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Importance: Postmastectomy radiation therapy (PMRT) improves local-regional disease control and patient survival. Hypofractionation (HF) regimens have comparable efficacy and complication rates with improved quality of life compared with conventional fractionation (CF) schedules. However, the use of HF after mastectomy in patients undergoing breast reconstruction has not been prospectively examined., Objective: To compare HF and CF PMRT outcomes after implant-based reconstruction., Design, Setting, and Participants: This randomized clinical trial assessed patients 18 years or older undergoing mastectomy and immediate expander or implant reconstruction for breast cancer (Tis, TX, or T1-3) and unilateral PMRT from March 8, 2018, to November 3, 2021 (median [range] follow-up, 40.4 [15.4-63.0] months), at 16 US cancer centers or hospitals. Analyses were conducted between September and December 2023., Interventions: Patients were randomized 1:1 to HF or CF PMRT. Chest wall doses were 4256 cGy for 16 fractions for HF and 5000 cGy for 25 fractions for CF. Chest wall toxic effects were defined as a grade 3 or higher adverse event., Main Outcomes and Measures: The primary outcome was the change in physical well-being (PWB) domain of the Functional Assessment of Cancer Therapy-Breast (FACT-B) quality-of-life assessment tool at 6 months after starting PMRT, controlling for age. Secondary outcomes included toxic effects and cancer recurrence., Results: Of 400 women (201 in the CF arm and 199 in the HF arm; median [range] age, 47 [23-79] years), 330 patients had PWB scores at baseline and at 6 months. There was no difference in the change in PWB between the study arms (estimate, 0.13; 95% CI, -0.86 to 1.11; P = .80), but there was a significant interaction between age group and study arm (P = .03 for interaction). Patients younger than 45 years had higher 6-month absolute PWB scores if treated with HF rather than CF regimens (23.6 [95% CI, 22.7-24.6] vs 22.0 [95% CI, 20.7-23.3]; P = .047) and reported being less bothered by adverse effects (mean [SD], 3.0 [0.9] in the HF arm and 2.6 [1.2] in the CF arm; P = .02) or nausea (mean [SD], 3.8 [0.4] in the HF arm and 3.6 [0.8] in the CF arm; P = .04). In the as-treated cohort, there were 23 distant (11 in the HF arm and 12 in the CF arm) and 2 local-regional (1 in the HF arm and 1 in the CF arm) recurrences. Chest wall toxic effects occurred in 39 patients (20 in the HF arm and 19 in the CF arm) at a median (IQR) of 7.2 (1.8-12.9) months. Fractionation was not associated with chest wall toxic effects on multivariate analysis (HF arm: hazard ratio, 1.02; 95% CI, 0.52-2.00; P = .95). Fewer patients undergoing HF vs CF regimens had a treatment break (5 [2.7%] vs 15 [7.7%]; P = .03) or required unpaid time off from work (17 [8.5%] vs 34 [16.9%]; P = .02)., Conclusions and Relevance: In this randomized clinical trial, the HF regimen did not significantly improve change in PWB compared with the CF regimen. These data add to the increasing experience with HF PMRT in patients with implant-based reconstruction., Trial Registration: ClinicalTrials.gov Identifier: NCT03422003.

Breast reconstruction (BR) after mastectomy is important to consider for a woman's body image enhancement and psychological well-being. Although post-mastectomy radiation (PMRT) significantly improves the outcome of patients with high-risk breast cancer (BC), PMRT after BR may affect cosmetic outcomes and may compromise the original goal of improving quality of life (QoL). With the lack of practical guidelines, it seems essential to work on a consensus and provide some "expert agreements" to offer patients the best option for PMRT after BR. We report a global "expert agreement" that results from a critical review of the literature on BR and PMRT during the 6th international multidisciplinary breast conference in March 2023., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Nipple areola complex-sparing surgeries, such as nipple-sparing mastectomy (NSM), are increasingly used for women with early-stage breast cancer. In the postoperative setting, 2 major indications for postoperative radiation (PORT) with/without regional nodal irradiation (RNI) are: positive margins (margin+) and pathologically involved lymph nodes (pN+). The frequency of these adverse pathologic features and the rate of PORT utilization following NSM for these 2 indications are unknown. We determined the frequency of margin+ and pN+ following NSM compared with nipple-sparing lumpectomy/breast-conserving surgery [BCS] and identified trends in appropriate PORT administration for these standard indications in the NSM setting., Methods and Materials: Using the National Cancer Database (NCDB), women diagnosed with cT1 to cT3,N0M0 invasive carcinoma between 2004 and 2017 who underwent NSM were compared with those who underwent BCS (with nipple preservation). The frequencies of margin+ and pN+ by surgical subtype and use of PORT with/without RNI were assessed by cohort to determine if the type of surgery was associated with radiation delivery. Overall survival between the 2 cohorts was also compared. We performed univariable/multivariable logistic and Cox regression with ORs to control for confounders., Results: Of 624,075 women included, 611,907 underwent BCS, and 12,168 underwent NSM. The surgical margin+ rate was significantly higher for NSM at 4.5% (n = 544) than for BCS at 3.7% (n = 22,449) ( P < .001) and remained significant on multivariable analysis (MVA; OR, 1.13; CI, 1.03-1.25; P = .012). Use of PORT for margins+ was significantly lower by MVA after NSM (OR, 0.07; CI, 0.06-0.09; P < .001). Similarly, pN+ rate was significantly higher for NSM at 22.5% (n = 2740) versus BCS at 13.5% (n = 82,288) ( P < .001), retaining significance on MVA (OR, 1.12; CI, 1.06-1.19; P < .001). For pN+ undergoing NSM, PORT with RNI was delivered significantly less often on MVA (OR, 0.73; CI, 0.67-0.81; P < .001). Neither high-risk subgroup had differences in overall survival on MVA., Conclusions: NSM is associated with a higher rate of margin+ and pN+ compared with BCS. Radiation is underused after NSM for these standard indications. Our results highlight the need to further refine patient selection for NSM and the importance of communicating the higher potential for adverse pathologic features (and thus, the potential need for radiation) to patients undergoing NSM., Competing Interests: Dr. Meena Moran is Vice Chair of the National Comprehensive Cancer Network (NCCN) Breast Panel., (© 2024 The Authors.)

