Margins In Breast-conserving Therapy Research Articles

Radiological Underestimation of Tumor Size as a Relevant Risk Factor for Positive Margin Rate in Breast-Conserving Therapy of Pure Ductal Carcinoma In Situ (DCIS).

Simple SummaryNegative margins are the most important prognostic factor in breast-conserving therapy (BCT) of ductal carcinoma in situ (DCIS). The impact of radiological underestimation ≥10 mm (defined as mammographic minus histological tumor size in millimeters) has not been further examined. The purpose was to verify the radiological underestimation of DCIS size as a risk factor for positive margins. A pooled analysis of two trials was performed. Inclusion criteria were patients receiving BCT in DCIS. The results show a clinically relevant radiological underestimation in 37% of patients. Radiological underestimation is an independent risk factor for positive margins in BCT of DCIS with microcalcifications. Furthermore, the influencing factors of radiological underestimation were analysed. In multivariate logistic regression, only a mammographic tumor size ≤20 mm was an independent risk factor associated with radiological underestimation. When planning and executing BCT, it has to be considered that a relevant radiological underestimation is significantly higher in mammographic DCIS sizes ≤20 mm.Background: Radiological underestimation of the actual tumor size is a relevant problem in reaching negative margins in ductal carcinoma in situ (DCIS) associated with microcalcifications in breast-conserving therapy (BCT). The aim of this study is to evaluate whether the radiological underestimation of tumor size has an influence on the histopathological margin status. Methods: Patients who underwent BCT with preoperatively diagnosed pure DCIS were included (pooled analysis of two trials). Multiple factors were analysed regarding radiological underestimation ≥10 mm. Radiological underestimation was defined as mammographic minus histological tumor size in mm. Results: Positive margins occurred in 75 of 189 patients. Radiological underestimation ≥10 mm was an independent influencing factor (OR 5.80; 95%CI 2.55–13.17; p < 0.001). A radiological underestimation was seen in 70 patients. The following parameters were statistically significant associated with underestimation: pleomorphic microcalcifications (OR 3.77; 95%CI 1.27–11.18), clustered distribution patterns (OR 4.26; 95%CI 2.25–8.07), and mammographic tumor sizes ≤20 mm (OR 7.47; 95%CI 3.49–15.99). Only a mammographic tumor size ≤20 mm was an independent risk factor (OR 6.49; 95%CI 2.30–18.26; p < 0.001). Grading, estrogen receptor status, and comedo necrosis did not influence the size estimation. Conclusion: Radiological underestimation is an independent risk factor for positive margins in BCT of DCIS associated with microcalcifications predominantly occurring in mammographic small tumors.

Complete excision with narrow margins provides equivalent local control to wider excision in breast conservation for invasive cancer.

BackgroundSociety of Surgical Oncology and American Society for Radiation Oncology guidelines define clear margins in breast‐conserving therapy (BCT) as ‘no ink on tumour’, in contrast to the attainment of margins of at least 1 mm widely practised in the UK. The primary aim of this study was to explore clinical, surgical and tumour‐related factors associated with local recurrence after BCT, with a secondary aim of assessing the impact of margin re‐excision on the risk of local recurrence.MethodsPatient demographics, surgical details, tumour characteristics and local recurrence were recorded for consecutive women with BCT undergoing surgery between January 1997 and January 2007. Margins were defined as clear (greater than 1 mm), close (less than 1 mm but no ink on tumour), reaches (ink on tumour) and clear after re‐excision.ResultsA total of 1045 women of median age 54 (range 18–86) years were studied. Median follow‐up was 89 (range 4–196) months. Local recurrence occurred in 52 patients (5·0 per cent). Ink on tumour was associated with local recurrence (hazard ratio (HR) 4·86, 95 per cent c.i. 1·49 to 15·79; P = 0·009). Risk of local recurrence was the same for close and clear margins (HR 1·03, 0·40 to 2·62; P = 0·954). In women with involved margins, re‐excision was still associated with an increased local recurrence risk (HR 2·50, 1·32 to 4·72; P = 0·005). Oestrogen receptor negativity increased risk (HR 2·28, 1·28 to 4·06; P = 0·005).ConclusionAdequately excised margins, even when under 1 mm, provide equivalent outcomes to wider margins in BCT. Achieving complete excision at primary surgery achieves the lowest rates of local recurrence.

