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.

Timing of Unplanned Reoperation After Lower Extremity Free Flap Reconstruction: What Are the Roles of Procedure Indication and Defect Etiology?

BACKGROUND: Advancements in lower extremity (LE) microsurgery have allowed for the expansion of indications for LE reconstructions. This project aims to better understand the temporal pattern and risk factors associated with LE free flap failure based on the clinical indication. MATERIALS AND METHODS: We analyzed all patients undergoing LE free flap reconstruction from the American College of Surgeons National Surgical Quality Improvement Program 2012-2019 prospectively collected data to determine rates and timing of reoperation. Free flaps were stratified by indication, type, and timing of reoperation. Weibull survival models were used to compare rates of takebacks among time intervals. Multivariable logistic regression was used to identify independent predictors for unplanned reoperation. RESULTS: Four hundred seven of LE free flaps were analyzed. There was a 14.5% rate (59/407) of unplanned reoperation within the first 30 postoperative days (PODs) after surgery. When stratified by the indication necessitating reoperation, patients with an underlying vascular indication had the highest rate of reoperation (40.9%). The reoperation rates were significantly different between indications (P < 0.05) The mean daily proportion of patients experiencing reoperation was highest during POD 0 to 2 (1.47% reoperations per day), which dropped significantly during POD 3 to 10 (0.55% per day) and again during POD 11 to 30 (0.28% per day, P < 0.05). African American race as well as malignant, prosthetic/implant, and wound/infectious indications were significant independent predictors for unplanned reoperation. CONCLUSIONS: Lower extremity reconstruction is an important reconstructive option for the coverage of a myriad of defects. Understanding the differences between postoperative reoperation timelines among indication subtypes is important for updated flap monitoring protocols, optimizing ERAS pathways, and beginning dangle protocols.

Significant Reduction in Length of Stay in Deep Inferior Epigastric Perforator Flap Breast Reconstruction With Implementation of Multimodal ERAS Protocol.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) implementation achieves earlier recovery, reduced hospital length of stay (LOS) and improved outcomes in patients undergoing deep inferior epigastric perforator (DIEP) free flaps. We sought to review our ERAS protocols and their impact on our patients' LOS compared with the literature. METHODS: This was a retrospective review of a single surgeon's experience from 2017 to 2021 of patients undergoing DIEP free-flap breast reconstruction with LOS as the primary outcome. Complication rates and patient demographics are described as secondary outcomes. RESULTS: One hundred twenty-one patients underwent DIEP free-flap breast reconstruction. After adapting ERAS protocols, there has been a 0.98 [SD, 0.17; confidence interval [CI], -1.3 to -0.64; P < 0.001) day decrease in length of stay comparing pre-ERAS to post-ERAS implementation. Length of stay has routinely decreased from an average discharge on day 4.17 (SD, 1.1; range, 3-8 days) in 2017 to discharge on day 2.91 (SD, 1.1; range, 1-5 days) in 2021. Seventy-five percent of patients in 2021 were hospitalized for 3 or fewer days compared with 75% of patients in 2017 hospitalized for 4 or more days. One patient experienced a flap failure. Our study supports successful discharge on postoperative days 2-3 compared with postoperative days 3-4 in the current literature. CONCLUSIONS: The implementation of our ERAS protocol for DIEP free-flap breast reconstruction has resulted in a shorter LOS compared with contemporary literature. The ERAS protocols can be efficiently adopted in microsurgical DIEP breast reconstruction to achieve a shorter LOS without jeopardizing patient outcomes.

Safe perioperative tamoxifen use in autologous breast free flap reconstruction: systematic review and meta-analysis.

BACKGROUND: Perioperative tamoxifen remains a valuable therapeutic modality for breast cancer patients. Studies in the existing literature have suggested a potential increased risk of thrombotic complications in autologous breast free flap reconstruction patients exposed to tamoxifen perioperatively. However, several recent publications have questioned the validity of these associations. Therefore, we aim to perform a systematic appraisal of the existing literature to determine if perioperative tamoxifen exposure increases the risk of flap complications in autologous breast-free flap reconstruction patients. METHODS: A systematic literature search was performed using: PubMed, EMBASE, Cochrane Central, Web of Science, EBSCOHost, ClinicalTrials.gov, and TRIP databases from their inception up to April 2021. Articles analyzing the impact of perioperative tamoxifen in autologous breast free flap patients were included. The outcomes assessed were total flap loss, overall flap complications, thrombotic flap complications, which was defined as the sum of arterial and venous flap thrombi, and systemic venous thromboembolism (VTE). Pooled estimates and relative risk were calculated using a random effects model. RESULTS: 9294 Articles were screened and 7 were selected for analysis, which included 3669 flaps in 2759 patients. Compared to patients who did not receive tamoxifen perioperatively, those who received tamoxifen did not have an increased risk of thrombotic flap complications (pooled RR 1.06; 95% CI 0.61-1.84), total flap loss (pooled RR 2.17; 95% CI 0.79-5.95), overall flap complications (pooled RR 1.04; 95% CI 0.76-1.41), or systemic VTE (pooled RR 1.93; 95% CI 0.72-5.13). The heterogeneity of the studies was not significant for any of the outcomes. CONCLUSIONS: The purpose of this study was to update the current understanding of the impact of perioperative tamoxifen on autologous breast free flap reconstruction outcomes. The existing literature supports that the perioperative continuation of tamoxifen in breast free flap patients is not associated with an increased risk of thrombotic flap complications, total flap loss, overall flap complications, or systemic VTE.

