Oncogenic lncRNA downregulates cancer cell antigen presentation and intrinsic tumor suppression.

How tumor cells genetically lose antigenicity and evade immune checkpoints remains largely elusive. We report that tissue-specific expression of the human long noncoding RNA LINK-A in mouse mammary glands initiates metastatic mammary gland tumors, which phenotypically resemble human triple-negative breast cancer (TNBC). LINK-A expression facilitated crosstalk between phosphatidylinositol-(3,4,5)-trisphosphate and inhibitory G-protein-coupled receptor (GPCR) pathways, attenuating protein kinase A-mediated phosphorylation of the E3 ubiquitin ligase TRIM71. Consequently, LINK-A expression enhanced K48-polyubiquitination-mediated degradation of the antigen peptide-loading complex (PLC) and intrinsic tumor suppressors Rb and p53. Treatment with LINK-A locked nucleic acids or GPCR antagonists stabilized the PLC components, Rb and p53, and sensitized mammary gland tumors to immune checkpoint blockers. Patients with programmed ccll death protein-1(PD-1) blockade-resistant TNBC exhibited elevated LINK-A levels and downregulated PLC components. Hence we demonstrate lncRNA-dependent downregulation of antigenicity and intrinsic tumor suppression, which provides the basis for developing combinational immunotherapy treatment regimens and early TNBC prevention.

Patient-reported Quality of Life After Breast-conserving Surgery With Radiotherapy Versus Mastectomy and Reconstruction.

OBJECTIVE: To compare long-term quality of life (QOL) outcomes in breast cancer survivors who received breast-conserving surgery with radiotherapy (BCS+RT) with those who received a mastectomy and reconstructive surgery (Mast+Recon) without radiotherapy and identify other important factors. BACKGROUND: The long-term differences in patient-reported QOL outcomes following BCS+RT and Mast+Recon are not well understood. METHODS: We identified patients from the Texas Cancer Registry with stage 0-II breast cancer diagnosed in 2009-2014 after BCS+RT or Mast+Recon without radiotherapy. Sampling was stratified by age and race and ethnicity. A paper survey was sent to 4800 patients which included validated BREAST-Q and PROMIS modules. Multivariable linear regression models were implemented for each outcome. Minimal clinically important difference for BREAST-Q and PROMIS modules, respectively, was 4 points and 2 points. RESULTS: Of 1215 respondents (25.3% response rate), 631 received BCS+RT and 584 received Mast+Recon. The median interval from diagnosis to survey completion was 9 years. In adjusted analysis, Mast+Recon was associated with worse BREAST-Q psychosocial well-being (effect size: -3.80, P =0.04) and sexual well-being (effect size: -5.41, P =0.02), but better PROMIS physical function (effect size: 0.54, P =0.03) and similar BREAST-Q satisfaction with breasts, physical well-being, and PROMIS upper extremity function ( P >0.05) compared with BCS+RT. Only the difference in sexual well-being reached clinical significance. Older (≥65) patients receiving BCS+RT and younger (<50) patients receiving autologous Mast+Recon typically reported higher QOL scores. Receipt of chemotherapy was associated with detriments to multiple QOL domains. CONCLUSIONS: Patients who underwent Mast+Recon reported worse long-term sexual well-being compared with BCS+RT. Older patients derived a greater benefit from BCS+RT, while younger patients derived a greater benefit from Mast+Recon. These data inform preference-sensitive decision-making for women with early-stage breast cancer.

Leveraging the Multidisciplinary Tumor Board for Dissemination of Evidence-Based Recommendations on the Staging and Treatment of Gastric Cancer: A Pilot Study.