Excision Margins in Breast Conserving Therapy

Excision Margins in Breast Conserving Therapy

Excision margins in breast conservation therapy (BCT) – The effect of the Society of Surgical Oncology (SSO) and American Society for Radiation Oncology (ASTRO) consensus on our practice

Introduction: Acceptable margin width following BCT is not clearly defined (NICE 2009, LCA 2013). One of the minimum standards in the ABS Surgical guidelines is that >95% of patients with invasive disease should have 3 or fewer therapeutic operations (EJSO 2009). In April 2015, our MDT standard for margins was changed to “clear at the inked margin” in line with the SSO and ASTRO consensus (Moran, 2014). An audit of margin re-excision rates was performed to assess the impact of implementing this change.

The role of specimen radiography in breast-conserving therapy of ductal carcinoma in situ

BackgroundTo assess the role of intraoperative specimen radiography (SR) and to define risk factors for positive margins in breast-conserving therapy (BCT) of ductal carcinoma in situ (DCIS). MethodsIn a retrospective study in calcification-associated DCIS treated with BCT between January 2009 and December 2011, digital mammographs and SR were reviewed and radiological margin width was determined. Clinical, radiological, and histological data were correlated with surgical histological data, and a histologically free margin of at least 2 mm was taken as evidence of successful BCT. Results47/91 patients (51.6%) fulfilling the inclusion criteria had histologically involved surgical margins. Univariate analyses revealed DCIS size, mammographic extension of calcification, presence of comedo necrosis, negative progesterone receptor status, and a small radiological margin on SR to be risk factors for unsuccessful BCT. Receiver Operating Characteristic (ROC) analysis showed a radiological margin width of 4 mm to be optimal, with a sensitivity of 72.3% and specificity of 52.3%. The likelihood of surgical free margins was increased 2.9-fold with a radiological margin width ≥4 mm. On multivariate logistic regression analysis, only histological DCIS size >20 mm clearly emerged as an independent predictive factor for surgically involved margins (p < 0.001), while an SR margin <4 mm trended toward significance (p = 0.066). ConclusionsSR is a reliable method for predicting free surgical margins in non-invasive breast cancer where a minimum radiological free margin of 4 Fmm is achieved. However, histological DCIS size remains the most important factor determining successful BCT.

Progress in the surgical management of breast cancer: Present and future

Recognition of differing risks of locoregional recurrence (LRR) in breast cancer patients based on estrogen receptor, progesterone receptor, and HER2 status, coupled with a reduction in LRR in patients receiving adjuvant systemic therapy, offers the opportunity to tailor surgical treatment and reduce the morbidity of therapy. New guidelines for margins in breast-conserving therapy of tumor not touching ink and avoidance of axillary dissection in sentinel node positive patients undergoing breast-conserving therapy are examples of this approach which have entered practice. Increased use of neoadjuvant therapy offers the opportunity to identify which patients are responsive to chemotherapy prior to surgery, potentially allowing further tailoring of treatment, and ongoing clinical trials will address the question of the extent of axillary surgery and radiotherapy after neoadjuvant therapy in patients with and without pathologic complete response.

Margin re-excision and local recurrence in invasive breast cancer: A cost analysis using a decision tree model.

SSO-ASTRO recently published guidelines defining adequate margins in breast conservation therapy (BCT) as no tumor on ink based on studies demonstrating little difference in local recurrence (LR) with wider margins. We hypothesize that not routinely re-excising close margins results in decreased costs without compromising care. A decision tree model was developed for the management of margins after BCT for invasive cancer. Patients were compared among three margin status groups: positive, close (≤2 mm) and negative (>2 mm). Ten publications provided re-excision rates (RER) and LR rates. The model assumed 140,000 BCT/year. Sensitivity analyses determined the most cost-effective strategy. Surgical costs were estimated using 2013 Medicare reimbursement rates. Re-excising close margins was significantly more costly than the alternative, $233.1 million versus $214.3 million, per year in the United States. Total surgical cost was most sensitive to re-excision of close margins-increasing the RER from 0% to 100% resulted in an $18.8 million cost difference. The strategy of re-excising close margins resulted in a predicted cost of $18.8 million per year. This does not include hospital costs, the cost of surgical complications after re-excision, and underestimates the potential savings by using Medicare reimbursement rates.

