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Preoperative Localization and Surgical Margins in Conservative Breast Surgery

Preoperative Localization and Surgical Margins in Conservative Breast Surgery Hindawi Publishing Corporation International Journal of Surgical Oncology Volume 2013, Article ID 793819, 9 pages http://dx.doi.org/10.1155/2013/793819 Review Article Preoperative Localization and Surgical Margins in Conservative Breast Surgery F. Corsi, L. Sorrentino, D. Bossi, A. Sartani, and D. Foschi Surgery Division, Department of Clinical Sciences, L. Sacco Hospital, University of Milan, Via G.B. Grassi 74, 20157 Milan, Italy Correspondence should be addressed to F. Corsi; fabio.corsi@unimi.it Received 14 September 2012; Revised 6 June 2013; Accepted 10 July 2013 Academic Editor: A. K. Dcruz Copyright © 2013 F. Corsi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Breast-conserving surgery (BCS) is the treatment of choice for early breast cancer. eTh adequacy of surgical margins (SM) is a crucial issue for adjusting the volume of excision and for avoiding local recurrences, although the precise definition of an adequate margins width remains controversial. Moreover, other factors such as the biological behaviour of the tumor and subsequent proper systemic therapies may influence the local recurrence rate (LRR). However, a successful BCS requires preoperative localization techniques or margin assessment techniques. Carbon marking, wire-guided, biopsy clips, radio-guided, ultrasound-guided, frozen section analysis, imprint cytology, and cavity shave margins are commonly used, but from the literature review, no single technique proved to be better among the various ones. u Th s, an association of two or more methods could result in a decrease in rates of involved margins. Each institute should adopt its most congenial techniques, based on the senologic equipe experience, skills, and technologies. 1. Introduction ArequirementforsuccessfulBCSisacarefulpreoperative planning with proper localization of the lesion, especially in Breast-conserving surgery (BCS) is the treatment of choice nonpalpable breast lesions [1]. In order to obtain adequate for early breast cancer [1, 2]. Various randomized trials excisions, margins assessment techniques are also available. have reported this approach to be safe and effective, thus Wire-guided localization, radio-guided occult lesion local- determining a decrease in the adoption of mastectomy as the ization (ROLL), carbon marking, intraoperative ultrasound- treatment of choice for early invasive breast cancer [3, 4]. guided localization, cavity shave margins, and biopsy markers BCS can almost be considered the gold standard of early are commonly used, with different results in terms of LRR. stage invasive breast cancer treatment, allowing to achieve eTh aimofthisreviewistoinvestigate howthese techniques adequate surgical margins (SM) with an acceptable cosmetic mayassistthe surgeontoobtainadequateresections. outcome. Some studies have defined the adequacy of SM by its correlation with the locoregional recurrence rate (LRR) [5–14], but the precise den fi ition of an adequate margins 2. What Is an Adequate Surgical Margin? width remains controversial [15–17]. However, there is no doubt that obtaining negative margins decreases the risk of A negative SM is defined by the absence of ink in any malig- local recurrence [1]. Some clinical trials have demonstrated nant cellsonhistology,and thedistancebetween theclosest malignantcellsandtheinkedsurfaceofthesurgicalspecimen that systemic therapies may also improve the local control in breast cancer [18, 19]. u Th s, there seems to be noted a defines the microscopic margin width ( Table 1)[1]. Gage et al. recent trend of reconsideration of the importance of margin and Schnitt et al. have described in 1996 four types of margins width on the incidence of local recurrences, in favour of other status: negative if>1 mm between tumor cells and the inked prognostic factors such as the biological behaviour of the surface; close if≤1 mm; positive if presence of carcinoma at tumor [15–19]. the inked margin; and focally positive if carcinoma is present 2 International Journal of Surgical Oncology Table 1: Local recurrence rates and corresponding threshold dis- Table 2: Most common features associated with positive surgical tances for negative margins are indicated for each study. margins [20–23]. Study Surgical margins Local recurrences Predicting factors of margin status Horiguchi et al., 2002 [9] 5 mm 3.2% Presence of DCIS 𝑃<0.0001 Karasawa et al., 2003 [10]5mm 1.7% Multifocal disease 𝑃=0.0197 Perez, 2003 [11] 3 mm 5.8% Tumor size 𝑃<0.0001 Peterson et al., 1999 [8] 2 mm 12.8% ( ) Lobular histology 𝑃=0.005 Santiago et al., 2004 [12] 2 mm 12.2% Microcalcifications on mammography 𝑃<0.0001 Karasawa et al., 2005 [13] 2 mm (2.1–5 mm) 3.4% (6.3%) Gage et al., 1996 [5] 1 mm 10.5% ( ) Park et al., 2000 [7]1mm 16%( ) as Kreike et al. who described in a series of 1024 patients (741 Kreike et al., 2008 [14] 1 mm 11.5% with known SM width) LRRs of 11.5% [14]. Average percentage calculated from single LRRs for each type of margins Houssami et al. reported in a meta-analysis of 21 retro- status. spective studies that the presence of positive or close SM increases the odds of local recurrences relative to negative margins (OR 2.02, 𝑃 < 0.001 ), but these odds are not at the margin in 3 or fewer low-power efi lds. eTh 5-year rates associated with the margins width. u Th s, there is not a of local recurrence were 3%, 2%, 28%, and 9%, respectively statistically significant difference on LRR between a margin [5, 6]. distance of 5 mm and 1 mm. However an evident association Park et al.haveanalyzedin2000 the8-yearoutcome of between the odds of local recurrences and the decreasing a series of 533 stage I or II breast cancers treated by BCS, of of threshold distances for negative margins was observed, which 490 could be classified in one of the four margin status confirming the influence of SM status on LRR [ 15]. types: for patients with negative or close margins, LRR was 7%. Patients with extensively positive margins had an LRR 3. What Influences Margins Status? of 27%, while patients with focally positive margins had an LRR of 14% [7]. In 1999 Peterson showed LRRs of 8%, Preoperative predicting of the SM status has recently gained 10%, and 17%, respectively, for negative, focally positive, and a key role in planning BCS, and some predictive factors of focally close (≤2 mm) margins from a series of consecutive positive margins have been described (Table 2). According to 1021 stage I or II breast malignancies [8]. A strong correlation Tartter et al., a preoperative diagnosis by n fi e needle aspira- between local recurrence rates and margins status has been tion, a small tumor size, and the absence of DCIS or the demonstrated in a large number of other studies based on absence of an extensive intraductal carcinoma are all asso- follow-up aeft r breast-conserving surgery plus local radio- ciated with a decreased risk of involved margins on surgical therapy [9–14], but the adequacy of microscopic margins specimen [20]. In astudy basedondatacollected from 1648 width remains controversial. Horiguchi has reported 7 local patients through a breast cancer screening program in Mel- recurrences in a series of 217 breast cancers (3.2%) treated bourne, Kurniawan has identified mammographic microcal- with BCS following a 50 Gy radiation therapy, while Karasawa cifications ( 𝑃<0.0001 ), presence of DCIS (𝑃<0.0001 ), high reported in a retrospective analysis of 348 patients who tumor grade, multifocal disease, and lobular histology (𝑃= underwent BCS an LRR of 1.7%. Both of these studies con- 0.005) as factors correlated with positive margins [21]. Reed- sidered negative SM width of 5 mm, and Horiguchi identified ijk et al. in a prospective study of 305 patients with nonpalpa- the microscopic SM as an independent predictive factor for ble breast lesions have reported that stereotactic versus sono- local recurrence in the conserved breast [9, 10]. graphic localization (𝑃 < 0.0001 ), presence of DCIS, multi- In 2003 Perez studied BCS outcomes in 1037 patients with focal disease, and larger tumor size (>2cm versus <1cm, T1 and 308 patients with T2 breast cancer, with a cumulative 𝑃 < 0.0001 ) are