Location and extent of positive resection margins and ductal carcinoma in situ in lumpectomy specimens of ductal breast carcinoma examined with a microscopic three-dimensional view

The location of positive margins in lumpectomy specimens for ductal carcinoma could be predicted due to the common pattern of the geographic relationship between the intraductal and invasive carcinomas. To test this hypothesis, 62 lumpectomy specimens for ductal carcinoma of the breast were submitted for this study. The specimens were microscopically examined by serially sectioning them into giant sections in a plane parallel to the chest wall (frontal plane). The margins were identified as proximal (closest to the nipple), distal (opposite to proximal), and peripheral (nonproximal or distal). We found that the location of positive or close margins was proximal in 6 cases, peripheral in 13 cases, and none were found to be distal. Ductal carcinoma in situ (DCIS) was found to be located in the area adjacent to the invasive carcinoma. The invasive carcinoma was located at the periphery of the intraductal carcinoma. All six specimens with invasive carcinoma without DCIS had free margins. Nine of 16 specimens (56%) with extensive intraductal carcinoma (EIC) component and 7 of 40 (18%) with DCIS but negative EIC contained positive or close margins involved by DCIS. One case with multifocal invasive carcinoma measuring 3.5 cm in diameter and with DCIS but EIC negative had margins involved by both DCIS and invasive carcinoma. In conclusion, in ductal carcinoma, invasive carcinoma arose at the peripheral areas of the DCIS. DCIS tends to spread toward the nipple and the peripheral margins of the resected specimens. Incomplete excision of the ductal carcinoma and the wide positive margins are most likely caused by the failure to estimate the extent and location of DCIS.     

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.     

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.     

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.     

Management of Positive Sub‐areolar/Nipple Duct Margins in Nipple‐Sparing Mastectomies

We evaluated management of positive sub‐areolar/nipple duct margins in nipple‐sparing mastectomies (NSM) at our institution. Retrospective chart review of all NSM from January 2007 to April 2012 was performed and patient, tumor, and treatment information was collected. Sub‐areolar/nipple duct margins included ductal tissue from within the nipple. Of 438 NSM, 22 (5%) had positive sub‐areolar/nipple duct margins; 21 of 220 cancer‐bearing breasts (10%) and 1 of 218 prophylactic mastectomies (0.5%). Positive margins included four with invasive lobular carcinoma and 18 with ductal carcinoma in situ (DCIS). Management included removal of eight nipples and nine nipple areola complexes (NAC). Four of 17 nipple/NAC specimens had evidence of residual DCIS and none had residual invasive cancer. The majority of nipple/NAC specimens excised for a positive margin had no residual malignancy. Future studies are needed to determine the extent of NAC tissue removal required for positive margins.     

Imaging of lumpectomy surface with large field-of-view confocal laser scanning microscope for intraoperative margin assessment - POLARHIS study

IntroductionBreast-conserving surgery (BCS) in case of breast cancer and/or in-situ-carcinoma lesions (DCIS) intends to completely remove breast cancer while saving healthy tissue as much as possible to achieve better aesthetic and psychological outcomes for the patient. Such modality should result in postoperative tumor-free margins of the surgical resection in order to carry on with the next therapeutical steps of the patient care. However, 10–40% of patients undergo more than one procedure to achieve acceptable cancer-negative margins. A 2nd operation or further operation (re-operation) has physical, psychological, and economic consequences. It also delays the administration of adjuvant therapy, and has been associated with an elevated risk of local and distant disease relapse. In addition, a high re-operation rate can have significant economic effects - both for the service provider and for the payer. A more efficient intraoperative assessment of the margin may address these issues. Recently, a large field-of-view confocal laser scanning microscope designed to allow real-time intraoperative margin assessment has arrived on the market - the Histolog Scanner. In this paper, we present the first evaluation of lumpectomy margins assessment with this new device.Materials and methods40 consecutive patients undergoing BCS with invasive and/or DCIS were included. The whole surface of the surgical specimens was imaged right after the operation using the Histolog Scanner (HLS). The assessment of all the specimen margins was performed intraoperatively according to the standard-of-care of the center which consists of combined ultrasound (IOUS) and/or conventional specimen radiography (CSR), and gross surgical inspection. Margin assessment on HLS images was blindly performed after the surgery by 5 surgeons and one pathologist. The capabilities to correctly determine margin status in HLS images was compared to the final histopathological assessment. Furthermore, the potential reduction of positive-margin and re-operation rates by utilization of the HLS were extrapolated.ResultsThe study population included 7/40 patients with DCIS (17.5%), 17/40 patients with DCIS and invasive ductal cancer (IDC NST) (42.5%), 10/40 patients with IDC NST (25%), 4/40 with invasive lobular cancer (ILC) (10%), and 1/40 patients with a mix of IDC NST, DCIS, and ILC. Clinical routine resulted in 13 patients with positive margins identified by final histopathological assessment, resulting in 12 re-operations (30% re-operation rate). Amongst these 12 patients, 10 had DCIS components involved in their margin, confirming the importance of improving the detection accuracy of this specific lesion. Surgeons, who were given a short familiarization on HLS images, and a pathologist were able to detect positive margins in 4/12 and 7/12 patients (33% and 58%), respectively, that were missed by the intraoperative standard of care. In addition, a retrospective analysis of the HLS images revealed that cancer lesions can be identified in 9/12 (75%) patients with positive margins.ConclusionThe present study presents that breast cancer can be detected by surgeons and pathologists in HLS images of lumpectomy margins leading to a potential reduction of 30% and 75% of the re-operations. The Histolog Scanner is easily inserted into the clinical workflow and has the potential to improve the intraoperative standard-of-care for the assessment of breast conserving treatments. In addition, it has the potential to increase oncological safety and cosmetics by avoiding subsequent resections and can also have a significant positive economic effect for service providers and cost bearers. The data presented in this study will have to be further confirmed in a prospective phase–III–trial.     

