Evaluation of margin status in lumpectomy specimens and residual breast carcinoma

Residual disease leads to most local recurrences, especially in those patients treated with breast-conserving therapy (BCT). This study evaluates whether assessment of excisional biopsy margins accurately predicts the presence or absence of residual tumor in the lumpectomy bed. The margin status of 201 consecutive lumpectomy specimens of 178 infiltrating and 23 in situ breast carcinomas followed by reexcision were evaluated microscopically and classified as "positive" (tumor at the inked margins), "negative" (tumor more than 0.1 cm from the inked margins), "close" (tumor within 0.1 cm of the inked margins, but not transecting it), and "indeterminate" (biopsy not inked or fragmented). Tumor size and grade were also analyzed, as potential predictors for residual disease. Residual tumor was found in 41% of the patients: in 21% of the cases with negative margins, in 63% with positive margins, in 30% with close margins, and in 56% with indeterminate margins. In 37% of the positive and 70% of the close margin cases, no tumor was found in reexcised specimens. In 24% of the cases the residual disease was composed entirely of an in situ component of the same histologic type as the initial biopsy. No relationship was found between tumor size or grade and residual disease. For breast tumors, histologically negative and "close" biopsy margins do not guarantee complete excision. A number of factors seem to be responsible for the discrepancy between the margin status and the presence/absence of residual cancer in the lumpectomy bed.     

A comparison of ink-directed and traditional whole-cavity re-excision for breast lumpectomy specimens with positive margins

Background: Excising a breast tumor with negative margins minimizes local recurrence. With a positive margin, the standard re-excision consists of excising the whole cavity and all surrounding breast tissue. By marking the sides of the lumpectomy specimen with six different colored inks, the surgeon can limit the re-excision to the involved margin. We compared the local recurrence rate after these two re-excision methods.Methods: Records were reviewed of 527 women (546 breasts) treated with lumpectomy at two institutions. The log-rank test was used to compare the local recurrence–free survival.Results: Of 546 tumors, 245 (45%) had negative margins on the initial lumpectomy and were not re-excised. Fifty-five percent had a positive or close margin; 181 underwent whole-cavity re-excision, and 120 had ink-directed re-excision. The mean follow-up time was 3.4 years. There was no significant difference in local recurrence for the patients whose initial margin was negative (3.7%) compared with the 243 patients with initially positive margins who underwent a re-excision (3.3%). Eleven of 181 (6%) patients undergoing a whole-cavity re-excision developed a local recurrence, compared with none of 120 (0%) patients with an ink-directed re-excision (P = not significant). Tissue mass excised was significantly smaller in the ink-directed group (23 vs. 83 g, P < .05).Conclusions: Ink-directed re-excision of lumpectomy specimens with positive margins minimizes the amount of breast tissue removed without increasing the incidence of local recurrence and is therefore preferable to the standard whole-cavity method.     

Intra-operative Touch Preparation Cytology; Does It Have a Role in Re-excision Lumpectomy?

Objective Breast carcinoma is the most frequently diagnosed malignancy in women of North America. The combination of breast conservation surgery and radiotherapy has become a standard of treatment for the majority of breast cancers. It is critical to obtain clear margins to minimize local recurrence. However, avoiding multiple re-excisions for margin clearance helps optimize cosmetic results in patients undergoing breast conservation surgery. Intra-operative touch preparation cytology (IOTPC) may decrease the need for multiple re-excisions and thereby improve cosmesis. The literature suggests that IOTPC can be useful in evaluation of margins. Klimberg et al. evaluated the touch preparation technique prospectively in 428 patients undergoing breast biopsy for undiagnosed breast masses. Margin evaluation was correct in 100% of the lesions and was used to re-excise the margins when touch prep results were positive. They reported a diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 100% for the touch prep technique. To the best of our knowledge, there has been no published data on the role of IOTPC for evaluation of margins in re-excision cases. This report describes our experience with IOTPC for margin assessment for re-excision partial mastectomy at Beth Israel Medical Center (BIMC). The purpose of this study is to determine whether IOTPC is reliable for evaluating margins in patients undergoing re-excision for involved or close margins. Methods A prospective study of 30 patients, who have undergone re-excision partial mastectomy for involved or close margins after breast conservation surgery with the use of IOTPC for margin assessment at BIMC was performed. The re-excision lumpectomy specimens were oriented by the surgeon intra-operatively and were submitted fresh to pathology for cytologic assessment. The touch prep method consisted of touching the corresponding margin onto the glass slide. The principle of this technique is that if cancer cells are present they will stick to the slide, while fat cells will not. A slide was prepared for each re-excision specimen. Air-dried samples were stained immediately using the Diff-Quik method and examined under the microscope by a cytopathologist. Results Thirty patients underwent re-excision lumpectomy for involved or close margins with touch preparation cytology for assessment of 68 margins. Twenty-six patients had invasive ductal carcinoma and/or ductal carcinoma in situ, three patients had invasive lobular carcinoma and the remaining one patient had a combination of invasive lobular and ductal carcinoma. There was a correlation between touch prep cytology and final pathology in 56/68 margins, which accounts for 82.4% of the cases. Conclusion Intra-operative touch preparation cytology for assessment of margins in patients undergoing re-excision lumpectomy for involved or close margins has a sensitivity of 75%, specificity of 82.8%, positive predictive value of 21.4%, and negative predictive value of 98.2%. This high negative predictive value and a single false negative margin are quite significant. Therefore, based on our experience, IOTPC can be a useful tool for intra-operative assessment of margins for patients undergoing re-excision partial mastectomy. Poster presentation at the 28th Annual san Antonio Breast Cancer Symposium, December 8–11, 2005, San Antonio, Texas.     

