Search

The effect of postoperative sensation on quality-of-life (QoL) following nipple-sparing mastectomy (NSM) with implant-based reconstruction is not well described. We evaluated the impact of breast and nipple sensation on patient QoL by using BREAST-Q.Patients undergoing NSM with implant reconstruction from 2008 to 2020 were mailed a survey to characterize their postoperative breast and nipple sensation. BREAST-Q metrics were compared between totally numb patients and those with sensation.A total of 349 patients were included. Overall, 131 (38%) responded; response rates regarding breast and nipple sensation were 36% (N = 124/349) and 34% (N = 117/349). Median time from surgery to survey completion was 6 years. The majority had bilateral procedures (101, 77%), including direct-to-implant (99, 76%) and tissue expander (32, 24%) reconstruction. Regarding breast sensation, the majority of patients reported their reconstructed breasts as totally numb (47, 38%) or much less sensation than before surgery (59, 48%). Regarding nipple sensation, the majority of patients reported their nipples were totally numb (67, 57%) or had much less sensation than before surgery (37, 32%). Total numbness of reconstructed breasts resulted in a significantly lower chest physical well-being (mean score: 73.5 vs. 81.2, respectively, P = 0.048). Total numbness of postoperative nipple(s) resulted in significantly lower chest physical (mean score: 74.8 vs. 85.2, respectively, P = 0.007), psychosocial (mean score 77.4 vs. 84.4, respectively, P = 0.041), and sexual well-being (mean score: 55.7 vs. 68.3, respectively, P = 0.002).Long-term breast and nipple sensation are significantly diminished after NSM with implant reconstruction. Patients with preserved sensation experience better physical, psychosocial, and sexual well-being.

Enhanced recovery after surgery (ERAS) protocols following mastectomy with or without implant-based breast reconstruction (IBBR) include ketorolac for multimodal perioperative analgesia. There are concerns that ketorolac could be associated with increased risk of postoperative hematoma formation.Retrospective review of patients undergoing mastectomy with or without IBBR between January 2013 and December 2019 at a single institution. Patients received 15 mg, 30 mg, or no ketorolac depending on ERAS protocol adherence, patient characteristics, and surgeon preference. Clinically significant hematoma was defined as requiring surgical intervention on day of surgery or postoperative day 1. Patients were compared by demographics, surgical characteristics, ketorolac dose, and hematoma prevalence. Univariable and multivariable logistic regression evaluated hematoma formation odds.Eight hundred patients met inclusion criteria: 477 received ketorolac. Those who received ketorolac were younger, had lower ASA scores, were more likely to have bilateral procedures and undergo concomitant IBBR, had longer operative times, were less likely to take antiplatelet or anticoagulation medications, had higher PACU pain scores, and had higher incidence of hematomas requiring surgical intervention. Of the cohort, 4.4% had clinically significant hematomas. The 15 mg and 30 mg ketorolac groups had similar prevalence (6.0% vs 5.8%, p = 0.95). On univariable regression, there were increased odds of hematoma formation in patients who were younger, had bilateral procedures, had longer OR times, and who received ketorolac. On multivariable regression, none of the prior variables remained significant.After accounting for associations with longer operative times, concomitant IBBR, and bilateral procedures, ketorolac administration did not remain an independent risk factor for hematoma formation.

We hypothesized full-thickness chest wall resection (FTCWR) with advanced surgical techniques and modern systemic therapy is safe, provides local control, and good overall survival.Retrospective review of FTCWR (including rib or part of sternum) for breast cancer between 2000 and 2020. Primary endpoints included 90-day morbidities and all-cause mortality. Secondary endpoints were loco-regional and distant recurrence, DFS and overall survival (OS).A total of 35 patients met the criteria. 34 FTCWR were for recurrence and the median time to chest wall recurrence was 6 years. Tumor subtype was triple-negative in 51% and the remainder HR+ Her2-. 58% were palliative resections. FTCWR included rib(s) in 89% and portion of sternum in 57%; 94% required reconstruction and 80% were R0 resections. There were no 90-day mortalities. Overall morbidity was 10/35(28%). 17(49%) patients received neoadjuvant systemic therapy for their recurrence and three received neoadjuvant radiation. Adjuvant treatment included chemotherapy (8), endocrine therapy (3), and both (8). Ten patients (28%) received adjuvant radiation. The Median follow-up was 31 months and there were 6 (17%) loco-regional and 7 (20%) distant recurrences. OS was 86% and 67% at 1 and 3 years, respectively.FTCWR was associated with low morbidity, mortality, recurrence rates, and good OS. Selective FTCWR is safe and has acceptable short-term survival rates.

Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy that usually occurs in the head/neck or extremities. However, there are reports of MCC developing in the lymph nodes or parotid gland without evidence of a primary cutaneous lesion.We reviewed 415 patients with biopsy-proven MCC. Patients with MCC of unknown primary (n = 37, 9%, MCCUP) made up the study cohort. The primary endpoints of the study were rate of recurrence, disease-free survival, and overall survival.Patients with MCCUP presented with tumors in lymph nodes (n = 34) or parotid gland (n = 3). Nodal disease was most commonly detected in the inguinal/external iliac (n = 15) or axillary (n = 14) regions. The mean age at diagnosis was 70 years and 24% were female. Patients presented with distant metastases in 24.3% of cases. Patients with stage IIIA disease treated with regional lymph node dissection (RLND) had a lower risk of disease recurrence (hazard ratio 0.26, p = 0.046). Recurrence-free survival was 59.3% at 5 years. Disease-specific survival was 63.3% at 5 years.Patients with MCCUP have a high risk of recurrence and mortality. The optimal treatment for MCCUP has yet to be elucidated, although therapeutic RLND appears beneficial for these patients.

