and prognosis

• 30-40% patients will have nodal metastases

• Sentinel lymph node biopsy (SLNB) accurate minimally invasive alternative to ALND

Sentinel lymph node biopsy compared with axillary lymph node dissection in early breast cancer: a meta-analysis. Wang. Breast Cancer Res Treat 2011.


LN +ve LN -ve

SLNB

LN +ve

ALND


LN -ve

SLNB

LN +ve

ALND

LN +ve LN -ve

SLNB

LN +ve

ALND

US +/- Biopsy

LN +ve

CRITERIA FOR LYMPH NODE BIOPSY

M O R P H O L O G Y

Use of ultrasound-guided axillary node core biopsy in staging of early breast cancer. Britton. Eur Radiol. 2009

1

C O RT I C A L T H I C K N E S S2

Value of Preoperative Ultrasound-Guided Axillary Lymph Node Biopsy for Preventing Completion Axillary Lymph Node Dissection in Breast Cancer: A Systematic Reviewand Meta-Analysis. Diepstraten. Ann Surg Oncol. 2014

Highest needle biopsy sensitivities in highest likelihood metastatic disease:

Palpable Multifocal Central >20mm

CRITERIA FOR LYMPH NODE BIOPSY

3 meta-analyses - pooled estimate sensitivity of axillary US and biopsy:

50%

Clinical utility of axillary US and biopsy triaging patients directly to ALND:

20%Pre-operative ultrasound guided needle biopsy of axillary nodes in invasive breast cancer: meta-analysis of its accuracy and utility in staging the axilla. Houssami. Ann Surg 2011

UTILITY OF AXILLARY ULTRASOUND

CRITERIA FOR LYMPH NODE BIOPSYUTILITY OF AXILLARY ULTRASOUND

Why is our axillary US pre-operative diagnosis so low?

1. The majority of lymph nodes metastases are too small to see on US

2. We only sample part of the node

3. We don’t know which is the sentinel node


How can we improve this?

More intelligent targeting of sentinel node

1. Elastography: Significantly harder cortex in metastatic nodes. Highest sensitivity and specificity (73%, 99.3%) with combination conventional US and elastography

2. Contrast enhanced US: microbubbles. 89% sensitivity sentinel node detection

Ultrasound elastography as an adjuvant to conventional ultrasound in the preoperative assessment of axillary lymph nodes in suspected breast cancer. Taylor. Clin Radiol. 2011


Pre-operative sentinel lymph node identification, biopsy and localisation using contrast enhanced ultrasound in patients with breast cancer: a systematic review and meta-analysis. Mood. Clin Rad. 2017

CT AND MRI FOR THE AXILLA

• Breast MRI, CT and whole body PET/CT, are often obtained in newly diagnosed breast cancer patients for clinical staging

• Can be used to provide regional nodal staging information

CT AND PET-CT

• Staging the axilla using both CT and ultrasound is no more accurate than ultrasound alone

• Specificity of PET/CT in the detection of lymph node metastases is high (95 to 100%)

• Pitfall of PET-CT is high false negative rate due to inability to detect small metastatic deposits

MRI AXILLA

• Breast MRI includes the axillary region in the field of view, with additional benefit both axillae can be compared easily

• Sensitivity and specificity of MRI assessment of ALN status are highly variable

• Systematic review: mean sensitivity and specificity values 88% and 73%

• BUT:

• Technically challenging

• Additional coils

• Use of a dedicated lymph node contrast agent

MRI AXILLA

• As with US, suspicious features cortical irregularity, loss of fatty hilum and round shape

• Short axis threshold 4mm best predictive value for metastatic nodal involvement -sensitivity and specificity of 79% and 62%

• Nodes with less intense enhancement - high negative predictive value

• MR specific imaging features potential diagnostic utility:

• Perifocal oedema

• Comet tail sign

Luciaina, 2004. Baltazar, scaranelo

ADVANCED MRI

• Advanced MRI techniques, including DWI, possible tools for improving the accuracy of MRI assessment of the ALNs

• DWI has not yet convincingly been shown to improve diagnostic performance

• Tumor luminal subtype independent factor for false-positive results regarding ALN status

• Suspicious ALN in luminal B tumor more likely to yield positive nodal disease than luminal A tumor (PPV 76.2% vs 28.0%)

• Potential management implications (sentinel node biopsy over pre-op biopsy in luminal A)

Esserman, 2017


• ACOSOG Z11 trial: SLNB positive patients clinical stage T1 – 2N0 randomised to ALND vs no further surgery

Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. Giuliano. JAMA. 2011

• No difference in survival or locoregional recurrence

• Evidence that Z0011 changing practice

• Little evidence reported about change in practice in Europe

• Data from EUSOMA – 34 European breast centres (not UK)