Role of Specimen Radiography in Patients Treated With Skin-Sparing Mastectomy for Ductal Carcinoma In Situ of the Breast

Background: Specimen radiography is an important part of breast conservation surgery for ductal carcinoma in situ (DCIS). The objective of this study was to determine whether mastectomy specimen radiography could help in obtaining negative resection margins in patients with DCIS undergoing skin-sparing mastectomy (SSM) with immediate breast reconstruction (IBR).Methods: Of 95 patients treated at our institution with SSM and IBR for DCIS, 35 had specimen radiography. The mastectomy specimen was first examined grossly and then inked, serially sectioned, and sent for radiographic assessment. Tissue slices containing calcifications were identified for pathologic evaluation. Additional tissue was excised if tumor was found near the inked margins or if calcifications were found near the radiographic margins.Results: Of the 35 patients who had specimen radiography, the radiographic margins were free of calcifications in 30 patients (86%); of these patients, the margins on the final histologic examination were free of tumor in 27 and within 1 mm in 3. The other five patients (14%) had calcifications close to the radiographic margin; four underwent an intraoperative re-excision, but the margin for one of those four patients was still positive on final histologic examination. Margins were found to be negative by both mastectomy specimen radiography and histology in 77% of the patients. Of the 95 patients with DCIS, three patients (3%), none of whom had specimen radiography, developed local recurrences. One of these was successfully re-treated, one died as a result of synchronous distant metastases, and one was lost to follow-up. At a median follow-up time of 3.7 years, 93 patients (98%) were alive and free of disease.Conclusions: Intraoperative radiography of mastectomy specimens may be useful for assessing margin status and for identifying the location of microcalcifications within tissue slices.     

Review of third and fourth re-excision for narrow or positive margins of invasive and intraductal carcinoma

The trend in breast surgery has shifted toward breast conservation. We reviewed our third and fourth breast re-excision cases, with an analysis of various factors used in making this decision. A retrospective analysis identified 585 patients who underwent re-excision surgery for positive or close margins of invasive carcinoma or ductal carcinoma in situ (DCIS). Of these patients 75 (13%) and 17 (3%) underwent third and fourth re-excisions, respectively. The indication for a third re-excision was the presence of positive and/or close (< or = 1 mm) margins for invasive carcinoma or DCIS in 72/75 patients. A third re-excision was done 31 days (range 8-123 days) after the second re-excision. Re-excision of margins was done in 45 (60%) patients, whereas 30 (40%) patients underwent mastectomy. Residual tumor mandated a fourth re-excision in 17 patients, which was done 45 days (range 14-87 days) after the third surgery. Re-excision of margins was done in 6 patients, whereas 11 patients underwent mastectomy. Involved or close margins with DCIS were the most common indication for re-excision, accounting for 61/75 (82%) of third and 16/17 (94%) of fourth re-excisions. Histopathology revealed that 28/75 (37%) of third and 7/17 (41%) of fourth re-excision patients had no residual tumor. In conclusion, the majority of re-excisions was done for margins < 1 mm. Lower rates of re-excision were noted in well-differentiated invasive carcinomas. A close or involved DCIS margin was more likely to lead to a third and even a fourth re-excision. The absence of residual tumors in 40% of patients undergoing third and fourth re-excisions calls for a review of margin guidelines for breast re-excision.     