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.

Critical Importance of the First Postoperative Days After Head and Neck Free Flap Reconstruction: An Analysis of Timing of Reoperation Using the National Surgical Quality Improvement Program Database.

BACKGROUND: Head and neck free flaps remain associated with considerable rates of take-back and prolonged hospital length of stay. However, there have been no studies on a national level benchmarking the timeline and predictors of head and neck free flap take-back. METHODS: Patients undergoing head and neck free flap reconstruction from the American College of Surgeons National Surgical Quality Improvement Program 2012-2019 database were analyzed to determine the rates of take-back. Timing and rates of unplanned head and neck free flap take-backs were stratified by tissue type and postoperative day (POD) over the first month. Weibull survival models were used to compare rates of take-backs among time intervals. Multivariable logistic regression was used to identify the independent predictors of take-back. RESULTS: Three thousand nine hundred six head and neck free flaps were analyzed. The mean daily proportion of patients experiencing take-back during PODs 0 to 1 was 0.95%; this dropped significantly to a mean daily proportion of 0.54% during POD 2 (P < 0.01). In addition, there were significant drops in take-back when comparing POD 2 (0.54%) to POD 3 (0.26%) and also when comparing POD 4 (0.20%) with PODs 5 to 30 (0.032% per day) (P < 0.05). The soft tissue and osseous flap populations demonstrated a similar trend in unplanned take-back. CONCLUSION: This is the first national study to specifically analyze the timing of take-back in the head and neck reconstruction population. These data highlight the importance of flap monitoring during the first 5 PODs, with ERAS pathway optimization aiming for discharge by the end of the first postoperative week.

Optimizing Abdominoplasty Surgical Site Morbidity Profiling Through an Effective and Nationally Validated Risk Scoring System.

BACKGROUND: Abdominoplasty complication rates are among the highest for cosmetic surgery. We sought to create a validated scoring system to predict the likelihood of wound complications after abdominoplasty using a national multi-institutional database. METHODS: Patients who underwent abdominoplasty in the American College of Surgeons National Surgical Quality Improvement Program 2007-2019 database were analyzed for surgical site complications, a composite outcome of wound disruption, and surgical site infections. The cohort was randomly divided into a 60% testing and a 40% validation sample. Multivariable logistic regression analysis was performed to identify independent predictors of complications using the testing sample (n = 11,294). The predictors were weighted according to ß coefficients to develop an integer-based clinical risk score. This system was validated using receiver operating characteristic analysis of the validation sample (n = 7528). RESULTS: A total of 18,822 abdominoplasty procedures were identified. The proportion of patients who developed a composite surgical site complication was 6.8%. Independent risk factors for composite surgical site complication included inpatient procedure (P < 0.01), smoking (P < 0.01), American Society of Anesthesiologists class ≥3 (P < 0.01), and body mass index ≥25.0 and ≤18.0 kg/m2 (P < 0.01). African American race was a protective factor against surgical site complications (P < 0.01). The factors were integrated into a scoring system, ranging from -5 to 42, and the receiver operating characteristic analysis revealed an area under the curve of 0.71. CONCLUSIONS: We present a validated scoring system for postoperative 30-day surgical site morbidity after abdominoplasty. This system will enable surgeons to optimize patient selection to decrease morbidity and unnecessary healthcare expenditure.

Nationally Validated Scoring System to Predict Unplanned Reoperation and Readmission after Breast Reduction.