BACKGROUND: Compliance with evidence-based treatment guidelines for gastric cancer across the United States is poor. This pilot study aimed to create and evaluate a change package for disseminating information on the staging and treatment of gastric cancer during multidisciplinary tumor boards and for identifying barriers to implementation. METHODS: The change package included a 10-min video, a brief knowledge assessment, and a discussion guide. Commission on Cancer-accredited sites that perform gastrectomy were invited to participate. Participants completed the Organizational Readiness for Implementing Change (ORIC) scale (range, 12-60) and scales to measure the feasibility, acceptability, and appropriateness (score range, 4-20). Semi-structured interviews were conducted to further define inner and outer setting barriers. RESULTS: Seven centers participated in the study. A total of 74 participants completed the pre-video knowledge assessment, and 55 participants completed the post-video assessment. The recommendations found to be most controversial were separate staging laparoscopy and modified D2 lymphadenectomy. Sum scores were calculated for acceptability (mean, 17.43 ± 2.51) appropriateness (mean, 16.86 ± 3.24), and feasibility (mean, 16.14 ± 3.07) of the change package. The ORIC scores (mean, 46.57 ± 8.22) correlated with responses to the open-ended questions. The key barriers identified were patient volume, skills in the procedures, and attitudes and beliefs. CONCLUSIONS: The change package was moderately to highly feasible, appropriate, and acceptable. The activity identified specific recommendations for gastric cancer care that are considered controversial and local barriers to implementation. Future efforts could focus on building skills and knowledge as well as the more difficult issue of attitudes and beliefs.

To Dissect or Not to Dissect: Can We Predict the Presence of Four or More Axillary Lymph Node Metastases in Postmenopausal Women with Clinically Node-Negative Breast Cancer?

BACKGROUND: Axillary lymph node (ALN) involvement is important for prognosis and guidance of multidisciplinary treatment of breast cancer patients. This study sought to identify preoperative clinicopathologic factors predictive of four or more pathologically positive ALNs in patients with cN0 disease and to develop a predictive nomogram to inform therapy recommendations. METHODS: Using an institutional prospective database, the study identified postmenopausal women with cN0 invasive breast cancer undergoing upfront sentinel lymph node biopsy (SLNB) with or without completion ALND (cALND) between 1993 and 2007. Logistic regression analyses identified factors predictive of four or more positive nodes in the cN0 population and patients with one, two, or more SLNs. RESULTS: The study identified 2532 postmenopausal women, 615 (24.3%) of whom underwent cALND. In the univariate analysis, tumor size, lymphovascular (LVI), histology, estrogen receptor (ER)-positive status, and multifocality/multicentricity were predictive of four or more positive nodes (n = 63; p < 0.05), and all except ER status were significant in the multivariate analysis. Of the 2532 patients, 1263 (49.2%) had hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative disease, and 30 (2.4%) were found to have four or more positive nodes. Of the 130 patients with exactly one positive SLN who underwent cALND (n = 130, 5.4%), 7 had four or more positive nodes, with grade as the only predictive factor (p = 0.01). Of the 33 patients with two or more positive SLNs who underwent cALND, 9 (27.3%) had four or more positive nodes after cALND, but no factors were predictive in this subset. CONCLUSION: Postmenopausal women with early-stage cN0 HR-positive, HER2-negative breast cancer with a single positive SLN had a very low risk (5%) of having four or more positive nodes on final pathology. With such a low risk of N2 disease, limited staging with SLNB may be sufficient to guide therapy decisions for this subset of patients.

A Randomized Phase II Study of Sequential Eribulin Versus Paclitaxel Followed by FAC/FEC as Neoadjuvant Therapy in Patients with Operable HER2-Negative Breast Cancer.

