Current Management of the Axilla in Breast Cancer

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

2. 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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 3 large RCTs

10. 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

11. 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

12. 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 6th edition of American Joint Committee on Cancer Staging System (AJCC)

13. 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

14. What comes after SLNB?

15. 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)

16. 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

17. 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

18. 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=0.0007 and p=0.0006 • Survival not affected by further AD • Advisable for further AD

19. 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-)

20. 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

21. Other treatment • Axillary irradiation • ?SLN alone in low risk group • Systemic adjuvant therapy

22. On-going trials

23. 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

24. The End! Thank you