independent predictors of positive mar- LRR of 5.8% (78/1345) based on a threshold distance for neg- gins in BCS [22]. Shin et al. have developed a nomo- ative/close margins equal to 3 mm, although margins status gram for predicting positive margins based on data col- was not found to be a predictor of ipsilateral breast relapse. lected from 1,034 patients, identifying microcalcifications on A higher LRR was rather noted in patients younger than mammography, grade of mammographic density, >0.5 cm 40 years with extensive intraductal component (EIC) [11]. difference in tumor size between MRI and US, DCIS, and Santiago et al.showedin937 womenwithstage IorIIbreast presence of lobular components on preoperative biopsy cancer LRRs of 12.2% (78/639, excluded 298 patients in which as independent predictive factors of involved margins the n fi al status of margins was unknown), considering close [23]. SM≤2mm [12]. Another study by Karasawa et al. performed on a Japanese multicentre survey in 2005 demonstrated a crude LRR of 3.4% for patients with equal or less than 2 mm 4. What about DCIS? margins and an LRR of 6.3% in those with 2.1–5 mm margins [13]. Other authors, besides Gage and Park, have reported Ductal carcinoma in situ represents 25–30% of all diagnosed LRRs on a threshold distance for close margins≤1 mm, such breast malignancies, and its treatment with BCS has increased International Journal of Surgical Oncology 3 over the past decades [24]. Since DCIS is frequently a multi- Interestingly, Down et al. have recently reported, in a study focal disease with a difficult surgical evaluation of its limits, of comparison between patients who underwent BCS alone the adequacy of SM in DCIS has gained a crucial importance with patients treated with BCS and oncoplastic surgery, wider and its definition remains controversial. Silverstein et al. clear margins (6.1 mm versus 14.3 mm), larger specimen 3 3 recommended in a retrospective study of 469 specimens of volumes (112.3 cm versus 484.5 cm ), and a subsequent lower DCIS a margin width of minimum 10 mm if radiotherapy reexcision rate (28.9% versus 5.4%) with the oncoplastic is not performed, but radiotherapy for margins width less approach, without increase in complication rates [32]. than 1 mm can be considered mandatory [25]. Rudloff et al. Also Losken et al. have recently highlighted the onco- reported in a retrospective study of 291 women with DCIS logical advantage of the oncoplastic surgery, publishing a who underwent BCS 10-year actuarial LRRs of 28%, 21%, and meta-analysis of comparison between 3165 patients treated 19% for SM<1 mm, 1–9 mm, and≥10 mm, respectively, with- by BCS with oncoplastic surgery and 5495 patients treated by out radiotherapy; these LRRs were reduced by radiotherapy BCSalone.Thereportedpositivemargins rate is signicfi antly [26]. lower in the oncoplastic group (12% versus 21%), although it should be noted that the rate of completion mastectomy is Vicini et al. studied in a series of 146 DCIS patients treated more common with oncoplastic surgery [33]. with BCS a 10-year actuarial rate of recurrence equal to 12.4% and identified margins of excision >5mm or negative (>2 mm) on reexcision as factors of decreasing risk for local 6. Preoperative Localization Techniques recurrence, while a total volume of excision<60 cm or a tumor size≥0.7 cm was correlated with higher LRRs. es Th e 6.1. Carbon Marking. Carbon marking technique is based data suggested that the adequacy of DCIS removal should be on injection of sterile charcoal powder diluted with saline basedonmargins status together with volume of resection solution into the site of a nonpalpable breast lesion aeft r and tumor size [27]. In a recent meta-analysis of 21 studies, a preoperative sonographic or stereotactic localization. A for a total of 7564 patients affected by DCIS, Wang et al. have charcoal trail is created from the lesion to the superficial demonstrated a reduced risk of ipsilateral local recurrence layers of the breast, leaving a tattoo on the skin. eTh if tumor resected with at least 10 mm of negative margin, subsequent surgical excision of the tumor is guided by the compared with a margin of 2 mm [28]. eTh refore, there seems presence of the carbon suspension, which is removed with the to be noted a general agreement on the need for relatively lesion [34]. Because of the stability of the charcoal powder, a large margins for DCIS, especially if adjuvant radiotherapy delayed surgery after the localization procedure is possible; is not performed. on the contrary, methylene blue has a fast dispersion in the tissue. A potential disadvantage of carbon marking is obstruction of needle tip due to precipitation of charcoal 5. Oncoplastic Surgery particles [35]; moreover, foreign-body giant-cell reactions mimicking malignancy have been reported aeft r vacuum- Oncoplastic surgery refers to a group of surgical techniques assisted breast biopsy with carbon marking [36]. Rose et al. that combine primary tumor excision with plastic surgery reported in a comparison study between carbon marking and techniques, and it allows to achieve good cosmetic outcomes wire-guidedexcisionacloseorinvolvedmarginsrateof18.9% also if wider excision is performed [29]. After resection of a (27/143) with the former technique [37]. breast cancer a correction of a small defect may be necessary, with basictechniquesoflocal volume replacement, more complex reconstruction techniques and may be needed to 6.2. Wire-Guided Technique. Wire-guided localization con- correct larger defects [29]. A common oncoplastic technique, sists of positioning a needle or a flexible wire into or ideal for tumors adjacent but not attached to the nipple alongside a nonpalpable breast lesion under mammographic, areolar complex, is the batwing mastopexy lumpectomy, in sonographic, or CT guidance. eTh mammographic approach which two half-circle incisions are made with angled wings to is based on measurements of distances between the lesion and each side of the areola, with subsequent excision of the lesion the nipple (or other reference points) performed on the two and advance of the superior breast tissue to close the defect projections of the mammogram. In this way an approximative [30]. estimate of the lesion localization is made by the radiologist Another common technique is lumpectomy with reduc- on the patient, who is supine or seated, and the wire is placed tion mammoplasty, particularly useful for tumors in large and anteroposteriorly or parallel to the chest wall. Subsequent ptotic breasts. Of note, this technique requires a careful pre- mammograms are then obtained in order to reposition the operative localization of the lesion, with an exact evaluation wire more accurately, and a conrfi matory mammogram is of its extent [31]. finally obtained [ 38]. The sonographic approach is performed Oncoplastic surgery is linked with a double connection with the patient in a supine position, with the aid of a with the question of margins: in fact, it allows to obtain 5 mHz or higher transducer, and the wire is positioned under excision with wider margins, but on the other hand, it is oen ft direct visualization [38, 39]. The CT approach requires a difficult to determine exactly the reexcision site if a positive preliminary positioning of a wire on the skin in order to margin is encountered on histopathological examination, due have a reference for measuring the lesion localization on to thehandlingofbreasttissuetocorrect volume defects.In slices,and thewireisthenintroduced. Varioustypes of these cases, completion mastectomy is oeft n required [ 29]. wires have been developed, such as standard needle, spinal 4 International Journal of Surgical Oncology needle, or curved-end retractable wire [38]. Although wire- thetumor to be drainedinthe sentinel node,which can guided techniqueisarelatively simple andcost-eeff ctive be easily identiefi dbythe gammaprobe andthenbiopsied method for nonpalpable breast lesions localization, some during theexcisionofthe primarytumor.This technique disadvantages have been reported, above all the eventu- was named “sentinel node and occult lesion localization” ality of wire dislodgment, which could affect an accurate (SNOLL), and it requires two scintigraphy scans [51]. A intraoperative finding of the lesion [ 40]. It should be also