Breast cancer is treated with a multidisciplinary approach involving surgical oncology, radiation oncology, and medical oncology. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget's disease, Phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The content featured in this issue focuses on the recommendations for overall management of systemic therapy (preoperative and adjuvant) options for nonmetastatic breast cancer. For the full version of the NCCN Guidelines for Breast Cancer, visit NCCN.org.

Purpose: Multiple studies have shown a low risk of ipsilateral breast events (IBEs) or other recurrences for selected patients age 65-70 years or older with stage I breast cancers treated with breast-conserving surgery (BCS) and endocrine therapy (ET) without adjuvant radiotherapy. We sought to evaluate whether younger postmenopausal patients could also be successfully treated without radiation therapy, adding a genomic assay to classic selection factors., Methods: Postmenopausal patients age 50-69 years with pT1N0 unifocal invasive breast cancer with margins ≥2 mm after BCS whose tumors were estrogen receptor-positive, progesterone receptor-positive, and human epidermal growth factor receptor 2-negative with Oncotype DX 21-gene recurrence score ≤18 were prospectively enrolled in a single-arm trial of radiotherapy omission if they consented to take at least 5 years of ET. The primary end point was the rate of locoregional recurrence 5 years after BCS., Results: Between June 2015 and October 2018, 200 eligible patients were enrolled. Among the 186 patients with clinical follow-up of at least 56 months, overall and breast cancer-specific survival rates at 5 years were both 100%. The 5-year freedom from any recurrence was 99% (95% CI, 96 to 100). Crude rates of IBEs for the entire follow-up period for patients age 50-59 years and age 60-69 years were 3.3% (2/60) and 3.6% (5/140), respectively; crude rates of overall recurrence were 5.0% (3/60) and 3.6% (5/140), respectively., Conclusion: This trial achieved a very low risk of recurrence using a genomic assay in combination with classic clinical and biologic features for treatment selection, including postmenopausal patients younger than 60 years. Long-term follow-up of this trial and others will help determine whether the option of avoiding initial radiotherapy can be offered to a broader group of women than current guidelines recommend.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer address all aspects of management for breast cancer. The treatment landscape of metastatic breast cancer is evolving constantly. The therapeutic strategy takes into consideration tumor biology, biomarkers, and other clinical factors. Due to the growing number of treatment options, if one option fails, there is usually another line of therapy available, providing meaningful improvements in survival. This NCCN Guidelines Insights report focuses on recent updates specific to systemic therapy recommendations for patients with stage IV (M1) disease.

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology , to patients seen in their own clinical practice .The following case represents a relatively common clinical scenario of a postmenopausal female patient who presents with low-risk, estrogen receptor-positive/progesterone receptor-positive/human epidermal growth factor receptor 2-negative, early-stage, left-sided breast cancer to discuss the role of postoperative radiation (RT) following wide local excision (WLE) and sentinel node biopsy. The spectrum of choices, ranging from omission of RT, accelerated partial breast irradiation (PBI), whole-breast radiation therapy, and the nuances of various dose/fractionation regimens for each option, are discussed in the context of the Danish Breast Cancer Study Group (DBCSG) PBI trial published in this issue, with additional review of other key trials that inform these treatment recommendations. After consideration of the clinical-pathologic features in the framework of the existing data and an in-depth discussion taking into consideration the patient's preferences/goals, the decision was made to deliver moderately hypofractionated RT (40 Gy/15 fractions) to a PBI volume, in concordance with the DBCSG-PBI trial.

Objective: The purpose of this analysis was to determine whether our "reflex testing" (RefT) intervention, implemented to address barriers in scheduling, communication, and diagnostic order placement for resolving BI-RADS 0 screening mammograms, resulted in decreased interval wait times (IWT) for patients with abnormal screening mammograms (abSM)., Methods: All BI-RADS 0 cases over two six-month periods (pre-RefT and post-RefT) were analyzed. Timelines were generated for each BI-RADS 0 case. Elapsed days were computed from date of BI-RADS 0 report to the date of biopsy, additional diagnostic testing, and final resolution. The means of each endpoint within the pre-RefT and post-RefT cohorts were statistically analyzed using Pearson chi-square analysis to assess whether IWT differed significantly after RefT implementation., Results: The analytic cohort consisted of 1523 BI-RADS 0 cases (n(pre-RefT) = 647, n(post-RefT) = 876). Reflex testing decreased the overall mean IWT from 23.5 to 8.2 days (P < 0.001). For patients not requiring biopsy (1190/1523, 78.1%), the mean IWT from the BI-RADS 0 designation to first diagnostic test or resolution decreased from 29.7 to 10.8 days (P < 0.010). For patients who had biopsy (333/1523, 21.9%), RefT significantly decreased the IWT from BI-RADS 0 to first diagnostic test from 31.4 to 7.7 days (P < 0.001) and also significantly decreased the IWT from first diagnostic test to biopsy (20.9 to 17.7 days; P < 0.013)., Conclusion: Reflex testing intervention streamlines the workflow and significantly decreases IWT for resolving BI-RADS 0 abSM. The RefT intervention could be considered to improve efficiency at other breast centers., (© Society of Breast Imaging 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