LESSONS LEARNED: The combination of eribulin with 5-fluorouracil, either doxorubicin or epirubicin, and cyclophosphamide (FAC/FEC) was not superior to the combination of paclitaxel with FAC/FEC and was associated with greater hematologic toxicity. Eribulin followed by an anthracycline-based regimen is not recommended as a standard neoadjuvant therapy in nonmetastatic operable breast cancer. BACKGROUND: Neoadjuvant systemic therapy is the standard of care for locally advanced operable breast cancer. We hypothesized eribulin may improve the pathological complete response (pCR) rate compared with paclitaxel. METHODS: We conducted a 1:1 randomized open-label phase II study comparing eribulin versus paclitaxel followed by 5-fluorouracil, either doxorubicin or epirubicin, and cyclophosphamide (FAC/FEC) in patients with operable HER2-negative breast cancer. pCR and toxicity of paclitaxel 80 mg/m2 weekly for 12 doses or eribulin 1.4 mg/m2 on days 1 and 8 of a 21-day cycle for 4 cycles followed by FAC/FEC were compared. RESULTS: At the interim futility analysis, in March 2015, 51 patients (28 paclitaxel, 23 eribulin) had received at least one dose of the study drug and were thus evaluable for toxicity; of these, 47 (26 paclitaxel, 21 eribulin) had undergone surgery and were thus evaluable for efficacy. Seven of 26 (27%) in the paclitaxel group and 1 of 21 (5%) in the eribulin group achieved a pCR, and this result crossed a futility stopping boundary. In the paclitaxel group, the most common serious adverse events (SAEs) were neutropenic fever (grade 3, 3 patients, 11%). In the eribulin group, nine patients (39%) had neutropenia-related SAEs, and one died of neutropenic sepsis. The study was thus discontinued. For the paclitaxel and eribulin groups, the 5-year event-free survival (EFS) rates were 81.8% and 74.0% (hazard ratio [HR], 1.549; 95% confidence interval [CI], 0.817-2.938; p = .3767), and the 5-year overall survival (OS) rates were 100% and 84.4% (HR, 5.813; 95% CI, 0.647-52.208; p = .0752), respectively. CONCLUSION: We did not observe a higher proportion of patients undergoing breast conservation surgery in the eribulin group than in the paclitaxel group. The patients treated with eribulin were more likely to undergo mastectomy and less likely to undergo breast conservation surgery, but the difference was not statistically significant. As neoadjuvant therapy for operable HER2-negative breast cancer, eribulin followed by FAC/FEC is not superior to paclitaxel followed by FAC/FEC and is associated with a higher incidence of neutropenia-related serious adverse events.

Impact of SSO-ASTRO "No Ink on Tumor" Guidelines on Reexcision Rates among Older Breast Cancer Patients.

BACKGROUND: The SSO-ASTRO consensus guideline on invasive breast cancer defined negative margin as no ink on tumor, obviating the need for reexcision in some patients. We evaluated the impact of these recommendations on the rates of reexcision in older breast cancer patients undergoing breast-conserving surgery (BCS). PATIENTS AND METHODS: Women age ≥ 66 years with stage I-II breast cancer who underwent BCS and radiation were identified in the SEER-Medicare linked database (2012-2015). We divided patients into three cohorts: pre-guideline (January 2012 to September 2013), peri-guideline (October 2013 to March 2014), and post-guideline (April 2014 to September 2016). Descriptive statistics were used, and the relative change in reexcision rate between the pre- and post-guideline periods was calculated. Multivariable logistic regression was used to evaluate factors associated with risk of reexcision. RESULTS: A total of 11,639 patients were included (pre-guideline, N = 5211; peri-guideline, N = 1366; post-guideline, N = 5062); overall, 21.7% of patients underwent reexcision. The reexcision rates decreased after the guideline was published (23.5% vs. 19.3%, p < 0.001). In the multivariable model, BCS during the post-guideline period was associated with a statistically significant decreased risk of reexcision (RR = 0.84; 95% CI 0.78-0.90). Lobular histology was associated with a higher risk of reexcision (RR = 1.32; 95% CI 1.19-1.46), and greater surgeon volume was associated with lower risk of reexcision (RR = 0.92; 95% CI 0.85-1.0). CONCLUSIONS: Among older breast cancer patients undergoing BCS for invasive cancer, reexcision rates decreased with the dissemination of the SSO-ASTRO consensus guideline. Identifying factors associated with higher rates of reexcision could improve guideline compliance and reduce the frequency of unnecessary interventions in older patients.

Clinical Course of Breast Cancer Patients with Local-Regional Progression During Neoadjuvant Systemic Therapy.

BACKGROUND: Neoadjuvant systemic therapy (NST) is standard for locally advanced breast cancer and is now frequently considered for those with early-stage and node-positive disease. We aimed to evaluate the treatment course and outcomes in patients with disease progression during NST. METHODS: Patients diagnosed with unilateral stage I-III breast cancer between 2005 and 2015 with documented local-regional progression while receiving NST, by clinical examination and/or imaging after two or more cycles of chemotherapy, were identified from a prospective database, stratified by receipt of surgery and outcomes analyzed. RESULTS: Of 6362 patients treated with NST during the study period, 124 (1.9%) developed disease progression. At a median live follow-up of 71 months, 23.4% were alive without disease and 70.2% had died from breast cancer. Median overall survival (OS) time for patients with progression was 26 months and median distant disease-free survival (DFS) was 14 months. Triple-negative breast cancer was associated with a higher likelihood of death (p < 0.001) and development of distant metastasis (p = 0.002). Among patients who had surgery (104, 89.3%), 40 (38.5%) developed local-regional recurrence, 67 (64.4%) developed distant metastasis, and 69 (66.3%) died from breast cancer. Median OS and median distant DFS in this subgroup was 31 and 16 months, respectively. CONCLUSIONS: High rates of local-regional and distant failure were seen following disease progression while receiving NST. This suggests aggressive tumor biology and the need to study novel systemic therapies. Poor survival outcomes despite surgical management highlight the importance of careful patient selection when considering operative intervention after progression while receiving NST.