Does the volume of ductal carcinoma in situ impact the positive margin rate in patients undergoing breast conservation for invasive breast cancer?

Background

We sought to investigate whether the volume of ductal carcinoma in situ (DCIS) impacts margin status in patients undergoing lumpectomy for invasive breast cancer.

Methods

We identified 358 patients with stages I–III invasive breast cancer and associated DCIS who were treated with breast-conserving therapy from 1999 to 2009. Data included patient and tumor characteristics, percentage of DCIS (<25%, 26%–50%, or >50%), and pathologic outcomes. Data were compared using chi-square and Fisher exact tests. A two-tailed P value of <0.05 was considered significant.

Results

The 358 patients had a mean age of 58 ± 13 y; 260 (72%) patients were >50 y. The volume of DCIS in lumpectomy specimens was <25% in 296 (83%) patients, 26%–50% in 29 (8%) patients, and >50% in 33 (9%) patients. Tumors with decreasing DCIS volume were more likely to be estrogen receptor positive (239 [82%] with <25% DCIS, 21 [72%] with 26%–50% DCIS, 22 [67%] with >50% DCIS; P = 0.026). DCIS volume was not significantly associated with patient age, tumor size, grade, and stage, nodal status, progesterone receptor status, or Her2 status (P > 0.05). Overall, 137 (38%) patients had one or more positive margins, including 97 of 296 (33%) with <25% DCIS volume, 17 of 29 (59%) with 26%–50% DCIS volume, and 23 of 33 (70%) with >50% DCIS volume (P < 0.0001).

Conclusions

The volume of DCIS associated with an invasive breast cancer in the final lumpectomy specimen is a strong predictor of positive surgical margins. Future analyses will focus on the ability of core pathology to provide this information for intraoperative surgical decision making.     

Relationship between initial margin status for invasive breast cancer and residual carcinoma after re-excision

Little data exists addressing the relationship between initial margin status in a specimen from an excisional biopsy and the presence of residual carcinoma in a subsequent specimen from lumpectomy or mastectomy. We sought to determine the relationship between initial margin status and the presence of residual invasive cancer, and to identify any relationship to other variables. This study was a retrospective review of pathology reports of 582 early-stage invasive duct carcinomas with open excisional biopsies. The initial specimen was classified into one of six margin categories: multiply focally positive (n = 174), focally positive (n = 132), margins < 1 mm (n = 98), margins 1 to 2 mm (n = 20), margins > 2 mm (n = 46), and margins undetermined (n = 90). All patients had a subsequent definitive second procedure. Pathology reports from the second procedure revealed the presence of residual invasive cancer by initial margin status as follows: in 30 per cent of the initial procedures with multiply focally positive margins, in 22 per cent with focally positive margins, in 8 per cent, 15 per cent, and 4 per cent with margins of < 1 mm, 1 to 2 mm, and > 2 mm, respectively, and in 28 per cent with undetermined margins. Women with palpable tumors, larger tumor size, and positive axillary nodes were more likely to have multiply focal and focally positive margins. Multiply focally positive and focally positive margins had similar residual invasive carcinoma rates and should be re-excised. All clear margins were equivalent; thus, re-excision was not necessary.     