There are few data on the quality of cancer treatment information available on social media. Here, we quantify the accuracy of cancer treatment information on social media and its potential for harm. Two cancer experts reviewed 50 of the most popular social media articles on each of the 4 most common cancers. The proportion of misinformation and potential for harm were reported for all 200 articles and their association with the number of social media engagements using a 2-sample Wilcoxon rank-sum test. All statistical tests were 2-sided. Of 200 total articles, 32.5% (n = 65) contained misinformation and 30.5% (n = 61) contained harmful information. Among articles containing misinformation, 76.9% (50 of 65) contained harmful information. The median number of engagements for articles with misinformation was greater than factual articles (median [interquartile range] = 2300 [1200-4700] vs 1600 [819-4700], P = .05). The median number of engagements for articles with harmful information was statistically significantly greater than safe articles (median [interquartile range] = 2300 [1400-4700] vs 1500 [810-4700], P = .007)., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Ductal carcinoma in situ (DCIS) represents 20% of all breast cancers. The treatment paradigm for the majority of patients with DCIS consists of breast-conserving surgery (BCS) and radiotherapy (RT), with adjuvant endocrine therapy offered for hormone-receptor positive disease. RT after BCS reduces the risk of in-breast recurrence, decreasing subsequent in-situ and invasive cancers by ≥50%, with 10-year breast-cancer specific survival outcomes approaching 98%. As local control rates are high, treatment efforts have focused on selective de-escalation of care. Traditionally, clinicians have used clinical-pathologic features (ie, grade, age, size, margin width) to guide selection of low-risk DCIS patients in whom postoperative RT may be omitted. More recently, genomic molecular assays including the Oncotype DX Breast DCIS Score and DCISionRT have been developed to provide individualized assessment of predicting RT benefit after BCS. These molecular assays have the potential for personalized risk assessment, particularly when used in combination with existing clinical-pathologic features for risk assessment. This article reviews the current status and existing published literature on DCIS molecular-risk assessment tools and their potential for guiding postoperative RT recommendations in the BCT setting. In addition, current trials studying omission of definitive surgery for low-risk DCIS are discussed., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The therapeutic options for patients with noninvasive or invasive breast cancer are complex and varied. These NCCN Clinical Practice Guidelines for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget disease, phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The content featured in this issue focuses on the recommendations for overall management of ductal carcinoma in situ and the workup and locoregional management of early stage invasive breast cancer. For the full version of the NCCN Guidelines for Breast Cancer, visit NCCN.org.

Introduction: The Commission on Cancer/National Quality Forum breast radiotherapy quality measure establishes that for women < 70 years, adjuvant radiotherapy after breast conserving surgery (BCS) should be started < 1 year from diagnosis. This was intended to prevent accidental radiotherapy omission or delay due to a long interval between surgery and chemotherapy completion, when radiation is delivered. However, the impact on patients not receiving chemotherapy, who proceed from surgery directly to radiotherapy, remains unknown., Patients and Methods: Patients aged 18-69, diagnosed with stage I-III breast cancer as their first and only cancer diagnosis (2004-2016), having BCS, for whom this measure would be applicable, were reviewed from the National Cancer Database., Results: Among 308,521 patients, the median age was 57.0 years, and > 99% of all patients were compliant with the measure. The cohort of interest included 186,650 (60.5%) patients not receiving chemotherapy, with a mean age of 57.9 years. Of these, 90.5% received external beam radiotherapy (EBRT) and 9.5% brachytherapy. Among them, 24.9% started radiotherapy > 8 weeks after surgery. In a multivariable model, delay from surgery to radiotherapy increased the hazard ratios for overall survival to 9.0% (EBRT) per month and 3.0% (brachytherapy) per week., Conclusion: While 99.9% of patients undergoing BCS without chemotherapy remain compliant with the current quality measure, 25% have delays > 8 weeks to start radiation, which is associated with impaired survival. These data suggest that the current quality measure should be dichotomized into two, with or without chemotherapy, in order to impel prompt radiotherapy initiation and maximize outcomes in all patients., (© 2021. Society of Surgical Oncology.)

Background: Although deep inspiratory breath-hold (DIBH) is routinely used for left-sided breast cancers, its benefits for right-sided breast cancer (rBC) have yet to be established. We compared free-breathing (FB) and DIBH treatment plans for a cohort of rBC undergoing regional nodal irradiation (RNI) to determine its potential benefits., Methods and Materials: rBC patients considered for RNI (internal mammary nodal chains, supraclavicular field, with or without axilla) from October 2017 to May 2020 were included in this analysis. For each patient, FB versus DIBH plans were generated and dose volume histograms evaluated the following parameters: mean lung dose, ipsilateral lung V 20 /V 5 (volumes of lung receiving 20 Gy and 5 Gy, respectively); mean heart dose and heart V 5 (volumes of heart receiving 5 Gy); liver V 20 absolute /V 30 absolute (absolute volume of liver receiving 20 Gy and 30 Gy, respectively), liver D max , and total liver volume irradiated (TVI liver ). The dosimetric parameters were compared using Wilcoxon signed-rank testing., Results: Fifty-four patients were eligible for analysis, comparing 108 FB and DIBH plans. DIBH significantly decreased all lung and liver parameters: mean lung dose (19.7 Gy-16.2 Gy, P < .001), lung V 20 (40.7%-31.7%, P < .001), lung V 5 (61.2%-54.5%, P < .001), TVI liver (1446 cc vs 1264 cc; P = .006) liver D max (50.2 Gy vs 48.9 Gy; P = .023), liver V 20 (78.8-23.9 cc, P < .001), and liver V 30 (58.1-14.6 cc, P < .001) compared with FB. DIBH use did not significantly improve heart parameters, although the V 5Heart trended on significance (1.25-0.6, P = .067)., Conclusions: This is the largest cohort to date analyzing DIBH for RNI-rBC. Our findings demonstrate significant improvement in all lung and liver parameters with DIBH, supporting its routine consideration for rBC patients undergoing comprehensive RNI., (Copyright © 2021. Published by Elsevier Inc.)

Bolus serves as a tissue equivalent material that shifts the 95-100% isodose line towards the skin and subcutaneous tissue. The need for bolus for all breast cancer patients planned for postmastectomy radiation therapy (PMRT) has been questioned. The work was initiated by the faculty of the European SocieTy for Radiotherapy & Oncology (ESTRO) breast cancer courses and represents a multidisciplinary international breast cancer expert collaboration to optimize PMRT. Due to the lack of randomised trials evaluating the benefits of bolus, we designed a stepwise project to evaluate the existing evidence about the use of bolus in the setting of PMRT to achieve an international consensus for the indications of bolus in PMRT, based on the Delphi method., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: Post mastectomy radiation therapy (PMRT) reduces locoregional recurrence (LRR) and breast cancer mortality for selected patients. Bolus overcomes the skin-sparing effect of external-beam radiotherapy, ensuring adequate dose to superficial regions at risk of local recurrence (LR). This systematic review summarizes the current evidence regarding the impact of bolus on LR and acute toxicity in the setting of PMRT., Results: 27 studies were included. The use of bolus led to higher rates of acute grade 3 radiation dermatitis (pooled rates of 9.6% with bolus vs. 1.2% without). Pooled crude LR rates from thirteen studies (n = 3756) were similar with (3.5%) and without (3.6%) bolus., Conclusions: Bolus may be indicated in cases with a high risk of LR in the skin, but seems not to be necessary for all patients. Further work is needed to define the role of bolus in PMRT., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The NCCN Guidelines for Breast Cancer include up-to-date guidelines for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget disease, phyllodes tumor, inflammatory breast cancer, male breast cancer, and breast cancer during pregnancy. These guidelines are developed by a multidisciplinary panel of representatives from NCCN Member Institutions with breast cancer-focused expertise in the fields of medical oncology, surgical oncology, radiation oncology, pathology, reconstructive surgery, and patient advocacy. These NCCN Guidelines Insights focus on the most recent updates to recommendations for adjuvant systemic therapy in patients with nonmetastatic, early-stage, hormone receptor-positive, HER2-negative breast cancer.