BACKGROUND: Reduction mammoplasty continues to be a commonly sought procedure with complication rates ranging from 4.3 to 8.2%. In the current study, we sought to identify the clinical and preoperative risk factors for unplanned reoperation and readmission within the first postoperative month on a national scale. METHODS: Patients who underwent reduction mammoplasty from the ACS-NSQIP 2012-2019 database were analyzed to determine rates of reoperation and readmission within 30 days of the initial breast surgery. The cohort was divided into 60 and 40% random testing and validation samples. A multivariable logistic regression analysis was then performed to isolate independent factors of unplanned readmission and reoperation using the testing sample (n = 22,743). The predictors were weighted according to beta coefficients to develop an integer-based clinical risk score predictive of complications. This system was then validated using receiver operating characteristics (ROC) analysis of the validation sample (n = 15,162). RESULTS: A total of 37,905 reduction mammoplasties were analyzed. 1.3% of patients had an unplanned readmission. Independent risk factors for unplanned readmission included age older than the median of 44 years (p < 0.01), inpatient procedure (p < 0.01), smoking (p < 0.01), hypertension (p = 0.01), COPD (p < 0.05), BMI ≥ 35 (p < 0.01), and operation time greater than the median of 142 minutes ( p < 0.01). The factors were integrated into a scoring system, ranging from 0 to 36, and an ROC analysis revealed an area under the curve of 0.66. 1.9% of patients underwent unplanned reoperation. Independent risk factors for unplanned reoperation in this population included age older than the median of 44 years (p < 0.01), inpatient status (p < 0.01), and a history of bleeding disorders (p < 0.05). The factors were integrated into a scoring system, ranging from 0 to 25, and the ROC analysis revealed an area under the curve of 0.61. CONCLUSIONS: We present a validated scoring system to better inform patients about their risk for unplanned reoperation and readmission following reduction mammoplasty. This system will enable surgeons to optimize patient selection and interventions in order to decrease morbidity and unnecessary health-care expenditure. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Postoperative Complications Associated with the Choice of Reconstruction in Head and Neck Cancer: An Outcome Analysis of 4,712 Patients from the ACS-NSQIP Database.

BACKGROUND: Microsurgical free flaps have largely supplanted pedicled flaps as the gold standard for head and neck cancer reconstruction. However, incidence of postoperative complications after accounting for patient comorbidities based on choice of reconstruction has not been well-defined in the literature in recent years. METHODS: Patients undergoing head and neck reconstruction were identified in the 2011-2016 ACS-NSQIP (American College of Surgeons National Surgical Quality Improvement Program) database and stratified into groups by free flap, myocutaneous pedicled flap, and other reconstruction. Demographics were analyzed and covariates balanced using overlap propensity score-based weighting. Logistic regression was used for binary outcomes and Gamma generalized linear model was used for length of stay. RESULTS: A total of 4,712 patients met inclusion criteria out of which 1,297 patients (28%) underwent free flap, 208 patients (4%) pedicled flap, and 3,207 patients (68%) had other, or no reconstruction performed. After adjusting for patient and disease-specific factors, pedicled flap reconstruction was associated with a higher risk of deep vein thrombosis (odds ratio [OR] = 2.64, confidence interval [CI] 1.02-6.85, p = 0.045), sepsis (OR = 2.95, CI 1.52-5.71, p = 0.001), and infection (OR = 2.03, CI 1.39-2.96, p <0.001) compared with free flap reconstruction. Free flaps had the longest mean operative time compared with the other two groups (unadjusted 578 vs. 440 vs. 326, p <0.001). Pedicled flaps had a lower incidence of bleeding requiring transfusion (adjusted OR = 0.65, CI 0.50-0.85, p = 0.002), and lower incidence of prolonged mechanical ventilation (adjusted OR = 0.33, CI 0.12-0.92, p = 0.034) compared with free flaps. There was no difference in rates of reoperation, hospital readmission, or hospital length-of-stay between pedicled and free flaps. CONCLUSION: Myocutaneous pedicled flaps are associated with higher overall short-term postoperative complications compared with free flaps in head and neck reconstruction, which demonstrate a more favorable morbidity profile without significantly impacting hospital readmission, reoperation, or length-of-stay.

Early postoperative outcomes in implant, pedicled, and free flap reconstruction for breast cancer: an analysis of 23,834 patients from the ACS-NSQIP datasets.

INTRODUCTION: Many patients seek breast reconstruction following mastectomy. Debate exists regarding the best reconstructive option. The authors evaluate outcomes comparing implant, free flap, and pedicled flap reconstruction. METHODS: Patients undergoing implant, pedicled flap, and free flap reconstruction were identified in the 2011-2016 NSQIP database. Demographics were analyzed and covariates were balanced using overlap propensity score. Logistic regression was used for binary outcomes and Gamma GLM for length of stay (LOS). RESULTS: Of 23,834 patients, 87.7% underwent implant, 8.1% free flap, and 4.2% pedicled flap reconstruction. The implant group had the lowest mean operative time (206 min, SD 85.6). Implant patients had less pneumonia (OR 0.09, CI 0.02-0.36, p < 0.01), return to operating room (OR 0.62, CI 0.50-0.75, p < 0.01), venous thromboembolism (VTE) (OR 0.33, CI 0.14-0.79, p = 0.01), postoperative bleeding (OR 0.10, CI 0.06-0.15, p < 0.01), and urinary tract infections (UTI) (OR 0.21, CI 0.07-0.58, p < 0.01) than free flap patients. Pedicled flap patients had less postoperative bleeding (OR 0.69, CI 0.49-0.96, p = 0.03) than free flap patients. Pedicled flap patients had more superficial surgical site infections (p = 0.03), pneumonia (p = 0.02), postoperative bleeding (p < 0.01), VTE (p = 0.04), sepsis (p = 0.05), and unplanned reintubation (p = 0.01) than implant patients. Implant patients had the lowest LOS (1.6 days, p < 0.01). CONCLUSION: Implant reconstruction has less short-term postoperative complications than free flaps and pedicled flap reconstructions. The overall complication rate among all reconstructive modalities remains acceptably low and patients should be informed of all surgical options.