Surgical Outcomes in Cancer Patients Undergoing Elective Surgery After Recovering from Mild-to-Moderate SARS-CoV-2 Infection.

BACKGROUND: An increasing number of patients with cancer diagnoses and prior SARS-CoV-2 infection will require surgical treatment. The objective of this study was to determine whether a history of SARS-CoV-2 infection increases the risk of adverse postoperative events following surgery in patients with cancer. METHODS: This was a propensity-matched cohort study from April 6, 2020 to October 31, 2020 at the UT MD Anderson Cancer Center. Cancer patients were identified who underwent elective surgery after recovering from SARS-CoV-2 infection and matched to controls based on patient, disease, and surgical factors. Primary study outcome was a composite of the following adverse postoperative events that occurred within 30 days of surgery: death, unplanned readmission, pneumonia, cardiac injury, or thromboembolic event. RESULTS: A total of 5682 patients were included for study, and 114 (2.0%) had a prior SARS-CoV-2 infection. The average time from infection to surgery was 52 (range 20-202) days. Compared with matched controls, there was no difference in the rate of adverse postoperative outcome (14.3% vs. 13.4%, p = 1.0). Patients with a SARS-CoV-2-related inpatient admission before surgery had increased odds of postoperative complication (adjusted odds ratio [aOR] 7.4 [1.6-34.3], p = 0.01). CONCLUSIONS: A minimal wait time of 20 days after recovering from minimally symptomatic SARS-CoV-2 infection appears to be safe for cancer patients undergoing low-risk elective surgery. Patients with SARS-CoV-2 infections requiring inpatient treatment were at increased risk for adverse events after surgery. Additional wait time may be required in those with more severe infections.

Prospective Registry Trial Assessing the Use of Magnetic Seeds to Locate Clipped Nodes After Neoadjuvant Chemotherapy for Breast Cancer Patients.

BACKGROUND: Targeted axillary dissection (TAD) involves locating and removing both clipped nodes and sentinel nodes for assessment of the axillary response to neoadjuvant chemotherapy (NAC) by clinically node-positive breast cancer patients. Initial reports described radioactive seeds used for localization, which makes the technique difficult to implement in some settings. This trial was performed to determine whether magnetic seeds can be used to locate clipped axillary lymph nodes for removal. METHODS: This prospective registry trial enrolled patients who had biopsy-proven node-positive disease with a clip placed in the node and treatment with NAC. A magnetic seed was placed under ultrasound guidance in the clipped node after NAC. All the patients underwent TAD. RESULTS: Magnetic seeds were placed in 50 patients by 17 breast radiologists. All the patients had successful seed placement at the first attempt (mean time for localization was 6.1 min; range 1-30 min). The final position of the magnetic seed was within the node (n = 44, 88%), in the cortex (n = 3, 6%), less than 3 mm from the node (n = 2, 4%), or by the clip when the node could not be adequately visualized (n = 1, 2%). The magnetic seed was retrieved at surgery from all the patients. In 49 (98%) of the 50 cases, the clip and magnetic seed were retrieved from the same node. Surgeons rated the transcutaneous and intraoperative localization as easy for 43 (86%) of the 50 cases. No device-related adverse events occurred. CONCLUSIONS: Localization and selective removal of clipped nodes can be accomplished safely and effectively using magnetic seeds.

Anatomy and physiology of the sentinel lymph nodes of the upper extremity: Implications for axillary reverse mapping in breast cancer.