Background: We aimed to explore whether cribriform and adenoid cystic carcinoma had comparable prognoses to mucinous, tubular and papillary carcinoma, which were long recognized as favorable histologies by NCCN guidelines., Methods: A retrospective analysis based on the Surveillance, Epidemiology, and End Results Study (SEER) database (1994-2014) was conducted. The prognostic significance of all clinicopathological factors was calculated using univariate and multivariate analyses. A systematic review based on PubMed and network meta-analysis was conducted., Results: From the SEER database, the histologic subtypes of breast cancer (tubular, cribriform, adenoid cystic, mucinous, and papillary) were sorted by overall survival (OS) (94.4%, 91.6%, 90.8%, 87.6%, and 84.2%, respectively) and tubular, cribriform, mucinous, papillary, and adenoid cystic carcinoma by breast cancer-specific survival (BCSS) (99.4%, 98.4%, 97.7%, 95.2%, and 94.9%, respectively). A network meta-analysis combining 11 studies (886,649 patients) was conducted, which demonstrated consistent outcomes. SEER-based analyses revealed that, among the favorable subtypes, systemic chemotherapy did not improve OS or BCSS in hormone receptor-positive, node-negative patients, validating that these subtypes are generally associated with excellent outcomes, for which systemic chemotherapy may not be warranted., Conclusions: Our data are consistent with guidelines suggesting that the mucinous, tubular, and papillary subtypes of breast cancer have favorable histologies. SEER data and meta-analysis supports this favorable category to include adenoid cystic and cribriform carcinoma, whose OS and BCSS outcomes are comparable to the former three. These findings add to the body of data, suggesting that patients with these histologic subtypes confer excellent prognosis, which may guide optimal therapeutic management strategies., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Regional nodal irradiation has gained interest in recent years with the publication of several important randomized trials and the availability of more conformal techniques. Target volume delineation represents a critical step in the radiation planning process. Adequate coverage of the microscopic tumor spread to regional lymph nodes must be weighed against exposure of critical structures such as the heart and lungs. Among available guidelines for delineating the clinical target volume for the breast/chest wall and regional nodes, the Radiation Therapy Oncology Group and European Society for Radiotherapy and Oncology guidelines are the most widely used internationally. These guidelines have been formulated based on anatomic boundaries of areas historically covered in 2-dimensional field-based radiation therapy but have not been validated by patterns-of-failure studies. In recent years, an important body of data has emerged from mapping studies documenting patterns of local and regional recurrence. We aim to review, discuss, and compare contouring guidelines for breast cancer radiation therapy in the context of contemporary data on locoregional relapse to improve their implementation in modern practice., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Several new systemic therapy options have become available for patients with metastatic breast cancer, which have led to improvements in survival. In addition to patient and clinical factors, the treatment selection primarily depends on the tumor biology (hormone-receptor status and HER2-status). The NCCN Guidelines specific to the workup and treatment of patients with recurrent/stage IV breast cancer are discussed in this article.

While there is now Level I data with long-term follow-up supporting the routine use of hypofractionated (HF) whole-breast radiation therapy (WBRT) after breast-conserving surgery, its adoption has been slow and variable. This article will review the literature supporting the efficacy and safety of hypofractionated radiation for breast cancer, discuss the radiobiological rationale specific to breast tumors, and make an argument for justifying the routine adoption of shorter, HF-WBRT courses when delivering breast radiation. Data using HF with regional nodal irradiation and in the post-mastectomy setting will also be reviewed. The aim is to provide an in-depth understanding of the use of hypofractionated radiation therapy for breast cancer, its applicability, and topics warranting future research., (© 2020 Wiley Periodicals, Inc.)

