The American College of Surgeons Oncology Group trial Z0011 was a prospective, randomized, multicenter trial comparing overall survival between patients with positive sentinel lymph nodes (SLNs) who ...did and did not undergo axillary lymph node dissection (ALND). The current study compares complications associated with SLN dissection (SLND) plus ALND, versus SLND alone.
From May 1999 to December 2004, 891 patients were randomly assigned to SLND + ALND (n = 445) or SLND alone (n = 446). Information on wound infection, axillary seroma, paresthesia, brachial plexus injury (BPI), and lymphedema was available for 821 patients.
Adverse surgical effects were reported in 70% (278 of 399) of patients after SLND + ALND and 25% (103 of 411) after SLND alone (P <or= .001). Patients in the SLND + ALND group had more wound infections (P <or= .0016), seromas (P <or= .0001), and paresthesias (P <or= .0001) than those in the SLND-alone group. At 1 year, lymphedema was reported subjectively by 13% (37 of 288) of patients after SLND + ALND and 2% (six of 268) after SLND alone (P <or= .0001). The difference between the two groups' lymphedema, assessed by arm measurements at 30 days (P = .36), 6 months (P = .22), and 1 year (P = .078), although close to the cutoff for significance at 1 year, was not significant. BPIs occurred in less than 1% of patients.
In trial Z0011, the use of SLND + ALND resulted in more wound infections, axillary seromas, and paresthesias than SLND alone. Lymphedema was more common after SLND + ALND but was significantly different only by subjective report. The use of SLND alone resulted in fewer complications.
Glyceraldehyde-3-phosphate dehydrogenase （GAPDH）, initially identified as a glycolytic enzyme and considered as a housekeeping gene, is widely used as an internal control in experiments on proteins, ...mRNA, and DNA. However, emerging evidence indicates that GAPDH is implicated in diverse functions independent of its role in energy metabolism; the expression status of GAPDH is also deregulated in various cancer cells. One of the most common effects of GAPDH is its inconsistent role in the determination of cancer cell fate. Furthermore, studies have described GAPDH as a regulator of cell death; other studies have suggested that GAPDH participates in tumor progression and serves as a new therapeutic target. However, related regulatory mechanisms of its numerous cellular functions and deregulated expression levels remain unclear. GAPDH is tightly regulated at transcriptional and pnsttranscriptional levels, which are involved in the regulation of diverse GAPDH functions. Several cancer-related factors, such as insulin, hypoxia inducible factor-1 （HIF-1）, p53, nitric oxide （NO）, and acetylated histone, not only modulate GAPDH gene expression but also affect protein functions via common pathways. Moreover, posttranslational modifications （PTMs） occurring in GAPDH in cancer cells result in new activities unrelated to the original glycnlytic function of GAPDH. In this review, recent findings related to GAPDH transcriptional regulation and PTMs are summarized. Mechanisms and pathways involved in GAPDH regulation and its different roles in cancer cells are also described.
Lymphatic mapping with sentinel lymph node biopsy has the potential for reducing the morbidity associated with breast carcinoma staging. It has become a widely used technology despite limited data ...from controlled clinical trials.
A systematic review of the world's literature of sentinel lymph node (SLN) biopsy in patients with early-stage breast carcinoma was undertaken by using electronic and hand searching techniques. Only studies that incorporated full axillary lymph node dissection (ALND), regardless of SLN results, were included. Individual study results along with weighted summary measures were estimated using the Mantel-Haenszel method. The correlations of outcomes with the study size, the proportion of positive lymph nodes, the technique used, and the study quality were evaluated.
Between 1970 and 2003, 69 trials were reported that met eligibility criteria. Of the 8059 patients who were studied, 7765 patients (96%) had successfully mapped SLNs. The proportion of patients who had successfully mapped SLNs ranged from 41% to 100%, with > 50% of studies reporting a rate < 90%. Lymph node involvement was found in 3132 patients (42%) and ranged from 17% to 74% across studies. The false-negative rate (FNR) ranged from 0% to 29%, averaging 7.3% overall. Eleven trials (15.9%) reported an FNR of 0.0, whereas 26 trials (37.7%) reported an FNR > 10%. Significant inverse correlations were observed between the FNR and both the number of patients studied (r = - 0.42; P < 0.01) and the proportion of patients who had successfully mapped SLNs nodes (r = - 0.32; P = 0.009).