BACKGROUND: This study characterizes the physiological drainage of the normal upper extremity using single-photon emission computed tomography/computed tomography (SPECT/CT) lymphoscintigraphy axillary reverse lymphatic mapping (ARM). METHODS: A consecutive series of patients assessed with SPECT/CT lymphoscintigraphy ARM of the upper extremity were included. Anatomical localization of the axillary sentinel lymph nodes (SLN) was completed in normal axillae in relation to consistent anatomic landmarks. Retrospective case note analysis was performed to collect patient demographic data. RESULTS: A total of 169 patients underwent SPECT/CT lymphoscintigraphy, and imaging of 182 normal axillae was obtained. All patients (100%) had an axillary SLN identified: 19% had a single contrast-enhanced SLN in the axilla and the remainder had multiple. The SLN(s) of the upper extremity was located in the upper outer quadrant (UOQ) of the axilla in 97% of cases (177 axillae). When the SLN(s) was found in the UOQ of the axilla, second-tier lymph nodes were found predominantly in the upper inner quadrant (50% of cases). CONCLUSIONS: The upper extremity SLN(s) is located in a constant region of the axilla. This study provides the most complete investigation to date and results can be directly applied clinically to ARM techniques and adjuvant radiation planning.

Acceptability of 3D-printed breast models and their impact on the decisional conflict of breast cancer patients: A feasibility study.

PURPOSE: To evaluate the acceptability and impact of 3D-printed breast models (3D-BMs) on treatment-related decisional conflict (DC) of breast cancer patients. METHODS: Patients with breast cancer were accrued in a prospective institutional review board-approved trial. All patients underwent contrast-enhanced breast magnetic resonance imaging (MRI). A personalized 3D-BM was derived from MRI. DC was evaluated pre- and post-3D-BM review. 3D-BM acceptability was assessed post-3D-BM review. RESULTS: DC surveys before and after 3D-BM review and 3D-BM acceptability surveys were completed by 25 patients. 3D-BM were generated in two patients with bilateral breast cancer. The mean patient age was 48.8 years (28-72). The tumor stage was Tis (7), 1 (8), 2 (8), and 3 (4). The nodal staging was 0 (19), 1 (7), and 3 (1). Tumors were unifocal (15), multifocal (8), or multicentric (4). Patients underwent mastectomy (13) and segmental mastectomy (14) with (20) or without (7) oncoplastic intervention. Neoadjuvant therapy was given to seven patients. Patients rated the acceptability of the 3D-BM as good/excellent in understanding their condition (24/24), understanding disease size (25/25), 3D-BM detail (22/25), understanding their surgical options (24/25), encouraging to ask questions (23/25), 3D-BM size (24/25), and impartial to surgical options (17/24). There was a significant reduction in the overall DC post-3D-BM review, indicating patients became more assured of their treatment choice (p = 0.002). Reduction post-3D-BM review was also observed in the uncertainty (p = 0.012), feeling informed about options (p = 0.005), clarity about values (p = 0.032), and effective (p = 0.002) Decisional Conflict Scale subscales. CONCLUSIONS: 3D-BMs are an acceptable tool to decrease DC in breast cancer patients.

Cancer Surgery Scheduling During and After the COVID-19 First Wave: The MD Anderson Cancer Center Experience.

OBJECTIVE: To summarize the multi-specialty strategy and initial guidelines of a Case Review Committee in triaging oncologic surgery procedures in a large Comprehensive Cancer Center and to outline current steps moving forward after the initial wave. SUMMARY OF BACKGROUND DATA: The impetus for strategic rescheduling of operations is multifactorial and includes our societal responsibility to minimize COVID-19 exposure risk and propagation among patients, the healthcare workforce, and our community at large. Strategic rescheduling is also driven by the need to preserve limited resources. As many states have already or are considering to re-open and relax stay-at-home orders, there remains a continued need for careful surgical scheduling because we must face the reality that we will need to co-exist with COVID-19 for months, if not years. METHODS: The quality officers, chairs, and leadership of the 9 surgical departments in our Division of Surgery provide specialty-specific approaches to appropriately triage patients. RESULTS: We present the strategic approach for surgical rescheduling during and immediately after the COVID-19 first wave for the 9 departments in the Division of Surgery at The University of Texas MD Anderson Cancer Center in Houston, Texas. CONCLUSIONS: Cancer surgeons should continue to use their oncologic knowledge to determine the window of opportunity for each surgical procedure, based on tumor biology, preoperative treatment sequencing, and response to systemic therapy, to safely guide patients through this cautious recovery phase.