Purpose: The purpose of the study was to evaluate the incidental dose delivered to the internal mammary nodes (IMNs) in patients treated with tangential 3-dimensional conformal radiation therapy and to identify potential parameters that may affect the IMN mean dose., Methods and Materials: The study cohort consisted of 362 consecutively treated patients with breast cancer in our center between January 2015 and July 2017 who had received adjuvant whole-breast radiation therapy or postmastectomy radiation with or without a supraclavicular ± axillary field and without intentional inclusion of the IMN chain. The clinical target volume (CTV) for the IMNs was contoured per the Radiation Therapy Oncology Group 3509/3510 protocol and was then divided into 3 subregions: upper, mid, and lower thirds. The planning target volume for the IMNs was generated by adding 5 mm to the CTV. The primary endpoint was to assess the V40 (volume receiving 40 Gy) to the IMN planning target volume and its potential influencing parameters using a linear regression model., Results: The mean (±standard deviation) dose to the CTV IMN chain was 36% ± 28.7%. The Kruskal-Wallis test demonstrated significant differences in the median dose delivered to each level: upper third (7.2%), mid third (21.5%), and lower third (41.7%) (P < .001). The mean V40 IMN planning target volume was 14.2% (standard deviation, 18.7%). Presternal fat thickness (regression coefficient [RC] = -16.4; P < .001), postmastectomy radiation (RC = 24; P < .001), reconstruction after mastectomy (RC = -22.4; P < .001), and the addition of a supraclavicular field (RC = 8.8; P = .03) were all significantly associated with IMN mean dose., Conclusions: For patients receiving standard breast/chest wall tangential radiation fields, the IMN chain is not incidentally covered with therapeutic doses in the vast majority of cases. Therefore, if regional nodal radiation is intended to include the IMNs, contouring and careful plan review are necessary to ensure adequate therapeutic coverage., (Copyright © 2019 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: There still exist some arguments regarding the use of postmastectomy radiotherapy (PMRT) for patients with breast cancer carrying one to three positive axillary lymph nodes considering the heterogeneity of this cohort. Here, we developed a prognostic nomogram to estimate the probability of long-term outcome in patients receiving or not receiving PMRT in order to assist in making individually locoregional treatment decisions for this particular cohort., Methods: Altogether, 20,336 women, aged 18 to 80 years, diagnosed with breast cancer, and carrying one to three positive nodes were identified in the Surveillance, Epidemiology, and End Results (SEER) database. We applied multivariant Cox hazard model to determine the impact of covariates on disease-specific survival (DSS) and overall survival (OS). Then, the nomogram was built accordingly. Internal and external validations were performed to examine the accuracy of nomograms., Results: Age of diagnosis, tumor grade, size, estrogen and progesterone receptor status, and number of positive nodes were independent factors of DSS and OS in the multivariate analysis. Incorporating these factors into the constructed nomogram showed high accuracy when predicting 5- and 10-year survival, with internally and externally bootstrap-corrected concordance indexes in the range of 0.6 to 0.8., Conclusion: Besides the number of involved nodes, extra variables existed as predictors of survival outcomes in this cohort; therefore, the recommendation of PMRT or no PMRT requires comprehensive consideration. This clinically validated nomogram provided a useful tool that could aid decision making by estimating DSS and OS benefits from PMRT, useful in predicting 5- and 10-year DSS and OS for patients with one to three positive nodes after mastectomy., Implications for Practice: This study evaluated population-based data to identify prognostic factors associated with patients with breast cancer with one to three lymph nodes and help clinicians to weigh the benefit of postmastectomy radiotherapy (PMRT). Surveillance, Epidemiology, and End Results (SEER) data were used to develop a prognostic nomogram to predict the likelihood of long-term survival with and without PMRT in order to optimize the individual locoregional control strategy for this particular cohort. This clinically validated nomogram provides a useful tool to predict 5- and 10-year disease-specific survival and overall survival for patients with one to three positive nodes and can aid tailored clinical decision making by estimating predicted benefit from PMRT., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2019.)

Invasive ductal carcinoma (IDC) often presents alone or with a co-existing ductal carcinoma in situ component (IDC + DCIS). Studies have suggested that pure IDC may exhibit different biological behavior than IDC + DCIS, but whether this translates to a difference in outcomes is unclear. Here, utilizing the National Cancer Database we identified 494,801 stage I-III breast cancer patients diagnosed with either IDC alone or IDC + DCIS. We found that IDC + DCIS was associated with significantly better overall survival (OS) compared to IDC alone (5-year OS, 89.3% vs. 85.5%, p < 0.001), and this finding persisted on multivariable Cox modeling adjusting for demographic, clinical, and treatment-related variables. The significantly superior OS observed for IDC + DCIS was limited to patients with invasive tumor size < 4 cm or with node negative disease. A greater improvement in OS was observed for tumors containing ≥25% DCIS component. We also found IDC + DCIS to be associated with lower T/N stage, low/intermediate grade, ER/PR positivity, and receipt of mastectomy. Thus, the presence of a DCIS component in patients with IDC is associated with favorable clinical characteristics and independently predicts improved OS. IDC + DCIS could be a useful prognostic factor for patients with breast cancer, particularly if treatment de-escalation is being considered for small or node negative tumors.

The progression of localized breast cancer to distant metastasis results in a poor prognosis and a high mortality rate. In this study, the contributions of miRNAs to tumor progression and the regulatory mechanisms leading to their expression alterations were investigated. Using highly lung-metastatic sub-lines from parental breast cancer cells, miRNA expression profiling revealed that the miR-17-92 cluster is significantly downregulated and the miR-18a-5p is the most evidently decreased. Ectopic expression and inhibition of miR-18a-5p demonstrated its capacity in suppressing migration and invasion of breast cancer cells. Further research identified sterol regulatory element binding transcription protein 1 (SREBP1), the master transcription factor that controls lipid metabolism, as a candidate target of miR-18a-5p. SREBP1 is overexpressed and strongly associated with worse clinical outcomes in breast cancer. Functionally SREBP1 promotes growth and metastasis of breast cancer both in vitro and in vivo. To unravel the underlying mechanism of SREBP1-mediated metastasis, mRNA profiling and subsequent gene set enrichment analyses (GSEA) were performed and SREBP1 was demonstrated to be significantly associated with epithelial-mesenchymal transition (EMT). Furthermore, SREBP1-mediated repression of E-cadherin was found to be deacetylation dependent and was augmented by recruiting Snail/HDAC1/2 repressor complex. In the light of these data, we propose that reduced expression of miR-18a-5p and concomitant overexpression of SREBP1 lead to induction of EMT states that in turn, promote breast cancer progression and metastasis. Taken together, our study reveals the crucial role of miR-18a-5p and SREBP1 in the EMT and metastasis, thus providing promising drug targets for tailored therapy in the advanced breast cancer setting.