Current Guidelines for Acceptable Surgical Margins in Breast Conservation Therapy

Patients treated with breast-conserving surgery for early stage breast cancer should preferably have a negative resection margin prior to postoperative radiation in order to minimize the risk for local recurrence. However, selected patients with focal margin involvement are still reasonable candidates for radiation without re-excision, particularly when the margin is at an anatomic boundary of the breast. Routine use of re-excision for close margins <1–2 mm is no longer routinely required—recent data have not confirmed a benefit to margins wider than no tumor on ink. Margins may have become of lesser prognostic importance in today’s environment due to improved preoperative imaging, careful surgical and pathological correlation, and modern systemic therapy. Clinical judgment is still needed in cases of close resection margins, such as when diffuse persistent disease is suspected, to weigh the need for re-excision prior to radiation.

The association of surgical margins and local recurrence in women with early-stage invasive breast cancer treated with breast-conserving therapy: a meta-analysis.

There is no consensus on what constitutes adequate negative margins in breast-conserving therapy (BCT). We systematically review the evidence on surgical margins in BCT for invasive breast cancer to support the development of clinical guidelines. Study-level meta-analysis of studies reporting local recurrence (LR) data relative to final microscopic margin status and the threshold distance for negative margins. LR proportion was modeled using random-effects logistic meta-regression. Based on 33 studies (LR in 1,506 of 28,162), the odds of LR were associated with margin status [model 1: odds ratio (OR) 1.96 for positive/close vs negative; model 2: OR 1.74 for close vs. negative, 2.44 for positive vs. negative; (P < 0.001 both models)] but not with margin distance [model 1: >0 mm vs. 1 mm (referent) vs. 2 mm vs. 5 mm (P = 0.12); and model 2: 1 mm (referent) vs. 2 mm vs. 5 mm (P = 0.90)], adjusting for study median follow-up time. There was little to no statistical evidence that the odds of LR decreased as the distance for declaring negative margins increased, adjusting for follow-up time [model 1: 1 mm (OR 1.0, referent), 2 mm (OR 0.95), 5 mm (OR 0.65), P = 0.21 for trend; and model 2: 1 mm (OR 1.0, referent), 2 mm (OR 0.91), 5 mm (OR 0.77), P = 0.58 for trend]. Adjustment for covariates, such as use of endocrine therapy or median-year of recruitment, did not change the findings. Meta-analysis confirms that negative margins reduce the odds of LR; however, increasing the distance for defining negative margins is not significantly associated with reduced odds of LR, allowing for follow-up time. Adoption of wider relative to narrower margin widths to declare negative margins is unlikely to have a substantial additional benefit for long-term local control in BCT.

Optimizing Clinical Management of Surgical Margins in Breast-Conserving Therapy for Breast Cancer

There has been, and continues to be, significant controversy over the definition of an "optimal" surgical margin in breast-conserving therapy (BCT). The historic basis of this controversy stems from the original trials documenting the safety of BCT and many conflicting retrospective studies that have sought to define the association between surgical margin width and outcomes over the last 20 years. It is important to understand that margin assessment is an inexact science, and current laboratory approaches to surgical-margin assessment represent only a sampling of the surgical margin. Currently available evidence suggests that decisions regarding surgical margins in BCT should be made in the context of what is known about the biology of breast cancer, as well the interactions of tumor biology, adjuvant treatment for breast cancer, and outcomes. Achieving consensus on management of surgical margins in BCT should be a clinical priority as it offers the opportunity to reduce the burden of breast cancer treatment on patients without compromising cancer-related outcomes.