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.

Breast Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology.

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.

NCCN Guidelines Insights: Breast Cancer, Version 3.2018.

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.

A Theoretical Model Describing the Dynamics of Venous Flow in the DIEP Flap.

BACKGROUND: The deep inferior epigastric artery flap is an integral component of autologous breast reconstruction. The technical aspects of performing the flap have been well-established. A prior mathematical model suggested using the largest perforator and concluded that the inclusion of additional perforators may decrease resistance and increase flow, but at the downside of increased tissue trauma. Many complications may result from inadequate venous drainage of the flap and the same mathematical concepts may be applied. We attempt to give a mathematical model, based on the physics of flow and properties of circuits, to explain clinical observations regarding venous drainage of the flap and the complications that may arise. METHODS: We compare the different possible venous drainage systems of a perforator flap to a complex circuit with multiple resistances. Multiple venous perforators will be represented by resistances in parallel, while the deep and superficial drainage systems will be represented by a complex circuit loop. RESULTS: Drainage of the flap may be optimized through the deep drainage system if the venous perforators are of sufficient size. Inclusion of additional perforators may decrease resistance and enhance drainage. Salvage procedures may be necessary when the venous perforators are insufficient in size or when there are insufficient connections between the deep and superficial systems. CONCLUSION: A single large sized vessel may provide adequate drainage in most DIEP flaps, while the use of multiple vessels may enhance drainage upon the encounter of smaller vessels. Salvage procedures may be needed to relieve venous congestion as the design of the venous system becomes more complicated.

Breast Cancer, Version 4.2017, NCCN Clinical Practice Guidelines in Oncology.

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.

NCCN Guidelines Insights: Breast Cancer, Version 1.2017.

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.

Invasive Breast Cancer Version 1.2016, NCCN Clinical Practice Guidelines in Oncology.

Breast cancer is the most common malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. The overall management of breast cancer includes the treatment of local disease with surgery, radiation therapy, or both, and the treatment of systemic disease with cytotoxic chemotherapy, endocrine therapy, biologic therapy, or combinations of these. This article outlines the NCCN Guidelines specific to breast cancer that is locoregional (restricted to one region of the body), and discusses the management of clinical stage I, II, and IIIA (T3N1M0) tumors. For NCCN Guidelines on systemic adjuvant therapy after locoregional management of clinical stage I, II and IIIA (T3N1M0) and for management for other clinical stages of breast cancer, see the complete version of these guidelines at NCCN.org.

Asymptomatic Deep Peroneal Vein Thrombosis During Free Fibula Flap Harvest: A Review of the Literature, Strategies for Preoperative Assessment, and an Algorithm for Reconstruction.

The free fibula flap is the preferred reconstructive method for oncologic defects of the mandible. Arterial inflow of the extremity is routinely evaluated with several modalities; however, venous screening is rarely performed. Patients with cancer are at elevated risk of occult deep venous thrombosis (DVT). An asymptomatic thrombus encountered during free fibula reconstruction is a serious concern. Although such cases have been reported, we suspect the incidence of DVT during fibula free flap harvest is underappreciated. This monograph uses a case example to review risk factors for occult DVT, present a strategy for preoperative assessment, and provide a reconstructive algorithm to for mandibular reconstruction in such instances.

NCCN Guidelines Insights Breast Cancer, Version 1.2016.

These NCCN Guideline Insights highlight the important updates to the systemic therapy recommendations in the 2016 NCCN Guidelines for Breast Cancer. In the most recent version of these guidelines, the NCCN Breast Cancer Panel included a new section on the principles of preoperative systemic therapy. In addition, based on new evidence, the panel updated systemic therapy recommendations for women with hormone receptor-positive breast cancer in the adjuvant and metastatic disease settings and for patients with HER2-positive metastatic breast cancer. This report summarizes these recent updates and discusses the rationale behind them.