Purpose: Three-dimensional conformal accelerated partial breast irradiation (APBI) is a treatment option for well selected women with breast cancer, despite reports of adverse cosmetic outcome with this technique. Dose-volume relationships may be responsible for this poor cosmesis. We aimed to determine the feasibility of limiting the exposure of nontarget breast tissue to radiation through smaller planning target volumes achieved through daily image guidance and 4-dimensional computed tomography simulation., Methods and Materials: Eligibility criteria included the following: women, age ≥50 years, Karnofsky performance status score ≥70, stage 0 and I breast cancer treated with breast-conserving surgery, margins clear by ≥2 mm, pathologic tumor size ≤2 cm, and 4-dimensional computed tomography with planning target volumes of 0.2 cm rather than the standard 1.0 cm. A dose of 3850 cGy was prescribed in 10 fractions. The study was considered successful if ≥50% of enrollees met dosimetric constraints on the breast (V50 < 45% and V100 < 23.5%)., Results: The study achieved its primary endpoint of feasibility of reducing the nontarget breast dose with a breast median of V50 = 31% and V100 = 11%. There were no recurrences and no toxicity grade >3. At baseline, fair/poor cosmesis was low (2.2%). By year 3, adverse cosmesis post-APBI had increased by 13.2% (to 15.4%). Patient decisional satisfaction was reached completely in 84.2% of patients., Conclusions: This study demonstrated that with 4-dimensional simulated APBI that uses stringent dosimetric constraints and image guidance radiation therapy, it is possible to obtain acceptable cosmetic outcomes. We report no locoregional recurrences in 3 years and no toxicity grade >3. The observed decline in cosmesis was acceptable compared with that of prior published studies, and patient satisfaction with APBI was excellent., (Copyright © 2019 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: Despite delays between diagnosis and surgery adversely affecting survival, patients frequently transfer their breast cancer care between institutions. This study was performed to assess the prevalence and effect of such transfers of care (TsOC) on the time to surgery, and its impact on current time-dependent breast cancer quality metrics at Commission on Cancer (CoC) and National Accreditation Program for Breast Centers (NAPBC)-accredited institutions., Methods: Patients having non-metastatic invasive breast cancer diagnosed between 2006 and 2015 at CoC and NAPBC centers ("reporting facilities") in the National Cancer Database were reviewed. TsOC refer to transferring into or out of a reporting facility between diagnosis and surgery., Results: Among 622,793 patients, 36.6% of patients transferred care. TsOC add 7.3, 7.8, 8.7, and 9.8 days in time to surgery, chemotherapy, radiotherapy, and endocrine therapy, respectively (p's < 0.0001). On multivariable analysis, the odds of surgery occurring > 90 days from diagnosis were greatest for patients undergoing unilateral or bilateral mastectomy, Black or Hispanic patients, and those having TsOC (ORs > 1.73, p's < 0.0001). TsOC increase the odds of non-compliance, per patient, for chemotherapy, radiotherapy and endocrine therapy time-dependent measures by 65.4%, 25.6%, and 56.5%, respectively (p < 0.0001)., Conclusions: TsOC for newly diagnosed breast cancers to or from an accredited facility result in delays in time to surgery which can affect compliance with time-dependent quality measures. Facilities frequently receiving transferred patients may be most adversely affected. Although non-compliance with these quality measures is low, institutions and accrediting bodies should be aware of these associations in order to comply with time-dependent standards.

These NCCN Guidelines Insights highlight the updated recommendations for use of multigene assays to guide decisions on adjuvant systemic chemotherapy therapy for women with hormone receptor-positive, HER2-negative early-stage invasive breast cancer. This report summarizes these updates and discusses the rationale behind them., (Copyright © 2019 by the National Comprehensive Cancer Network.)

Background: Limited data exists demonstrating the clinical benefit of proton radiotherapy (PRT) in breast cancer. Using the National Cancer Database, we evaluated predictors associated with PRT use for patients with breast cancer. An exploratory analysis also investigates the impact of PRT on overall survival (OS). Methods: Patients with non-metastatic breast cancer treated with adjuvant radiotherapy from 2004 to 2014 were identified. Patients were stratified based on receipt of PRT or non-PRT (i.e., photons ± electrons). A logistic regression model was used to determine predictors for PRT utilization. For OS, Multivariable analysis (MVA) was performed using Cox proportional hazard model. Results: A total of 724,492 patients were identified: 871 received PRT and 723,621 received non-PRT. 58.3% of the PRT patients were group stage 0-1. Median follow-up time was 62.2 months. On multivariate logistic analysis, the following factors were found to be significant for receipt of PRT (all p < 0.05): academic facility (odds ratio [OR] = 2.50), South (OR = 2.01) and West location (OR = 12.43), left-sided (OR = 1.21), ER-positive (OR = 1.59), and mastectomy (OR = 1.47); pT2-T4 disease predicted for decrease use (OR = 0.79). PRT was not associated with OS on MVA for all patients: Hazard Ratio: 0.85, p = 0.168. PRT remained not significant on MVA after stratifying for subsets likely associated with higher heart radiation doses, including: left-sided ( p = 0.140), inner-quadrant ( p = 0.173), mastectomy ( p = 0.095), node positivity ( p = 0.680), N2-N3 disease ( p = 0.880), and lymph node irradiation (LNI) ( p = 0.767). Conclusions: Receipt of PRT was associated with left-sided, ER+ tumors, mastectomy, South and West location, and academic facilities, but not higher group stages or LNI. PRT was not associated with OS, including in subsets likely at risk for higher heart doses. Further studies are required to determine non-OS benefits of PRT. In the interim, given the high cost of protons, only well-selected patients should receive PRT unless enrolled on a clinical trial.

Background: The SSO-ASTRO-ASCO consensus guideline on margins for breast-conserving surgery with whole breast irradiation in ductal carcinoma in situ (DCIS) recommended a 2-mm margin. We sought to determine the impact of guideline publication on clinician practice., Methods: A total of 3081 members of the American Society of Breast Surgeons (ASBrS) received a survey. Respondents' clinical practice type and duration, guideline familiarity, and margin width preferences before and after publication were assessed. Clinical practice pattern differences before and after publication were investigated using McNemar's test., Results: A total of 767 (24.9%) of those surveyed responded. Most (92.4%) indicated guideline familiarity. Of those familiar, re-excision preference for DCIS and a positive margin remained the same before (94.4%) and after (94.3%) publication (McNemar's test p = 1.0). Following publication, surgeons were more likely to avoid re-excision to achieve margins wider than 2-mm (82.3% pre versus 87.5% post, p = 0.002). More surgeons performed re-excision for a close margin with pure DCIS (25.9% pre versus 36.5% post, p < 0.001) and with DCIS with microinvasion (DCIS-M) (40.7% pre versus 52.3% post, p < 0.001). For patients with invasive disease with extensive intraductal component (EIC) and a close margin, preference to avoid re-excision was similar (51.2% per versus 55.2% post, p = 0.071)., Conclusion: Since guideline publication, surgeons are less likely to perform re-excision to obtain a margin greater than 2-mm and more likely to perform re-excision to obtain a 2-mm margin for both pure DCIS and DCIS-M. Preference to avoid re-excision with a close margin and EIC was similar before and after publication.

Ductal carcinoma in situ (DCIS) of the breast represents a heterogeneous group of neoplastic lesions in the breast ducts. The goal for management of DCIS is to prevent the development of invasive breast cancer. This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS., (Copyright © 2018 by the National Comprehensive Cancer Network.)

