The use of no ink on tumor as the standard for an adequate margin in invasive cancer in the era of multidisciplinary therapy is associated with low rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs. J Clin Oncol 32. 2014 American Society of Clinical Oncology®, American Society for Radiation Oncology®, and Society of Surgical Oncology®. All rights reserved. No part of this document may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without written permission by the American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology.

Purpose. Controversy exists regarding the optimal margin width in breast-conserving surgery for invasive breast cancer. Methods. A multidisciplinary consensus panel used a meta-analysis of margin width and ipsilateral breast tumor recurrence (IBTR) from a systematic review of 33 studies including 28,162 patients as the primary evidence base for consensus. Results. Positive margins (ink on invasive carcinoma or ductal carcinoma in situ) are associated with a two-fold increase in the risk of IBTR compared with negative margins. This increased risk is not mitigated by favorable biology, endocrine therapy, or a radiation boost. More widely clear margins than no ink on tumor do not significantly decrease the rate of IBTR compared with no ink on tumor. There is no evidence that more widely clear margins reduce IBTR for young patients or for those with unfavorable biology, lobular cancers, or cancers with an extensive intraductal component. Conclusion. The use of no ink on tumor as the standard for an adequate margin in invasive cancer in the era of multidisciplinary therapy is associated with low rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs.

PurposeControversy exists regarding the optimal negative margin width for ductal carcinoma in situ (DCIS) treated with breast-conserving surgery and whole-breast irradiation.MethodsA multidisciplinary consensus panel used a meta-analysis of margin width and ipsilateral breast tumor recurrence (IBTR) from a systematic review of 20 studies including 7,883 patients and other published literature as the evidence base for consensus.ResultsNegative margins halve the risk of IBTR compared with positive margins defined as ink on DCIS. A 2-mm margin minimizes the risk of IBTR compared with smaller negative margins. More widely clear margins do not significantly decrease IBTR compared with 2-mm margins. Negative margins narrower than 2 mm alone are not an indication for mastectomy, and factors known to affect rates of IBTR should be considered in determining the need for re-excision.ConclusionUse of a 2-mm margin as the standard for an adequate margin in DCIS treated with whole-breast irradiation is associated with lower rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs. Clinical judgment should be used in determining the need for further surgery in patients with negative margins narrower than 2 mm.

Summary Changes in the management of breast cancer over time have led to decreased rates of IBTR. The 2013 SSO/ASTRO guidelines on margins in breast-conserving surgery for invasive cancer are summarized in this document.

Background Increased pathologic complete response (pCR) rates observed with neoadjuvant chemotherapy (NCT) for some subsets of patients with invasive breast cancer has prompted interest in whether patients with pCR can be identified preoperatively and potentially spared the morbidity of surgery. This multicenter retrospective study was performed to estimate the accuracy of preoperative MRI in predicting pCR in the breast. Methods MRI at baseline and after completion of NCT plus data regarding pathologic response was collected retrospectively from 746 women treated at 8 institutions between 2002–2011. Tumors were characterized by immunohistochemical (IHC) phenotype into 4 categories based on receptor expression: hormone (estrogen & progesterone) receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2) negative (n=327), HR-positive, HER2-positive, (n=148), HR-negative, HER2-positive, (n=101), and triple-negative (HR-negative, HER2-negative, n=155). 194/249 (78%) patients with HER2-positive tumors received trastuzumab. Univariate and multivariate analyses of factors associated with radiographic complete response (rCR) and pCR were performed. Results rCR and pCR for total group were 182/746 (24%) and 179/746 (24%), respectively, with the highest rate of pCR seen among triple-negative (57/155; 37%) and HER2 positive (38/101; 38%) subtypes. Overall accuracy of MRI for pCR prediction was 74%. Sensitivity, NPV, PPV, and accuracy differed significantly among tumor subtypes, with the greatest NPV in the TN (60%) and HER2 positive (62%) subtypes. Conclusion Overall accuracy of MRI for predicting pCR in invasive breast cancer patients receiving NCT was 74%. MR performance differed among subtypes possibly influenced by differences in pCR rates between groups. Future studies will determine whether MRI in combination with directed core biopsy improves predictive value for pathologic response.