Defining negative margins in DCIS patients treated with breast conservation therapy: The University of Chicago experience

Management of ductal carcinoma in situ (DCIS) has been evolving and the majority of women are now being treated with breast-conserving surgery and radiation therapy (i.e. breast conservation therapy [BCT]). Controversies still exist regarding the histologic features and margin status that are associated with local recurrence. The goal of this study was to review our institution's experience in patients diagnosed with DCIS and treated with BCT to determine pathologic features that can predict local recurrence, with particular emphasis on the final surgical margin status. We analyzed 103 consecutive patients with DCIS who were treated with BCT between 1986 and 2000. The slides were reviewed to determine the final margin status, type of DCIS, size of DCIS, nuclear grade, presence of necrosis and calcification, and volume of excised specimen. Margins were considered positive when DCIS touched or was transected at an inked margin. Negative margins were further categorized as close (less than 1 mm), 1--5 mm, and more than 5 mm. The size of the DCIS was determined based on either the maximal dimension on a slide or from the number of consecutive slides containing DCIS. Morphology and immunohistochemical profiles of the recurrent DCIS cases were compared with original DCIS. All patients were treated uniformly with external beam radiation therapy to the entire breast (median dose 46 Gy) with a boost to the tumor bed (median dose 14 Gy). The median follow-up was 63 months (range 7--191 months). The actuarial 5-year local control rate was 89%. The median time to local recurrence was 55 months. There were 13 local recurrences, of which 9 recurred as pure DCIS and 4 as invasive ductal carcinomas. Univariate analysis showed a significant association with local recurrence for positive margin (p=0.008), high nuclear grade (p=0.02), and young age at diagnosis (p=0.03). If margins were negative, the 5-year local control was 93%, as compared to 69% if margins were positive. A multivariate analysis showed that early age at diagnosis, positive margin status, and high nuclear grade were independently associated with local recurrence. The morphology and immunohistochemical stains of all nine recurrent DCIS were similar to those of the original DCIS. Breast conservation can be achieved with excellent local control by obtaining microscopically negative margins as strictly defined by DCIS not touching the inked surgical margins, and postoperative radiation that includes boost therapy to the tumor bed.     

The Role of Frozen Section Analysis of Margins during Breast Conversation Surgery

abstract Purpose. The role of frozen section analysis during breast conversation surgery is undefined. Assessment of margins using eprmanent section evaluation is the standard method of ensuring complete tumor excision. If the margin is positive, however, surgical re-excision is necessary to reduce the likelihood of subsequent local recurrence. Therefore, biopsy of the surgical cavity with immediate pathological evaluation during lumpectomy was performed to evaluate the effect on local recurrence, the number of re-excisions, and cosmesis. Patients and Methods. One hundred sixty patients underwent attempted lumpectomy with frozen section margin determination. One hundred forty patients were available for long-term follow-up (mean = 57 months, median = 46 months). All patients underwent attempted breast conservation surgery, which consisted of tumorectomy with excision of a greater than 1-cm rim of grossly normal tissue. Tumor margins were obtained by intraoperative biopsy with frozen section analysis of the lumpectomy cavity walls. Results. In 21 patients (15%), frozen section analyses (FSA) revealed positive margins, resulting in immediate re-excision. In seven of these patients (%), margins were persistetly positive, and these patients therefore underwent mastectomy. Fourteen patients were successfully re-excised to a negative margin. The sensitivity and specificity of FSA were 91% and 100%, respectively. Five percent of patients definitively managed by lumpectomy with FSA of margins recurred locally. The mean cosmesis score after radiotherapy was 7.0 out of a possible 10, correlating with a good to excellent result. Discussion. The accuracy of FSA, low recurrence rate, avoidance of reoperation, and good cosmesis indicate that intraoperative frozen section analysis should be adopted as a safe and effective method of margin analysis during breast conservation surgery.     