Endocrine responsiveness of primary breast cancers with borderline estrogen receptor expression (ER + [1%-9%]) remains unclear. We aimed at investigating differences in endocrine responsiveness, prognosis, and clinicopathological characteristics between the ER + (1%-9%) cohort and the ER - cohort or ER + (≥10%) cohort. Eligible literature published from inception to November 20, 2016 was retrieved from the PubMed database on the basis of Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data on survival outcomes were extracted and pooled odds ratios (ORs), 95% confidence intervals (CIs), and 2-tailed P values are reported. P values of the χ 2 test for comparison of clinicopathological characteristics among included patients in the ER + (1%-9%) cohort and the other 2 cohorts were calculated respectively. The analysis included 6 studies with 16,606 patients. Significant differences were detected between the ER + (1%-9%) cohort and the other 2 cohorts on the basis of clinicopathological characteristics respectively. When taking all of the patients into analysis without consideration of treatment modality, the ER + (1%-9%) cohort presented better prognosis than the ER - group in terms of 5-year disease-free survival (OR, 1.47; P = .046) and 5-year overall survival (OR, 1.23; P = .046). However, patients with ER + (1%-9%) breast cancer who received endocrine therapy seemed to have a prognosis similar to those without any endocrine therapy (P = .684) and those with ER - carcinoma who received endocrine therapy (P = .145). Patients with ER + (≥10%) tumors had better endocrine responsiveness compared with their ER + (1%-9%) counterparts (OR, 0.52; P = .034, ER + [1%-9%] vs. ER + [≥10%]). Our results indicate that primary breast cancer patients with ER + (1%-9%) expression gained no significant survival benefit from endocrine therapy, but manifested overall better prognosis than those with ER - cancer., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Significant technologic advances in radiation treatment delivery now allow for more personalized delivery considerations which incorporate individual patient characteristics (such as tumor location and patient anatomy) and more precise delivery in the breast conservation or post-mastectomy setting. The combined advancements with other treatment modalities (i.e., systemic therapy, surgical management) have had direct effects on local-regional management and outcomes such that currently, local-regional relapses after definitive treatment for localized disease are now rarely experienced. Recent advances in the radiation therapy field have come from careful patient selection for a variety of three-dimensional treatment delivery techniques and alternatives to conventional tangential radiation. These advances have been demonstrated to diminished acute/long-term toxicity, minimized dose to surrounding normal tissue structures such as the heart and lung, and ultimately result in an improvement in the therapeutic ratio for radiation treatment. This chapter discusses recent radiation innovations and appropriate patient selection for their application, for a more personalized approach to radiation therapy for breast cancer patients.

Background: Women ≥70 years old with clinically (c) lymph node (LN) negative (-), hormone receptor (HR) positive (+) breast cancer are recommended not to be routinely staged with a sentinel LN biopsy. We sought to determine how this affects adjuvant decision-making., Methods: Statistical analyses were performed to determine the association of LN evaluation with adjuvant chemotherapy and radiation therapy in cLN-, HR + breast cancer patients in the National Cancer Database., Results: Between 2004 and 2013, there were 193,728 patients aged 70-90 with cLN-, HR + breast cancer; 15.0% were LN+. LN + patients were more likely to receive chemotherapy (28.3% vs. 5.5%, p < 0.001), hormonal therapy (83.6% vs. 71.4%, p < 0.001), post-lumpectomy radiation therapy (81.4% vs. 73.6%, p < 0.001) and post-mastectomy radiation therapy (30.3% vs. 5.1%, p < 0.001)., Conclusion: 15% of patients aged 70-90 will be LN+. These patients more frequently receive systemic and radiation therapy. LN status may affect treatment in these patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Importance: The use of a radiotherapy (RT) boost to the tumor bed after whole-breast RT (WBRT) for ductal carcinoma in situ (DCIS) is largely extrapolated from invasive cancer data, but robust evidence specific to DCIS is lacking., Objective: To compare ipsilateral breast tumor recurrence (IBTR) in women with DCIS treated with vs without the RT boost after breast-conserving surgery and WBRT., Design, Setting, and Participants: This retrospective analysis pooled deidentified patient-level data from 10 academic institutions in the United States, Canada, and France from January 1, 1980, through December 31, 2010. All patients had newly diagnosed pure DCIS (no microinvasion), underwent breast-conserving surgery, and received WBRT with or without the boost with a minimum of 5 years of follow-up required for inclusion in the analysis. Given the limited events after WBRT, an a priori power analysis was conducted to estimate the DCIS sample size needed to detect the anticipated benefit of the boost. Data were uniformly recoded at the host institution and underwent primary and secondary reviews before analysis. Sample size calculations (ratio of patients who received the boost dose to those who did not, 2:1; α = .05; power = 80%) estimated that 2982 cases were needed to detect a difference of at least 3%. The final analysis included 4131 patients (2661 in the boost group and 1470 in the no-boost group) with a median follow-up of 9 years and media boost dose of 14 Gy. Data were collected from July 2011 through February 2014 and analyzed from March 2014 through August 2015., Interventions: Radiotherapy boost vs no boost., Main Outcomes and Measures: Ipsilateral breast tumor recurrence., Results: The analysis included 4131 patients (median [SD] age, 56.1 [10.9] years; range, 24-88 years). Patients with positive margins, unknown estrogen receptor status, and comedo necrosis were more likely to have received an RT boost. For the entire cohort, the boost was significantly associated with lower IBTR (hazard ratio [HR], 0.73; 95% CI, 0.57-0.94; P = .01) and with IBTR-free survival (boost vs no-boost groups) of 97.1% (95% CI, 0.96-0.98) vs 96.3% (95% CI, 0.95-0.97) at 5 years, 94.1% (95% CI, 0.93-0.95) vs 92.5% (95% CI, 0.91-0.94) at 10 years, and 91.6% (95% CI, 0.90-0.93) vs 88.0% (95% CI, 0.85-0.91) at 15 years. On multivariable analysis accounting for confounding factors, the boost remained significantly associated with reduced IBTR (HR compared with no boost, 0.68; 95% CI, 0.50-0.91; P = .01) independent of age and tamoxifen citrate use., Conclusions and Relevance: This patient-level analysis suggests that the RT boost confers a statistically significant benefit in decreasing IBTR across all DCIS age groups, similar to that seen in patients with invasive breast cancer. These findings suggest that a DCIS RT boost to the tumor bed could be considered to provide an added incremental benefit in decreasing IBTR after a shared discussion between the patient and her radiation oncologist.