• Axillary dissection rates decreased from 89% (2010) to 46% (2016)

• Wide differences in centres and countries – need unified clinical guidelines in Europe

• POSNOC – address deficiencies in published literature

• Primary tumour <5cm and 1-2 SLNs randomised adjuvant therapy alone or adjuvant therapy and completion axillary dissection or axillary radiotherapy

Trends in axillary lymph node dissection for early-stage breast cancer in Europe: Impact of evidence on practice C A Garcia-Etienne, Breast June 2019

• pN1 – 1-2 macrometatases – further local axillary treatment is not required if all of the following criteria are met:

• Patient is post-menopausal and will receive whole breast radiotherapy and endocrine therapy

• The tumour is T1, grade 1-2, ER positive, HER2 negative

• The risks and benefits of no further axillary treatment are discussed with the patient

•• All other patients require further axillary treatment: either surgery or radiotherapy. The risks and

benefits of surgery versus radiotherapy may vary between individuals and will be discussed at multidisciplinary team meeting

•

• Local Policy : Management of the cN0 axilla following primary surgery

• 53% node positive patients undergoing axillary clearance had ≤2 positive nodes

• 47% (Pilewski) 38% (Farrell)

OVERTREATMENT DUE TO AXILLARY ULTRASOUND

• Significant potential over-treatment because of pre-operative US axillary staging

• Importance of counting, and documenting, number of nodes

• 78% with tumour size < 2 cm and one abnormal node on US have two or fewer positive nodes at histology after ALND

• Subsequent focus on imaging to improve discrimination between limited and advanced disease

DISCRIMINATING ADVANCED VS LIMITED DISEASE

• Negative axillary US excludes advanced nodal disease with a NPV of 96%

• False negatives: Lobular cancer, larger, multifocal

• Omit SLNB?

• SOUND trial

Axillary ultrasound for preoperative nodal staging in breast cancer patients: is it of added value? Schipper. Breast. 2013


• When at least two nodes on US, pN2 or higher disease highly likely (PPV 82%)

• Triage directly to surgery

Does a Positive Axillary Lymph Node Needle Biopsy Result Predict the Need for an Axillary Lymph Node Dissection in Clinically Node-Negative Breast Cancer Patients in the ACOSOG Z0011 Era? Pilewskie. Ann Surg Oncol. 2015

Total +ve LNs for women with +ve pre-operative needle biopsy identified on US

• What if we only see one abnormal node on axillary US?

• 50% patients ≤2 positive nodes : risk of overtreatment

• Should you leave solitary node alone?

• 78% concordance biopsied node and sentinel node

• Clip, wire, tattooing or radioactive iodine

• If not retrieved: ALND


Axillary tumour burden in women with one abnormal node on ultrasound compared to women with multiple abnormal nodes. Puri. Clin Radiol. 2018

• Neoadjuvant chemotherapy (NAC) as effective as adjuvant treatment

• Decreased disease burden allows less extensive surgery

• pCR in axilla more frequently than the breast

• 40-60% become node negative

• Lower for ER +ve/HER 2 –ve (21%), higher for triple negative and ER –ve/HER 2 +ve (97%)

• Traditionally always ALND following NAC

• Now NAC for earlier stage breast cancer and node negative disease in triple negative breast cancer patients

THE AXILLA AND NEO-ADJUVANT CHEMOTHERAPY

Incidence and impact of documented eradication of breast cancer axillary lymph node metastases before surgery in patients treated with neoadjuvant chemotherapy. Kuerer. Ann Surg.1999

• Timing of SLNB subject of much debate

• SLNB before NAC• Higher identification rates

• Influence adjuvant treatment (mainly radiotherapy)


• SLNB after NAC• More meaningful predictor of locoregional recurrence

• If PCR, more conservative axillary surgery possible

• BUT concern about FNR; should be <10%

• cN0 - SNB before or after NACT, practice moving towards after for patient benefit

• No further treatment to axilla if SLNB negative

• Even low volume residual disease in SLNB after NACT associated worse outcome - ALND

MULTIDISCIPLINARY GUIDANCE RCR

1. Sentinel node biopsy and neoadjuvant chemotherapy: Multidisciplinary Guidance from the Association of Breast Surgery, Faculty of Clinical Oncology of The Royal College ofRadiologists, UK Breast Cancer Group & the National Coordinating Committee for Breast Pathology 2019 (awaiting ratification and publication)

• cN1 - Discuss after MDT on completion NACT

• Clinically / radiologically extensive nodal involvement still requires ALND

• No firm evidence base to advise on treatment for patients who have complete pathological response

