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Intraoperative Evaluation of Surgical Margins in Breast-Conserving Therapy
Importance of Margins in Breast-Conserving Surgery
Breast-conserving surgery (BCS) is the preferred treatment approach for most patients with early-stage breast cancer. The combination of complete resection of the breast cancer lesion with tumor-free margins followed by radiotherapy provides excellent local tumor control. There is a balance between the extent of lumpectomy performed to achieve clear surgical margins and the resultant cosmesis of the breast. Because pathologic margin status is an important prognostic factor for local failure after segmental resection of in situ or invasive breast carcinoma, pathologic examination of margin status plays a key role in BCS.
The breast cancer consensus guidelines for surgical management of margins for both invasive and in situ disease have standardized the recommendations for tumor resection margin width.
Invasive Cancer Margins
In 2014 a multidisciplinary consensus panel from the Society of Surgical Oncology and The Society for American Radiation Oncology reported the results of a meta-analysis evaluating invasive breast cancer margin width and ipsilateral breast tumor recurrence (IBTR). The panel recommended that the use of “no ink on tumor” should be the standard margin in patients with stages I and II invasive breast cancer undergoing BCS in the context of modern multidisciplinary therapy. Young patient age or aggressive tumor biology did not correlate with benefit from a wider surgical margin. Furthermore, wider margin widths were not associated with improved recurrence outcomes. Positive surgical margins and subsequent risk of recurrence could not be improved by favorable tumor biology, receipt of a radiation boost, or delivery of systemic therapy (chemotherapy or endocrine therapy). In cases with invasive cancer and ductal carcinoma in situ (DCIS) combined, the recommended margin is no tumor on ink. In the case of an invasive tumor present at an inked surgical margin, reexcision is recommended, as a positive margin is related to a twofold increase in cancer recurrence compared to a negative margin.
Ductal Carcinoma in Situ Margins
In 2016 a multidisciplinary consensus panel from the Society of Surgical Oncology and The Society for American Radiation Oncology reported the results of a meta-analysis evaluating DCIS margin width and IBTR. The panel recommended that a 2-mm margin should be the standard margin for a patient with DCIS undergoing BCS and subsequent whole-breast radiation. A margin of <2 mm is the most effective predictor of patients who may have residual disease and may benefit from a reexcision procedure. The panel concluded that a 2-mm margin minimizes the risk of IBTR compared with smaller negative margins, and conversely, a >2 mm margin did not significantly decrease IBTR. They also concluded that wider margins did not obviate the need for radiation. The panel also recommended that DCIS with microinvasion (<1 mm) should ideally be treated similarly to DCIS and have a margin resection width of 2 mm.
Lobular Carcinoma in Situ Margins
The presence of classic lobular carcinoma in situ (LCIS) at the resection margin was not recommended as an indication for reexcision, and the significance of pleomorphic LCIS at the margin was uncertain.
Margin Positivity Incidence and Dilemma
The present-day dilemma is that final tumor margin status is only appreciated microscopically, and negative margins cannot be reliably assessed intraoperatively. The inability to obtain clear surgical margins at the time of BCS for malignancy remains a significant clinical problem and therefore cases with positive or close margins on final pathology require margin reexcision at a second surgical procedure. Margin reexcision rates vary widely in the literature but generally range from 10% to 40%. This translates to a risk that approximately one-fourth of all patients who undergo BCS will require an additional re-excision surgery. Margin reexcision is associated with patient anxiety, increased surgical complications, a less desirable cosmetic outcome, a delay in adjuvant therapy, and increased costs to the health care system.
Intraoperative evaluation of margin status may permit immediate reexcision of involved margins, minimizing the need for secondary operative procedures. Traditional operative margin assessment techniques include frozen section, cytology, intraoperative ultrasound, and specimen radiography. Unfortunately, all methods used to evaluate margin status intraoperatively have some technical or practical limitations. Moreover, the technique of margin evaluation varies significantly between surgeons and institutions, and therefore, it is unclear which approach is most accurate and cost-effective. Any method used to evaluate margin status in the operating room must be relatively simple, rapid, reproducible, and inexpensive in order for it to be practical and cost-effective. This has prompted extensive and technological research in the field of intraoperative analysis of the margins to reduce the need for reexcision of involved margins. This chapter reviews data regarding the prognostic significance of margin status, describes the techniques currently used for intraoperative evaluation of margins and compares the relative benefits and limitations of each approach.
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