Nearly all women who receive radiotherapy (RT) for breast cancer experience some degree of radiation dermatitis. However, evidence describing the appropriate management of radiation dermatitis is often lacking or contradictory. Here, we summarize the available literature regarding radiation dermatitis causes, the presentation and timing of symptoms, methods for dermatitis assessment and prevention, and review evidence-based management strategies., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

These NCCN Guidelines Insights highlight the important updates/changes to the surgical axillary staging, radiation therapy, and systemic therapy recommendations for hormone receptor-positive disease in the 1.2017 version of the NCCN Guidelines for Breast Cancer. This report summarizes these updates and discusses the rationale behind them. Updates on new drug approvals, not available at press time, can be found in the most recent version of these guidelines at NCCN.org., (Copyright © 2017 by the National Comprehensive Cancer Network.)

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 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. Conclusion 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.

Purpose: Controversy exists regarding the optimal negative margin width for ductal carcinoma in situ (DCIS) treated with breast-conserving surgery and whole-breast irradiation., 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 7,883 patients and other published literature as the evidence base for consensus., Results: Negative 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., Conclusion: Use 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.

Purpose: Controversy exists regarding the optimal negative margin width for ductal carcinoma in situ (DCIS) treated with breast-conserving surgery and whole-breast irradiation., Methods and Materials: 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 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., Conclusion: Use 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., Competing Interests: NOTIFICATION The authors have no conflicts of interest to disclose., (Copyright © 2016. Published by Elsevier Inc.)

Radiotherapy is a critical treatment strategy for breast cancer. However, its wide application is sometimes restricted by radioresistance and radiotoxicity. Trametes robiniophila Murr. (Huaier), an officinal fungus used as a traditional Chinese medicine (TCM), is reported to have multi-biological functions during cancer treatment. Yet, its radiosensitization effects have not been evaluated to date. In the present study, using HTA 2.0 transcriptome microarray assay, Huaier was found to downregulate genes related to the cell cycle, cell division, cell cycle phases and DNA repair. This investigation utilized a colony formation assay to confirm the ability of Huaier to sensitize breast cancer cells to radiotherapy. Flow cytometry, immunofluorescence staining and western blotting were used to illustrate the sensitization mechanism. Our findings suggest that Huaier causes G0/G1 arrest through downregulation of cell cycle-regulating proteins in MCF-7 and MDA-MB-468 cells, prolongs the persistence of γ-H2Ax foci after radiotherapy and interferes with the homologous recombination (HR) pathway of DNA repair by downregulating RAD51. These results suggest that Huaier has the ability to sensitize breast cancer cells to radiotherapy through regulation of the cell cycle and DNA repair pathway. Thus, Huaier may be a promising radiosensitizer for the treatment of breast cancer.

Introduction: Inflammatory breast cancer (IBC) is an aggressive and rare cancer with a poor prognosis and a need for novel targeted therapeutic strategies. Preclinical IBC data showed strong activation of the phosphatidylinositide-3-kinase/mammalian target of rapamycin (mTOR) and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways, and expression of inflammatory cytokines and tumor-associated macrophages (TAMs)., Patients and Methods: Archival tumor tissue from 3 disease types (IBC treated with neoadjuvant chemotherapy [NAC], n = 45; invasive ductal carcinoma [IDC] treated with NAC [n = 24; 'treated IDC'; and untreated IDC [n = 27; 'untreated IDC']) was analyzed for the expression of biomarkers phospho-S6 (pS6) (mTOR), phospho-JAK2 (pJAK2), pSTAT3, interleukin (IL)-6, CD68 (monocytes, macrophages), and CD163 (TAMs). Surrounding nontumor tissue was also analyzed., Results: Biomarker levels and surrogate activity according to site-specific phosphorylation were shown in the tumor tissue of all 3 disease types but were greatest in IBC and treated IDC and least in untreated IDC for pS6, pJAK2, pSTAT3, and IL-6. Of 37 IBC patients with complete biomarker data available, 100% were pS6-positive and 95% were pJAK2-positive. In nontumor tissue, biomarker levels were observed in all groups but were generally greatest in untreated IDC and least in IBC, except for JAK2., Conclusion: IBC and treated IDC display similar levels of mTOR and JAK2 biomarker activation, which suggests a potential mechanism of resistance after NAC. Biomarker levels in surrounding nontumor tissue suggested that the stroma might be activated by chemotherapy and resembles the oncogenic tumor-promoting environment. Activation of pS6 and pJAK2 in IBC might support dual targeting of the mTOR and JAK/STAT pathways, and the need for prospective studies to investigate combined targeted therapies in IBC., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The recently published SSO-ASTRO consensus guideline on margins concluded "no ink on tumor" is the standard for an adequate margin. This study was conducted to determine how this guideline is aligned with current clinical practice., Methods: A survey was sent to 3057 members of the American Society of Breast Surgeons. Questions assessed respondents' clinical practice type and duration, familiarity with the guideline, and preferences for margin re-excision., Results: Of those surveyed, 777 (25%) responded. Most (92%) indicated familiarity with the guideline. Of these respondents, the majority (n = 678, or 94.7%) would re-excise all or most of the time when tumor extended to the inked margin. Very few (n = 9, or 1.3%) would re-excise all or most of the time when tumor was within 2 mm of the margin. Over 12 % (n = 90) would re-excise all or most of the time for a triple-negative tumor within 1 mm of the margin, whereas 353 (49.6%) would re-excise all or most of the time when imaging and pathology were discordant, and tumor was within 1 mm of multiple margins. Finally, 330 (45.8%) would re-excise all or most of the time when multiple foci of ductal carcinoma in situ extended to within 1 mm of multiple inked margins., Conclusions: Surgeons are in agreement to re-excise margins when tumor touches ink and generally not to perform re-excisions when tumor is close to (but not touching) the inked margin. For more complex scenarios, surgeons are utilizing their individual clinical judgment to determine the need for re-excision.