Invited commentary on “A prospective study of tumor and technical factors associated with positive margins in breast-conservation therapy for nonpalpable malignancy” by Reedijk et al

This commentary accompanies the article by Reedijk et al in which the authors analyzed prospectively collected data from a randomized trial of radioactive iodine seed versus wire localization to determine factors predictive of positive margins after breast-conserving procedures for nonpalpable breast cancers. Margins were considered positive when disease was found at,1 mm from the inked margin. Given this definition, the rate of positive margins was 20%. Multivariable analysis of pooled data from the 2 arms of the trial revealed that localizations performed using stereotactic guidance, the presence of ductal carcinoma in situ, tumors .2 cm, and multifocal disease were predictive of positive margins. These data confirmed prior retrospective studies from these same and other authors, who identified young age, the presence of calcifications on mammography, lobular histology, and lymphovascular invasion as predictors of positive margins, in addition to the factors identified earlier in the current article. The relatively high rate of margin positivity begs 2 questions. The first relates to methods for lowering the risk of positive margins in breast-conserving operations. Pathologic touch preparation cytology and frozen section analyses are used in some centers for intraoperative margin assessment but have not gained wide popularity because of

Optimizing Clinical Management of Surgical Margins in Breast-Conserving Therapy for Breast Cancer

There has been, and continues to be, significant controversy over the definition of an optimal surgical margin in breast-conserving therapy (BCT). The historic basis of this controversy stems from the original trials documenting the safety of BCT and many conflicting retrospective studies that have sought to define the association between surgical margin width and outcomes over the last 20 years. It is important to understand that margin assessment is an inexact science, and current laboratory approaches to surgical-margin assessment represent only a sampling of the surgical margin. Currently available evidence suggests that decisions regarding surgical margins in BCT should be made in the context of what is known about the biology of breast cancer, as well the interactions of tumor biology, adjuvant treatment for breast cancer, and outcomes. Achieving consensus on management of surgical margins in BCT should be a clinical priority as it offers the opportunity to reduce the burden of breast cancer treatment on patients without compromising cancer-related outcomes.

The Effect of Simultaneous Peripheral Excision in Breast Conservation upon Margin Status

Background Negative margins in breast conservation therapy (BCT) decrease local recurrence risk. Excision may be performed via two techniques: either as a single lumpectomy specimen or as a central segment with simultaneously resected peripheral segments (PSs). There is little data directly comparing these methods for their effect on margin status.

A prospective study of tumor and technical factors associated with positive margins in breast-conservation therapy for nonpalpable malignancy

BackgroundThe purpose of this study was to identify factors that predict an increased risk of a positive surgical margin after breast-conserving therapy for nonpalpable carcinoma of the breast. MethodsIn this prospective study, 305 patients with nonpalpable invasive breast cancer or ductal carcinoma in situ were identified and underwent localization lumpectomy. Patient, technical, and tumor factors with a potential to predict margin status were documented. ResultsA 20% positive margin rate was observed. Univariate analysis of patient, tumor, and technical factors revealed that localizations performed under stereotactic guidance (P < .001), presence of in situ disease, high tumor grade, larger tumor size, multifocal disease, and presence of mammographic microcalcifications (P < .02) were predictive of positive margins. With the exception of tumor grade and mammographic microcalcifications, multivariable analysis identified the same factors. ConclusionsThis study identified several factors associated with positive margins that should be considered when planning breast-conserving therapy for nonpalpable tumors.

305 A Validated Web-based Nomogram for Predicting Positive Surgical Margins in Breast-conserving Therapy

305 A Validated Web-based Nomogram for Predicting Positive Surgical Margins in Breast-conserving Therapy

Evaluation of resection margins in breast conservation therapy: the pathology perspective-past, present, and future.

Tumor surgical resection margin status is important for any malignant lesion. When this occurs in conjunction with efforts to preserve or conserve the afflicted organ, these margins become extremely important. With the demonstration of no difference in overall survival between mastectomy versus lumpectomy and radiation for breast carcinoma, there is a definite trend toward smaller resections combined with radiation, constituting “breast-conserving therapy.” Tumor-free margins are therefore key to the success of this treatment protocol. We discuss the various aspects of margin status in this setting, from a pathology perspective, incorporating the past and current practices with a brief glimpse of emerging future techniques.