• If SLNB negative, for axillary radiotherapy or no further treatment as part of trial / cohort study

• If SLNB positive, for ALND as not good evidence to support radiotherapy


• SLNB after NAC• More meaningful predictor of locoregional recurrence

• If PCR, more conservative axillary surgery possible

• BUT concern about FNR; should be <10%

• Residual disease in nodes or fibrosis may mean errant mapping

• FNR threshold may depend on patient population

• Most women ongoing treatment with trastuzumab and/or endorcrine therpay eradicating residual disease in the axilla

• Triple negative patients who have no further systemic therapy may need lower threshold

• Further work needed on different phenotypes


• Predictive factors for residual metastatic axillary lymph node disease in patients with negative imaging findings after NAC

• ER positive / HER2 negative status predictors of residual metastatic ALN disease

• In Her2 +ve tumours breast pCR predicts nodal pCR favouring use of SLNB

• Impact of breast cancer subtypes on breast and nodal pCR rates in node positive disease.

• 28% pCR in both breast and axilla – highest Her2 +ve and triple negative

• Higher in Her2 +ve and luminal B like

• In the Her2 +ve group nodal pCR only if same in breast - support use of SLNB in this group avoid ALND


Breast cancer subtypes affect the nodal response after neoadjuvant chemotherapy in locally advanced breast cancer: Are we ready to endorse axillary conservation? Cerbelli, Breast 2019

Restaging the axilla after neo-adjuvant chemotherapy for breast cancer: Predictive factors for residual metastatic lymph node disease with negative imaging findings. Jung N Breast 2019

https://www.ncbi.nlm.nih.gov/pubmed/?term=Jung%20N%5bAuthor%5d&cauthor=true&cauthor_uid=30714256

• Importantly for radiologists, post NAC assessment of the axilla with US can lower FNR

• Normal axillary US plus SLNB - FNR 9.8 % (Boughey)

• Overall conclusion is that technique matters; to reduce FNR:

• Dual tracer mapping

• Removal >3 SLNs removed

• Use of immunohistochemistry

• SLN marking


Factors affecting sentinel lymph node identification rate after neoadjuvant chemotherapy for breast cancer patients enrolled in ACOSOG Z0171 (Alliance). Boughey. Ann Surg. 2015

Image; Somatex and Donker et al Ann Surgery 2015

Feasibility and accuracy of sentinel lymph node biopsy in clinically node-positive breast cancer after neoadjuvant chemotherapy: a meta-analysis. Fu. PLoS One. 2014

• MARI procedure (Marking Axillary Lymph nodes with Radioactive Iodine seeds) - NPV 83%

• TAD (targeted axillary dissection) - clip placement in biopsy proven axillary LN then localisation clipped node with I125 seed after NAC completion –2% FNR

• Black carbon tattooing – no radiation or localisation


Improved axillary evaluation following neoadjuvant therapy for patientswith node-positive breast cancer using selective evaluation of clipped nodes:implementation of targeted axillary dissection. Caudle. J Clin Oncol. 2016

Initial results with preoperative tattooing of biopsied axillary lymph nodes and correlation to sentinel lymph nodes in breast cancer patients. Choy. Ann Surg Oncol.2015

ATNEC TRIALAXILLARY MANAGEMENT IN T1-3N1M0 BREAST CANCER PATIENTS WITH FNA OR CORE BIOPSY

PROVEN NODAL METASTASES AT PRESENTATION WHO CONVERT TO NODE NEGATIVE AFTER NEOADJUVANT

CHEMOTHERAPY

• Amit Goyal, Derby

T1-3,N1,M0 breast cancerFNA/core biopsy documented

axillary metastasis

NEOADJUVANT CHEMOTHERAPY (NACT)

Breast conserving surgery or mastectomy + Targeted (dual agent)

sampling + at least 3 nodes removed + removal of clipped/tattooed node

Axillary ultrasound and FNA or core biopsy of abnormal nodes

Not malignant

No nodal metastasis

RANDOMISATION 1:1

Axillary treatment

ALND or ART

No Axillary treatment

nodes positive (micro or

macrometastases)

Failed localisation of

clipped/tattooed node

Axillary lymph node dissection(ALND)

malignant

Marking the positive node• Clip placed (localisation of clipped node using iodine

or magseed)or

• SPOT dye tattoo – cortex and perinodal tissue

SUMMARY

• Significant shift post Z11 / POSNOC to doing less in the axilla

• Pre-operative axillary US and biopsy still useful for triaging directly to surgery

• Post NAC treatment of the axilla evolving

• Radiologists and lymph node marking can improve accuracy and safety

THANK YOU

doing less in….the axilla · • evaluation axillary lymph node status important for staging,...

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