potential complication of this procedure is the widespread remembered that this technique requires a good compliance dispersal of the isotope by accidental intraductal injection, from the patient, who has to keep the wire in position all the which may cause a failure in identification of the lesion; time long before the surgery. Clear margins obtained with therefore, this method has to be performed by an expe- wire-guided excision are reported to be 70.8–87.4% [37, 41– rienced breast surgeon [52]. Another concern with ROLL 43]. regards its cost: Medina-Franco et al. reported a total cost of $209 (USD) per each procedure versus $132 (USD) with wire-guided excision [53]. Negative margins reported with 6.3. Clip Marker aer ft a Stereotactic or Sonographic Vacuum- ROLL rangefrom75to93.5%insomestudies [41–43, Assisted Breast Biopsy. Positioning a biopsy clip is necessary 51]. when an occult breast lesion detected by mammography (i.e., microcalcifications), by ultrasound, or by MRI is completely removed within a breast biopsy procedure. Aeft r a vacuum- 7. Margin Assessment Techniques assisted breast biopsy conducted under stereotactic or sono- graphic guidance, a clip marker may be placed through the 7.1. Ultrasound-Guided Excision. Many breast lesions are biopsy probe into the biopsy cavity to permit an eeff ctive clearly visible on ultrasound (US), and thus an intraoperative and accurate preoperative or intraoperative localization, or sonographic localization with a high frequency (7.5 mHz) to facilitate a follow-up of the lesion, especially aer ft a probe may be performed with a subsequent immediate neoadjuvant chemotherapy which could lead to a nearly positioning of a wire, injection of dye, marking on skin, complete tumor regression, with no longer clear visibility or directly calibrating the excision. This procedure there- on imaging [44]. The first type of biopsy clip introduced fore avoids the need of a preoperative localization. An was the radiopaque metallic marker of titanium or stainless ultrasound scanning of the surgical specimen can also be steel, developed for stereotactic procedures [45]. Metallic done to assess the presence of the lesion and the ade- markers embedded with a bioresorbable material (collagen quacy of SM [54, 55]. However, it must be remembered plug of bovine origin, polylactic acid, polyglycolic acid) later that ductal carcinoma in situ rarely has a clear visibility appeared on market; while the metallic core of titanium on US [56], and since it represents an increasing number guarantees long-term visibility and radiopacity, the packing of breast malignancies, some methods for improving its plug of collagen aids for hemostasis aeft r the biopsy proce- visibility on ultrasound have been developed. The hematoma- dure, reduces the risk of clip displacement by its expanding directed US-guided technique consists of obtaining from in the biopsy cavity, and allows an easy identification of the patient 2–5 mL of blood which is left to clot, and the clip on ultrasound until its reabsorption in 6–8 weeks then this blood in injected through a needle near to the [46, 47]. Both of these types of clips may be used preop- lesion or into the biopsy cavity if previously performed. eratively for localization of the tumor by mammography This iatrogenically induced hematoma is visible on a 7.5 mHz or ultrasound, with the possibility of positioning a wire or probe during the surgery [57, 58]. Another technique used marking the lesion’s projections on the skin. An intraop- to enhance US visibility is the positioning of a titanium erative localization without a wire is also possible, either embedded with collagen clip aeft r a breast biopsy. Krekel with a radiography of the surgical specimen in order to et al.haveshowedinastudyon201 excisionsfor non- assess the presence of the clip or by its direct visibility palpable invasive breast cancer that negative margins with on ultrasound during the resection [44–47]. Clear margins US-guided lumpectomy are obtained in 89–96.2% of cases obtained with this method are reported in 90–92% of cases [42, 59]. [48, 49]. A recent multicentre randomized trial named cos- metic outcome of the breast after lumpectomy treatment 6.4. Radio-Guided Occult Lesion Localization (ROLL). Luini (COBALT) has investigated how US-guided excision of pal- et al. described in 1998 the ROLL technique, which con- pablebreastlesions caninufl encethe qualityofresection, sists of a preoperative injection of particles of colloidal with negative margins and smaller volumes of resection human serum albumin labeled with radioactive technetium reported in 97% of patients [60]. Subsequently these patients 99m ( Tc) into the tumor under sonographic or mammo- could avoid a reexcision, or a boost of radiotherapy, with graphic guidance. A scintigraphy scan of the breast is then a reduced psychological stress and a better cosmesis. The obtained to check the correct inoculation of the tracer rationale for this better outcome is that sonography allows by comparison between its position and the localization to visualize directly location and margins of the tumor, of thelesiononmammograms. During thesurgery,the while preoperative imaging with mammography or magnetic tumor can be detected by a gamma probe, directly used resonance imaging is obtained with the patient being in a by the surgeon to verify the adequacy of excision [50]. In dieff rent position compared to that in the operating theatre addition, another radioactive tracer can be injected near to [60]. International Journal of Surgical Oncology 5 7.2. Frozen Sections and Imprint Cytology. Frozen section achieving clear margins on local recurrence rate has been analysis is performed with freezing and sectioning the surgi- discussed in relation to other clinical factors correlated cal specimen with subsequent xa fi tion and staining in order with the prognosis, such as the biological behaviour of the to have an extemporaneous assessment of margins; it takes tumor (i.e., ER+/ER− or HER2) [18, 19, 68]. The NSABP about 30 minutes. Although this technique is extensively B-14 trial has demonstrated an improved local control in used by many surgeons to avoid the need of a postponed node-negative, ER positive breast cancer patients receiving reexcision, some pitfalls have been reported, such as the tamoxifen, with a 10-year LRR of 4.3% compared to 14.7% occurrence of artifacts due to the freezing and thawing of if tamoxifen was not administered [18]. The NSABP B-13 adipose tissue in the specimen [61]. A different intraoperative trial has shown a reduction of LRR from 13.4% to 2.6% method for margins evaluation is imprint cytology (“touch in patients with node-negative, ER negative breast cancer prep”), which consists of pressing each of the 6 faces of the if chemotherapy administered [19]. u Th s, there seems to be specimen on 6 different slides so that any malignant cell on noted a recent trend of reconsideration of the role of surgery an involved margin is theoretically present on the cytology of in the local control of the malignancy, with a lesser interest in the respective slide, because of the tendency of tumor cells to margins width [16, 17]. This more balanced implementation adhere on glass compared to adipocytes [61, 62]. Confusion of systemic therapy and surgery is expanding also in the on cytology interpretation may exist for specimens with therapeutic strategy for positive sentinel node, and some irregular surfaces or presence of atypical cells, although authors are proposing not to perform the axillary dissection some immunou fl orescence stains (i.e., anti-MUC-1 or anti-E- aer ft the detection of micrometastases in the sentinel node cadherin antibodies) may aid the pathologist in identifying [69, 70]. cancer cells on slides [63]. With frozen section analysis and In 2012,Morrowetal. asserted that marginswidth hasno imprint cytology, adequate SM is achieved in 89–91% of cases influence on LRR, since systemic therapies reduce both risks [61]. of distant metastases and of local recurrence, concluding that LRR could be more correlated with the biological features of the tumor. However, it is also highlighted that adequacy 7.3. Cavity Shave Margins. Excision of cavity shave margins of surgical resection depends on clinical judgement, so that consists of resection of breast tissue