The American Journal of Surgery (2017) 213, 171-180

Review

Is sentinel lymph node biopsy indicated inpatients with a diagnosis of ductal carcinomain situ? A systematic literature review andmeta-analysis

Hiba El Hage Chehade, M.D., M.R.C.S.*, Hannah Headon, M.B.B.S., B.Sc.,Umar Wazir, M.B.B.S., M.R.C.S., M.Sc., Houssam Abtar, M.D.,Abdul Kasem, M.D., F.R.C.S., Kefah Mokbel, M.S., F.R.C.S.

The London Breast Institute, Princess Grace Hospital, 42-52

Nottingham Place, London W1U 5NY, UK

KEYWORDS:Sentinel lymph nodebiopsy;Ductal carcinoma insitu;Breast cancer

This review was funded by grants fro

dation (London, UK).

The authors declare no conflicts of i

* Corresponding author. Tel.: 144 2

2275.

E-mail address: haj_shehadeh_hiba@

Manuscript received February 24, 20

2016

0002-9610/$ - see front matter Crown

http://dx.doi.org/10.1016/j.amjsurg.20

AbstractBACKGROUND: Recent discussion has suggested that some cases of ductal carcinoma in situ (DCIS)

with high risk of invasive disease may require sentinel lymph node biopsy (SLNB).METHODS: Systematic literature review identified 48 studies (9,803 DCIS patients who underwent

SLNB). Separate analyses for patients diagnosed preoperatively by core sampling and patients diagnosedpostoperatively by specimen pathology were conducted to determine the percentage of patients withaxillary nodal involvement. Patient factors were analyzed for associations with risk of nodal involvement.

RESULTS: The mean percentage of positive SLNBs was higher in the preoperative group (5.95% vs3.02%; P 5 .0201). Meta-regression analysis showed a direct association with tumor size (P 5 .0333)and grade (P 5 .00839) but not median age nor tumor upstage rate.

CONCLUSIONS: The SLNB should be routinely considered in patients with large (.2 cm) high-grade DCIS after a careful multidisciplinary discussion. In the context of breast conserving surgery,the SLNB is not routinely indicated for low- and intermediate-grade DCIS, high-grade DCIS smallerthan 2 cm, or pure DCIS diagnosed by definitive surgical excision.Crown Copyright � 2016 Published by Elsevier Inc. All rights reserved.

Ductal carcinoma in situ (DCIS) is the predominantnoninvasive breast neoplasia in the United Kingdom,comprising 83% of all in situ breast cancers diagnosed.1

m the Breast Cancer Hope Foun-

nterest.

07 908 2101; fax: 144 207 908

hotmail.com

16; revised manuscript April 19,

Copyright � 2016 Published by Elsev

16.04.019

At present, the treatment of DCIS comprises wide localexcision or mastectomy to achieve local control of the dis-ease. In patients treated with breast conserving surgery,radiotherapy may be considered to reduce the risk of localrecurrence.

In breast cancer, the status of the regional lymph nodes hasbeen found to be the most important prognostic factor andpredictor of survival and therefore has important implica-tions for future treatment decisions.2 As DCIS is noninvasiveby definition, this implies that there should be no spread to theaxillary lymph nodes. Subsequently, omission of axillarydissection is now the standard of treatment since previous

ier Inc. All rights reserved.

Table 1 Characteristics of studies included in the preoperative sample

Study DesignNumber ofcases

Medianage

Positive results Upstagerate(%)Total (%) ITC (%) Micrometastases (%) Macrometastases (%)

Francis et al, 20155 Retrospective 1,234 54 132 (10.7) 66 (5.4) 36 (2.9) 30 (2.4) NRTunon-de-Lara et al,201539

Prospective 196 54.3 27 (14.1) 8 (4.1) 8 (4.1) 11 (5.6) NR

Nowikiewicz et al,201528

Retrospective 111 55 4 (3.6) NR NR NR NR

Ruvalcaba-Limonet al, 201435

Retrospective 50 51.6 5 (10) 0 (0) 3 (6) 2 (4) NR

Walters et al, 201543 Retrospective 84 57.7 1 (1.2) 0 (0) 1 (1.2) 0 (0) 17.2Banys et al, 20149 Retrospective 316 55 3 (.9) 1 (.3) NR NR 0Namm et al, 201527 Retrospective 52 54.8 3 (6) 0 (0) 2 (3.8) 1 (1.9) 32Osako et al, 201430 Retrospective 336 NR 23 (6.8) 0 (0) 6 (1.8) 17 (5) 33.6Ozkan-Gurdal et al,201431

