Tumor Size and Sentinel Node

Procedure

A. Ph. MAKAR, MD, Ph.D.

R. Van Den Broecke, MD, Ph.D.

Depart of Senology & Gynaecologic OncologyThe Middelheim Hospital

University Hospital of Ghent

Tumor size

I. Carcinoma in situ II. T1 & T2 (<3cm ) tumorsIII. Large T2 & T3 tumorsIV. Inflammatory breast cancerV. Multi-centric / multi-focal disease

Prospective analysis Middelheim hospital 1998-2001, 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 SNmacro-metasmicro-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 %

0-5

6-10

11-20

0-20

21-50

>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-32ACSOG Z0010

III. Large T2 & T3 tumors

Authors No 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%

SN in tumors <=3cm vs >3 cmLeidenius 2005

<= 3cm > 3cm P value

Axillary metas %

Micro-metas/ITC %

Pos para-sternal SN %

AD omitted (neg SN)%

38%

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

0%10%20%30%40%50%60%70%80%90%

100%

SNmicrometastasis

SNmacrometastasis

% patients

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 remission Persistent 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)

1-10

11-20

21-30

>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