from all 6 margins a wider excision could be recommended, for example, in a (anterior, posterior, superior, inferior, medial, and lateral) young woman with an extensive DCIS [16]. Of note, Jatoi aer ft the excision of the primary specimen, in the same has responded that, while systemic therapies may improve procedure. This approach allows to precisely assess which control on early local recurrences, late recurrences are more margin is involved in order to calibrate the resection of frequent among patients treated with BCS than those treated the tumor. Kobbermann et al. have demonstrated with this with mastectomy [71, 72]. Finally, while there is not statistical technique 91.3% of negative or close margin if routinely significance in a margin of 2 mm versus a margin of 5 mm performed. Interestingly, of the patients requiring reexcision for invasive breast cancer [15], the role of margins width of the tumor, no significant difference has been noted in for DCIS, which represents 25–30% of all diagnosed breast terms of surgical localization technique [64]. Bolger et al. malignancies, remains even less clear [28]. In the 13th St. have recently reported with cavity shave margins a reexcision Gallen International Breast Cancer Conference 2013, it was rate of 25%, compared with 34% if no margins assessment is stated that systemic therapy and excellent radiation therapy carried out. u Th s, cavity shave margins reduced significantly techniques couldmakemargins widthlessimportant,but the likelihood of having residual disease (𝑃 = 0.02 ). Of the best recommendation remains a case-by-case judgement note, close margins (<2mm) arecorrelatedwiththe presence basedonclinicaland biological features of thetumor [73]. of residual disease (𝑃 = 0.01 )[65]. Marudanayagam et Moreover, a recent position statement by the American al. showed negative margins in 94.4% of 394 patients who Society of Breast Surgeons on breast cancer lumpectomy underwent lumpectomy plus cavity shave margins, compared margins suggests a reexcision in the case of ink positive mar- to 87.5% of 392 patients with lumpectomy only [66]. Although gins but a case-by-case decision if close (<1 mm) or focally this techniqueiscosteeff ctiveand it signicfi antly reducesthe positive margin, evaluating proper adjuvant radiotherapy and rate of positive margins, it may lengthen the operating time, systemic therapies [74]. but it is not correlated with a worse cosmetic outcome due to However, since achieving negative margins (indepen- larger final volumes of resection [ 67]. dently of the definition of adequate margins width) remains a key point of breast cancer surgery, a precise localization of the lesion is of particular importance, especially for nonpalpable 8. Discussion breast lesions or in case of oncoplastic approach (Table 3). The adequacy of SM in BCS still remains a crucial point Certainly, it should be highlighted that obtaining negative of controversy, ranging from 10 mm for DCIS to 1–5 mm margins depends not only on localization method or margin for invasive cancers [15, 25–28]. Singletary et al. stated in assessment technique, but also on extent of the lesion, on the surgical procedure, and on the pathological handling of the a review published in 2002 that it is not clear how much SM width influences LRR, although it is unacceptable to specimen. have involved margins, because the presence of tumor cells An easy and cost-effective method is carbon marking: Rose et al. reported in a comparison study a close or directly at the cut edge of the specimen may not be overcome merely by adjuvant therapy [1]. eTh n, the importance of involved margins rate of 18.9% (27/143) and 2 (0.9%) missed 6 International Journal of Surgical Oncology Table 3: Rates of adequate margins and main disadvantages for each technique. Rate of adequate Technique Disadvantages margins Possible foreign-body reactions mimicking malignancy on follow up; Carbon marking 81.1% obstruction of needle tip due to charcoal precipitation. Wire-guided 70.8–87.4% Wire dislodgment; vasovagal episodes; pneumothorax. Possible widespread dispersal of the tracer by accidental intraductal ROLL 75–93.5% injection; nuclear medicine department required; for experienced surgeons; expensive. Clip marker 90–92% Clip migration. US-guided 89–97% DCIS rarely visible on US if not marked with a clip or hematoma. Cavity shave 91.3–94.4% Long operative times. Sensibility equal to 72–83%; possible difficult interpretation by pathologist Imprint cytology and frozen 89–91% due to presence of irregular specimen’s surfaces or atypical cells; long section analysis operative times. lesions with carbon marking, while positive margins were histopathology (PH), a reexcision rate of 35%, 11% and 10% encountered in 29.2% (21/72) with 3 (1%) missed lesions with PH, IC and FSA, respectively. eTh pooled sensibility with wire-guided localization. These differences have been resulted to be 72%for IC and83% forFSA,withapooled nonstatistically significant, but carbon marking resulted to specificity of 97% and 95% for IC and FSA. An intraoperative be less expensive than wire-guided technique [37]. Wire- assessment permits an immediate correction of the adequacy guided localization is a widely used and relatively simple of excision but with an elongation of the surgery time equal technique, but some complications may be encountered, such to 13–27 minutes [61]. as wire dislodgment, vasovagal episodes, or pneumothorax, and it requires a good compliance from the patient who has 9. Conclusion to keep in position thewireall thetimelongbeforethe surgery. Moreover clear margins obtained with wire-guided The effectiveness of breast-conserving therapy for treat- excision are reported to be 70.8–87.4%, a lower percentage ment of early stage invasive breast malignancies has been in comparison with those reported with other methods like established. Surely the adequacy of margins is a crucial ROLL or ultrasound-guided in many systematic reviews [37, issue for adjusting the volume of excision, for avoiding 41–43, 53]. unnecessary resection of healthy breast parenchyma, and Negative margins reported with ROLL range from 75 to for a good cosmetic outcome. u Th s the surgical accuracy, 93.5% in some studies [41–43, 51], but a Nuclear Medicine together with improved systemic therapy and better radiation Department is required. Another concern with ROLL is the techniques, avoids reexcisions which generally are poorly eventuality of a dispersal of the radioactive tracer causing tolerated by the patients. From the literature review, no a failure in the identification of the lesion, and thus an single technique proved to be better among the various experienced surgeon is required [52]. Clip placement aeft r ones described for achieving adequate SM, because all of a vacuum-assisted breast biopsy appears to be effective, them have some advantages and disadvantages, although especially if the intraoperative localization is performed many reviewshavestatedthe wire-guidedexcisiontobe under sonographic guidance: Nurko et al. have reported probably the less effective method in obtaining clear margins. clear margins in 90% (37/41) of cases [48]. A US-visible clip According to our opinion, each surgeon should adopt his marker may be positioned aeft r breast biopsies performed most congenial localization or margin assessment technique, under sonographic or stereotactic guidance, with positive based on the senologic equipe experience and on available margins encountered in 8% of cases [49]. A disadvantage in skills and technologies. Moreover, an association of two or clip markers is their possible dislodgment, but the average more methods could result in a decrease in rates of involved distance between the target lesion and the clip has been found margins. Certainly both margins status and the biological to be<10 mm in 71.3% of cases [44], with an average distance behaviourofthe malignancy contribute to localrecurrence of 1.1mmifthe biopsy hasbeenperformed on US [75]. Krekel rate, and future studies are needed to ascertain the relevance et al. have shown in a study on 201 excisions for nonpalpable of both factors. invasive breast cancer negative margins in 96.2% with the aid of US-guided lumpectomy [42], while Rahusen has reported clear SM in 89% of cases with the same technique [59]. 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Preoperative Localization and Surgical Margins in Conservative Breast Surgery