Prospective 33 51 1 (3.3) NR NR NR 0

Guillot et al, 201418 Prospective 109 51 11 (9) 8 (7.3) 2 (1.8) 1 (.9) NRRajan et al, 201338 Retrospective 25 56.9 0 (0) 0 (0) 0 (0) 0 (0) NRChin-Lenn et al,201410

Retrospective 306 57 3 (2.1) NR NR NR 17

Zapardiel et al,201344

Retrospective 84 NR 6 (6.9) NR NR NR NR

Ballehaninna et al,20138

Retrospective 267 57 13 (4.8) 4 (1.5) 6 (2.2) 3 (1.1) 15.4

Fancellu et al,201217

Prospective 140 56 2 (1.4) NR NR NR 1.4

Park et al, 201332 Prospective 238 48.5 10 (4.2) NR NR NR 42.6Ansari et al, 20127 Retrospective 61 NR 3 (4.9) 1 (1.6) 0 (0) 2 (3.3) NROsako et al, 201229 Prospective 623 50 13 (2.1) NR NR NR NRMeretoja et al,201225

Prospective 280 58 21 (7.5) 16 (5.7) 3 (1.1) 2 (.7) NR

Chvalny et al, 201111 Retrospective 44 NR 4 (9) NR NR NR NRUsmani et al, 201141 Prospective 23 48 1 (4) NR NR NR 30Miyake et al, 201126 Prospective 103 49 2 (5.4) NR NR NR 35.9Han et al, 201119 Retrospective 131 55 18 (13.7) NR NR NR 36.6Prendeville et al,201534

Retrospective 181 NR 7 (4) 6 (3.3) 0 (0) 1 (.6) 30

Matsen et al, 201424 Retrospective 414 54 32 (7.7) 0 (0) 26 (6.3) 6 (1.4) NRKotani et al, 201623 Retrospective 161 NR 1 (.62) NR NR NR 20Son et al, 201137 Retrospective 48 50.6 1 (2.08) NR NR NR NRCollado et al, 201012 Prospective 65 NR 11 (16.9) NR NR NR 33.8D’Eredita et al,200914

Prospective 52 56 1 (1.9) 0 (0) 1 (1.9) 0 (0) NR

Hung et al, 201020 Retrospective 103 54 12 (11.6) 3 (2.9) 5 (4.9) 4 (3.9) 29.9Doyle et al, 200916 Retrospective 145 NR 11 (7.6) 4 (2.8) 3 (2.1) 4 (2.8) 37.9Polom et al, 200933 Retrospective 183 57 10 (5.5) NR NR NR 4Tunon-de-Lara et al,200840

Prospective 161 56 6 (3.73) 0 (0) 4 (2.5) 2 (1.2) 30

Intra et al, 200821 Prospective 854 NR 16 (1.9) 4 (.47) 7 (.8) 5 (.6) NRDominguez et al,2008 15

Retrospective 179 48 20 (11.3) 18 (10.1) 2 (1.1) 0 (0) 11.2

Cserni et al, 200213 Prospective 10 NR 1 (10) 0 (0) 1 (10) 0 (0) NRVeronesi et al,200542

Prospective 508 NR 9 (1.8) 0 (0) 5 (1.0) 4 (.8) NR

Katz et al, 200622 Retrospective 110 55 8 (7.34) 0 (0) 8 (7.3) 0 (0) NRSakr et al, 200636 Prospective 39 54 4 (10) 0 (0) 4 (10.3) 0 (0) 25.7

This table outlines the studies included in the preoperative sample (n 5 39).

ITC 5 isolated tumor cells; NR 5 not reported.