Cytologic evaluation of lumpectomy margins in patients with ductal carcinoma in situ: Clinical outcome

Backround: Breast conservation therapy is controversial for ductal carcinoma in situ (DCIS) due to recently reported high recurrence rates. We believe that cytologic evaluation of lumpectomy margins improves efficiency and leads to a lower recurrence rate following lumpectomy for DCIS. Methods: A prospectively accrued database of 1255 breast cancer patients at the H. Lee Moffitt Cancer Center and Research Institute was found to have 218 patients with DCIS (17.4%). Of those 218 cases, 114 were treated with lumpectomy, axillary dissection, and radiation therapy; the remaining 104 patients were treated with mastectomy with or without reconstruction. Imprint cytology was used to evaluate all lumpectomy margins. Permanent sections and imprint cytology were reviewed by the same pathologist. Results: All lumpectomy specimens (116 tumors in 114 patients) were evaluated. The median follow up was 57.5 months (range 2–110 months). One hundred and three patients with 104 tumors were selected on the basis of pure DCIS (with or without microinvasion), and treated with lumpectomy, axillary dissection and radiation therapy. Of the 104 tumors utilizing attempted breast conservation therapy, 7 (6.6%) required mastectomy. There were 6 recurrences (6.1%) with a median time for recurrence of 47.5 months (range 27–85 months); four recurrences were comedo and two were noncomedo at original diagnosis. Conclusions: The determination of lumpectomy margins in DCIS patients using imprint cytology leads to an overall recurrence rate of 6.1% with reduction in operative time, and re-excision rate. Significant recurrence rates were associated with microinvasion and multifocal tumors (28%) versus simple DCIS at 5 years. Breast conservation therapy and surgical margin determination with imprint cytology for DCIS is a cost-effective and reliable method of treatment for simple DCIS.     

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.     

Presence of Lobular Carcinoma In Situ Does Not Increase Local Recurrence in Patients Treated with Breast-Conserving Therapy

Background  Lobular carcinoma in situ (LCIS) is known to be a risk factor for the development of invasive breast cancer. Debate continues as to whether LCIS is also a precursor lesion. We hypothesized that, if LCIS were a precursor, its presence in the lumpectomy specimen, particularly at the margin, could increase local recurrence (LR) after breast-conserving therapy (BCT). Methods  2894 patients treated with BCT for ductal carcinoma in situ (DCIS), stage I or II breast cancer between 1/80 and 5/07 were identified. Patients with DCIS or invasive cancer at the margins or those receiving neoadjuvant therapy were excluded. Group A had 290 patients with LCIS in the lumpectomy; 84 had LCIS at the final margin. Group B included 2604 patients with no evidence of LCIS. Results  Median patient age in group A and B was 57 and 58 years, respectively (P = 0.05); 12% and 13%, respectively, of patients in group A and B had margins <2 mm (P = NS). The histologic distribution of tumor types in group A was lobular in 47.2%, ductal in 34.5%, DCIS in 11.4%, and other invasive histologies in 6.9%, compared with 4.1%, 76.3%,13.6%, and 6.0% for group B, respectively (P < 0.0001). There was no significant difference between the groups in tumor–node–metastasis (TNM) stage. The crude rate of LR was 4.5% in group A and 3.8% in group B (P = NS). Five- and 10-year actuarial LR rates for LCIS at the margin were 6% and 6%, 1% and 15% for LCIS present but not at the margin, and 2% and 6% for no LCIS (P = NS), for group A and B, respectively. In multivariate analysis, menopausal status and adjuvant therapy use were significant predictors of LR. LCIS, either in the specimen or at the margin, was not significantly associated with LR. Conclusion  Presence of LCIS, even at the margin, in BCT specimens does not have an impact on LR. Re-excision is not indicated if LCIS is present or close to margin surfaces. These findings do not support consideration of LCIS as a precursor to the development of invasive lesions. Abstract presentation at the Scientific Session of the 61st Annual Cancer Symposiumof the Society of Surgical Oncology, Chicago, IL, March 13–16, 2008.     

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.     

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.     

