Current Management of the Axilla in Breast Cancer Joint Hospital Surgical Grand Round 25 th July, 2009 Princess Margaret Hospital Law Hang Sze

Axillary Dissection most accurate qualitative and quantitative assessment of axilla Most powerful single variable in estimation of prognosis Accurate assessment of risk of relapse Guiding systemic therapy Achieve loco-regional control (1.3% relapse) Disease-free interval and overall survival related to no. of nodes with metastases Survival benefits debatable

Complications of AD Seroma Wound infection Reduced shoulder mobility and stiffness Numbness and paresthesia lymphoedema Damage to motor nerves: – medial pectoral nerve – Long thoracic nerve – Thoracodorsal nerve

Staging of axilla – alternative to AD ~70% of AD specimen is negative ?over- treatment ?need for routine axillary dissection – Non-operative – Axillary sampling – Sentinel node biopsy

Sentinel node biopsy Lymphatic drainage from each breast first drains into one or several specific LNs before draining into more distal ones in an orderly manner The first LN has been termed ‘sentinel’ if SLN is –ve for metastatic disease, then the remainder of axillary nodes are negative as well Aim to provide accurate staging by use of minimal invasive technique

According to latest guidelines by American Society of Breast Surgeons, indicated in virtually ALL with node-negative T1-3 invasive tumour (4th revision, 2005), relative contraindications: – Prior breast surgery, axillary surgery, RT, palpable axillary LN, following neoadjuvant therapy, pregnancy DCIS

Turner et al in 1997 performed histopathological validation of SLNB, – if SLN is free of tumour, probability of non-sentinel node involvement <0.1% Numerous studies comparing SLNB and ALND in breast cancer, validated the technique, – with high sentinel node identification rates and consistently low false negative rates

3 large RCTs AccuracyNegative predictive value False negative rate NSABP B32 trial 97.1%96.1%9.7% Veronesi trial 96.9%95.4% 8.8% Canavese trial 93%91.1% 8.9%

SLN vs AD  morbidity lymphoedema 5% vs 13%, P<0.001 in ALMANAC trial, relative risk 0.37 Sensory deficit: 11% vs 31% at 12 months, RR 0.37 Shoulder dysfunction: less on shoulder flexion and abduction P=.004 and.001 Shorter mean hospital stay, usage of drain, infection, resumption to normal day-to-day activity

SLN vs AD  quality of life (ALMANAC trial) TOI score, p=0.001 at all times Arm functioning subscale FACT-B+4 score STAI score

 morbidity and improved QoL Serial sectioning and use of IHC  more accurate Use of IHC  detection rate from 9% to 47% (compared to HE stain)  detection of micrometastasis and consequent upstaging – 44.6% by IHC – 66% by PCR analytic technique The 6 th edition of American Joint Committee on Cancer Staging System (AJCC)

Disadvantage: if +ve needs a second operation, longer operative time Labour and cost intensive Intra-operative frozen section or imprint cytology: – up to 50% false –ve for micrometastasis

What comes after SLNB?

SLNB (negative) Local recurrence – no axillary recurrence at median follow-up of 5.5 years, Canavese trial One in 169 patients axillary metastasis after FU for 79 months in Veronesi trial Overall survival and event-free survival not statistically different 5-year survival 98.4% in SLN vs 96.4% in AD group (Veronesi trial)

macrometastasis Non SLN involvement: 39% to 79%, mostly depends on tumour size Risk of axillary recurrence high without other adjuvant treatment Proceed to AD for locoregional control

micrometastasis single nodal deposit of tumour >0.2mm but <2mm, pN1mi Up to 50% of LN negative cases  upstaging Additional axillary disease (positive non-SLNs) – 15.5% for micrometastasis (Cox et al, 2008) – 21.4% (Viale et al) Among them 93% macrometastasis i.e. N1 Risk of local relapse <1.4% if AD not done

Conflicting evidence on prognosis Distant metastasis higher than N0 group (Gobardhan et al, 2009, Cohort study) Survival (overall and disease-free) differs substantially from N0 patients, p= and p= Survival not affected by further AD Advisable for further AD

Isolated tumour cells single cells or small clusters of cells <0.2mm, with no histological evidence of malignant activity (e.g. proliferation or stromal reaction), pN0(i+) In a meta-analysis by Carolien et al, pooled risk of 12.3% Non-SLN involvement: 9.3% by Cox et al. 2.27% local recurrence (without AD) in Cox et al vs 0.28%in N0(i-)

Risk of non SLN involvement only marginally higher than risk of false-negative SLNB (7-8%) Unknown survival benefit Very low rate of axillary recurrence for those omit AD Controversial for whether proceed with AD

Other treatment 1.Axillary irradiation 2.?SLN alone in low risk group 3.Systemic adjuvant therapy

On-going trials

Summary SLN is a valid and accurate staging method for axilla Risk of non-SLN involvement, all SLN macrometastasis and micrometastasis should proceed with AD Subgroup of patient with SLN ITC or micrometastasis along with small tumour size may be spared from AD Axillary RT maybe helpful to control local disease if AD is not carried out

The End! Thank you