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Hindawi Publishing Corporation International Journal of Surgical Oncology Volume 2013, Article ID 793819, 9 pages http://dx.doi.org/10.1155/2013/793819 Review Article Preoperative Localization and Surgical Margins in Conservative Breast Surgery F. Corsi, L. Sorrentino, D. Bossi, A. Sartani, and D. Foschi Surgery Division, Department of Clinical Sciences, L. Sacco Hospital, University of Milan, Via G.B. Grassi 74, 20157 Milan, Italy Correspondence should be addressed to F. Corsi; fabio.corsi@unimi.it Received 14 September 2012; Revised 6 June 2013; Accepted 10 July 2013 Academic Editor: A. K. Dcruz Copyright © 2013 F. Corsi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Breast-conserving surgery (BCS) is the treatment of choice for early breast cancer. eTh adequacy of surgical margins (SM) is a crucial issue for adjusting the volume of excision and for avoiding local recurrences, although the precise definition of an adequate margins width remains controversial. Moreover, other factors such as the biological behaviour of the tumor and subsequent proper systemic therapies may influence the local recurrence rate (LRR). However, a successful BCS requires preoperative localization techniques or margin assessment techniques. Carbon marking, wire-guided, biopsy clips, radio-guided, ultrasound-guided, frozen section analysis, imprint cytology, and cavity shave margins are commonly used, but from the literature review, no single technique proved to be better among the various ones. u Th s, an association of two or more methods could result in a decrease in rates of involved margins. Each institute should adopt its most congenial techniques, based on the senologic equipe experience, skills, and technologies. 1. Introduction ArequirementforsuccessfulBCSisacarefulpreoperative planning with proper localization of the lesion, especially in Breast-conserving surgery (BCS) is the treatment of choice nonpalpable breast lesions [1]. In order to obtain adequate for early breast cancer [1, 2]. Various randomized trials excisions, margins assessment techniques are also available. have reported this approach to be safe and effective, thus Wire-guided localization, radio-guided occult lesion local- determining a decrease in the adoption of mastectomy as the ization (ROLL), carbon marking, intraoperative ultrasound- treatment of choice for early invasive breast cancer [3, 4]. guided localization, cavity shave margins, and biopsy markers BCS can almost be considered the gold standard of early are commonly used, with different results in terms of LRR. stage invasive breast cancer treatment, allowing to achieve eTh aimofthisreviewistoinvestigate howthese techniques adequate surgical margins (SM) with an acceptable cosmetic mayassistthe surgeontoobtainadequateresections. outcome. Some studies have defined the adequacy of SM by its correlation with the locoregional recurrence rate (LRR) [5–14], but the precise den fi ition of an adequate margins 2. What Is an Adequate Surgical Margin? width remains controversial [15–17]. However, there is no doubt that obtaining negative margins decreases the risk of A negative SM is defined by the absence of ink in any malig- local recurrence [1]. Some clinical trials have demonstrated nant cellsonhistology,and thedistancebetween theclosest malignantcellsandtheinkedsurfaceofthesurgicalspecimen that systemic therapies may also improve the local control in breast cancer [18, 19]. u Th s, there seems to be noted a defines the microscopic margin width ( Table 1)[1]. Gage et al. recent trend of reconsideration of the importance of margin and Schnitt et al. have described in 1996 four types of margins width on the incidence of local recurrences, in favour of other status: negative if>1 mm between tumor cells and the inked prognostic factors such as the biological behaviour of the surface; close if≤1 mm; positive if presence of carcinoma at tumor [15–19]. the inked margin; and focally positive if carcinoma is present 2 International Journal of Surgical Oncology Table 1: Local recurrence rates and corresponding threshold dis- Table 2: Most common features associated with positive surgical tances for negative margins are indicated for each study. margins [20–23]. Study Surgical margins Local recurrences Predicting factors of margin status Horiguchi et al., 2002 [9] 5 mm 3.2% Presence of DCIS 𝑃<0.0001 Karasawa et al., 2003 [10]5mm 1.7% Multifocal disease 𝑃=0.0197 Perez, 2003 [11] 3 mm 5.8% Tumor size 𝑃<0.0001 Peterson et al., 1999 [8] 2 mm 12.8% ( ) Lobular histology 𝑃=0.005 Santiago et al., 2004 [12] 2 mm 12.2% Microcalcifications on mammography 𝑃<0.0001 Karasawa et al., 2005 [13] 2 mm (2.1–5 mm) 3.4% (6.3%) Gage et al., 1996 [5] 1 mm 10.5% ( ) Park et al., 2000 [7]1mm 16%( ) as Kreike et al. who described in a series of 1024 patients (741 Kreike et al., 2008 [14] 1 mm 11.5% with known SM width) LRRs of 11.5% [14]. Average percentage calculated from single LRRs for each type of margins Houssami et al. reported in a meta-analysis of 21 retro- status. spective studies that the presence of positive or close SM increases the odds of local recurrences relative to negative margins (OR 2.02, 𝑃 < 0.001 ), but these odds are not at the margin in 3 or fewer low-power efi lds. eTh 5-year rates associated with the margins width. u Th s, there is not a of local recurrence were 3%, 2%, 28%, and 9%, respectively statistically significant difference on LRR between a margin [5, 6]. distance of 5 mm and 1 mm. However an evident association Park et al.haveanalyzedin2000 the8-yearoutcome of between the odds of local recurrences and the decreasing a series of 533 stage I or II breast cancers treated by BCS, of of threshold distances for negative margins was observed, which 490 could be classified in one of the four margin status confirming the influence of SM status on LRR [ 15]. types: for patients with negative or close margins, LRR was 7%. Patients with extensively positive margins had an LRR 3. What Influences Margins Status? of 27%, while patients with focally positive margins had an LRR of 14% [7]. In 1999 Peterson showed LRRs of 8%, Preoperative predicting of the SM status has recently gained 10%, and 17%, respectively, for negative, focally positive, and a key role in planning BCS, and some predictive factors of focally close (≤2 mm) margins from a series of consecutive positive margins have been described (Table 2). According to 1021 stage I or II breast malignancies [8]. A strong correlation Tartter et al., a preoperative diagnosis by n fi e needle aspira- between local recurrence rates and margins status has been tion, a small tumor size, and the absence of DCIS or the demonstrated in a large number of other studies based on absence of an extensive intraductal carcinoma are all asso- follow-up aeft r breast-conserving surgery plus local radio- ciated with a decreased risk of involved margins on surgical therapy [9–14], but the adequacy of microscopic margins specimen [20]. In astudy basedondatacollected from 1648 width remains controversial. Horiguchi has reported 7 local patients through a breast cancer screening program in Mel- recurrences in a series of 217 breast cancers (3.2%) treated bourne, Kurniawan has identified mammographic microcal- with BCS following a 50 Gy radiation therapy, while Karasawa cifications ( 𝑃<0.0001 ), presence of DCIS (𝑃<0.0001 ), high reported in a retrospective analysis of 348 patients who tumor grade, multifocal disease, and lobular histology (𝑃= underwent BCS an LRR of 1.7%. Both of these studies con- 0.005) as factors correlated with positive margins [21]. Reed- sidered negative SM width of 5 mm, and Horiguchi identified ijk et al. in a prospective study of 305 patients with nonpalpa- the microscopic SM as an independent predictive factor for ble breast lesions have reported that stereotactic versus sono- local recurrence in the conserved breast [9, 10]. graphic localization (𝑃 < 0.0001 ), presence of DCIS, multi- In 2003 Perez studied BCS outcomes in 1037 patients with focal disease, and larger tumor size (>2cm versus <1cm, T1 and 308 patients with T2 breast cancer, with a cumulative 𝑃 < 0.0001 ) are independent predictors of positive