Role for Intraoperative Margin Assessment in Patients Undergoing Breast-Conserving Surgery

Background Positive/close margins are associated with higher in-breast failure rates after breast-conserving surgery (BCS). We investigated whether intraoperative margin assessment aids in obtaining negative margins, and to evaluate the local control thus achieved. Methods Between 1994 and 1996, 264 patients underwent BCS for stages 0–III breast cancer [invasive, n = 200; ductal carcinoma in situ (DCIS), n = 64]. Intraoperative margin assessment included gross tissue inspection, specimen radiography, with or without frozen section. Results Ninety-two patients (46%) with invasive cancer and 24 (38%) with DCIS had positive/close margins on the permanent section analysis of their initial surgical specimens. Fifty-eight patients (29%) with invasive cancer and six (9%) with DCIS had initial positive/close margins, and were rendered margin-negative by intraoperative analysis and immediate re-excision. Final margins on permanent pathology were positive/close in 52 patients (20%): 34 patients (17%) with invasive cancer and 18 patients (28%) with DCIS. By multivariate analysis, excisional biopsy for diagnosis, larger tumor size, and multifocality were associated with final positive/close margins. Of these 52 patients, 23 underwent a second operation to achieve widely negative margins (13 completion mastectomies, 10 re-excisions). The 5-year ipsilateral breast recurrence-free survival rates after BCS and radiation were 99% for invasive cancer (n = 167) and 100% for DCIS (n = 27). Conclusions Intraoperative assessment of margins assisted in identifying positive/close margins and allowed over a quarter of the patients to be rendered margin-negative with intraoperative re-excision at their original operation. This approach resulted in excellent local control in patients treated with BCS and radiation.     

Breast Conservation Therapy in Patients with Early-Stage Breast Cancer Who Have Undergone a Second Re-Excision of the Primary Tumor Bed: A Report of Four Cases

Abstract: For the women with early-stage breast cancer who are candidates for breast conservation therapy, re-excision of the primary tumor bed has commonly been used in patients for several indications. These indications include positive margin or uncertain margin status of the primary excision or residual microcalcifications on postbiopsy mammogram. If the pathology from the re-excision does not confirm negative margin status, mastectomy is generally recommended. This article examines patients who have undergone a second re-excision (i.e., a lumpectomy followed by two re-excisions) who have been treated with breast conservation therapy rather than a mastectomy.
From September 1977 to November 1995, 1,562 patients underwent breast conserving therapy at this institution. Seven hundred forty of these patients underwent a re-excisional biopsy because of positive or uncertain margin status or residual microcalcifications after the first excision. Four patients (0.5%) underwent a second re-excision because of positive or uncertain margin status or residual microcalcifications on mammogram after the first re-excision. The final margin status after the second re-excision of all four patients was negative. The radiation dose was 4,600–5,000 cGy to the whole breast followed by a conedown to bring the total dose to 6,400–6,800 cGy to the primary tumor bed.
Follow-up in the four patients was 13 years, 4 years, 14 months, and 8 months respectively. All four patients are clinically without disease and have not had a locoregional recurrence. Cosmesis was excellent in all four patients. One patient had an adriamycin-induced recall reaction causing a cellulitis, which resolved with antibiotics. There were no other complications.
Highly selected patients may undergo breast-conserving therapy after a second re-excision. Good outcome and cosmesis can be achieved for this small subset of patients with avoidance of a mastectomy.     

Low re-excision rate for positive margins in patients treated with ultrasound-guided breast-conserving surgery

BackgroundRe-excision is a necessary procedure in obtaining clean margins for breast-conserving surgery (BCS)-treated patients. Re-excision rates vary widely among different breast cancer management procedures. The aim of this study was to evaluate the efficacy of ultrasound (US)-guided BCS to decrease the re-excision rate in patients with US-detectable breast cancer, as well as the relationship between positive margins and ultrasonographic characteristics of tumor.MethodsBetween 2008 and 2009, we identified consecutive patients who underwent initial US-guided BCS for breast in situ or invasive carcinoma, which was preoperatively detected using US examination and on the basis of image-guided biopsy findings. The margins achieved after BCS were separately assessed by performing frozen section analysis of shaved margins. The negative margin and positive margin groups were compared for clinicopathological features and ultrasonographic findings.ResultsOf 381 patients undergoing US-guided BCS, 126 (33.1%) had palpable tumors and 255 (66.9%) had nonpalpable tumors. Positive margins were noted in 35 patients (9.2%). These patients underwent re-excision and were margin-free; no further surgery was required for these patients. There were no significant intergroup differences in clinicopathological features and ultrasonographic findings.ConclusionBreast US is an effective modality for intraoperative tumor localization and can thus help obtain clean margins and reduce the re-excision rate in cases in which breast-conserving therapy has been performed. Furthermore, frozen section analysis of cavity shaved margins is a feasible method for minimizing the need for further surgery.     