172 The American Journal of Surgery, Vol 213, No 1, January 2017

Table 2 Characteristics of studies included in the postoperative sample

Study DesignNumber ofcases

Medianage

Positive results

Total (%) ITC (%)Micrometastases(%)

Macrometastases(%)

Zetterlund et al,201452

Retrospective 753 60 11 (1.5) 6 (.8) 3 (.4) 2 (.3)

Tada et al, 201050 Retrospective 225 51.2 1 (.39) 0 (0) 0 (0) 1 (.4)Sakr et al, 200849 Retrospective 110 NR 7 (6) 4 (3.6) 0 (0) 3 (2.7)Takacs et al,200951

Retrospective 48 55.8 0 (0) 0 (0) 0 (0) 0 (0)

Kelly et al, 200346 Retrospective 41 55.4 1 (2.44) NR NR NRIntra et al, 200345 Prospective 223 50.1 7 (3.14) 0 (0) 5 (2.2) 2 (.9)Zavagno et al,200553

Prospective 102 59.4 1 (.98) 0 (0) 1 (.98) 0 (0)

Mabry et al, 200648 Prospective 171 50 10 (5.8) 10 (5.8) 0 (0) 0 (0)Leidenius et al,200647

Retrospective 71 56 5 (7) 3 (4.2) 1 (1.4) 1 (1.4)

This table outlines the studies include in the postoperative sample (n 5 9).

ITC 5 isolated tumor cells; NR 5 not reported.

H. El Hage Chehade et al. SLNB in DCIS patients 173

reports have established that this practice had no adverseeffect on overall survival or disease recurrence in thosewith pure in situ disease.3 Despite this, recent studies havesuggested that some DCIS cases do in fact harbor an invasivecomponent,meaning that leaving the lymph nodes intactmayincrease the risk of local recurrence.4

It has been proposed that select patients diagnosed withDCIS determined to be at high risk of harboring an invasivecomponent should undergo sentinel lymph node biopsy(SLNB). If positive, a complete axillary dissection may beconsidered, weighing the risk of recurrence disease and themorbidities of the procedure.

This study aims to evaluate whether the use of SLNB isappropriate in DCIS and investigate whether there are anyfactors contributing toward a higher risk of invasive disease

Table 3 Statistical tests for heterogeneity

Preoperative sample Po

Model

Effect size and95% interval

2-tailedt test

MNumberof studies

Pointestimate

Lowerlimit

Upperlimit Z-value

Pvalue

Fixed 39 .073 .067 .08 251.847 0 FiRandom 39 .053 .042 .067 222.25 0 Ra

Heterogeneity

Q-value df (Q) P value I squared

196.462 38 0 80.658Tau squared Standard error Variance Tau

.424 .189 .036 .651

This table outlines the statistical tests carried out for heterogeneity. Sign

sample and 65.7% in the postoperative sample.

and add to previous reviews such as that by Francis et al5 byincluding the latest research and examining any factors thatmay predispose toward a greater risk of having a positiveSLNB result. From this, we hope to be able to identify a sub-set of patients with a diagnosis of DCIS who would benefitfrom undergoing an SLNB as part of their management plan.

Methods

Literature search

A literature search of electronic databases includingPubMed and Ovid was conducted including entries up untilMarch 2016 with no upper limit. The following searchterms were used: sentinel lymph node biopsy AND ductal

stoperative sample

odel

Effect size and95% interval

2-tailedt test

Numberof studies

Pointestimate

Lowerlimit

Upperlimit Z-value

Pvalue

xed 9 .033 .025 .045 221.759 0ndom 9 .03 .017 .053 211.488 0

Heterogeneity

Q-value df (Q) P value I squared

23.432 8 .003 65.859Tau squared Standard error Variance Tau

.454 .392 .154 .673

ificant heterogeneity was observed with an I2 of 80.7% in preoperative

Figure 1 Forest plot for the meta-analysis for the preoperative sample. A random-effects model for meta-analysis was adopted for thepreoperative sample. This forest plot was generated which shows a pooled estimate of 5.3%.

174 The American Journal of Surgery, Vol 213, No 1, January 2017

carcinoma in situ; DCIS AND sentinel lymph node biopsy;sentinel node mapping and DCIS and sentinel lymph nodemapping and ductal carcinoma in situ. The ‘‘relatedarticles’’ command was used to broaden the search, andthe bibliographies of appropriate articles were studied toidentify any further records.