PURPOSE Distant metastases are present in 6% or more of patients with newly diagnosed breast cancer. In this context, locoregional therapy for the intact primary tumor has been hypothesized to improve overall survival (OS), but clinical trials have reported conflicting results. METHODS Women presenting with metastatic breast cancer and an intact primary tumor received systemic therapy for 4-8 months; if no disease progression occurred, they were randomly assigned to locoregional therapy for the primary site (surgery and radiotherapy per standards for nonmetastatic disease) or continuing sysmetic therapy. The primary end point was OS; locoregional control and quality of life were secondary end points. The trial design provided 85% power to detect a 19.3% absolute difference in the 3-year OS rate in randomly assigned patients. The stratified log-rank test and Cox proportional hazards model were used to compare OS between arms. Cumulative incidence of locoregional progression was compared using Gray's test. Quality-of-life assessment used standard instruments. RESULTS Of 390 participants enrolled, 256 were randomly assigned: 131 to continued systemic therapy and 125 to early locoregional therapy. The 3-year OS was 67.9% without and 68.4% with early locoregional therapy (hazard ratio = 1.11; 90% CI, 0.82 to 1.52; P = .57). The median OS was 53.1 months (95% CI, 47.9 to not estimable) in the systemic therapy arm and 54.9 months (95% CI, 46.7 to not estimable) in the locoregional therapy arm. Locoregional progression was less frequent in those randomly assigned to locoregional therapy (3-year rate: 16.3% v 39.8%; P < .001). Quality-of-life measures were largely similar between arms. CONCLUSION Early locoregional therapy for the primary site did not improve survival in patients presenting with metastatic breast cancer. Although it was associated with improved locoregional control, this had no overall impact on quality of life.

Malnutrition is common among patients with cancer and is a known risk factor for poor postoperative outcomes; however, preoperative nutritional optimization guidelines are lacking in this high-risk population. The objective of this study was to review the evidence regarding preoperative nutritional optimization of patients undergoing general surgical operations for the treatment of cancer.A literature search was performed across the Ovid (MEDLINE), Cochrane Library (Wiley), Embase (Elsevier), CINAHL (EBSCOhost), and Web of Science (Clarivate) databases. Eligible studies included randomized clinical trials, observational studies, reviews, and meta-analyses published between 2010 and 2020. Included studies evaluated clinical outcomes after preoperative nutritional interventions among adult patients undergoing surgery for gastrointestinal cancer. Data extraction was performed using a template developed and tested by the study team.A total of 5,505 publications were identified, of which 69 studies were included for data synthesis after screening and full text review. These studies evaluated preoperative nutritional counseling, protein-calorie supplementation, immunonutrition supplementation, and probiotic or symbiotic supplementation.Preoperative nutritional counseling and immunonutrition supplementation should be considered for patients undergoing surgical treatment of gastrointestinal malignancy. For malnourished patients, protein-calorie supplementation should be considered, and for patients undergoing colorectal cancer surgery, probiotics or symbiotic supplementation should be considered.

Genome-wide fragmentation patterns in cell-free DNA (cfDNA) in plasma are strongly influenced by cellular origin due to variation in chromatin accessibility across cell types. Such differences between healthy and cancer cells provide the opportunity for development of novel cancer diagnostics. Here, we investigated whether analysis of cfDNA fragment end positions and their surrounding DNA sequences reveals the presence of tumor-derived DNA in blood. We performed genome-wide analysis of cfDNA from 521 samples and analyzed sequencing data from an additional 2147 samples, including healthy individuals and patients with 11 different cancer types. We developed a metric based on genome-wide differences in fragment positioning, weighted by fragment length and GC content [information-weighted fraction of aberrant fragments (iwFAF)]. We observed that iwFAF strongly correlated with tumor fraction, was higher for DNA fragments carrying somatic mutations, and was higher within genomic regions affected by copy number amplifications. We also calculated sample-level means of nucleotide frequencies observed at genomic positions spanning fragment ends. Using a combination of iwFAF and nine nucleotide frequencies from three positions surrounding fragment ends, we developed a machine learning model to differentiate healthy individuals from patients with cancer. We observed an area under the receiver operative characteristic curve (AUC) of 0.91 for detection of cancer at any stage and an AUC of 0.87 for detection of stage I cancer. Our findings remained robust with as few as 1 million fragments analyzed per sample, demonstrating that analysis of fragment ends can become a cost-effective and accessible approach for cancer detection and monitoring.

Purpose Accurately predicting the clinical breast cancer subtypes could be extremely helpful for radiologists, pathologists, surgeons, and clinicians and inform future treatment prediction algorithms. Therefore, we evaluate and compare the accuracy of radiomic features extracted from contrast enhanced mammography (CEM) and magnetic resonance imaging (MRI) scans to make predictions to subtypes of breast cancer. Methods This HIPAA-compliant prospective single institution study was approved by the local institutional review board with written informed consent. Women with breast tumors 2 cm or larger underwent dynamic contrast-enhanced MRI and/or CEM for surgical staging. Semi-manual regions of interest were drawn by radiologist using Cancer Imaging Phenomics Toolkit (CaPTk). Radiomic features were obtained using PyRadiomics and MR- and CEM- based classification models were built on a low-dimensional representation of the features obtained via kernel principal component analysis. We subscribed to an ensemble tree-based learning approach called extremely randomized trees (ERT) to predict cancer subtypes captured via immunohistochemistry markers. Results For MRI analysis, 124 women with newly diagnosed breast cancer were included in the analysis comprising 49 HR+HER2-, 37 HR+HER2+, 11 HR-HER2+, and 27 HR-HER2- cases. For CEM analysis, models were built using data from 170 female patients including 74 HR+HER2-, 41 HR+HER2+, 14 HR-HER2+, and 43 HR-HER2-. CEM based model resulted in accuracies of 55%, 72%, 88%, and 71% respectively for HR+HER2-, HR+HER2+, HR-HER2+, and HR-HER2- whereas MRI based model alone led to accuracies of 54%, 62%, 89%, and 76% respectively for HR+HER2-, HR+HER2+, HR-HER2+, and HR-HER2-. Conclusions Radiomic features extracted from CEM and MR were strong predictors of breast cancer subtypes with CEM-based radiomic features performing slightly better, though not statistically significantly better (p = 0.82), than its MRI counterpart.