Performance and Clinical Utility of Models Predicting Eradication of Nodal Disease in Patients with Clinically Node-Positive Breast Cancer Treated with Neoadjuvant Chemotherapy by Tumor Biology.

INTRODUCTION: Prediction models are useful to guide decision making. Our goal was to compare three published nomograms predicting axillary response to neoadjuvant chemotherapy (NAC), clinically node-positive breast cancer. METHODS: Patients with cT1-T4, cN1-N3 breast cancer treated with NAC and surgery from 2008 to 2019 were reviewed. The predicted probability of pathologic node-negative (ypN0) status was estimated for each nomogram. Area under the curve (AUC) was compared across models, overall and by biologic subtype. RESULTS: Of 581 patients, 253 (43.5%) were ypN0. ypN0 status varied by subtype: 23.9% for estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-), 68.9% for HER2-positive (HER2+), and 47.2% for ER-negative (ER-)/HER2-. The three nomograms had similar AUC values (0.761-0.769; p = 0.80). The Mayo model-predicted probability was significantly lower (p < 0.001) than the observed probability of ypN0 status, while the MD Anderson Cancer Center (MDACC) 1- and 2-predicted probabilities were similar to the observed probability. At a predicted probability threshold of 50%, the Mayo model had the highest sensitivity (89.6%) for detecting ypN+ patients compared with MDACC models 1 and 2 (76.5%; p < 0.001). However, both MDACC models had higher specificity in identifying ypN0 status among HER2+ (81.7%) and ER-/HER2- (75.9-77.6%) patients compared with the Mayo model (59.5% and 43.1%; each p < 0.001). None of the models identified the ER+/HER2- patients with ypN0 status well at the ≥ 50% threshold (specificity 0-9.4%). CONCLUSION: All three models predicting nodal response to NAC performed well overall with respect to discrimination, but differed with respect to calibration and performance at a 50% probability threshold. However, none of the models performed well at the 50% threshold for ER+/HER2- patients.

Opioid Use after Breast-Conserving Surgery: Prospective Evaluation of Risk Factors for High Opioid Use.

BACKGROUND: Responsible opioid prescribing for postoperative pain control is critical. We sought to identify both patient and surgical factors associated with increased opioid use after breast-conserving surgery (BCS). METHODS: Patients (N = 316) undergoing BCS were surveyed to determine postoperative opioid use. Univariate and multivariate analyses were used to determine factors contributing to increased opioid use (highest quartile of use). All opioid prescriptions were converted to oral morphine equivalents (OME) for analysis. RESULTS: The mean opioid prescription was 33.2 OMEs. Fourteen patients (4.4%) did not receive a narcotic prescription at discharge. Seventy-eight patients (24.7%) did not take any opioids after discharge. Those in the highest quartile of use consumed more than 50 OMEs. Surgical factors, such as bilateral oncoplastic surgery (60.8 OMEs vs. 33.1 OMEs, p = 0.0001), axillary lymph node dissection (ALND) (61.5 vs. 30.5, p = 0.0003), and drain use (2 drains 71.1, 1 drain 40.4, no drains 26.2, p = 0.0001), were associated with higher opioid use. In a multivariate analysis, smoking, preoperative opioid use, bilateral oncoplastic surgery, high postoperative reported pain score, placement of at least one surgical drain, and receiving a discharge prescription greater than 150 OMEs were associated with the highest quartile of opioid use. CONCLUSIONS: Smoking, preoperative opioid use, bilateral oncoplastic surgery, ALND, use of surgical drains, high reported postoperative pain score, and receiving a higher OME discharge prescription are associated with higher postoperative opioid use. Given the wide variability of analgesic needs, these criteria should be used to guide the appropriate tailoring of opioid prescriptions.

Sonographic features of benign and malignant axillary nodes post-neoadjuvant chemotherapy.

