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

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 , 268 patients, single surgeon

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 ?

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

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

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%

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

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)

Rate of Non-SN involved in case of micro- metastases in SN according to tumor size Tumor size (mm) Involved Non-SN % >50 4.8% 8.2% 15.3% 13.4% 30.8% 50%

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

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

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

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% % 63% 2% 83 82% 58% 10% % 73% 4% % 76% 3% 70 95% 71% NS % 52% 2%

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

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

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

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%

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

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

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

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

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

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

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

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

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

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