Background Capsular contracture causes pain, poor cosmesis, and reoperations. This study analyzes its incidence and risk factors in a more modern treatment era. Methods Patients undergoing mastectomy with implant reconstruction from 2010 to 18 were reviewed. Univariate and multivariate analysis evaluated rates and risk factors for capsular contracture. Results Among 451 patients, the majority underwent nipple-sparing mastectomy (262, 58.1%) with one-stage reconstruction (283, 62.7%) utilizing subpectoral implants (353, 77.4%) and acellular dermal matrix (354, 78.5%). Overall capsular contracture incidence was 9.8%; the rate after post-mastectomy radiation therapy (PMRT) was 18.7%, and 7.5% for patients without PMRT. Significant factors included neoadjuvant chemotherapy (P = 0.006), hematoma (P = 0.047), and PMRT (P = 0.001). Multivariate analysis showed that PMRT increased risk of capsular contracture (OR = 3.12, 95% CI 1.55–6.26, P = 0.001), and adjuvant chemotherapy was protective (OR = 0.289, 95% CI 0.114–0.731, P = 0.01). Conclusions Incidence of capsular contracture is lower than previously reported. Advancing therapeutic techniques may reduce the risk of this complication.

Study conducted to determine frequency and timing of unplanned breast implant removal after mastectomy, reconstruction, and postmastectomy radiation (PMRT). From 2010-2017, 52 patients underwent mastectomy, reconstruction, and PMRT. With median follow-up of 3.1 years, 23 patients (44%) experienced implant removal. Implant removal occurred in 9 (17%) patients before starting PMRT and 14 (27%) patients after starting PMRT. Implant removal rates were similar for hypofractionated PMRT compared with standard fractionation and for proton compared with photon PMRT. Implant removal is common for women undergoing mastectomy and reconstruction followed by PMRT. The risk is clinically significant even before starting radiation.

Our purpose was to report the results of a phase II trial of patients with breast cancer treated with hypofractionated whole breast radiation therapy (RT) before breast-conserving surgery (BCS).Between 2019 and 2020, patients with cT0-T2, N0, M0 breast cancer were enrolled. Patients were treated with hypofractionated whole breast RT, 25 Gy in 5 fractions, 4 to 8 weeks before BCS. Pathologic assessment was performed using the residual cancer burden (RCB). Toxicities were assessed according to Common Terminology Criteria for Adverse Events (version 4). Quality of life was assessed with Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events, The Breast Cancer Treatment Outcome Scale, Linear Analogue Self-Assessment, and Patient-Reported Outcomes Measurement Information System.Twenty-two patients were enrolled. Median follow-up was 7.6 months (range, 0.2-16.8). Seven (32%) and 2 (9%) patients experienced grade 2+ or 3 toxicities, respectively. Overall quality of life Linear Analogue Self-Assessment and Patient-Reported Outcomes Measurement Information System did not change significantly from baseline (Extremely hypofractionated whole breast RT before BCS is a feasible approach. There were low rates of toxicities and good cosmesis. Further investigation into this approach with RT before BCS is warranted.

Objective and Rationale: To investigate the utility of screening Contrast Enhanced Mammography (CEM) imaging as a supplemental screening tool in women at elevated risk for breast cancer. Materials and Methods: This prospective, single institution, IRB approved observational study was conducted in asymptomatic women 35 years of age or older who were deemed at elevated risk of breast cancer, defined as IBIS v.8.0 lifetime risk of breast cancer score >15% or a prior personal history of breast cancer. Enrollment started in January 2019 and is on-going. An interim data analysis was performed. Women were invited to undergo supplemental CEM screening within 180 days of negative (BI-RADS 1 or 2) conventional 2D/3D screening mammography (MG). Patients with prior screening MBI, ultrasound or MR imaging within 12 months were excluded from study participation. Outcome measures were supplemental cancer detection rates, sensitivity, specificity, positive predictive value, and negative predictive value of CEM, along with their 95% confidence intervals, as well as the biologic profiles of MG-occult, CEM detected cancers. Results: A total of 351 women were enrolled in this prospective study over a 20-month period. To date, we have 1 year follow up on 106 cases with negative follow-up MG. Average age of the participants was 56 years ± 9.44 (standard deviation); 11 patients had screening 2D MG, 333 had combined 3-D and 2-D screening MG; 309 dense and 37 non-dense breasts based on ACR BI-RADS categories. CEM depicted 8 additional breast cancers (table 1), which were otherwise MG occult, for an overall supplemental cancer detection rate of 22.7 per 1000 patients, 95% CI (9.9, 44.3). 1 false negative cancer on CEM imaging which was further detected on MR imaging only. Biopsy revealed 16 benign changes (16/28=57%), 4 high-risk lesions (4/28=14%), and 8 breast cancers (8/28=29%) (table 2). CEM imaging screening offered high specificity (0.942, 95% CI (0.917, 0.967), high NPV 0.997, 95% CI (0.991, 1.000) and moderate PPV (0.286, 95% CI (0.118, 0.453) and sensitivity (0.889, 95% CI (0.684, 1.000)). Size of CEM detected cancers ranged from 7 to 57 mm. Conclusion: This pilot trial demonstrates a supplemental cancer detection rate of 22.7 per 1000 during prevalence round of CEM screening in women at an elevated risk for breast cancer. These initial results are comparable to results reported for high-risk surveillance MR imaging. Larger, multi-institutional high-risk CEM trials are needed for those patients who are not otherwise undergoing regular supplemental surveillance MR imaging. Citation Format: Bhavika K. Patel, Victor Pizzitola, Donald Northfelt, Karen Anderson, Marina Giurescu, Gina Mazza, Roxanne Lorans, William Eversman, Richard Sharpe, Juliana Kling, Denise Millstine, Ernst Brenda, Patricia Cronin, Heidi Apsey, Jennifer Palmieri, Barbara Pockaj, Michele Halyard. Supplemental contrast enhanced mammography screening of women with elevated risk of breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS2-41.