Lumpectomy margins, reexcision, and local recurrence of breast cancer

BACKGROUND: The diagnosis of breast cancer is often made by excisional biopsy without margin assessment for mammographic findings or palpable masses. Many patients treated with breast conservation undergo reexcision to obtain clear margins although the relationship between clear margins and local recurrence remains controversial. METHODS: Patients undergoing breast conservation and adjuvant radiation therapy with complete follow-up over 5 years were studied. Factors associated with obtaining clear histopathologic margins and undergoing reexcision to obtain clear margins were studied in relation to the risk of local recurrence. RESULTS: Clear biopsy margins were associated with diagnosis by fine-needle aspiration cytology (fine-needle aspiration 42%, spot localization 11%, excisional biopsy 10%; P <0.001). Reexcision was significantly related to diagnostic method (spot localization 63%, excisional biopsy 36%, fine-needle aspiration 10%; P <0.001), first margin status (clear 0%, close 11%, positive 46%, unknown 48%; P <0.001), patient age (54 years for reexcised patients and 58 for non-reexcised patients; P <0.001), and tumor size (mean tumor size 1. 4 cm for reexcised patients and 1.7 cm for non-reexcised patients; P = 0.003). Patients undergoing reexcision were significantly more likely to be diagnosed by spot localization, have nonnegative excisional biopsy margins, be younger, and have smaller tumors than patients not undergoing reexcision. Local recurrence was not significantly related to margin status (8% with clear margins, 7% with positive margins, 19% with close margins, and 11% with unknown margins) or reexcision (10% local recurrence rate for patients with negative final margins after reexcision and 12% with positive, close or unknown first margin without reexcision). Estrogen receptor status was the only variable related to local recurrence in Cox proportional hazards model (P = 0.009). Estrogen receptor negative patients with nonnegative margins experienced a 20% rate of local recurrence compared with 10% for estrogen receptor negative patients with negative margins and 7% for estrogen receptor positive patients regardless of margin status (P = 0.021). CONCLUSIONS: Clear excision margins are facilitated by preoperative diagnosis by fine-needle cytology. For patients with nonnegative margins, reexcision was more commonly performed in young patients with small tumors diagnosed by spot localization biopsy. The relationship of local recurrence to margins and reexcision was not statistically significant. Estrogen receptor negative tumors with nonnegative margins had a significantly higher rate of local recurrence than estrogen receptor negative tumors with clear margins and estrogen receptor positive tumors regardless of margin status.     

Significance of Linear Extent of Breast Carcinoma at Surgical Margin

Background: Our objective was to correlate the extent of margin positivity and the findings on re-excision specimens of infiltrating mammary carcinoma.Methods: We selected 50 consecutive cases of infiltrating mammary carcinoma, including both infiltrating ductal carcinoma and infiltrating lobular carcinoma, with positive margins followed by re-excision. Margin positivity was defined as the presence of cancer at the inked margin. The extent of margin positivity was assessed by measuring the linear involvement of the inked margin by the carcinoma.Results: Twenty-one of 50 cases (42%) showed positive findings on re-excision, including either infiltrating carcinoma or carcinoma in situ or both. Nine of 14 cases (64%) with ductal carcinoma in situ or infiltrating ductal carcinoma on re-excision and 4 of 7 cases (57%) with lobular carcinoma in situ or infiltrating lobular carcinoma on re-excision had initial linear margins >1.0 cm, whereas 28 of 29 cases (96%) with negative findings on re-excision had initial linear margins &<1.0 cm.Conclusions: Linear measurement of the inked margin involved by infiltrating mammary carcinoma can be used as a predictor of findings on re-excisions.     

Separate cavity margin sampling at the time of initial breast lumpectomy significantly reduces the need for reexcisions

