Elsevier

Surgical Oncology

Volume 23, Issue 2, June 2014, Pages 81-91
Surgical Oncology

Review
Perioperative measures to optimize margin clearance in breast conserving surgery

https://doi.org/10.1016/j.suronc.2014.03.002Get rights and content

Abstract

Margin status is one of the most important determinants of local recurrence following breast conserving surgery. The fact that up to 60% of patients undergoing breast conserving surgery require re-excision highlights the importance of optimizing margin clearance. In this review we summarize the following perioperative measures that aim to enhance margin clearance: (1) patient risk stratification, specifically risk factors and nomograms, (2) preoperative imaging, (3) intraoperative techniques including wire-guided localization, radioguided surgery, intraoperative ultrasound-guided resection, intraoperative specimen radiography, standardized cavity shaving, and ink-directed focal re-excision; (4) and intraoperative pathology assessment techniques, namely frozen section analysis and imprint cytology. Novel surgical techniques as well as emerging technologies are also reviewed. Effective treatment requires accurate preoperative planning, developing and implementing a consistent definition of margin clearance, and using tools that provide detailed real-time intraoperative information on margin status.

Introduction

Screening mammography increased the incidence of ductal carcinoma in situ (DCIS) and early stage invasive breast cancer [1], [2]. Previously, mastectomy was the standard treatment, but the physical and psychological morbidity associated with it led to the study of less aggressive approaches. Surgical treatment shifted from mastectomy to breast conserving surgery (BCS) in conjunction with adjuvant therapies as several major randomized clinical trials (RCTs) showed no significant difference in disease-free and overall survival between both approaches [3], [4], [5], [6], [7], [8]. The treatment of DCIS underwent similar changes; although the role of adjuvant radiation therapy for DCIS is controversial [9], [10], [11].

Despite the advantages, BCS has a higher risk of local recurrence (LR) than mastectomy [3], [8]. Predictors of LR include patient age, tumour stage, tumour grade, disease distribution, lymphovascular invasion (LVI) status, molecular subtype, and surgical margin status [12]. Of these, the strongest predictor of LR is surgical margin status [13], [14]. The risk of LR from a positive margin is 2–3 times that with a negative margin [15].

Positive margins are managed with re-excision or mastectomy, depending on the number of positive margins and the remaining amount of breast tissue. Positive margin rates after BCS for breast cancer and DCIS are 15–47% [16], [17], [18], [19] and 20–81% [9], [20], [21], [22], [23], [24], [25], [26], respectively. Re-excision rates range from 23% to 59% depending on the treatment centre and the surgeon's practice [27], [28], [29]. The completion mastectomy rate is approximately 14% [30]. Re-excision may result in poor cosmetic outcome, increased medical cost, and patient anxiety. As the rate of patients with early invasive cancer and DCIS continues to increase, obtaining negative margins during primary BCS is essential. This review summarizes the perioperative approaches that aim to optimize margin clearance for patients undergoing BCS.

Section snippets

Surgical margins

Ideally BCS should consist of removing the whole tumour, a thin layer of normal tissue to absorb the margin ink, and no other normal breast tissue, but this is technically impossible; therefore several millimetres of normal tissue are excised around the tumour. Margins are measured grossly and microscopically by determining the presence of cancer cells at a fixed distance from the cut edge. Margins are negative if no invasive cancer and/or DCIS are identified microscopically at the edge of the

Preoperative assessment of patients undergoing breast conserving surgery (BCS)

Multiple studies have evaluated clinical, pathological, and treatment-related risk factors associated with LR, all of which should be considered preoperatively. These risk factors include young age [39], positive lymph nodes [40], high tumour grade [41], comedo and lobular histology [42], microcalcifications on mammography [43]; presence of LVI [39], high nuclear grade [44], high mitotic count [44], >20% Ki-67 positive cells [44], absence of oestrogen (ER) and progesterone receptors (PR) [42],

Preoperative imaging

Preoperative imaging determines disease burden and helps plan surgical treatment. Standard imaging modalities include mammography and ultrasound, and, in some cases, MRI. Recent films, no more than 3 months old, should be reviewed preoperatively. Elements to consider when interpreting mammography include obtaining bilateral two-view films; noting the characteristics and location of the tumour and any microcalcifications; and determining if the tumour is multifocal and/or multicentric.

Wire-guided localization (WGL)

The gold standard for the treatment of clinically non-palpable tumours is wide local excision by WGL. A thin guide wire is introduced under local anaesthesia and with ultrasound, mammography, or MRI guidance into the tumour's core. After the tumour is excised, the specimen is evaluated by mammography and/or ultrasound to confirm complete excision. The major limitation of WGL is that it does not provide a three-dimensional image of the lesion; therefore the specimen tends to be non-uniform with

Standardized cavity shaving

In the majority of practices, surgical margins are oriented with sutures or staples and inked by pathology. With this practice, approximately 50% of patients who require a re-excision because of positive margins are later found to not have residual tumour on re-excision [91], [92], [93], [94]. Surgeons should also be aware of the fact that “negative” specimens may actually have had limited histopathological work-up instead of truly lacking residual cancer. If there is reason to believe that

Surgical specimen orientation

To orient the surgical specimen sutures or staples are placed at the cut edge to mark two or more of the six surfaces. Using these markers, pathologists systematically ink the cut edges. Single-colour ink technique allows margins assessment but does not provide spatial orientation; therefore whole-cavity re-excision is sometimes necessary if a margin is positive. Alternatively, surgeons can perform ink-directed focal re-excision in which each one of the six surfaces is inked with different

Frozen section analysis (FSA)

FSA is the most widely used intraoperative pathology margin assessment technique. After the specimen is excised, it is oriented with sutures, margins are inked, and it is thinly sliced and inspected. Samples from any area of concern are cut, frozen with embedding medium, and processed in under 30 minutes. There is some level of technical difficulty when processing breast samples as adipose tissue is difficult to cut. The re-excision rate associated with FSA ranges from 3 to 10%, which is

Discussion

Minimizing the risk of LR is one of the primary aims of BCS. LR leads to additional procedures, patient distress, and has been associated with increased mortality. Features associated with LR are predominantly related to patient characteristics, tumour biology, and margin status. Of these, margin status is the only factor that can be controlled. Obtaining negative margins requires adequate preoperative imaging and implementing intraoperative margin assessment tools (Table 1).

Surgeons should

Conflict of interest statement

None declared.

Authorship statement

Guarantor of the integrity of the study: Fernando A. Angarita, Siham Zerhouni, Ashlie Nadler, Jaime Escallon.

Study concepts: Fernando A. Angarita, Siham Zerhouni, Ashlie Nadler, Jaime Escallon.

Study design: Fernando A. Angarita, Siham Zerhouni, Jaime Escallon.

Definition of intellectual content: Fernando A. Angarita, Siham Zerhouni, Ashlie Nadler, Jaime Escallon.

Literature research: Fernando A. Angarita, Siham Zerhouni, Ashlie Nadler, Jaime Escallon.

Data acquisition: Fernando A. Angarita, Siham

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