mar- LRR of 5.8% (78/1345) based on a threshold distance for neg- gins in BCS [22]. Shin et al. have developed a nomo- ative/close margins equal to 3 mm, although margins status gram for predicting positive margins based on data col- was not found to be a predictor of ipsilateral breast relapse. lected from 1,034 patients, identifying microcalcifications on A higher LRR was rather noted in patients younger than mammography, grade of mammographic density, >0.5 cm 40 years with extensive intraductal component (EIC) [11]. difference in tumor size between MRI and US, DCIS, and Santiago et al.showedin937 womenwithstage IorIIbreast presence of lobular components on preoperative biopsy cancer LRRs of 12.2% (78/639, excluded 298 patients in which as independent predictive factors of involved margins the n fi al status of margins was unknown), considering close [23]. SM≤2mm [12]. Another study by Karasawa et al. performed on a Japanese multicentre survey in 2005 demonstrated a crude LRR of 3.4% for patients with equal or less than 2 mm 4. What about DCIS? margins and an LRR of 6.3% in those with 2.1–5 mm margins [13]. Other authors, besides Gage and Park, have reported Ductal carcinoma in situ represents 25–30% of all diagnosed LRRs on a threshold distance for close margins≤1 mm, such breast malignancies, and its treatment with BCS has increased International Journal of Surgical Oncology 3 over the past decades [24]. Since DCIS is frequently a multi- Interestingly, Down et al. have recently reported, in a study focal disease with a difficult surgical evaluation of its limits, of comparison between patients who underwent BCS alone the adequacy of SM in DCIS has gained a crucial importance with patients treated with BCS and oncoplastic surgery, wider and its definition remains controversial. Silverstein et al. clear margins (6.1 mm versus 14.3 mm), larger specimen 3 3 recommended in a retrospective study of 469 specimens of volumes (112.3 cm versus 484.5 cm ), and a subsequent lower DCIS a margin width of minimum 10 mm if radiotherapy reexcision rate (28.9% versus 5.4%) with the oncoplastic is not performed, but radiotherapy for margins width less approach, without increase in complication rates [32]. than 1 mm can be considered mandatory [25]. Rudloff et al. Also Losken et al. have recently highlighted the onco- reported in a retrospective study of 291 women with DCIS logical advantage of the oncoplastic surgery, publishing a who underwent BCS 10-year actuarial LRRs of 28%, 21%, and meta-analysis of comparison between 3165 patients treated 19% for SM<1 mm, 1–9 mm, and≥10 mm, respectively, with- by BCS with oncoplastic surgery and 5495 patients treated by out radiotherapy; these LRRs were reduced by radiotherapy BCSalone.Thereportedpositivemargins rate is signicfi antly [26]. lower in the oncoplastic group (12% versus 21%), although it should be noted that the rate of completion mastectomy is Vicini et al. studied in a series of 146 DCIS patients treated more common with oncoplastic surgery [33]. with BCS a 10-year actuarial rate of recurrence equal to 12.4% and identified margins of excision >5mm or negative (>2 mm) on reexcision as factors of decreasing risk for local 6. Preoperative Localization Techniques recurrence, while a total volume of excision<60 cm or a tumor size≥0.7 cm was correlated with higher LRRs. es Th e 6.1. Carbon Marking. Carbon marking technique is based data suggested that the adequacy of DCIS removal should be on injection of sterile charcoal powder diluted with saline basedonmargins status together with volume of resection solution into the site of a nonpalpable breast lesion aeft r and tumor size [27]. In a recent meta-analysis of 21 studies, a preoperative sonographic or stereotactic localization. A for a total of 7564 patients affected by DCIS, Wang et al. have charcoal trail is created from the lesion to the superficial demonstrated a reduced risk of ipsilateral local recurrence layers of the breast, leaving a tattoo on the skin. eTh if tumor resected with at least 10 mm of negative margin, subsequent surgical excision of the tumor is guided by the compared with a margin of 2 mm [28]. eTh refore, there seems presence of the carbon suspension, which is removed with the to be noted a general agreement on the need for relatively lesion [34]. Because of the stability of the charcoal powder, a large margins for DCIS, especially if adjuvant radiotherapy delayed surgery after the localization procedure is possible; is not performed. on the contrary, methylene blue has a fast dispersion in the tissue. A potential disadvantage of carbon marking is obstruction of needle tip due to precipitation of charcoal 5. Oncoplastic Surgery particles [35]; moreover, foreign-body giant-cell reactions mimicking malignancy have been reported aeft r vacuum- Oncoplastic surgery refers to a group of surgical techniques assisted breast biopsy with carbon marking [36]. Rose et al. that combine primary tumor excision with plastic surgery reported in a comparison study between carbon marking and techniques, and it allows to achieve good cosmetic outcomes wire-guidedexcisionacloseorinvolvedmarginsrateof18.9% also if wider excision is performed [29]. After resection of a (27/143) with the former technique [37]. breast cancer a correction of a small defect may be necessary, with basictechniquesoflocal volume replacement, more complex reconstruction techniques and may be needed to 6.2. Wire-Guided Technique. Wire-guided localization con- correct larger defects [29]. A common oncoplastic technique, sists of positioning a needle or a flexible wire into or ideal for tumors adjacent but not attached to the nipple alongside a nonpalpable breast lesion under mammographic, areolar complex, is the batwing mastopexy lumpectomy, in sonographic, or CT guidance. eTh mammographic approach which two half-circle incisions are made with angled wings to is based on measurements of distances between the lesion and each side of the areola, with subsequent excision of the lesion the nipple (or other reference points) performed on the two and advance of the superior breast tissue to close the defect projections of the mammogram. In this way an approximative [30]. estimate of the lesion localization is made by the radiologist Another common technique is lumpectomy with reduc- on the patient, who is supine or seated, and the wire is placed tion mammoplasty, particularly useful for tumors in large and anteroposteriorly or parallel to the chest wall. Subsequent ptotic breasts. Of note, this technique requires a careful pre- mammograms are then obtained in order to reposition the operative localization of the lesion, with an exact evaluation wire more accurately, and a conrfi matory mammogram is of its extent [31]. finally obtained [ 38]. The sonographic approach is performed Oncoplastic surgery is linked with a double connection with the patient in a supine position, with the aid of a with the question of margins: in fact, it allows to obtain 5 mHz or higher transducer, and the wire is positioned under excision with wider margins, but on the other hand, it is oen ft direct visualization [38, 39]. The CT approach requires a difficult to determine exactly the reexcision site if a positive preliminary positioning of a wire on the skin in order to margin is encountered on histopathological examination, due have a reference for measuring the lesion localization on to thehandlingofbreasttissuetocorrect volume defects.In slices,and thewireisthenintroduced. Varioustypes of these cases, completion mastectomy is oeft n required [ 29]. wires have been developed, such as standard needle, spinal 4 International Journal of Surgical Oncology needle, or curved-end retractable wire [38]. Although wire- thetumor to be drainedinthe sentinel node,which can guided techniqueisarelatively simple andcost-eeff ctive be easily identiefi dbythe gammaprobe andthenbiopsied method for nonpalpable breast lesions localization, some during theexcisionofthe primarytumor.This technique disadvantages have been reported, above all the eventu- was named “sentinel node and occult lesion localization” ality of wire dislodgment, which could affect an accurate (SNOLL), and it requires two scintigraphy scans [51]. A intraoperative finding of the lesion [ 40]. It should be also potential complication of this procedure is