In breast conservation therapy, the margin status of the specimen predicts local recurrence and determines the need for reexcision. Many surgeons now take, at the time of lumpectomy, multiple separate "cavity margins" (CM) (the entire wall of the residual cavity) as final margins that supersede the oriented lumpectomy margins (LMs). We studied the efficacy of this method in 126 patients (23 with ductal carcinoma in situ [DCIS] only and 103 with invasive carcinoma with or without DCIS) who had an oriented lumpectomy specimen and also had four to six additional CMs. The tumors were evaluated for the following: size, grade, LM status (distance of tumor from margin and, if involved, extent of involvement), vascular invasion, lymph node status, and presence or absence of extensive intraductal component. The additional CM specimens were evaluated for residual carcinoma (if any) and its distance from the inked true margins, and the results were correlated with the corresponding LMs. Only approximately 50% of patients (52 of 103) with histologically positive LMs (defined as carcinoma within 2 mm of the inked surface) had residual carcinoma in their CMs. Additional CM sampling rendered the overall final margin status histologically negative in 61 of 103 (59%) cases with histologically positive LMs, therefore significantly reducing the need for reexcision. Younger patient age, higher number of positive LMs, high tumor grade, and the presence of extensive intraductal component were predictive of residual carcinoma in CM specimens, whereas the distance of carcinoma from the inked surface and the extent of tumor involvement of histologically positive LMs were not. Because CM specimens taken from patients with histologically positive LMs usually lack tumor, we suspect that many positive LMs are likely false positives. Possible factors accounting for false-positive LMs include seepage of ink into crevices of the specimen promoted by excessive inking, tumor friability promoting displacement of tumor into ink, manipulation of specimens for radiographs, and retraction artifact.     

Understanding the mechanisms creating false positive lumpectomy margins

OBJECTIVE: All breast surgeons deal with the frustration of initial pathologic close or positive margins that have no residual cancer upon re-excision. To understand the mechanisms that create false positive margins, specimen handling was standardized in a single surgeon's practice and margin issues were tracked. METHODS: Prospectively over a 3.5-year period, needle-localized lumpectomies for the management of early-stage breast cancer were standardized in all aspects of specimen handling, including surgeon inking and specimen compression for specimen radiography for quality assurance. The current study reviews 220 such cases where the original lumpectomy included a small piece of overlying skin from over the target lesion. All specimen radiography was performed with compression at the skin to deep level to bias the "pancaking" effect of pushing tumor to specimen surface to the deep margin. RESULTS: Of the 220 therapeutic lumpectomies performed for clinical stage 0-2 breast cancer in this fashion, 175 (79.5%) had negative margins by a distance of 10 mm or more. Margins less than 10 mm were classified as close and were present in 20 (9.1%) of cases. These were heavily biased toward margins closer than 2 mm. Positive initial margins accounted for 25 (11.4%) of cases. Of the 45 close or positive margin cases, 12 involved the deep margin only, and on re-excision none was found to have residual tumor. When other single margins were involved, re-excision found tumor in 5 of 14 cases (35.7%). When multiple margins were close or positive, 9 of 19 cases (47.3%) were found to have residual tumor at re-excision. CONCLUSIONS: Specimen compression increases the incidence of false margin positivity. The best predictors of true margin positivity are multiple close or positive margins or margin positivity in a direction not associated with specimen ex vivo compression.     

Results of conservative surgery and radiation therapy for breast cancer

For stage I or II breast cancer, conservative surgery and radiation therapy are as effective as modified radical or radical mastectomy. In most cases, cosmetic considerations and the availability of therapy are the primary concerns. The extent of a surgical resection less than a mastectomy has not been a subject of a randomized trial and is controversial. It appears that removal of a quadrant of the breast for small lesions is safe but excessive. Using histologic findings in the biopsy as a guide, it may be possible to limit the breast resection to gross tumor removal for most patients while using wider resections for patients with an extensive intraductal component or for invasive lobular carcinoma. It also appears that excluding patients from breast conservation on the basis of positive margins on the first attempt at tumor excision may be unnecessarily restrictive. Although patients with an extensive intraductal component or invasive lobular carcinoma should have negative margins, it appears that a patient with predominantly invasive ductal carcinoma can be treated without re-excision if all gross tumor has been resected and there is no reason to suspect extensive microscopic disease. Patients with indeterminate margins should have a re-excision. Axillary dissection provides prognostic information and prevents progression of the disease within the axilla. Axillary dissections limited to level I will accurately identify a substantial number of patients who have pathologically positive but clinically negative nodes. When combined with radiation therapy to the axilla, a level I dissection results in a limited number of patients with progressive axillary disease. Patients with pathologically positive axillas and patients at particularly high risk for systemic disease because of the extent of axillary node involvement can be identified by dissections of levels I and II. Radiation therapy can be avoided safely in patients who have pathologically negative axillas by level I and II dissection. There appears to be no advantage to routine dissection of level III lymph nodes. Lymphedema of the arm and breast increases with more extensive dissections and with radiation therapy.     