Multivariate analysis of predictors of positive or close margins in breast-conserving therapy.

105 Background: Local recurrence rates after breast-conserving therapy (BCT) are increased with positive or close margin lumpectomy. This group of patients usually requires a re-excision lumpectomy or a completion mastectomy, causing delays in systemic therapy, and a less desirable cosmetic outcome. The objectives of this study were to identify any predictive risk factors that might be associated with positive or close lumpectomy margins (&lt;1mm), and thus have implications for the planning of appropriate primary surgical excision. Methods: This was a retrospective cohort study of 195 consecutive patients from a prospectively collected, single-institution database. Patients who underwent primary lumpectomy for ductal carcinoma in situ (DCIS), invasive ductal carcinoma, and invasive lobular carcinoma from October 2007 to July 2010 were reviewed. Statistical analysis of the data was performed using Chi-squared analyses, multivariate logistic regression and Student’s t-test to identify significant predictors of a close or positive margin following lumpectomy. Results: In this study, 53.8% had positive or close margins. Ninety-two percent of this group underwent re-excision (86.5%) and total mastectomy (13.5%). We also observed that 53.1% of patients who underwent second operation had no residual disease. Factors significantly associated with positive or close margins include a family history of breast cancer (OR=2.3, p=0.01), a non-palpable mass (OR=2.4, p=0.01), or an excisional biopsy (OR=6.02, p=0.022). Age, race, use of hormone replacement therapy, menopausal status, use of preoperative MRI or US, BIRAD, use of neoadjuvant chemotherapy, tumor size, staging, waiting time, histology, receptor status, and axillary status were not significantly correlated with positive or close margins. Conclusions: For patients who were recommended to have a lumpectomy, an increased risk of a positive or close margin was significantly associated with a family history of breast cancer, a nonpalpable mass, or an excisional biopsy. These predictors should be weighed in the decision for attempting lumpectomy with the goal of a negative margin versus the ability to obtain a satisfactory cosmetic outcome.

Meta-analysis of the impact of surgical margins on local recurrence in women with early-stage invasive breast cancer treated with breast-conserving therapy

Purpose There is no consensus on what constitutes adequate negative margins in breast-conserving therapy (BCT). We review the evidence on surgical margins in BCT for early-stage invasive breast cancer. Methods Meta-analysis of studies reporting local recurrence (LR) relative to quantified final microscopic margin status and the threshold distance for negative margins. The proportion of LR was modelled using random effects logistic meta-regression. Results Based on 21 studies (LR in 1,026 of 14,571 subjects) the odds of LR were associated with margin status [model 1: odds ratio (OR) = 2.02 for positive/close versus negative; model 2: OR = 1.80 for close versus negative, 2.42 for positive versus negative ( P < 0.001 both models)] but not with margin distance [1 mm versus 2 mm versus 5 mm ( P > 0.10 both models)], adjusting for median follow-up time. However, there was weak evidence in both models that the odds of LR decreased as the threshold distance for declaring negative margins increased. This bordered significance in model 2 [OR for 1 mm, 2 mm, 5 mm: 1.0, 0.75, 0.51 ( P = 0.097 for trend)], and was not significant in model 1 [OR for 1 mm, 2 mm, 5 mm: 1.0, 0.85, 0.58 ( P = 0.11 for trend)] but was evident when one study (of women ⩽ 40 years) was excluded from this model [OR for 1 mm, 2 mm, 5 mm: 1.0, 0.72, 0.52 ( P = 0.058 for trend)]: this trend was rendered insignificant by adjustment for the proportion of subjects receiving a radiation boost or the proportion of subjects receiving endocrine therapy. Conclusions Margin status has a prognostic effect in all women treated for invasive breast cancer; increasing the threshold distance for declaring negative margins is weakly associated with reduced odds of LR, however adjustment for covariates (adjuvant therapy) removes the significance of this effect. Adoption of wider margins, relative to narrower widths, for declaring negative margins is unlikely to a have substantial additional benefit for long-term local control in BCT.

