1. Tumor Size and Sentinel Node Procedure A. Ph. MAKAR, MD, Ph.D. R. Van Den Broecke, MD, Ph.D. Depart of Senology & Gynaecologic Oncology The Middelheim Hospital University Hospital of Ghent

2. Tumor size I.Carcinoma in situ II. T1 & T2 (<3cm ) tumors III. Large T2 & T3 tumors IV. Inflammatory breast cancer V.Multi-centric / multi-focal disease Prospective analysis Middelheim hospital 1998-2001, 268 patients, single surgeon

3. Sense of SN procedure Impact on further surgical management, postoperative treatment or prognosis False negative rate: acceptable Number to be saved complete ALND : high Number that needs second surgery: low –increased morbidity: swelling, numbness, pain –increased coasts –completeness of axillary dissection ?

4. I. Ductal Carcinoma In Situ Silverstein: rate of axillary metastases < 1% Survival rate > 98% Axillary staging is generally not necessary IHC: micro-metastases in 5-15% of cases Lara (2003) & Broekhuizen & Marby (2006): –No impact on local failure or distant metastasis

5. ADH/DCIS in core biopsy: underestimation risk Underestimation risk of invasive disease : 20-40% SN procedure can be justified: –Mammographic lesion >5cm –Underlying mass/distortion –Palpable lesion & Core biopsy under sonography –High grade lesion & micro-invasion &LVSI

6. II. T1 &T2 tumors (<3cm) Extensive evaluation: ASCO guide lines Identification rate >95% –Failed identification: Age >60 years Capsular invasion, high number of positive nodes FNR <10%: removal of all radioactive nodes IHC: more micro-metastases 15% (10-67%) SN metastases in <50% of tumors SN only site of metastases in 40%

7. Positive SN macro-metas micro-metas Complete ALND Alternatives ? ? Radiotherapy Observation (EORTC) ACSOG00Z11 Historical NSBAP-04

8. Micro-metastases in SN: Risk factors predicting Non-SN metastases LVSI Tumor size Extra-nodal spread Micro-metastasis: –Size of micro-metastasis –Micro-metastasis detected by HES vs IHC –Location of micro-metas: sinusal vs intranodal Number of pos SN/total nr of SN: (1/3)

9. Rate of Non-SN involved in case of micro- metastases in SN according to tumor size Tumor size (mm) Involved Non-SN % 0-5 6-10 11-20 0-20 21-50 >50 4.8% 8.2% 15.3% 13.4% 30.8% 50%

10. T1 tumors & micro-metastasis in SN Houvenaeghel (2006) & Leikola (2006): pT1a, pT1b (IHC) pT1a- pT1c of tubular, colloid or medullary types –Risk of Non-SN involvement: <5% –Risk of involvement of >1 Non-SN : 0% –ALND can be omitted with minimal risk

11. Prediction of Non-SN metastases in case of micro-metstases in SN Turner (2000): likelihood model Van Zee (2003): nanogram (9 variables) Meta-analysis: –No combination of factors was able to predict non-SN metastases –10% of the micro-metastases in the SN were associated with one or more macro-metastases in Non-SN

12. ALND dissection is recommended in every case with micro-metastases in the SN The prognostic significance micro- metastases: The Ludwig Breast Cancer Study Group NSABP-32 ACSOG Z0010

13. III. Large T2 & T3 tumors AuthorsNo SN LN False pts identified metas neg rate O’Hea (1998) Winchester (1999) Bedrosian (2000) Cohen (2001) Wong (2002) Chung (2001) Leidenius (2005) Makar 25 82% 25% 31 90% 20% 104 99% 63% 2% 83 82% 58% 10% 59 100% 73% 4% 41 100% 76% 3% 70 95% 71% NS 106 82% 52% 2%

14. SN in tumors 3 cm Leidenius 2005 <= 3cm> 3cmP value Axillary metas % Micro-metas/ITC % Pos para-sternal SN % AD omitted (neg SN) % 38% 1.9% T1a-b: 72% T1c: 57% 71% 20% 2.8% 28.5% <.0001 <.02 NS <.001

15. % patients with tumors > 3cm and pos SN that have an additional disease in Non-SN

16. SN with T3 tumors The high risk of nodal metastases warrants complete ALND unless: –Motivated patient to have LN conservation

17. SN procedure following pre-operative CT: Meta analysis Identification rate (IR): 91% –IR isotope 95% vs 93% blue dye –No serious concern regarding the fibrotic effect of CT on lymphatic pathways False negative rate: 12%

18. Neo-adjuvant chemotherapy & axillary downstaging Anthracyclin / cyclophosph based CT provides up to 30 % axillary down staging –Size of residual LN metastases after neo-adjuvant CT is of prognostic significance Changing concept: –SN prior to neo-adjuvant CT followed by “2nd look” axillary dissection post CT = better prognostic information

19. Tumors >3cm with macro-metastases in SN = almost 100% non-SN metastases SN prior to CT (better staging) Axillary dissection post CT Pathologic remissionPersistent disease Less morbidity

20. IV. Inflammatory breast cancer Insufficient data. High risk of nodal spread False negative rate: –Occlusion of subdermal lymphatics (tumor emboli)

21. V. Multicentric tumors Occurs in up to 10% of cases Were excluded by most SN investigators Hypothesis “sentinel for the entire breast”: –High success ratio –No increase in false negative ratio –Peri-areolar injection

22. Increased risk of nodal metastases with multi-focal tumors Tumor size (mm) Uni-focal Multi-focal ( 877 tumors) (107 tumors) 1-10 11-20 21-30 >30 22% 45% 37% 51% 53% 72% 68% 100%

23. Conclusions-1 DCIS: –In some cases of core biopsy with risk of underestimation: Lesions > 5cm Underlying lesion: density/distortion High grade tumors & micro-invasion, LVSI Immediate reconstruction

24. Conclusions-2 T1 –T2 (< 3cm): –Standard procedure with N0 –With few exceptions “ T1a and T1a-T1c of certain pathology ”, a full ALND is indicated in case of microscopic disease in the SN –The prognostic significance of micro-metastases needs further evaluation

25. Conclusions-3 Large T2 & T3 tumors: –IR and FNR are comparable with T1 tumors –Yet the high incidence of LN metastases makes the clinical relevance of SN procedure of limited value except in case of neo-adjuvant CT Multi-centric /multi-focal disease: –More reports suggest safety of the procedure –Yet multifocal tumors have higher risk of nodal spread than unifocal ones of same diameter

26. Conclusion-4 2nd axillary surgery carries more morbidity: Prospective multi-centric trial comparing immediate versus “second-look” axillary surgery post chemotherapy in patients with positive SN: Welcome to participate

27. Sentinel Node Team Nuclear medicine: –K. Melis –F. Van Acker Pathology: –S. Declercq –L. Van Leuevn –C.Mattelaer Radiotherapy: –D. Van denWeyngaert –S. Vanderkam –I. Jacobs Medical Oncology –E. Joossens –D. Becquart –A..Vandebroek