The aim was to determine whether sonographic features of metastatic axillary lymph nodes predict pathologic nodal status post-neoadjuvant chemotherapy (NCT) and help to tailor less invasive surgical management of the axilla. Patients with biopsy-proven cN1 primary breast malignancy who received NCT between January 2011 and December 2014 and had performed ultrasound were included in this study. Sonographic features of biopsy-proven clipped metastatic axillary nodes pre- and post-NCT were retrospectively reviewed by two independent readers. Changes in lymph node shape, fatty hilum status, cortical thickness, and cortical echogenicity were compared in patients with and without nodal pathologic complete response (pCR) using univariate and multivariate logistic regression models. Inter-reader variation was analyzed to determine the reproducibility of data. Of the 195 patients included in the study, 75 (45%) showed nodal pCR and 90 (55%) persistent metastatic disease post-NCT. pCR was significantly more likely in lymph nodes with isoechoic or hypoechoic cortical echogenicity post-NCT, (P = .02), conversion to normal cortical thickness (P = .0001), and oval shape (odds ratio = 0.17, P = .004), compared to lymph nodes with anechoic cortical echogenicity, persistent or diffuse cortical thickening, and irregular shape, respectively. The overall accuracy of sonographic nodal features in the prediction of pCR was 65% (95% CI: 58%-72%). The overall accuracy of sonographic features of biopsy-proven metastatic axillary lymph nodes post-NCT is not sufficiently high to predict pCR of axillary nodal status and thereby should not be solely used in guiding less invasive surgical approaches to the axilla.

Feasibility of fine-needle aspiration for assessing responses to chemotherapy in metastatic nodes marked with clips in breast cancer: A prospective registry study.

BACKGROUND: Clips are often placed to mark axillary nodes with biopsy-confirmed metastases in patients with breast cancer. The evaluation of clipped nodes after chemotherapy can identify patients who have eradication of nodal disease. The goal of this study was to determine whether preoperative fine-needle aspiration (FNA) of clipped nodes after neoadjuvant chemotherapy (NAC) could predict the presence of residual disease. METHODS: This prospective registry study enrolled 50 patients with a clip placed to mark nodes with biopsy-confirmed metastases who had completed NAC. Participants underwent FNA of the clipped node before seed-localized lymph node excision. FNA pathology was compared with surgical pathology. RESULTS: There were 36 patients (72%) with residual disease on surgical pathology: 3 (8%) had a nondiagnostic aspirate, carcinoma was seen in 14 (39%), and 19 (53%) had a false-negative result. The sensitivity of FNA was 42.4%, its specificity was 100%, and its negative predictive value was 40.6%. In a univariate analysis, the odds of a true-positive result increased significantly with the mean initial size of the clipped node (odds ratio [OR], 4.3; P = .004) and the size of the metastatic focus after NAC (OR, 1.3; P = 0.003), whereas normalization of nodes after chemotherapy (OR, 0.1) and a lack of response on ultrasound (OR, 0.11) were associated with a false-negative result (P = .01). CONCLUSIONS: FNA of marked nodes after chemotherapy has a high false-negative rate. This highlights the need for surgical staging of the axilla after NAC to assess the response.

Facilitation of Surgical Innovation: Is It Possible to Speed the Introduction of New Technology While Simultaneously Improving Patient Safety?

OBJECTIVE: To review efficiency metrics and patient safety data before and after implementation of a structured review process for surgical innovations. SUMMARY BACKGROUND DATA: Surgical innovation ranges from minor incremental improvement to radical experimentation. Although innovation paradigms have been described, these are not widely adopted or enforced in the surgical community. METHODS: A Continuous Quality Improvement Team (CQIT) of surgical quality officers and perioperative nurses was organized to perform structured reviews of proposed new surgical devices and procedures at a large quaternary cancer care center. The CQIT process was placed to precede an established Value Analysis Team business evaluation. Pre- and post-CQIT implementation metrics of approval process efficiency and patient safety data were compared. Seven novel procedures were also vetted by the CQIT. RESULTS: Forty-six product requests were evaluated after CQIT implementation. Compared with 34 products evaluated prior to CQIT establishment, the total mean evaluation time decreased from 124 to 51 days (P= 0.007). For new devices requiring intraoperative trial, the time between product proposal and trial decreased from a mean of 260 to 99 days (P= 0.014). The rate of device-related complications in the pre-CQIT group was 10% compared with 0% post-CQIT. Two devices, which administratively bypassed CQIT review, had both minor and major complications, including a mortality. Five novel procedures approved by CQIT with simulation were performed without complications. CONCLUSIONS: Using novel algorithms, the addition of a dedicated team of surgical quality officers to the surgical innovation evaluation process improved both the efficiency and the safety associated with introducing new devices and procedures into practice.

Evolution in practice patterns of axillary management following mastectomy in patients with 1-2 positive sentinel nodes.

