Underuse of Postoperative Radiation After Nipple-Sparing Mastectomy for Standard Radiation Indications.

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.

Hypofractionated vs Conventionally Fractionated Postmastectomy Radiation After Implant-Based Reconstruction: A Randomized Clinical Trial.

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 Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology.

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.

Post-mastectomy radiation therapy after breast reconstruction: from historic dogmas to practical expert agreements based on a large literature review of surgical and radiation therapy considerations.

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.

Omission of Radiotherapy After Breast-Conserving Surgery for Women With Breast Cancer With Low Clinical and Genomic Risk: 5-Year Outcomes of IDEA.

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.

NCCN Guidelines® Insights: Breast Cancer, Version 4.2023.

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.

Radiation Therapy for Low-Risk Breast Cancer: Whole, Partial, or None?

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.

DCIS: Risk Assessment in the Molecular Era.

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.

Breast Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.

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.

The Impact of Radiotherapy Delay in Breast Conservation Patients Not Receiving Chemotherapy and the Rationale for Dichotomizing the Radiation Oncology Time-Dependent Standard into Two Quality Measures.

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.

Cancer Misinformation and Harmful Information on Facebook and Other Social Media: A Brief Report.

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).

Benefit of Deep Inspiratory Breath Hold for Right Breast Cancer When Regional Lymph Nodes Are Irradiated.

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 V20/V5 (volumes of lung receiving 20 Gy and 5 Gy, respectively); mean heart dose and heart V5 (volumes of heart receiving 5 Gy); liver V20 absolute /V30 absolute (absolute volume of liver receiving 20 Gy and 30 Gy, respectively), liver Dmax, and total liver volume irradiated (TVIliver). 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 V20 (40.7%-31.7%, P < .001), lung V5 (61.2%-54.5%, P < .001), TVIliver (1446 cc vs 1264 cc; P = .006) liver Dmax (50.2 Gy vs 48.9 Gy; P = .023), liver V20 (78.8-23.9 cc, P < .001), and liver V30 (58.1-14.6 cc, P < .001) compared with FB. DIBH use did not significantly improve heart parameters, although the V5Heart 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.

Decreasing the Interval Wait Times for Screening Mammogram Results Using the "Reflex Testing" Algorithm.

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.

NCCN Guidelines® Insights: Breast Cancer, Version 4.2021.

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.

A Delphi study and International Consensus Recommendations: The use of bolus in the setting of postmastectomy radiation therapy for early breast cancer.

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.

The use of bolus in postmastectomy radiation therapy for breast cancer: A systematic review.

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.

Special subtypes with favorable prognosis in breast cancer: A registry-based cohort study and network meta-analysis.

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.

Recommendations for prioritization, treatment, and triage of breast cancer patients during the COVID-19 pandemic. the COVID-19 pandemic breast cancer consortium.

The COVID-19 pandemic presents clinicians a unique set of challenges in managing breast cancer (BC) patients. As hospital resources and staff become more limited during the COVID-19 pandemic, it becomes critically important to define which BC patients require more urgent care and which patients can wait for treatment until the pandemic is over. In this Special Communication, we use expert opinion of representatives from multiple cancer care organizations to categorize BC patients into priority levels (A, B, C) for urgency of care across all specialties. Additionally, we provide treatment recommendations for each of these patient scenarios. Priority A patients have conditions that are immediately life threatening or symptomatic requiring urgent treatment. Priority B patients have conditions that do not require immediate treatment but should start treatment before the pandemic is over. Priority C patients have conditions that can be safely deferred until the pandemic is over. The implementation of these recommendations for patient triage, which are based on the highest level available evidence, must be adapted to current availability of hospital resources and severity of the COVID-19 pandemic in each region of the country. Additionally, the risk of disease progression and worse outcomes for patients need to be weighed against the risk of patient and staff exposure to SARS CoV-2 (virus associated with the COVID-19 pandemic). Physicians should use these recommendations to prioritize care for their BC patients and adapt treatment recommendations to the local context at their hospital.