Abstracts of the results were analyzed, and records whichseemed to fit inclusion criteria had the full manuscriptaccessed. These records were fully read, and all those whichfit the inclusion criteria were included in analysis.

Inclusion and exclusion criteria

Inclusion criteria comprised studies performed onfemale patients with a diagnosis of DCIS who underwent

an SLNB as part of their management. Studies had to reportthe number of patients who had positive SLNBs.

Exclusion criteria included studies which did not reportthe number of positive SLNBs, did not specify that patientshad been diagnosed with DCIS, or did not specify whetherthis was a preoperative diagnosis on the basis of tripleassessment and/or core samples, or a postoperative diag-nosis after analysis of the surgical specimen. Letters,commentaries, and reviews were also excluded.

Analysis

The meta-analysis of the studies included was performedas advised by the Cochrane Library.6

Figure 2 Forest plot for the meta-analysis in the postoperative sample. A random-effects model for the meta-analysis was adopted for thepostoperative sample. This forest plot was generated showing a pooled estimate of 3.5%.

H. El Hage Chehade et al. SLNB in DCIS patients 175

Some studies assessed the SLNB-positive rate in defin-itive DCIS, ie, those with a postoperative diagnosis ofDCIS, whereas others reported this as a function of thosewith a preoperative diagnosis of DCIS. We, therefore,performed separate analyses in these groups as thefrequency of a positive SLNB may differ between the 2.

Data on the number of patients, the SLNB technique, thenumber of patients with positive SLNBs, the median age,and the biopsy method were collected, tabulated, andsubsequently analyzed.

An analysis of variance analysis was conducted to lookfor any significant difference in the mean percentage of

Figure 3 A funnel plot from the preoperative sample. A funnel plot wpublication bias. As not all the points are within the prescribed margin

positive SLNBs between preoperative and postoperativediagnoses. To carry out the meta-analysis, we separatedthe included studies depending on whether the diagnosisof DCIS was given preoperatively or postoperatively andthen conducted 2 separate meta-analyses. Pooled estimateswere calculated with 95% confidence intervals. Cochran’sQ test was used to test the null hypothesis, and heteroge-neity was calculated using an I2 index. For both groups, afunnel plot was created to look for publication bias, andboth the Begg and Mazumdar Rank Correlation test andEgger’s test of the intercept were performed to supportthis. Duval and Tweedie’s trim and fill method was used

as generated for the preoperative sample to look for evidence ofs, there is evidence of publication bias in this sample.

Figure 4 A funnel plot from the postoperative sample. A funnel plot was generated for the postoperative sample to look for evidence ofpublication bias. Again, there is some evidence of publication bias.

176 The American Journal of Surgery, Vol 213, No 1, January 2017

to look for differences between observed and adjustedpooled rates.

In addition, a meta-regression analysis was carried out toidentify factors associated with a higher risk of having apositive SLNB result. Statistical significance was consid-ered at P , .05.

Table 4 Statistical tests for publication bias

TestTestresult Preoperative

Classic fail-safeN (per study)

N 581

Begg andMazumdar rankcorrelation test

Tau 2.217z-value for tau 1.948P value (1 tailed) .026P value (2 tailed) .051

Egger’s Test ofthe intercept

Intercept 22.13995% CI lower limit(2 tailed)

23.288

95% CI upper limit(2 tailed)

2.990

P value (1 tailed) .000P value (2 tailed) .001

Duval andTweedie’s Trimand Fill

Observed pooled effect .053Adjusted pooled effect .073Studies trimmed 11.000Missing values To right of

mean

This table outlines the statistical tests carried out to assess for

evidence of publication bias in the preoperative sample. The results are

suggestive of publication bias, resulting in an adjusted pooled

estimate of 7.3%.

Results

Forty-eight articles were identified and analyzedyielding a total of 9,803 patients. This included bothretrospective and prospective studies.