Background: Contrast-enhanced mammography (CEM) is an emerging breast imaging technique utilizing iodinated contrast to highlight areas of neovascularity. The role of CEM in patients with breast implants has not yet been characterized. We report our clinical experience of CEM in patients with breast augmentation surgery to better understand the potential diagnostic utility and limitations of CEM in the setting of breast implants. Materials and Methods: A HIPPA compliant, IRB exempt single-institution review of prospective CEM cases who had “breast implants” in their report between 01/2015 and 03/2020. Medical records were reviewed to supplement database information. Results: Forty-six patients were included with a mean age of 52 years (range 33-72). Clinical indications included: high risk research screen 3 (6%), diagnostic evaluation for abnormal imaging 24 (52%), further evaluation of newly diagnosed breast cancer 12 (26%) or assessment of neoadjuvant treatment response 7 (15%). Thirty patients had malignant lesions. Histology was invasive ductal carcinoma (90%), invasive lobular carcinoma (7%), and ductal carcinoma in situ (3%). CEM identified the index cancer and extent of disease in 28/30 (93%) of malignant cases. In two patients (7%), the malignant lesion was not included in the field-of-view due to its location. One of these lesions was a far medial mass within the breast which was detected by ultrasound alone. The other false negative CEM was a palpable axillary mass negative on both mammogram (MG) and MRI but seen by ultrasound. Twenty-three (50%) underwent additional breast MRI of which 20 had an already diagnosed cancer. the findings on CEM were concordant with MR imaging for the index lesion in 19/20 (95%) cases (kappa=0.86; p Six additional lesions were found by CEM and confirmed by MRI. Of these lesions, 33% were found to be malignant and changed the surgical procedure. Four were only seen on CEM (no MRI comparison was available) and 75% were found to be malignant. One was only seen on MRI and was benign. One additional lesion was only seen as an asymmetry on MG without CEM or MRI correlate. This was benign on both the biopsy and surgical pathology. Conclusions: CEM appears to be a valuable breast imaging modality for diagnostic evaluations and surgical staging, including patients with breast implants. Due to technical artifacts and positioning limitations for posterior lesions, we recommend performing CEM with implant displaced views. Breast centers that use CEM, should be aware of field of view as a potential limitation when evaluating extent of disease in patients with breast augmentation. Citation Format: Molly Carnahan, Barbara Pockaj, Victor Pizzitola, Marina Giurescu, Roxanne Lorans, William Eversman, Richard Sharpe, Patricia Cronin, Donald Northfelt, Karen Anderson, Brenda Ernst, Bhavika Patel. Experience of contrast-enhanced mammography in patients with breast augmentation surgery [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS3-23.

The burden of cancer continues to increase in society and negatively impacts the lives of numerous patients. Due to the high cost of current treatment strategies, there is a crucial unmet need to develop inexpensive preclinical platforms to accelerate the process of anti-cancer drug discovery to improve outcomes in cancer patients, most especially in female patients. Many current methods employ expensive animal models which not only present ethical concerns but also do not often accurately predict human physiology and the outcomes of anti-cancer drug responsiveness. Conventional treatment approaches for cancer generally include systemic therapy after a surgical procedure. Although this treatment technique is effective, the outcome is not always positive due to various complex factors such as intratumor heterogeneity and confounding factors within the tumor microenvironment (TME). Patients who develop metastatic disease still have poor prognosis. To that end, recent efforts have attempted to use 3D microengineered platforms to enhance the predictive power and efficacy of anti-cancer drug screening, ultimately to develop personalized therapies. Fascinating features of microengineered assays, such as microfluidics, have led to the advancement in the development of the tumor-on-chip technology platforms, which have shown tremendous potential for meaningful and physiologically relevant anti-cancer drug discovery and screening. Three dimensional microscale models provide unprecedented ability to unveil the biological complexities of cancer and shed light into the mechanism of anti-cancer drug resistance in a timely and resource efficient manner. In this review, we discuss recent advances in the development of microengineered tumor models for anti-cancer drug discovery and screening in female-related cancers. We specifically focus on female-related cancers to draw attention to the various approaches being taken to improve the survival rate of women diagnosed with cancers caused by sex disparities. We also briefly discuss other cancer types like colon adenocarcinomas and glioblastoma due to their high rate of occurrence in females, as well as the high likelihood of sex-biased mutations which complicate current treatment strategies for women. We highlight recent advances in the development of 3D microscale platforms including 3D tumor spheroids, microfluidic platforms as well as bioprinted models, and discuss how they have been utilized to address major challenges in the process of drug discovery, such as chemoresistance, intratumor heterogeneity, drug toxicity, etc. We also present the potential of these platform technologies for use in high-throughput drug screening approaches as a replacements of conventional assays. Within each section, we will provide our perspectives on advantages of the discussed platform technologies.

Ramifications of postoperative complications on long-term survival after mastectomy are uncertain.Overall complications (Clavien-Dindo Grades I-IIIB) and wound complications were analyzed using the Kaplan-Meier method for impact on 5-year overall (OS) and disease-free survival (DFS).A total of 378 patients underwent mastectomy alone (157, 41%) or mastectomy with reconstruction (221, 59%) for Stage I-III disease with a median follow-up of 5 years. Postoperative complications occurred in 186 patients (49%), requiring non-surgical (I/II = 83, 22%) or surgical (IIIa/IIIb = 103, 27%) management. Wound complications occurred in 140 patients (37%). Reconstruction was associated with a higher rate of complication (P 0.001). Postoperative complications after mastectomy (with or without reconstruction) did not significantly affect OS or DFS. Wound complications also showed no significant effect on OS or DFS following mastectomy alone, or mastectomy with reconstruction.Postoperative complications after mastectomy, with or without reconstruction, bear no significant impact on 5-year survival.