Clinical Series of Oncoplastic Mastopexy to Optimize Cosmesis of Large-Volume Resections for Breast Conservation

Background

Oncoplastic mastopexy has been popularized as a method to hide the cosmetic effects of central or large-volume resections associated with breast conservation surgery for breast cancer.

Materials and Methods

This review was undertaken to study the uses and limitations of these techniques in providing adequate breast conservation lumpectomy for breast cancer of any stage in a single surgeon’s practice. A review of breast cancer cases March 2004 through December 2009 were analyzed for the use of oncoplastic reconstruction in breast conservation surgery.

Results

A total of 167 patients had lumpectomies during this period associated with oncoplastic mastopexy reconstruction. The average age was 55.6 years with a range of 33–85 years. Stage 0 breast cancer accounted for 33 cases (19.8%), and 134 cases were invasive cancers stages 1–3 (stage 1, 34.1%; stage 2, 30.6%; and stage 3, 15.6%). The most common oncoplastic techniques used were, in order of frequency: batwing mastopexy, parallelogram mastopexy, and Modified Wise pattern mastopexy. Positive or close margins (≤2 mm) were present in 37 of 167 cases (22%). Positive margins were most associated with higher stage, positive nodes, positive lymphovascular invasion (LVI), use of neoadjuvant chemotherapy, and larger initial T stage, positive estrogen receptor (ER), and younger age. Of these higher stage, node positive, and use of neoadjuvant chemotherapy were statistically significant in this small series (P values = 0.034, 0.016, and 0.022, respectively). Ki-67 and HER2 status were not associated with positive margins. Positive margins were manageable by local re-excision of a solitary face of the prior resection wall in more than 2/3 of cases to achieve negative pathologic margins. Only 11 of 167 required mastectomy because of failure to achieve adequate margins for oncologic control.

Conclusions

Oncoplastic mastopexy allows the surgeon to address large tumors or tumors in cosmetically difficult sites adequately for breast conservation. Careful margin marking and re-excision of close or positive margins is still often feasible to achieve adequate negative margin with acceptable cosmesis in spite of the large initial volumes of resection.     

Frozen Section Analysis for Intraoperative Margin Assessment During Breast-Conserving Surgery Results in Low Rates of Re-excision and Local Recurrence

Background Negative surgical margins minimize the risk of local recurrence after breast-conserving surgery. Intraoperative frozen section analysis (FSA) is one method for margin evaluation. We retrospectively analyzed records of patients who received breast-conserving therapy with intraoperative FSA of the lumpectomy cavity to assess re-excision rates and local control. Methods Records were retrospectively reviewed for individuals who underwent breast-conserving surgery for ductal carcinoma in situ (DCIS) or invasive carcinoma between 1993 and 2003. Inclusion criteria were a minimum of 2 years follow-up and intact tumor at the time of operation. The major outcome measure was local recurrence. The Kaplan-Meier test was used to evaluate local recurrence rates between groups. Results 290 subjects with an average age of 57.2 years (range 27–89) underwent 292 lumpectomies with FSA. 11.3% had DCIS, 73.3% had infiltrating ductal, 5.8% had infiltrating lobular, and 9.6% exhibited other forms of invasive carcinoma. 70 subjects underwent additional resection at the time of breast surgery, 16 underwent subsequent re-excision, and 17 underwent subsequent mastectomy. At a median follow-up of 53.4 months (range 5.8–137.8), there were six local recurrences (2.74%) in patients who had breast-conserving procedures and two local recurrences in patients who underwent mastectomy. There were no statistically significant associations among local recurrence rate, tumor size, nodal status, or overall stage. Local recurrences were higher in patients with DCIS compared with invasive carcinoma, and tumors >2cm. Conclusions Intraoperative FSA allows resection of suspicious or positive margins at the time of lumpectomy and results in low rates of local recurrence and re-excision. The low local recurrence rate reported here is comparable to those reported with other margin assessment techniques.     