the widespread remembered that this technique requires a good compliance dispersal of the isotope by accidental intraductal injection, from the patient, who has to keep the wire in position all the which may cause a failure in identification of the lesion; time long before the surgery. Clear margins obtained with therefore, this method has to be performed by an expe- wire-guided excision are reported to be 70.8–87.4% [37, 41– rienced breast surgeon [52]. Another concern with ROLL 43]. regards its cost: Medina-Franco et al. reported a total cost of $209 (USD) per each procedure versus $132 (USD) with wire-guided excision [53]. Negative margins reported with 6.3. Clip Marker aer ft a Stereotactic or Sonographic Vacuum- ROLL rangefrom75to93.5%insomestudies [41–43, Assisted Breast Biopsy. Positioning a biopsy clip is necessary 51]. when an occult breast lesion detected by mammography (i.e., microcalcifications), by ultrasound, or by MRI is completely removed within a breast biopsy procedure. Aeft r a vacuum- 7. Margin Assessment Techniques assisted breast biopsy conducted under stereotactic or sono- graphic guidance, a clip marker may be placed through the 7.1. Ultrasound-Guided Excision. Many breast lesions are biopsy probe into the biopsy cavity to permit an eeff ctive clearly visible on ultrasound (US), and thus an intraoperative and accurate preoperative or intraoperative localization, or sonographic localization with a high frequency (7.5 mHz) to facilitate a follow-up of the lesion, especially aer ft a probe may be performed with a subsequent immediate neoadjuvant chemotherapy which could lead to a nearly positioning of a wire, injection of dye, marking on skin, complete tumor regression, with no longer clear visibility or directly calibrating the excision. This procedure there- on imaging [44]. The first type of biopsy clip introduced fore avoids the need of a preoperative localization. An was the radiopaque metallic marker of titanium or stainless ultrasound scanning of the surgical specimen can also be steel, developed for stereotactic procedures [45]. Metallic done to assess the presence of the lesion and the ade- markers embedded with a bioresorbable material (collagen quacy of SM [54, 55]. However, it must be remembered plug of bovine origin, polylactic acid, polyglycolic acid) later that ductal carcinoma in situ rarely has a clear visibility appeared on market; while the metallic core of titanium on US [56], and since it represents an increasing number guarantees long-term visibility and radiopacity, the packing of breast malignancies, some methods for improving its plug of collagen aids for hemostasis aeft r the biopsy proce- visibility on ultrasound have been developed. The hematoma- dure, reduces the risk of clip displacement by its expanding directed US-guided technique consists of obtaining from in the biopsy cavity, and allows an easy identification of the patient 2–5 mL of blood which is left to clot, and the clip on ultrasound until its reabsorption in 6–8 weeks then this blood in injected through a needle near to the [46, 47]. Both of these types of clips may be used preop- lesion or into the biopsy cavity if previously performed. eratively for localization of the tumor by mammography This iatrogenically induced hematoma is visible on a 7.5 mHz or ultrasound, with the possibility of positioning a wire or probe during the surgery [57, 58]. Another technique used marking the lesion’s projections on the skin. An intraop- to enhance US visibility is the positioning of a titanium erative localization without a wire is also possible, either embedded with collagen clip aeft r a breast biopsy. Krekel with a radiography of the surgical specimen in order to et al.haveshowedinastudyon201 excisionsfor non- assess the presence of the clip or by its direct visibility palpable invasive breast cancer that negative margins with on ultrasound during the resection [44–47]. Clear margins US-guided lumpectomy are obtained in 89–96.2% of cases obtained with this method are reported in 90–92% of cases [42, 59]. [48, 49]. A recent multicentre randomized trial named cos- metic outcome of the breast after lumpectomy treatment 6.4. Radio-Guided Occult Lesion Localization (ROLL). Luini (COBALT) has investigated how US-guided excision of pal- et al. described in 1998 the ROLL technique, which con- pablebreastlesions caninufl encethe qualityofresection, sists of a preoperative injection of particles of colloidal with negative margins and smaller volumes of resection human serum albumin labeled with radioactive technetium reported in 97% of patients [60]. Subsequently these patients 99m ( Tc) into the tumor under sonographic or mammo- could avoid a reexcision, or a boost of radiotherapy, with graphic guidance. A scintigraphy scan of the breast is then a reduced psychological stress and a better cosmesis. The obtained to check the correct inoculation of the tracer rationale for this better outcome is that sonography allows by comparison between its position and the localization to visualize directly location and margins of the tumor, of thelesiononmammograms. During thesurgery,the while preoperative imaging with mammography or magnetic tumor can be detected by a gamma probe, directly used resonance imaging is obtained with the patient being in a by the surgeon to verify the adequacy of excision [50]. In dieff rent position compared to that in the operating theatre addition, another radioactive tracer can be injected near to [60]. International Journal of Surgical Oncology 5 7.2. Frozen Sections and Imprint Cytology. Frozen section achieving clear margins on local recurrence rate has been analysis is performed with freezing and sectioning the surgi- discussed in relation to other clinical factors correlated cal specimen with subsequent xa fi tion and staining in order with the prognosis, such as the biological behaviour of the to have an extemporaneous assessment of margins; it takes tumor (i.e., ER+/ER− or HER2) [18, 19, 68]. The NSABP about 30 minutes. Although this technique is extensively B-14 trial has demonstrated an improved local control in used by many surgeons to avoid the need of a postponed node-negative, ER positive breast cancer patients receiving reexcision, some pitfalls have been reported, such as the tamoxifen, with a 10-year LRR of 4.3% compared to 14.7% occurrence of artifacts due to the freezing and thawing of if tamoxifen was not administered [18]. The NSABP B-13 adipose tissue in the specimen [61]. A different intraoperative trial has shown a reduction of LRR from 13.4% to 2.6% method for margins evaluation is imprint cytology (“touch in patients with node-negative, ER negative breast cancer prep”), which consists of pressing each of the 6 faces of the if chemotherapy administered [19]. u Th s, there seems to be specimen on 6 different slides so that any malignant cell on noted a recent trend of reconsideration of the role of surgery an involved margin is theoretically present on the cytology of in the local control of the malignancy, with a lesser interest in the respective slide, because of the tendency of tumor cells to margins width [16, 17]. This more balanced implementation adhere on glass compared to adipocytes [61, 62]. Confusion of systemic therapy and surgery is expanding also in the on cytology interpretation may exist for specimens with therapeutic strategy for positive sentinel node, and some irregular surfaces or presence of atypical cells, although authors are proposing not to perform the axillary dissection some immunou fl orescence stains (i.e., anti-MUC-1 or anti-E- aer ft the detection of micrometastases in the sentinel node cadherin antibodies) may aid the pathologist in identifying [69, 70]. cancer cells on slides [63]. With frozen section analysis and In 2012,Morrowetal. asserted that marginswidth hasno imprint cytology, adequate SM is achieved in 89–91% of cases influence on LRR, since systemic therapies reduce both risks [61]. of distant metastases and of local recurrence, concluding that LRR could be more correlated with the biological features of the tumor. However, it is also highlighted that adequacy 7.3. Cavity Shave Margins. Excision of cavity shave margins of surgical resection depends on clinical judgement, so that consists of resection of breast tissue from all 6 margins a wider excision