BACKGROUND: The goal of this study was to assess the impact of trastuzumab on locoregional failure. METHODS: The analysis included 2763 patients with HER2-positive (HER2+) breast cancer who were randomly assigned to adjuvant doxorubicin (A), cyclophosphamide (C), paclitaxel (T) and trastuzumab (H) (arm A, AC→T [n = 922]; arm B, AC→T→H [n = 988]; arm C, AC→T+H→H [n = 853]). Radiotherapy was given after AC→T concurrently with H. Radiotherapy was given after lumpectomy (L) or after mastectomy (M) with ≥4 positive lymph nodes but was optional for 1 to 3 positive lymph nodes. Locoregional failures at 10 years (LFR10) as first events were compared using competing risk analysis. RESULTS: The median follow-up was 13.0 years. The first site of failure was local-only in 96 cases, locoregional in 16 cases, regional in 32 cases, and not specified in 2 cases; LFR10 was 4.8% (95% CI 4.1%–5.7%). LFR10 was 5.5% (95% CI 4.3%–7.2%), 4.9% (95% CI 3.7%–6.4%), and 2.8% (95% CI 1.9%–4.1%) in arms A, B, and C (B vs A: hazard ratio [HR] 0.91, P = .62; C vs A: HR 0.72, P = .12). For estrogen receptor–positive patients, LFR10 was 3.7% (95% CI 2.8%–4.8%) and for estrogen receptor–negative patients, it was 6.1% (95% CI 5.0%–7.4%; HR 0.61, P = .004). Local treatment included L+RT (n = 1044 [38%]), M+RT (n = 1025 [37%]), and M (n = 694 [25%]). LFR10 was 6.% (95% CI 5.0%–7.8%), 3.0% (95% CI 2.1%–4.3%), and 5.5% (95% CI 4.0%–7.4%) for L+RT, M+RT, and M, respectively (M+RT vs L+RT: HR 0.43, P < .001; M vs L+RT: HR 0.88, P = .57). For 1 to 3 positive lymph nodes, LFR10 was 6.5% (95% CI 4.8%–8.9%), 4.1% (95% CI 2.4%–7.0%), and 4.3% (95% CI 2.9%–6.5%) in L+RT, M+RT, and M, respectively (M vs L+RT: HR 0.68, P = .14; M vs M+RT: HR 1.2, P = .6). CONCLUSION: Low 10-year LFRs were seen regardless of trastuzumab use. Differences in local therapy in patients with 1 to 3 positive lymph nodes did not appear to improve local control. Local therapy studies for HER2+ and other tumor characteristics are important as the role of local therapies continues to evolve.

Background It is unknown whether all thick melanomas share the same prognostic features. We present a large, multi-institutional study on thick melanoma, evaluating for factors prognostic of survival. Methods We queried the database of the Sentinel Lymph Node Working Group for patients with thick melanoma (>4 mm) who had a sentinel lymph node biopsy from 1993 to 2018. Clinicopathologic characteristics were correlated with overall survival. Results There were 1,235 patients with a median follow-up of 28 months. Median thickness was 5.9 mm, with 713, 356, and 166 cases having a thickness of >4 to 6, >6 to 10, and >10 mm, respectively. Ulceration was seen in 51.2% of cases, while sentinel lymph node metastases were seen in 439 of 1,235 (35.5%) cases. For melanomas >4 to 6 mm, age, thickness, ulceration, lymphovascular invasion, and sentinel lymph node metastasis were correlated with overall survival (all P 6 to 10 mm, only sex and sentinel lymph node metastasis were prognostic of overall survival (both P 10 mm, only sentinel lymph node metastasis predicted overall survival on multivariable analyses (P Conclusion Prognostic markers of overall survival for thick melanoma include thickness, ulceration, and sentinel lymph node metastasis, but also include other unique factors such as lymphovascular invasion. Moreover, certain prognostic markers for survival are associated with different subgroups of thick melanoma, which vary based on thickness group.

Lynch syndrome (LS) arises in patients with pathogenic germline variants in DNA mismatch repair genes. LS is the most common inherited cancer predisposition condition and confers an elevated lifetime risk of multiple cancers notably colorectal and endometrial carcinomas. A distinguishing feature of LS associated tumors is accumulation of variants targeting microsatellite repeats and the potential for high tumor specific neoepitope levels. Recurrent somatic variants targeting a small subset of genes have been identified in tumors with microsatellite instability. Notably these include frameshifts that can activate immune responses and provide vaccine targets to affect the lifetime cancer risk associated with LS. However the presence and persistence of targeted neoepitopes across multiple tumors in single LS patients has not been rigorously studied. Here we profiled the genomic landscapes of five distinct treatment naïve tumors, a papillary transitional cell renal cell carcinoma, a duodenal carcinoma, two metachronous colorectal carcinomas, and multi-regional sampling in a triple-negative breast tumor, arising in a LS patient over 10 years. Our analyses suggest each tumor evolves a unique complement of variants and that vaccines based on potential neoepitopes from one tissue may not be effective across all tumors that can arise during the lifetime of LS patients.

Sentinel lymph node biopsy (SLNB) is recommended for intermediate thickness melanoma, but for thick melanoma, guidelines are less definitive about the use of SLNB in this population. We present a study on thick melanoma evaluating for prognostic factors.The Sentinel Lymph Node Working Group database was queried for thick ( 4 mm) melanoma cases that had a SLNB from 1993 to 2018. Clinicopathologic characteristics were correlated with SLN status and melanoma-specific survival (MSS).There were 1235 patients. Median follow-up was 28 months. Median thickness was 5.9 mm, with 956, 175, and 104 cases presenting thickness 4-8, 8-12, and 12 mm, respectively. SLN metastases were seen in 439 of 1235 (35.5%) cases and in 33.9%, 40.6%, and 42.3% of melanomas 4-8, 8-12, and 12 mm, respectively. In each thickness group, MSS was significantly worse for SLN-positive compared with SLN-negative cases (all P 0.005). Multivariable analysis showed that SLN metastasis, male gender, increasing thickness, lymphovascular invasion, and microsatellitosis significantly predicted worse MSS for melanomas 4-8 mm, with SLN metastasis showing the greatest risk (HR 2.17, 95% CI 1.64-2.87, P 0.0001). For melanomas 8 mm, only SLN metastasis significantly predicted MSS ( 8-12 mm: HR 3.93, 95% CI 2.00-7.73, P 0.0001; 12 mm: HR 3.58, 95% CI 1.56-8.22, p 0.0027).Thick melanoma patients with SLN metastasis have significantly worse MSS compared with SLN-negative patients, even in the thickest cases, and SLN status is the most powerful and/or only predictor of MSS. Given these results, SLNB shows important prognostic value in this population and is indicated for clinically localized thick melanoma.