Predictive factors for residual disease in re-excision specimens after breast-conserving surgery

Local recurrence is an issue of concern after breast-conserving therapy and removing the primary tumor with negative surgical margins is the most important determinant of local recurrence. However, some patients with positive margins after initial surgery will have no residual tumor in the re-excision specimen. To avoid unnecessary re-excisions, factors predicting residual disease in re-excision material should be determined. This study aimed to determine the predictive factors for residual disease in the re-excision material in a homogeneous group of patients with positive margins and only invasive ductal carcinoma. Breast cancer patients treated between 2005 and 2008 with breast-conserving surgery and subsequent re-excisions due to positive surgical margins after initial surgery were included in the study. Patients were divided into two groups as those with and without residual disease in the re-excision material. One hundred and four breast cancer patients were included in the study. Forty-seven patients (45.2%) had residual tumor in re-excision specimen. Patient characteristics such as age (p = 0.42) and physical findings (p = 1.0) and specimen volume (p = 0.24), tumor grade (p = 0.33), estrogen (p = 1.0), and progesterone (p = 0.37) receptor status, axillary lymph node metastases (p = 0.16), extensive intraductal component (p = 0.8), and lymphovascular invasion (p = 0.064) were found as insignificant factors for predicting residual tumor. Large tumor size (>3 cm) (p = 0.026), human epidermal growth factor receptor2 (HER2) positivity (p = 0.013), and tumor to specimen volume ratio of >70% (p = 0.002) significantly increased the probability of finding residual disease after re-excision. In multivariate analysis, HER2 positivity (p = 0.046) and tumor to specimen volume ratio of >70% (p = 0.006) independently predicted the presence of residual disease. As a result, in patients with HER2 positive tumors larger than 3 cm, larger volume of breast tissue around the tumor should be removed to decrease the number of re-excisions due to positive surgical margins.     

Role of re-excision for positive and close resection margins in patients treated with breast-conserving surgery

PurposeTo evaluate the incidence of residual disease after additional surgery for positive/close margins and the impact on the rate of local and distant recurrence.MethodsA retrospective analysis on 1339 patients treated for breast cancer with breast conserving-surgery and radiotherapy at a single Institution between 2000 and 2009 was performed.ResultsDuring primary surgery 526 patients (39.3%) underwent intraoperative re-excision. At the final pathological report, the margins were positive in 132 patients (9.9%) and close in 85 (6.3%). To obtain clear margins, 142 of these women underwent a second surgery; 35 patients with positive margins (27%) and 40 with close margins (47%) did not receive additional surgery because of different reasons (patients refusal, old age, comorbidity or for focal margin involvement). At second surgery, residual disease was found in 62.9% of patients with positive margins and in 55.5% of those with close margins. At a median follow-up time of 4 years, local recurrence (LR) rate was 2.9% for patients with clear margins, 5.2% (p = 0.67) for patients with unresected close margins and 11.7% (p = 0.003) for those with unresected positive margins. The HER-2 and the basal-like subtypes had the higher rate of LR and the luminal A the lowest.ConclusionsA significantly higher LR rate was found only among patients with positive margins not receiving additional surgery, but not in those with unresected close margins. Positive margins are a strong predictor for LR and need re-excision that can be avoided for close margins.     

eRFA: Excision Followed by RFA—a New Technique to Improve Local Control in Breast Cancer

Introduction Excision followed by RFA (eRFA) may allow improved cosmesis while ensuring negative margins in patients with breast cancer. This technique utilizes heat to create an additional tumor-free zone around the lumpectomy cavity. We hypothesized that eRFA will decrease the need for re-excision of inadequate margins.Methods Between July 2002 and January 2005, we conducted a multiphase trial of RFA of prophylactic mastectomy specimens and of women desiring lumpectomy. In both models, a lumpectomy was performed, the RFA probe was deployed 1 cm circumferentially into the walls of the lumpectomy cavity and maintained at 100°C for 15 min. Whole mount slides were used to measure the zone of ablation for ex vivo specimens. Hematoxylin and eosin staining of in vivo lumpectomy margins <3 mm was considered inadequate.Results Nineteen prophylactic mastectomy ablations revealed a consistent perimeter of ablation. Forty-one patients (mean age 63 ± 14 years) had an average tumor size of 1.6 ± 1.5 cm underwent in vivo eRFA, and 25% had inadequate margins: one focally positive, one <2 mm, eight <1 mm and one grossly positive. Only the grossly positive margin was re-excised. Overall complication rate of in vivo ablations was 7.5%. Twenty-four of 41 patients did not have post-eRFA XRT. No in-site local recurrences have occurred during a median follow-up of 24 months (12–45 months). Two patients have occurred elsewhere.Conclusions The ex vivo ablation model reliably created a 5–10 mm perimeter of ablation. In vivo, this zone reduced the need for re-excision for inadequate margins by 91% (10/11). Short-term follow-up suggests that eRFA could reduce re-excision surgery and local recurrence.