could be recommended, for example, in a (anterior, posterior, superior, inferior, medial, and lateral) young woman with an extensive DCIS [16]. Of note, Jatoi aer ft the excision of the primary specimen, in the same has responded that, while systemic therapies may improve procedure. This approach allows to precisely assess which control on early local recurrences, late recurrences are more margin is involved in order to calibrate the resection of frequent among patients treated with BCS than those treated the tumor. Kobbermann et al. have demonstrated with this with mastectomy [71, 72]. Finally, while there is not statistical technique 91.3% of negative or close margin if routinely significance in a margin of 2 mm versus a margin of 5 mm performed. Interestingly, of the patients requiring reexcision for invasive breast cancer [15], the role of margins width of the tumor, no significant difference has been noted in for DCIS, which represents 25–30% of all diagnosed breast terms of surgical localization technique [64]. Bolger et al. malignancies, remains even less clear [28]. In the 13th St. have recently reported with cavity shave margins a reexcision Gallen International Breast Cancer Conference 2013, it was rate of 25%, compared with 34% if no margins assessment is stated that systemic therapy and excellent radiation therapy carried out. u Th s, cavity shave margins reduced significantly techniques couldmakemargins widthlessimportant,but the likelihood of having residual disease (𝑃 = 0.02 ). Of the best recommendation remains a case-by-case judgement note, close margins (<2mm) arecorrelatedwiththe presence basedonclinicaland biological features of thetumor [73]. of residual disease (𝑃 = 0.01 )[65]. Marudanayagam et Moreover, a recent position statement by the American al. showed negative margins in 94.4% of 394 patients who Society of Breast Surgeons on breast cancer lumpectomy underwent lumpectomy plus cavity shave margins, compared margins suggests a reexcision in the case of ink positive mar- to 87.5% of 392 patients with lumpectomy only [66]. Although gins but a case-by-case decision if close (<1 mm) or focally this techniqueiscosteeff ctiveand it signicfi antly reducesthe positive margin, evaluating proper adjuvant radiotherapy and rate of positive margins, it may lengthen the operating time, systemic therapies [74]. but it is not correlated with a worse cosmetic outcome due to However, since achieving negative margins (indepen- larger final volumes of resection [ 67]. dently of the definition of adequate margins width) remains a key point of breast cancer surgery, a precise localization of the lesion is of particular importance, especially for nonpalpable 8. Discussion breast lesions or in case of oncoplastic approach (Table 3). The adequacy of SM in BCS still remains a crucial point Certainly, it should be highlighted that obtaining negative of controversy, ranging from 10 mm for DCIS to 1–5 mm margins depends not only on localization method or margin for invasive cancers [15, 25–28]. Singletary et al. stated in assessment technique, but also on extent of the lesion, on the surgical procedure, and on the pathological handling of the a review published in 2002 that it is not clear how much SM width influences LRR, although it is unacceptable to specimen. have involved margins, because the presence of tumor cells An easy and cost-effective method is carbon marking: Rose et al. reported in a comparison study a close or directly at the cut edge of the specimen may not be overcome merely by adjuvant therapy [1]. eTh n, the importance of involved margins rate of 18.9% (27/143) and 2 (0.9%) missed 6 International Journal of Surgical Oncology Table 3: Rates of adequate margins and main disadvantages for each technique. Rate of adequate Technique Disadvantages margins Possible foreign-body reactions mimicking malignancy on follow up; Carbon marking 81.1% obstruction of needle tip due to charcoal precipitation. Wire-guided 70.8–87.4% Wire dislodgment; vasovagal episodes; pneumothorax. Possible widespread dispersal of the tracer by accidental intraductal ROLL 75–93.5% injection; nuclear medicine department required; for experienced surgeons; expensive. Clip marker 90–92% Clip migration. US-guided 89–97% DCIS rarely visible on US if not marked with a clip or hematoma. Cavity shave 91.3–94.4% Long operative times. Sensibility equal to 72–83%; possible difficult interpretation by pathologist Imprint cytology and frozen 89–91% due to presence of irregular specimen’s surfaces or atypical cells; long section analysis operative times. lesions with carbon marking, while positive margins were histopathology (PH), a reexcision rate of 35%, 11% and 10% encountered in 29.2% (21/72) with 3 (1%) missed lesions with PH, IC and FSA, respectively. eTh pooled sensibility with wire-guided localization. These differences have been resulted to be 72%for IC and83% forFSA,withapooled nonstatistically significant, but carbon marking resulted to specificity of 97% and 95% for IC and FSA. An intraoperative be less expensive than wire-guided technique [37]. Wire- assessment permits an immediate correction of the adequacy guided localization is a widely used and relatively simple of excision but with an elongation of the surgery time equal technique, but some complications may be encountered, such to 13–27 minutes [61]. as wire dislodgment, vasovagal episodes, or pneumothorax, and it requires a good compliance from the patient who has 9. Conclusion to keep in position thewireall thetimelongbeforethe surgery. Moreover clear margins obtained with wire-guided The effectiveness of breast-conserving therapy for treat- excision are reported to be 70.8–87.4%, a lower percentage ment of early stage invasive breast malignancies has been in comparison with those reported with other methods like established. Surely the adequacy of margins is a crucial ROLL or ultrasound-guided in many systematic reviews [37, issue for adjusting the volume of excision, for avoiding 41–43, 53]. unnecessary resection of healthy breast parenchyma, and Negative margins reported with ROLL range from 75 to for a good cosmetic outcome. u Th s the surgical accuracy, 93.5% in some studies [41–43, 51], but a Nuclear Medicine together with improved systemic therapy and better radiation Department is required. Another concern with ROLL is the techniques, avoids reexcisions which generally are poorly eventuality of a dispersal of the radioactive tracer causing tolerated by the patients. From the literature review, no a failure in the identification of the lesion, and thus an single technique proved to be better among the various experienced surgeon is required [52]. Clip placement aeft r ones described for achieving adequate SM, because all of a vacuum-assisted breast biopsy appears to be effective, them have some advantages and disadvantages, although especially if the intraoperative localization is performed many reviewshavestatedthe wire-guidedexcisiontobe under sonographic guidance: Nurko et al. have reported probably the less effective method in obtaining clear margins. clear margins in 90% (37/41) of cases [48]. A US-visible clip According to our opinion, each surgeon should adopt his marker may be positioned aeft r breast biopsies performed most congenial localization or margin assessment technique, under sonographic or stereotactic guidance, with positive based on the senologic equipe experience and on available margins encountered in 8% of cases [49]. A disadvantage in skills and technologies. Moreover, an association of two or clip markers is their possible dislodgment, but the average more methods could result in a decrease in rates of involved distance between the target lesion and the clip has been found margins. Certainly both margins status and the biological to be<10 mm in 71.3% of cases [44], with an average distance behaviourofthe malignancy contribute to localrecurrence of 1.1mmifthe biopsy hasbeenperformed on US [75]. Krekel rate, and future studies are needed to ascertain the relevance et al. have shown in a study on 201 excisions for nonpalpable of both factors. invasive breast cancer negative margins in 96.2% with the aid of US-guided lumpectomy [42], while Rahusen has reported clear SM in 89% of cases with the same technique [59]. 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