The primary endpoint was the percentage of DCISpatients with positive SLNBs. Studies were divided basedon the time of diagnosis of DCIS (ie, preoperative vspostoperative diagnosis). Characteristics of the includedstudies are shown in Tables 1 and 2. The incidence ofSLNB positivity was significantly higher in the preopera-tive diagnosis group (n 5 39 studies),5,7–44 with a meanof 5.95% (range 5 0% to 16.9%) vs a mean of 3.02%(range 5 0% to 7%) in the postoperative diagnosis group(n 5 9 studies)45–53 (P 5 .0201). Further analysis showedthat axillary nodal metastasis harbored isolated tumor cells(ITCs), micrometastasis, and macrometastasis in 24.4%(median 12.5%), 48.5% (median 43.8%), and 23.1% (me-dian 22.7%), respectively in the preoperative diagnosisstudies, vs 33.95% (median 27.3%), 27.3 (median 10%),and 26.2% (median 19.1%) in the postoperative diagnosisgroup. However, not all studies reported the incidence ofITCs; therefore, this should be interpreted with caution.

In the meta-analysis, significant heterogeneity wasobserved between the studies with an I2 statistic of 80.7%and 65.7% in the preoperative and postoperative groups,respectively (Table 3). Thus, a random-effects model wasadopted, and pooled estimate of positive SLNB of 5.3%and 3.0% were reported in the preoperative and postopera-tive diagnosis, respectively (Figs. 1 and 2). A funnel plotwas subsequently created which showed evidence of publi-cation bias in both groups (Figs. 3 and 4) supported byBegg and Mazumdar rank correlation test and Egger’s

Table 5 Statistical tests for publication bias

Test Test result Postoperative

Classic fail-safeN (per study)

N 105

Begg andMazumdar rankcorrelation test

Tau 2.167z-value for tau .626P value (1 tailed) .266P value (2 tailed) .532

Egger’s Test ofthe intercept

Intercept 21.19195% CI lower limit(2 tailed)

24.266

95% CI upper limit(2 tailed)

1.884

P value (1 tailed) .195P value (2 tailed) .390

Duval andTweedie’s Trimand Fill

Observed pooled effect .030Adjusted pooled effect .037Studies trimmed 2.000Missing values To right of

mean

This table outlines the statistical tests carried out to assess for

evidence of publication bias in the postoperative sample. The results

are suggestive of publication bias, resulting in an adjusted pooled

estimate of 3.7%.

CI 5 confidence interval.

H. El Hage Chehade et al. SLNB in DCIS patients 177

test of the intercept. Subsequently, an adjusted estimate wascomputed using Duval and Tweedie’s trim and fill methodwhich was calculated at 7.3% in the preoperative diagnosisstudies and 3.7% in the postoperative diagnosis ones(Tables 4 and 5).

A meta-regression was also performed to determine thevariables associated with SLNB positivity. Neither themedian age nor the upstage rate was associated withincreased likelihood of positive SLNB (P 5 .303 and.1585, respectively). However, larger tumor size and highergrade were significantly associated with SLNB positivity(P 5 .03333 and P 5 .00839, respectively; Table 6).

Comments

With the development and widespread introduction ofhigh-quality digital mammography, DCIS is now consideredthe most rapidly growing subgroup of breast carcinomas

Table 6 Meta-regression

Covariate Coefficient Standard error 95

Tumor grade vs nodal involvementIntercept .00946 .00359High grade % 22.947 23.28096 2

Tumor sizevs nodalinvolvement

Intercept .08947 .04204Tumor size 22.74722 .13064 2

This table outlines the statistical test for meta-regression which was pe

significantly associated with a higher risk of having a positive SLNB result. Si

accounting for 15.7% of all neoplasia detected through theNationa Health Service (NHS) Breast Screening Programmebetween 2003 and 2011.3 There are several points of conten-tion in the management of DCIS, one of which is the use ofSLNB.