Enhanced recovery after surgery (ERAS®) principles have been beneficial in major abdominal surgery. ERAS® was instituted in our breast surgery practice in 2017. The goal of this study was to evaluate the feasibility of outpatient mastectomies before and after ERAS®. A retrospective review of all mastectomies between 1/2013 and 6/2018 was performed. Patients receiving autologous flap reconstruction were excluded. The institution-specific ERAS® pathway began on February 1, 2017. Patient characteristics, operative intervention, and postoperative outcomes were compared between pre-ERAS® and post-ERAS® groups and between outpatient and inpatient subgroups. Continuous and categorical variables were compared using Wilcoxon rank-sum and Chi-square analyses. A total of 487 patients were analyzed. Three hundred and forty-seven (71%) were prior to ERAS® and 140 after (29%). The two groups were not significantly different in background characteristics. Same-day discharge occurred in 58.6% of post-ERAS® patients versus 7.2% of pre-ERAS® patients (p

We sought to evaluate the impact of mastectomy type, post-mastectomy reconstruction choice, and procedure bilaterality, on patient perceived postoperative quality of life (QoL).Patients who underwent post-mastectomy reconstruction between 2008 and 2020 were identified in a prospective database. QoL was assessed with the BREAST-Q and the Was It Worth It (WIWI) questionnaires. The results were compared between reconstruction type, reconstruction laterality, and type of mastectomy. Responses were compared using one-way analysis of variance (ANOVA) and chi-square tests.568 patients met inclusion criteria, and 244 patients responded (43%). QoL did not significantly vary between different reconstructions selected, procedure laterality, or mastectomy type. Patients who underwent DIEP flap were significantly more satisfied with their reconstructed breasts than implant-based reconstruction. Overall, over 85% of patients experienced improved or unchanged QoL no matter what reconstruction choices were made.Most domains of QOL are not impacted by mastectomy type, post-mastectomy reconstruction, or laterality.

The significance of tumor-infiltrating lymphocytes (TILs) in melanoma is debated. This article presents a multicenter, retrospective study assessing the predictive and prognostic value of TILs.The Sentinel Lymph Node Working Group database was queried from 1993 to 2018 for cases with known TIL data. TILs were categorized as absent or present, which included nonbrisk (NB), brisk (B), and present but unspecified TIL levels. Clinicopathologic factors were correlated with TILs, sentinel lymph node (SLN) status, and melanoma-specific survival (MSS).Overall, 3203 patients were included. The median thickness was 1.5 mm, and 469 cases had SLN metastases. TILs were present in 2458 cases (76.7%), with NB, B, and unspecified TILs seen in 1691 (68.8%), 691 (28.1%), and 76 (3.1%), respectively. Multivariable analysis showed that the presence of TILs significantly predicted a negative SLN biopsy (P.05). The median follow-up was 25.2 months. MSS was significantly better for cases with TILs than cases without TILs (P.001). According to multivariable analysis, age, gender, thickness, mitotic rate, ulceration, lymphovascular invasion, and SLN status were significantly prognostic of MSS (all P values.05). Although TILs were not prognostic of MSS, when multiple imputation was used and the SLN status was excluded, the presence of TILs was significantly prognostic of improved MSS (hazard ratio, 0.78; 95% confidence interval, 0.64-0.95; P = .0154).TILs are a favorable marker because their presence significantly predicts a negative SLN, and the absence of TILs may be a prognostic marker of worse survival in patients with a positive SLN but not a negative SLN. TILs may also serve as a prognostic marker of survival when the SLN status is not considered.

Introduction: Amplification of chromosome 9p24.1 encoding PDL1, PDL2, and JAK2 (the PDJ amplicon) has been detected in 5-25% of triplenegative breast cancers (TNBC), and is associated with poor outcome and activation of the JAK/STAT pathway. Here, we have developed a robust multiplexed fluorescence in situ hybridization (FISH) assay for detection of 9p24.1 amplification, and assessed the frequency and cellular distribution of the PDJ amplicon in a cohort of African American (AA) women with TNBC. Methods: The FISH assay combines three chromosome 9 probes to simultaneously target JAK2 and PD-L1 (9p24.1, PDJ), chromosome 9q22, and the 9q34.1 regions. This enables discrimination of PDJ amplicons from whole chromosome 9p arm gains and from chromosome 9 ploidies that occur in the background of genomic instability in aneuploid cancer genomes. Fifty cells were scored for each probe and the average copy number was obtained. We defined PDJ amplification as PDJ>4, PDJ/9q22 ratio≥2, and/or PDJ/9q34.1 ratio≥2. The assay was benchmarked to array CGH of flow sorted TNBC tissue from Mayo Clinic Arizona (n=14). Tissue microarrays from TNBC PDX tumors (n=20) and from African American women with TNBC (n=87) were assessed. Results: Using selected TNBC tissue with known CGH data, the FISH assay tightly correlated with PDJ copy number in 13/14 cases. The discordant case was negative by CGH on a biopsy with low tumor content, but FISH positive on tissue section (PDJ >7.5 and a PDJ/9q22 ratio=4). Of 20 TNBC PDX tumors, 5 were amplified by FISH. Twelve of 87 (14%) of tumors had PDJ amplification by FISH, of which ten were from breast tissue and two were from lymph node. Of these 12, PDJ>4 (n=0), PDJ/9q22 ratio≥2 (n=6), and PDJ/9q34.1 ratio≥2 (n=10). Significant intratumoral variation was observed with the presence of single cells with >10 PDJ copies in 8/17 (47%) amplified and 0/90 non-amplified total cases. Conclusion: 9p24.1 (PDJ) amplification encoding JAK2, PD-L1, and PD-L2 is detected by three-color FISH in 14% of TNBC from African American women. Individual cells with ≥10 copies of PDJ was seen exclusively in 8/17 amplified cases. We identified 5 PDX tumors which may provide valuable preclinical models for the amplicon. The association of this biomarker with clinical outcome will be presented. Citation Format: Karen S. Anderson, Tammey Naab, Lori K Koslosky, Megan Anderson, Michael Lewis, Yasmine Kanaan, Ali Afsari, Luisel Ricks-Santi, Barbara A. Pockaj, Michael T Barrett. Tissue prevalence and cellular heterogeneity of 9p24.1 amplification in TNBC in African American women [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-10-17.