The role of reexcision for positive margins in optimizing local disease control after breast-conserving surgery for cancer

One of the most important factors associated with local recurrence after lumpectomy in breast cancer patients is the status of the surgical margin. Standard surgical practice is to obtain clear margins even if this requires a second surgical procedure. It is assumed that reexcision to achieve clear margins when positive margins are present at initial excision is as effective as complete tumor removal at a single procedure; however, the efficacy of reexcision in this context has not been well studied. A retrospective search of the Henrietta Banting Breast Centre database from 1987 to 1997 identified 1430 patients who underwent lumpectomy for invasive breast cancer: 1225 patients (group A) had negative margins at the initial surgery and 152 patients (group B) underwent one or more reexcisions to achieve negative margins. Fifty-three patients had positive margins at final surgery, but no reexcision was done (group C). Logistic regression was used to identify factors that were predictive of a positive margin; predictors of local recurrence in women whose tumors were completely resected were determined using Cox's proportional hazards model. Patients in groups A, B, and C differed with respect to mean age at diagnosis (58 years, 51 versus, and 56 years, respectively, p < 0.0001), mean tumor size (19 mm, 16 mm, and 26 mm, respectively, p < 0.0001), node positivity (30%, 22%, and 41%, respectively, p = 0.004), and the presence of a ductal carcinoma in situ (DCIS) component (60%, 64%, and 79%, respectively, p = 0.007). The mean follow-up period was similar for the three groups (8 years, 8 years, and 9 years, respectively, p = 0.17). Young age was the only variable predictive of positive margins. Among patients undergoing complete tumor excision, there was a suggestion of a higher 10 year local recurrence rate in reexcision group B, but the difference did not reach statistical significance (11.6% versus 16.6%, p = 0.11). Cox's multivariate regression analyses identified older age, smaller tumor size, receiving radiation therapy, and tamoxifen use as significantly decreasing the rate of local recurrence in patients with negative margins at initial surgery or after reexcision. Our data confirm the results of previous studies indicating that young age is an independent predictor of positive margins after lumpectomy for invasive breast cancer. The only independent predictor of local recurrence in our study cohort was large tumor size. There was a trend toward a higher local recurrence rate if more than one procedure was required to secure clear margins, although this effect was not independent of other factors. Reexcision to clear involved margins is an important surgical intervention for both younger and older women.     

Determination of the presence and extent of pure ductal carcinoma in situ by mammography and magnetic resonance imaging

The purpose of this study was to compare the ability of magnetic resonance imaging (MRI) and mammography to determine the presence and extent of ductal carcinoma in situ (DCIS). Retrospective review of medical records of women who underwent MRI and mammographic examination during a 23-month period revealed 39 sites of pure DCIS in 33 breasts of 32 women. No invasive or microinvasive tumor was found. Women ranged in age from 34 to 79 years (mean age 53 years). In these 33 breasts, both MRI and mammography were done before surgery. Reports and images of mammography and MRI were reviewed to determine if each study was positive for the presence of single or multiple sites of DCIS and the imaging patterns associated with these sites. Of 33 breasts involved, DCIS was discovered by MRI alone in 21 (64%), by both MRI and mammography in 8 (24%), and by mammography alone in 1 (3%); in 3 breasts (9%), DCIS was found at mastectomy without findings on mammography or MRI. MRI had significantly higher sensitivity than mammography for DCIS detection (29/33=88% versus 9/33=27%, p<0.00001). Multiple sites of disease were present in five breasts; these were better demonstrated with MRI in three, mammography in one, and equally by both in one. The predominant enhancement pattern of DCIS on MRI was linear/ductal in 18 of 29 breasts (62%); mammography found calcifications associated with DCIS in 8 of 9 (89%). The nuclear grade of DCIS found with MRI and mammography was similar; size of lesions was larger on MRI; breast density did not impact results. In this study, MRI was significantly more sensitive than mammography in DCIS detection. In women with known or suspected DCIS, MRI may have an important role to play in assessing the extent of disease in the breast.     

Duct carcinoma in situ: A personal perspective

In the recent past, DCIS was a rare diagnosis established by biopsy of palpable breast masses or nipple changes. Mammography increased the frequency of a DCIS diagnosis by 20 × resulting in a tsunami of small circa 10 mm lesions detected only by mammography. The impact of pathologic technique in examining and characterizing such lesions is reviewed, and the development of algorithms incorporating prognostic factors and histology based on serial sequential processing techniques are described and contrasted with those which relied on tissue sampling. The development of the initial clinical trails of irradiation all demonstrated the significant benefit of irradiation but none could identify subsets with a more favorable outcome. The latter was precluded by their common practice of tissue sampling: Size could not be calculated and margin width and microinvasion could not be reliable demonstrated. Multigene signature assays are increasingly being utilized, most prominently Oncotype DCIS. However, these assays must be interpreted in conjunction with the limitations set forth in the validating studies—in the case of Oncotype DCIS—the size, margin width, and grade which defined the baseline study (E5194). Tamoxifen and other anti‐hormonal agents (aromatase inhibitor therapy) have been shown to have a limited impact on ipsilateral recurrence which makes their use given their morbidities problematic. Such interventions do impact the frequency of contralateral occult in situ and invasive lesions. In the one study which permitted a comparison of local recurrence in irradiated vs nonirradiated breast, there was no added benefit of Tamoxifen in irradiated breasts. Some are attempting to identify a low‐risk subset of DCIS which can be treated without surgical re‐excision for margins or adjuvant irradiation. These studies are in progress but surrogates identified within the Van Nuys prospective series defined by grade and inadequate margins (≤ 1 mm) would suggest a significant recurrence and progression rate. DCIS remains a work in progress both in terms of classification and treatment. However, limited our progress in these areas we have certainly advanced from the oft‐proclaimed mantra: “Radiation and Tamoxifen are standard of care.”     