Although SLNB has become the standard treatmentoption in clinically node negative invasive breast cancer, itsroutine use in the current management of DCIS is notwarranted and would not be without its risks: the AxillaryLymphatic Mapping Against Nodal Axillary Clearance(ALMANAC) trial demonstrated that 5% of patients un-dergoing SLNB alone developed arm lymphedema.54

Furthermore, an increasing number of immediate hypersen-sitivity reactions have been reported after the use of PatentBlue V for breast cancer surgery with 1 multicenter trialshowing an incidence of .34% in 1,742 patients, 2 casesof which required admission into the intensive careunit.55 A number of case studies also illustrated cases ofanaphylactic reactions.56–59 However, its use has nowlargely been replaced by methylene blue which is safer.60,61

Other potential complications include seromas, hematomas,and arm pain.62,63

Standard preoperative diagnostic techniques are knownto miss areas of small foci of invasive disease due tosampling and slicing.64 This is acknowledged by the mostrecent guidelines published by the American Society ofClinical Oncology which state that SLNB should be per-formed for DCIS in 2 circumstances: First, in patients un-dergoing mastectomy, as it would technically infeasible toperform an SLNB in the aftermath. Second, as a second-stage SLNB if an invasive component was found on the his-tological analysis of the tumor after breast conservingsurgery.65 However, it is unclear whether there is a rolefor a routine SLNB in DCIS patients undergoing breastconserving surgery.

This meta-analysis has demonstrated a significantlyhigher SLNB positivity in patients with preoperativediagnosis of DCIS than in those with postoperativediagnosis with a reported mean of 5.95% and 3.02%,respectively (P 5 .0201). Especially if the cases with ITCare omitted, the final number of clinically relevant positivenodes is too low to justify the routine use of SLNB in allcases of DCIS. However, identification of factors predictiveof a positive SLNB in the setting of DCIS would be of

% lower 95% upper Z-value P value

.00243 .01649 2.63608 .008393.28096 22.61303 217.29528 0

.00707 .17187 2.12813 .033333.00328 22.49116 221.0284 0

rformed to investigate whether high tumor grade and tumor size was

gnificance was assumed when P , .05 (bold).

178 The American Journal of Surgery, Vol 213, No 1, January 2017

clinical utility. Our meta-analysis has established a signifi-cant association between SLNB positivity and high tumorgrade and large tumor size but not with age at diagnosisnor the upstage rate.

Our finding of positive association between high tumorgrade and positive SLNB in DCIS patients is consistent withfindings in other studies where high-grade disease has beenearmarked as an independent risk factor for clinically occultinvasion.66,67 Boler et al67 reported that patients with high-grade disease were more likely to undergo SLNB althoughother studies failed to demonstrate a correlation betweenthe likelihood of SLN metastases and high tumor grade.22

Likewise, our finding of increased possibility of SLNBpositivity in larger tumors is similar to previous reports.Kondoet al68 observed that tumors larger than 2 cmwere significantlyassociated with upstaging a previous DCIS tumor to invasivedisease. Furthermore, an audit from the UK NHS BreastScreening Programme has suggested that axillary surgery inthe setting of preoperatively diagnosed DCIS was associatedwith larger tumor size.3 Similarly, Chin-Lenn et al10 observedthat in cases where DCIS was diagnosed preoperatively, hav-ing a larger tumor was associated with undergoing a SLNB.This is likely being done in conjunction with a mastectomyperformed in cases where extensive DCIS has made breast-conserving surgery infeasible.

Our analysis did not find an association of positive SLNBwith clinically occult invasion. This is in contrast to severalstudies included in our analysis.5,25,26 Indeed, it stands toreason that patients with large areas of high-grade DCISare more likely to harbor areas of clinically occult microin-vasion, which should account for the increased rate of posi-tive SLNB. Previous studies have found associationsbetween features of high-grade DCIS, such as opacity onmammogram and palpable tumors, and subsequent detectionof invasion.18,42,43 Unfortunately, not all studies included inour meta-analysis reported on upstage rate after a preopera-tive diagnosis of DCIS. Of those that did, the mean upstagerate reported was 23.2% (range 0% to 42.6%).5,9–11,13,16,17,19,20,23,26,27,30,32,33,36,39,41,43 This equated to 714of 3,246 cases (22%) in studies reporting upstage rate. Hope-fully, explicit reporting of the upstage rate in future studieswould resolve this anomaly. Alternatively, it is possiblethat portion of the positive SLNBs may be due to other fac-tors, such as seeding core biopsies, or mechanical displace-ment, and therefore may not be of great clinical import.69,70

Furthermore, we did not observe a significant correlationbetween age at diagnosis and the risk of SLNB positivity inthe present study. However, Yen et al71 reported that an ageof less than 55 years was an independent factor forharboring invasive disease and suggested that youngerpatients with DCIS should be considered for SLNB. Like-wise, Shah et al72 observed that women with DCIS olderthan 56 years were less likely to undergo SLNB.