Introduction The aim of this study was to investigate long-term breast reconstruction outcomes at a single institution in order to offer data-driven counseling for patients. Methods A retrospective review was performed of 399 patients who underwent mastectomy with 1-stage implant-based breast reconstruction (IBBR), 2-stage IBBR, or autologous tissue reconstruction (ATR) for invasive breast cancer or ductal carcinoma in situ at our institution from 2010 to 2017. Complications were classified as major for any unplanned return to the operating room (OR). Results Overall complication rates were similar among 1-stage IBBR (59%), 2-stage IBBR (60%), and ATR (52%, p = 0.54). Factors independently associated with major complications were diabetes (OR = 25.4 95% CI: 3.2–202.4; p = 0.002), and 1-stage IBBR vs. ATR (1-stage: OR = 2.0 95% CI: 1.0–4.0; p = 0.04). Bilateral procedures were also at increased risk of major complications on univariate analysis (OR = 1.59 95% CI: 1.0–2.5; p = 0.04). Conclusions Long-term breast reconstruction complication rates are higher than previously anticipated. Patients should be counseled that IBBR is associated with higher rates of complications, including unplanned return to the OR, compared to ATR.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been associated with increased postoperative complications and a prolonged length of stay (LOS). We report on our experience following implementation of an Enhanced Recovery After Surgery (ERAS) program for CRS and HIPEC. Patients were divided into pre- and post-ERAS groups. Modifications in the ERAS group included routine use of transversus abdominis plane blocks, intra- and postoperative fluid restriction, and minimizing the use of narcotics, drains, and nasogastric tubes. Of a total of 130 procedures, 49 (38%) were in the pre-ERAS group and 81 (62%) were in the ERAS group. Mean LOS was reduced from 10.3 ± 8.9 days to 6.9 ± 5.0 days (p = 0.007) and the rate of grade III/IV complications was reduced from 24 to 15% (p = 0.243) following ERAS implementation. The ERAS group received less intravenous fluid during hospitalization (19.2 ± 18.7 L vs. 32.8 ± 32.5 L, p = 0.003) and used less opioids than the pre-ERAS group (median of 159.7 mg of oral morphine equivalents vs. 272.6 mg). There were no significant changes in the rates of 30-day readmission or acute kidney injury between the two groups (p = non-significant). On multivariable analyses, ERAS was significantly associated with a reduction in LOS (− 2.89 days, 95% CI − 4.84 to − 0.94) and complication rates (odds ratio 0.22, 95% CI 0.08–0.57). Implementation of an ERAS program for CRS and HIPEC is associated with a reduction in overall intravenous fluids, postoperative narcotic use, complication rates, and LOS.

Supplemental Digital Content is available in the text., The breast is a rare site for metastases, and their molecular characteristics have not been studied yet. Intrinsic molecular genetics, cancer characteristics, and breast tissue immune responses in diverse metastases to the breast have not been previously studied. We identified 64 patients with cancers metastatic to the breast: 51 carcinomas and 13 melanomas. Programmed death ligand 1 (PD-L1), steroid receptors, and HER2/neu expressions were evaluated using immunohistochemistry. Gene sequencing, copy number alterations, microsatellite instability, and tumor mutational burden were performed using next-generation sequencing platforms. The 3 most common primary sites for metastatic carcinomas were lung (37%), ovary (29%), and fallopian tubes/peritoneum (14%). TP53 mutations were commonly (50%) observed among the carcinoma cases, while other mutations were characteristic for the primary cancers (VHL in renal, BRCA1 in the fallopian tube, and BRAF in melanomas). High tumor mutational burden was detected in 5/14 carcinomas and 3/7 melanomas. Tumor cell PD-L1 expression was detected in 6 carcinomas, but not in any of the melanomas, whereas immune cells’ expression of PD-L1 was seen in 17 carcinomas and 6 melanomas. Estrogen receptor status was positive in 13/49 carcinomas including 12 adenocarcinomas originating from the ovary and fallopian tube or peritoneum and 1 duodenal neuroendocrine carcinoma. No carcinoma was HER2/neu positive. Intrinsic genetic characteristics of the metastases to the breast followed the pattern commonly seen in primary tumors. Biomarkers of potential benefit to immune checkpoint inhibition therapy were limited to PD-L1-positive non–small cell lung cancer. No common characteristics of the heterogeneous group of tumor metastases to this organ were identified.

Histologic subtypes of appendiceal cancer vary in their propensity for metastases to regional lymph nodes (LN). A predictive model would help direct subsequent surgical therapy.The National Cancer Database was queried for patients with appendiceal cancer undergoing surgery between 1998 and 2012. Multivariable logistic regression was used to develop a predictive model of LN metastases which was internally validated using Brier score and Area under the Curve (AUC).A total of 21,647 patients were identified, of whom 9079 (41.9%) had node negative disease, 4575 (21.1%) node positive disease, and 7993 (36.9%) unknown LN status. The strongest predictors of LN positivity were histology (carcinoid tumors OR 12.78, 95% CI 9.01-18.12), increasing T Stage (T3 OR 3.36, 95% CI 2.52-4.50, T4 OR 6.30, 95% CI 4.71-8.42), and tumor grade (G3 OR 5.55, 95% CI 4.78-6.45, G4 OR 5.98, 95% CI 4.30-8.31). The coefficients from the regression analysis were used to construct a calculator that generated predicted probabilities of LN metastases given certain inputs. Internal validation of the overall model showed an AUC of 0.75 (95% CI 0.74-0.76) and Brier score of 0.188. Histology-specific predictive models were also constructed with an AUC that varied from 0.669 for signet cell to 0.75 for goblet cell tumors.The risk for nodal metastases in patients with appendiceal cancers can be quantified with reasonable accuracy using a predictive model incorporating patient age, sex, tumor histology, T-stage, and grade. This can help inform clinical decision making regarding the need for a right hemicolectomy following appendectomy.