BackgroundControversy exists regarding the optimal negative margin width for ductal carcinoma in situ (DCIS) treated with breast-conserving surgery and whole-breast irradiation (WBRT).MethodsA multidisciplinary consensus panel used a meta-analysis of margin width and ipsilateral breast tumor recurrence (IBTR) from a systematic review of 20 studies including 7883 patients and other published literature as the evidence base for consensus.ResultsNegative margins halve the risk of IBTR compared with positive margins defined as ink on DCIS. A 2 mm margin minimizes the risk of IBTR compared with smaller negative margins. More widely clear margins do not significantly decrease IBTR compared with 2 mm margins. Negative margins less than 2 mm alone are not an indication for mastectomy, and factors known to impact rates of IBTR should be considered in determining the need for re-excision.ConclusionThe use of a 2 mm margin as the standard for an adequate margin in DCIS treated with WBRT is associated with low rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcome, and decrease health care costs. Clinical judgment should be used in determining the need for further surgery in patients with negative margins < 2 mm.

Background Controversy exists regarding the optimal negative margin width for ductal carcinoma in situ (DCIS) treated with breast-conserving surgery and whole breast irradiation (WBRT). Methods A multidisciplinary consensus panel used a meta-analysis of margin width and ipsilateral breast tumor recurrence (IBTR) from a systematic review of 20 studies including 7883 patients and other published literature as the evidence base for consensus. Results Negative margins halve the risk of IBTR compared to positive margins defined as ink on DCIS. A 2 mm margin minimizes the risk of IBTR compared to smaller negative margins. More widely clear margins do not significantly decrease IBTR compared to 2 mm margins. Negative margins less than 2 mm alone are not an indication for mastectomy, and factors known to impact rates of IBTR should be considered in determining the need for re-excision. Conclusions The use of a 2 mm margin as the standard for an adequate margin in DCIS treated with WBRT is associated with low rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcome, and decrease health care costs. Clinical judgment should be used in determining the need for further surgery in patients with negative margins < 2 mm.

Summary This phase I dose-escalation trial evaluates the feasibility of single-dose preoperative partial breast irradiation delivered with external beam techniques in early stage breast cancer patients. No acute dose-limiting toxicity was observed at 15, 18, or 21Gy. Paired pre- and post-radiation imaging and tumor biopsies offer unique insight into the biology of breast cancer radiation response. Purpose Women with biologically favorable early stage breast cancer are increasingly treated with accelerated partial breast radiation (PBI). However, treatment-related morbidities have been linked to the large post-operative treatment volumes required for external beam PBI. Relative to external beam delivery, alternative PBI techniques require equipment that is not universally available. To address these issues, we designed a phase I trial utilizing widely available technology to 1) evaluate the safety of a single radiation treatment delivered preoperatively to the small-volume, intact breast tumor and 2) identify imaging and genomic markers of radiation response. Methods Women 55 or older with clinically node negative, ER+ and/or PR+, HER2-, T1 invasive carcinomas or low-intermediate grade in situ disease ≤2cm were enrolled (n=32). Intensity-modulated radiotherapy was used to deliver 15 Gy (n=8), 18 Gy (n=8), or 21Gy (n=16) to the tumor with a 1.5cm margin. Lumpectomy was performed within 10 days. Paired pre- and post-radiation MRI images and patient tumor samples were analyzed. Results No dose-limiting toxicity was observed. At a median follow-up of 23 months, there have been no recurrences. Physician-rated cosmetic outcomes were good/excellent and chronic toxicities were grade 1-2 (fibrosis, hyperpigmentation) in patients receiving preoperative radiation only. Evidence of dose-dependent changes in vascular permeability, cell density, and expression of genes regulating immunity and cell death were seen in response to radiation. Conclusions Preoperative single-dose radiotherapy to intact breast tumors is well-tolerated. Radiation response is marked by early indicators of cell death in this biologically favorable patient cohort. This study represents a first-step towards a novel PBI approach. Preoperative radiation should be tested in future clinical trials as it has the potential to challenge the current treatment paradigm and provide a path forward to identify radiation response biomarkers.