This study is not without limitations. Our meta-analysisdid not examine the type of the metastasis (ie, ITC vsmicrometastasis vs macrometastasis) due to the absence ofthis information in many of the included studies. ITCs are

defined as deposits less than .2 mm or less than 200 cellsand have been reported with increasing frequency sincethe introduction of immunohistochemistry. It is notcurrently considered an indication for further treatmentof the axilla.65,73 Micrometastases are defined as depositsbetween .2 and 2 mm and have been found to be associ-ated with a poorer prognosis than negative SLNB. Man-agement should be performed after multidisciplinarydiscussion to identify those patients who have a highrisk of harboring lymphatic spread since axillary lymphnode dissection may be safely omitted.74 ITCs accountedfor a large portion of our data and as the presence of ITCswould not likely change treatment or disease outcomes, abetter reporting of the proportion of cases with ITCswould have provide more clarity regarding the clinicalimplications of a positive SLNB.

Furthermore, the extent of the histological analysis (ie,the number of sections, the technique of specimen slicing,and the use of IHC) of either the core biopsy or thedefinitive histology is likely to be heterogeneous among thestudies; nevertheless, the available data did not allow us toexamine these potentially significant parameters.

Similarly, clinical palpability of the tumor19,38 and re-ceptor status39,68 have been cited as predictors of axillaryinvolvement. However, the lack of data precluded their in-clusion in this study.

Finally, the current data did not permit the study of theassociation between the type of core biopsy (ie, standardcore-needle biopsy [CNB] vs vacuum-assisted biopsy[VAB]) and the incidence of sentinel lymph node metastasis.However, the included studies failed to specify the pre-operative biopsy modality (ie, conventional CNB or VAB).This is a significant limitation since VAB has a greateraccuracy than CNB in identifying invasive disease.75 Kotaniet al23 reported a positive SLNB rate of .6% in 199 DCIS pa-tients who were diagnosed with preoperative stereotacticVAB although 20% of these patients were upstaged on finalpathology. Hence, they recommended avoiding SLNB in thissubgroup of DCIS patients. In contrast, Meijnen et al76

emphasized the importance of SLNB in CNB-diagnosedDCIS patients as they have reported an upstage of 26.2%and SLNB positivity of 12.08%. Similarly, Omranipouret al77 suggested that SLNB should be indicated wheneverthe diagnosis of DCIS is based on CNB.

Moreover, questions arise regarding the optimal manage-ment of patients with positive SLNB results who have apreoperative diagnosis of DCIS: the significance of positivefindings remains unclear. In our study, the most commonfinding was either ITCs or micrometastases. The AmericanSociety of Clinical Oncology guidelines indicate that clini-cians should not recommend axillary lymph node dissectionwith early breast cancer patients who have 1 or 2 sentinellymph node metastases and receive breast conserving therapyand radiotherapy.64 Although SLNB would be inappropriatein most cases of DCIS, the selected use of SLNB in thecase of extensive high-grade DCIS could be considered aftera thorough discussion within the multidisciplinary team.

H. El Hage Chehade et al. SLNB in DCIS patients 179

Conclusions

To our knowledge, this is the largest analysis to date forthe use of the SLNB in DCIS. The SLNB should be routinelyconsidered in patients with large (.2 cm) high-grade DCIS.In the context of breast conserving surgery, the SLNB is notroutinely indicated for low- and intermediate-grade DCIS,high-grade DCIS smaller than 2 cm, or pure DCIS diagnosedby definitive surgical excision. Furthermore, we believe thatthe clinical effect of such selective SLNB for DCIS would bean important area of research for future prospective studiesand randomized trials as this would enable better informeddecisions in the treatment of DCIS.

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