The Effect of Simultaneous Peripheral Excision in Breast Conservation upon Margin Status

Negative margins in breast conservation therapy (BCT) decrease local recurrence risk. Excision may be performed via two techniques: either as a single lumpectomy specimen or as a central segment with simultaneously resected peripheral segments (PSs). There is little data directly comparing these methods for their effect on margin status. A retrospective review of all patients undergoing BCT for invasive breast cancer was conducted to evaluate and compare the two techniques. Presentation, pathologic characteristics, surgical technique, specimen volume, and final margin status were recorded. Among 259 cancers in 257 women, 33 had positive margins. A single segment was removed in 69 patients, while 190 patients had 1-6 PSs simultaneously removed. By univariate analysis, smaller tumor size (P=.017) and greater numbers of segments removed (P=.01) lowered the risk of positive margins. In a multivariate model, smaller tumor size (P=.0024), lack of EIC (P=.049), and greater numbers of segments removed (P=.0061) lowered the risk of margin positivity. Despite this last predictor, the total resected specimen volume did not increase with the number of PSs removed (P=.4). There was no residual tumor in 49.2% of PSs despite a compromised primary segment margin. Smaller tumor size, lack of EIC, and greater numbers of simultaneous PSs excised decrease the likelihood of positive margins, despite a lack of correlation between segment numbers and excised volume. These findings suggest that excision of simultaneous PSs may assist in achieving negative margins, in part, because of avoidance of pathologic artifact.

Impact of Virtual MRI Sonography with Magnetic Navigation on Detecting Residual Tumors in Patients with Breast Cancer Who Undergo Neoadjuvant Chemotherapy; Initial Experience.

Abstract Objective: The accurate evaluation of the extent of residual disease after neoadjuvant chemotherapy (NAC) for breast cancer appears essential for successful clinical outcomes. However, there are limited date about the success of achieving negative margins in breast conservation therapy. Recently, we have developed virtual MRI sonography with magnetic navigation (real-time virtual sonography; RVS). RVS can overlay high-resolution structural image taken by sonography with functional image reflecting vascular permeability taken by MRI of the same site in real time. The objective of our study was to determine the relative accuracy of RVS in detecting residual tumors after NAC.Materials and Methods: Between April 2007 and May 2009, 96 breast conservation therapy were performed for invasive ductal carcinoma at our hospital. Fourteen patients with stage IIA-IIIB palpable invasive ductal carcinoma were enrolled in a study investigating the effects of NAC on tumor imaging. All patients underwent mammography, sonography, MRI, and RVS before and after NAC. MRI was performed with a 1.5-T scanner in the supine position using a flexible body surface coil to achieve the same position as that used in sonography. Based on MRI results, the absence or presence of residual tumors was used to classify treatment response into a clinically complete response (cCR) or non-cCR, respectively. Nine patients received lumpectomy, and 5 received mastectomy. The surgical resection area was determined by RVS. Detection rate was determined for residual tumors with or without RVS. The pathologically complete response (pCR) was defined as no invasive carcinoma.Results: All index tumors were detected by sonography and MRI before NAC. After NAC, a cCR was seen in 5 (5 of 14, 36%) patients. MRI correctly diagnosed pCR in 4 (4 of 5, 80%) patients. Detection rate for residual tumors was 9% (1 of 11) for mammography, 33% (3 of 9) for sonography alone, 78% (7 of 9) for MRI, and 89% (8 of 9) for RVS. It was noteworthy that 5 (5 of 5, 100%) cases with cCR were accurately localized onto the body surface with supplementation using RVS combined with pre- and post-NAC imaging while we were checking sonography. Although surgical excision was incomplete in 5 (5 of 9, 56%) patients, all positive surgical margins were ductal carcinoma in situ.Conclusions: By using RVS, two different forms of diagnostic imaging can be integrated in real time and thereby complement each other. The present results suggest that RVS is a useful imaging technique for detecting residual tumors that have been associated with local recurrence after NAC. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5024.