Lymphatic mapping with SLN biopsy is used widely to reduce the complications associated with ALND in patients with low-risk breast carcinoma. This systematic review revealed a wide variation in test performance.
Background
Radioactive seed localization (RSL) and the Savi scout® radar (SSR) are newer alternatives to wire‐guided localization (WL) for nonpalpable breast lesions.
Objective
To compare three types ...of localization devices used in breast conserving surgery.
Methods
A total of 293 patients had a partial mastectomy (n = 194) or breast biopsy (n = 99) with preoperative image‐guided localization of a single nonpalpable lesion between July 2017 to July 2018. Lesions were localized by WL, RSL, or SSR. Although all operations performed were outpatient, due to workflow differences at our institution, operations performed in the hospital operating rooms were defined as “hospital setting.” Operations performed at an outpatient surgery facility without the capacity to admit patients were defined as “ambulatory.” Delay in operating room start times and total perioperative times in both the hospital and ambulatory setting, localization time, explant of localization device, positive margins, volume of tissue excised, and 30‐day complications were evaluated.
Results
A total of 126 patients (43%) had WL; 59 patients (20%) had RSL; and 108 patients (37%) had SSR localization. SSR localization took longer to perform with an average time of 19 minutes, compared with 15 minutes for WL and 14 minutes for RSL (P = .020). In 93.52% of cases, the first specimen contained both the clip and localization device, which was similar among groups (P = .073). There was no difference in retained biopsy clip among the groups (average 3.4%, P = .173). For operations performed in the hospital, the time from patient arrival to the preoperative area and incision was significantly longer in the WL group with a median of 233 minutes (range 56‐486), 130 minutes (range 64‐294) in RSL, and 108 minutes (range 59‐240) for SSR (P < .001). There was no difference in operative time among the groups with a median of 51 minutes (range 17‐122) (P = .108). There was, however, significantly longer perioperative time of 469 minutes (range 210‐926) in the WL group compared with 399 minutes (range 240‐871) for RSL and 381 minutes (range 232‐711) for SSR (P ≤ .001). For the ambulatory setting, although there was no difference in operating time among the groups (median 50 minutes, range 18‐127, P = .715), only the RSL showed a decreased perioperative time compared to WL (WL 356 vs RSL 275, P < .001; SSR 279, p = NS). A total of 131 patients (44.7%) had same day localizations. Among operations with delayed start times, there was a longer average delay of 85 minutes (range 1‐304) for WL group compared with 69 minutes (range 13‐219) in RSL and 53 minutes (range 0‐228) in SSR (P < .001). There was no difference among the three groups in positive margin rate, volume of tissue excised, and 30‐day complications.
Conclusion
Nonwire localization devices are associated with reduced overall perioperative time compared to wire localization, with few complications.
DNA palindromes are a type of chromosomal aberration that appears frequently during tumorigenesis. They are characterized by sequences of nucleotides that are identical to their reverse complements ...and often arise due to illegitimate repair of DNA double-strand breaks, fusion of telomeres, or stalled replication forks, all of which are common adverse early events in cancer. Here, we describe the protocol for enriching palindromes from genomic DNA sources with low-input DNA amounts and detail a bioinformatics tool for assessing the enrichment and location of de novo palindrome formation from low-coverage whole-genome sequencing data.
Controversy exists regarding the optimal margin width in breast-conserving surgery for invasive breast cancer.
A multidisciplinary consensus panel used a meta-analysis of margin width and ipsilateral ...breast tumor recurrence (IBTR) from a systematic review of 33 studies including 28,162 patients as the primary evidence base for consensus.
Positive margins (ink on invasive carcinoma or ductal carcinoma in situ) are associated with a two-fold increase in the risk of IBTR compared with negative margins. This increased risk is not mitigated by favorable biology, endocrine therapy, or a radiation boost. More widely clear margins do not significantly decrease the rate of IBTR compared with no ink on tumor. There is no evidence that more widely clear margins reduce IBTR for young patients or for those with unfavorable biology, lobular cancers, or cancers with an extensive intraductal component.
The use of no ink on tumor as the standard for an adequate margin in invasive cancer in the era of multidisciplinary therapy is associated with low rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs. J Clin Oncol 32. 2014 American Society of Clinical Oncology®, American Society for Radiation Oncology®, and Society of Surgical Oncology®. All rights reserved. No part of this document may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without written permission by the American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology.