Background More than 20% of patients undergoing initial breast-conserving surgery (BCS) for cancer require reoperation. To address this concern, the American Society of Breast Surgeons (ASBrS) endorsed 10 processes of care (tools) in 2015 to be considered by surgeons to de-escalate reoperations. In a planned follow-up, we sought to determine which tools were associated with fewer reoperations. Methods A cohort of ASBrS member surgeons prospectively entered data into the ASBrS Mastery® registry on consecutive patients undergoing BCS in 2017. The association between tools and reoperations was estimated via multivariate and hierarchical ranking analyses. Results Seventy-one surgeons reported reoperations in 486 (12.3%) of 3954 cases (mean 12.7% [standard deviation (SD) 7.7%], median 11.5% [range 0–32%]). There was an eightfold difference between surgeons in the 10th and 90th percentile performance groups. Actionable factors associated with fewer reoperations included routine planned cavity side-wall shaves, surgeon use of ultrasound (US), neoadjuvant chemotherapy, intra-operative pathologic margin assessment, and use of a pre-operative diagnostic imaging modality beyond conventional 2D mammography. For patients with invasive cancer, ≥ 24% of those who underwent reexcision did so for reported margins of

Tumor–stroma interactions significantly influence cancer cell metastasis and disease progression. These interactions are partly comprised of the cross-talk between tumor and stromal fibroblasts, but the key molecular mechanisms within the cross-talk that govern cancer invasion are still unclear. Here, we adapted our previously developed microfluidic device as a 3D in vitro organotypic model to mechanistically study tumor–stroma interactions by mimicking the spatial organization of the tumor microenvironment on a chip. We cocultured breast cancer and patient-derived fibroblast cells in 3D tumor and stroma regions, respectively, and combined functional assessments, including cancer cell migration, with transcriptome profiling to unveil the molecular influence of tumor–stroma cross-talk on invasion. This led to the observation that cancer-associated fibroblasts (CAF) enhanced invasion in 3D by inducing expression of a novel gene of interest, glycoprotein nonmetastatic B (GPNMB), in breast cancer cells, resulting in increased migration speed. Importantly, knockdown of GPNMB blunted the influence of CAF on enhanced cancer invasion. Overall, these results demonstrate the ability of our model to recapitulate patient-specific tumor microenvironments to investigate the cellular and molecular consequences of tumor–stroma interactions. Significance: An organotypic model of tumor–stroma interactions on a microfluidic chip reveals that CAFs promote invasion by enhancing expression of GPNMB in breast cancer cells.

Background Upstaging from DCIS to invasive ductal carcinoma varies widely from 0 to 59%. We aim to identify risk factors associated with upstaging in all DCIS patients and based on specific surgical intervention. Methods Patients with a pre-operative diagnosis of DCIS undergoing BCT or mastectomy were reviewed. Multivariable analysis was performed to identify risk factors for upstaging. Results In total, 623 patients had a preoperative diagnosis of DCIS. Upstaging occurred in 74 patients (12%) overall. There was no difference in upstaging rates between mastectomy and BCT (11% v 14% p = 0.27). Sentinel lymph node biopsy was positive in 4/212 patients (1%). Multivariable analysis revealed suspicion of microinvasion (OR 5.7 95%CI2.2–14.9), surgeon suspicion of invasive disease (OR 2.7, 95% CI 1.2–6.4) and larger size/multicentric/extensive tumor (OR 1.9 95% CI 1.1–3.4) increase risk of upstaging. Conclusions Suspicion of microinvasion, surgeon suspicion, and tumor size can be used to help guide the use of sentinel lymph node biopsy. For patients without these high risk characteristics, it is hard to justify the use of concurrent SLN biopsy for patients who undergo BCT.

Factors that predict melanoma recurrence after a negative sentinel lymph node biopsy (SLNB) are not well-defined. We evaluated melanoma recurrence patterns, factors prognostic for recurrence, and the impact of recurrence on outcomes after a negative SLNB. The Sentinel Lymph Node Working Group database was evaluated from 1996 to 2016 for negative SLNB melanoma patients. Clinicopathologic characteristics were correlated with recurrence, overall survival (OS), and melanoma-specific survival (MSS). Median follow-up was 32.1 months. Recurrences developed in 558 of 5351 negative SLN patients (10.4%). First-site of recurrence included a local or in-transit recurrence (LITR) in 221 cases (4.1%), nodal recurrence (NR) in 109 cases (2%), and distant recurrence (DR) in 220 cases (4.1%). On multivariable analysis, age, thickness, head/neck or lower extremity primary, and microsatellitosis significantly predicted for an LITR as first-site. Having an LITR as first-site significantly predicted for a subsequent NR and DR, and significantly predicted for worse OS and MSS. Furthermore, thickness and head/neck or lower extremity primary significantly predicted for an NR as first-site, while a prior LITR significantly predicted for a subsequent NR. Factors significantly predictive for a DR included thickness, head/neck or trunk primary, ulceration, and lymphovascular invasion. Patients with any type of locoregional recurrence were at higher risk for a DR. Recurrences occur in 10.4% of negative SLN patients, with LITR and DR being the most common types. Importantly, having an LITR significantly predicts for a subsequent NR and DR, and is prognostic for worse survival after a negative SLNB.