PURPOSE: The optimal management of breast cancer patients with a positive sentinel lymph node (SLN) who undergo mastectomy remains controversial. This study aimed to describe treatment patterns of patients with positive SLNs who undergo mastectomy using a large population-based database. METHODS: The NCDB was queried for cT1-2N0 breast cancer patients treated with mastectomy between 2006 and 2014 who had 1-2 positive SLNs. Patients receiving neoadjuvant chemotherapy were excluded. Axillary management included SLN dissection (SLND) alone, axillary lymph node dissection (ALND), post-mastectomy radiation (PMRT) alone, and ALND + PMRT. Trends of axillary management and patient characteristics were examined. RESULTS: Among 12,190 patients who met study criteria, the use of ALND dropped with a corresponding increase in other approaches. In 2006, 34% of patients had SLND alone, 47% ALND, 8% PMRT and 11% ALND + PMRT. By 2014, 37% had SLND, 23% ALND, 27% PMRT and 13% ALND + PMRT. Patients who underwent SLND alone were older (mean 60.6 years) with more comorbidities (Charlson-Deyo score > 2), smaller primary tumors (mean 2.1 cm), well-differentiated histology, hormone receptor-positive, HER2-negative tumors, without lymphovascular invasion (all P values < 0.01). Treatment with SLND alone was more likely if patients had only one positive SLN (P < 0.001) or micrometastatic disease (P < 0.001), and were treated at community centers compared with academic centers (P < 0.001). CONCLUSIONS: The management of breast cancer patients undergoing mastectomy with positive SLNs has evolved over time with decreased use of ALND and increased use of radiation. Some patient subsets are underrepresented in recent clinical trials, and therefore, future trials should focus on these patients.

Sentinel Node Lymph Node Surgery After Neoadjuvant Therapy: Principles and Techniques.

Surgical management of the axilla in breast cancer has been a topic of great interest. While sentinel lymph node biopsy (SLNB) is an established approach for patients undergoing surgical treatment as the first element of their care, there is continued debate regarding surgical management of the axilla in patients receiving neoadjuvant chemotherapy (NAC). In clinically node-negative patients, it has been debated whether or not SLNB should be performed before chemotherapy to accurately determine the clinical stage, or after chemotherapy, thus prioritizing the response to therapy and potentially minimizing axillary surgery. Node-positive patients have undergone axillary lymph node dissection in the past, however this paradigm has been challenged in recent years. Thus, surgeons must understand the importance of accurate axillary information both before and after NAC, and its role in multidisciplinary planning. We present a summary of the data surrounding axillary management in patients receiving NAC, and recommendations for surgical technique.

Neoadjuvant Chemotherapy does not Increase Complications in Oncoplastic Breast-Conserving Surgery.

BACKGROUND: Oncoplastic breast-conserving surgery (OBCS) broadens the indications for breast conservation. Neoadjuvant systemic chemotherapy (NAC) is used increasingly in the treatment of patients with early-stage and locally advanced breast cancer. This study aimed to evaluate the outcomes for patients who received NAC followed by OBCS. METHODS: A retrospective chart review was performed for all patients who underwent OBCS involving the mastopexy/breast-reduction technique, including synchronous mastopexy/breast reduction for symmetry, at the University of Texas MD Anderson Cancer Center between January 2010 and January 2016. Patients who had received NAC were compared with those who had undergone surgery first. Demographic, treatment, and outcomes data were collected. RESULTS: The study included 429 patients, corresponding to 713 breasts. Of these patients, 122, corresponding to 199 breasts, received NAC. The patients who received NAC were younger (p < 0.001) and had a more advanced cancer stage (p < 0.001). The overall complication rate per patient was 25.9%, with major complications occurring in 9.1% of the patients. After adjustment for risk factors, NAC was not shown to be associated with an increased risk of complications or delayed adjuvant radiation therapy (p = 0.37), irrespective of the chemotherapy regimen used or whether the interval between NAC and surgery was 4 weeks or longer. CONCLUSIONS: In a high-volume center, OBCS can be performed safely for carefully selected patients after NAC without an increased risk of complications or delayed adjuvant radiation therapy. An interval of at least 4 weeks between completion of NAC and surgery can be regarded as safe irrespective of the chemotherapy regimen used.