Purpose
The potential of targeting forkhead box C1 (FOXC1) as a therapeutic approach for triple-negative breast cancer (TNBC) is promising. However, a comprehensive understanding of FOXC1 regulation, ...particularly upstream factors, remains elusive. Expression of the L1 cell adhesion molecule (L1CAM), a transmembrane glycoprotein associated with brain metastasis, was observed to be positively associated with FOXC1 transcripts. Thus, this study aims to investigate their relationship in TNBC progression.
Methods
Publicly available FOXC1 and L1CAM transcriptomic data were obtained, and their corresponding proteins were analyzed in four TNBC cell lines. In BT549 cells, FOXC1 and L1CAM were individually silenced, while L1CAM was overexpressed in BT549-shFOXC1, MDA-MB-231, and HCC1937 cells. CCK-8, transwell, and wound healing assays were performed in these cell lines, and immunohistochemical staining was conducted in tumor samples.
Results
A positive correlation between L1CAM and FOXC1 transcripts was observed in publicly available datasets. In BT549 cells, knockdown of FOXC1 led to reduced L1CAM expression at both the transcriptional and protein levels, and conversely, silencing of L1CAM decreased FOXC1 protein levels, but interestingly, FOXC1 transcripts remained largely unaffected. Overexpressing L1CAM resulted in increased FOXC1 protein expression without significant changes in FOXC1 mRNA levels. This trend was also observed in BT549-shFOXC1, MDA-MB-231-L1CAM, and HCC1937-L1CAM cells. Notably, alterations in FOXC1 or L1CAM levels corresponded to changes in cell proliferation, migration, and invasion capacities. Furthermore, a positive correlation between L1CAM and FOXC1 protein expression was detected in human TNBC tumors.
Conclusion
FOXC1 and L1CAM exhibit co-regulation at the protein level, with FOXC1 regulating at the transcriptional level and L1CAM regulating at the post-transcriptional level, and together they positively influence cell proliferation, migration, and invasion in TNBC.
Background
Radioactive seed localization (RSL) and the Savi Scout
®
radar (SSR) are newer alternatives to wire-guided localization (WL) for nonpalpable breast lesions.
Objective
The aim of this study ...was to compare three localization devices when multiple devices were used for preoperative localization for breast surgery.
Methods
Between July 2017 and July 2018, 68 patients had a partial mastectomy (
n
= 54) or breast biopsy (
n
= 14) with preoperative image-guided localization using multiple wires or device placement for nonpalpable lesions. Operative timing, outcomes, and 30-day complications were evaluated.
Results
Overall, 41 patients (60%) had WL, 11 patients (16%) had RSL, and 16 patients (24%) had SSR localization. Fifty-four patients (79.4%) had localization of two lesions and 13 patients (19.1%) had localization of three lesions. Twenty-three patients (33.8%) had a lesion that was bracketed. There was no difference in retained biopsy clip among the groups (average 7.4%;
p
= 0.962). For operations performed in the hospital, there was no difference in operative time among the groups, with a median of 77.5 min (
p
= 0.705) or total perioperative time of 508 min (
p
= 0.210). Among operations with delayed start times, there was a longer average delay of 95.5 min in WL, compared with 42 min in SSR (
p
= 0.004). A greater volume of tissue was excised in the WL group (29.5 g WL vs. 15.9 g RSL vs. 12.1 g SSR;
p
= 0.022). There was no difference in positive margin rate and 30-day complications among groups.
Conclusion
SSR and RSL can be used to localize multiple breast lesions, with no difference in positive margin rates or complications and less tissue excised compared with WL.
Purpose
Controversy exists regarding the optimal margin width in breast-conserving surgery for invasive breast cancer.
Methods
A multidisciplinary consensus panel used a meta-analysis of margin width ...and ipsilateral breast tumor recurrence (IBTR) from a systematic review of 33 studies including 28,162 patients as the primary evidence base for consensus.
Results
Positive margins (ink on invasive carcinoma or ductal carcinoma in situ) are associated with a two-fold increase in the risk of IBTR compared with negative margins. This increased risk is not mitigated by favorable biology, endocrine therapy, or a radiation boost. More widely clear margins than no ink on tumor do not significantly decrease the rate of IBTR compared with no ink on tumor. There is no evidence that more widely clear margins reduce IBTR for young patients or for those with unfavorable biology, lobular cancers, or cancers with an extensive intraductal component.
Conclusion
The use of no ink on tumor as the standard for an adequate margin in invasive cancer in the era of multidisciplinary therapy is associated with low rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs.
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