Margin width as the sole determinant of local recurrence after breast conservation in patients with ductal carcinoma in situ of the breast

BACKGROUND: A previous study showed a 3% local recurrence risk at 8 years in ductal carcinoma in situ (DCIS) patients treated with excision alone with surgical margins of 10 mm or greater. This study updates those data. METHODS: A total of 272 DCIS patients treated conservatively with 10 mm or greater margins were reviewed in a prospective database. RESULTS: Among 212 excision-alone patients, there were 9 DCIS and 3 invasive recurrences. The 12-year probability of any local recurrence was 13.9%; of invasive recurrence it was 3.4%. Among 60 excision plus radiation patients, there was 1 local (invasive) recurrence (P = .06). The 12-year probability of local recurrence was 2.5%. CONCLUSIONS: Local recurrence in DCIS patients treated with excision alone with margins of 10 mm or greater compares favorably with local recurrence in DCIS patients with nontransected margins and treated with postoperative radiation. The risk of invasive recurrence among widely excised DCIS patients is extremely low.     

Is the systematic circumferential tumor cavity shaving a representative sample for the remaining mammary gland? About 75 cases

IntroductionThe conservative surgery is more and more indicated for breast cancer. However, we still fear local recurrence which is mostly due to residual tumors?. Several techniques have been used to minimize theses residual tumors; one of them is the systematic circumferential tumor cavity shaving (SCTCS).MethodsWe sampled 75 female patients who had conservative surgery with positive shaved margins in the anatomopathology examination and to whom a complementary treatment with mastectomy have been decided.ResultsThe median age was 48 years old. The median tumor size was 23 mm. In the histological examination of the tumors, 93% were invasive ductal carcinoma associated in 50% of the cases to the presence of ductal carcinoma in situ (DCIS) where all the lumpectomies had clear margin. For the SCTCS, 62,2% were DCIS and in 17,6% of the cases were invasive ductal carcinoma. A complementary treatment with mastectomy was indicated to all the patients. A residual tumor was detected in the remaining mammary gland in 47,7% of the cases out of which 50% were DCIS. Local recurrence happened in three patients (4,6%) after a median of follow up of 36 months. The overall survival and the disease free survival at five years were respectively 83,6% and 75,5%.ConclusionStandardized lumpectomy cavity shaving provides a backup to lumpectomy margins in conservative breast surgery but it can also be used as a sample for the remaining breast, helping to detect the residual tumor, and decreasing the rates of local recurrence after BCT.     

Atypical Ductal Hyperplasia at Margin of Breast Biopsy—Is Re-Excision Indicated?

Background Atypical duct hyperplasia (ADH) observed during core needle biopsy is associated with a high rate of cancer upon excision. Controversy exists regarding the need to re-excise ADH involving a margin. The purpose of this study was to determine the rate of residual pathology in patients that underwent re-excision for ADH involving the margin. Methods In a retrospective review of the pathology database from 1 January 2000 to 1 June 2006, we identified 44 lumpectomy specimens with ADH involving the margin; 24 patients (55%) had a re-excision. Slides were reviewed to verify the diagnosis of ADH near the margin and the presence of residual disease on re-excision associated with the biopsy cavity. Results Patients had pure ADH (15, 63%), ADH and ductal carcinoma in situ (DCIS) (7, 29%) or ADH with invasive carcinoma (2, 8%). Residual ADH or cancer was found in 14 of 24 patients (58%). Of 15 patients with pure ADH, 6 (40%) had residual pathology: ADH (2), DCIS (2) and invasive carcinoma (2). In this group, 27% of patients were reassessed as having DCIS or invasive carcinoma. Of the 9 patients with cancer, 8 (89%) had residual disease in the form of ADH (4) or DCIS (4). Conclusions ADH found at the margin of a lumpectomy specimen is associated with a high rate of residual ADH and cancer. Over one quarter of the patients with an initial diagnosis of ADH were reassessed as having DCIS or invasive carcinoma. Re-excision in all patients with ADH involving the margin is recommended.     

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.