Benefit of adjuvant chemotherapy in lymph node-negative, T1b and T1c triple-negative breast cancer.

INTRODUCTION: Current guidelines recommendations regarding chemotherapy in small (T1b and T1c), node-negative triple-negative breast cancer (TNBC) differ due to lack of high-quality data. Our study aimed to assess the benefit of adjuvant chemotherapy in patients with T1bN0M0 and T1cN0M0 TNBC. METHODS: We obtained data from the Surveillance, Epidemiology, and End Results database for patients with node-negative, T1b/T1c TNBC diagnosed between 2010 and 2020. Logistic regresion models assessed variables associated with chemotherapy administration. We evaluated the effect of chemotherapy on overall survival (OS) and breast cancer specific survival (BCSS) with Kaplan-Meier methods and Cox proportional hazards methods. RESULTS: We included 11,510 patients: 3,388 with T1b and 8,122 with T1c TNBC. During a median follow-up of 66 months, 305 patients with T1b and 995 with T1c died. After adjusting for clinicopathological, demographic and treatment factors, adjuvant chemotherapy improved OS in T1b TNBC (HR, 0.52; 95% CI, 0.41-0.68 p < 0.001) but did not improve BCSS (HR, 0.70; 95% CI, 0.45-1.07; p = 0.10); the association between chemotherapy and BCSS was not statistically significant in any subgroup. In T1c TNBC, adjuvant chemotherapy improved OS (HR, 0.54; 95% CI, 0.47-0.62; p < 0.001) and BCSS (HR, 0.79; 95% CI, 0.63-0.99; p = 0.043); the benefit of chemotherapy in OS varied by age (Pinteraction=0.024); moreover, the benefit in BCSS was similar in all subgroups. CONCLUSIONS: Our study results support the use of adjuvant chemotherapy in patients with node-negative, T1c TNBC. Patients with node-negative, T1b TNBC had excellent long-term outcomes; furthermore, chemotherapy was not associated with improved BCSS in these patients.

Indocyanine green and methylene blue dye guided sentinel lymph node biopsy in patients with penile cancer (PeCa): results of 50 inguinal basins assessed at a single institution in India.

AIM: The primary aim of this study was to validate the reliability, sensitivity and safety profile of novel combination of ICG- methylene blue dye as an SN tracer for PeCa. METHODS: This is a validation and non-randomised prospective observational study involving 25 patients (50 inguinal basins) who underwent SLNB where in ICG and methylene blue were used for localisation. The patients with clinically node negative groins were recruited in the study. SNs were identified intraoperatively using near infrared fluorescence imaging (NIRF Imaging system, SPY-PHI, Stryker, Sweden) and blue dye. The numbers of SNs identified by each tracer and the rates of complications and nodal recurrence during the followup. RESULTS: Overall 137 SNs were identified intraoperatively. Among the 137 SNs excised fluorescence, blue dye and Combined (blue + green) identified 57(41.6%), 27 (19.7%), and 51 (37.2%), respectively. The average number of SLNs removed per patient was 5 (range, 1-11) with sentinel lymph nodes detection rate at 94% (47/50). Seven patients had malignancy on SLNB and underwent ipsilateral radical inguinal lymphadenectomy. One patient had false negative SN and positive node in modified inguinal lymphadenectomy specimen. No adverse events were observed in all cases. CONCLUSION: The Novel combination of ICG fluorescence-Methylene blue dye technique is simple, reliable and safe. Moreover, it demonstrates a high SLN detection rate with a low false-negative rate, and it avoids radiation exposure.

The short- and long-term outcomes of laparoscopic D2 lymphadenectomy plus complete mesogastrium excision for lymph node-negative gastric cancer.

BACKGROUND: Patients with T1-3N0M0 gastric cancer (GC) who undergo radical gastrectomy maintain a high recurrence rate. The free cancer cells in the mesogastric adipose connective tissue (Metastasis V) maybe the reason for recurrence in these individuals. We aimed to evaluate whether D2 lymphadenectomy plus complete mesogastrium excision (D2 + CME) was superior to D2 lymphadenectomy with regard to safety and oncological efficacy for T1-3N0M0 GC. METHODS: Patients with T1-3N0M0 GC who underwent radical resection from January 2014 to July 2018 were retrospectively analyzed; there were 323 patients, of whom 185 were in the D2 + CME group and 138 in the D2 group. The primary endpoint was 5-year disease-free survival (DFS). Secondary endpoints include the 5-year overall survival (OS), recurrence pattern, morbidity, mortality, and surgical outcomes. RESULTS: D2 + CME was associated with less intraoperative bleeding loss, a greater number of lymph nodes harvested, and less time to first postoperative flatus, but the postoperative morbidity was similar. The 5-year DFS was 95.6% (95% CI 92.7-98.5%) and 90.4% (95% CI 85.5-95.3%) in the D2 + CME group and the D2 group, respectively, with a hazard ratio (HR) of 0.455 (95% CI 0.188-1.097; p = 0.071). In terms of recurrence patterns, local recurrence was more prone to occur in the D2 group (p = 0.031). Subgroup analysis indicated that for patients with T1b-3N0M0 GC, the 5-year DFS in the D2 + CME group was considerably greater than that in the D2 group (95.3% [95% CI 91.6-99.0%] vs. 87.6% [95% CI 80.7-94.5%], HR 0.369, 95% CI 0.138-0.983; log-rank p = 0.043). CONCLUSION: Laparoscopic D2 + CME for T1-3N0M0 GC is safe and feasible. Furthermore, it not only reduces the local recurrence rate but also improves the 5-year DFS in cases of T1b-3N0M0 GC.

Node-negative colon cancer: histological, molecular, and stromal features predicting disease recurrence.

BACKGROUND: Within the group of node-negative colon cancer patients, presumed to have a good prognosis, a significant percentage of patients develops cancer-recurrence. Current high-risk features prove inadequate to select these particular high-risk patients. In the process of tailor-made care and shared decision-making the need to identify these patients grows. In this study we investigate the value of adding molecular markers and the tumour-stroma ratio (TSR) to conventional histological tumour staging methods to improve the selection of high risk patients. METHODS: We retrospectively analysed 201 patients diagnosed with TNM-stage I-II colon cancer and treated by complete oncological resection between November 1st 2002 and December 31st 2012 at the Jeroen Bosch Hospital. Conventional histological tumour staging, BRAF mutations, KRAS mutations, MSI status and TSR were determined. Differences between groups based on TSR and mutation status, in disease free survival were analysed using Cox-Regression analyses. RESULTS: Poorly differentiated histology (p = 0.002), high-TSR (p = 0.033), BRAF-mutation (p = 0.008) and MSI (p = 0.011) were identified as significant risk factors for cancer recurrence. The risk of recurrence increased in the presence of both a BRAF-mutation and high-TSR compared to the absence of both factors or presence of only one factor (HR = 3.66 BRAF-mt/TSR-low (p = 0.006), HR 2.82 BRAF-wt/TSR-high (p = 0.015), HR = 4.39 BRAF-mt/TSR-high (p = 0.023)). This was also seen in tumours with MSI and high-TSR (HR = 2.46 MSS/TSR-high (p = 0.041), HR = 3.31 MSI/TSR-high (p = 0.045). CONCLUSION: Judging by the higher HR for the combination of the prognostic factors TSR and BRAF compared to the HRs of these prognostic factors individually, the prognostication for disease free survival can be improved by determining both TSR and BRAF instead of BRAF alone, as is done in current daily practise. In this study MSI also shows additional value to TSR in the prognostication of disease free survival. Adopting TSR into daily diagnostics will be of additional value next to currently used molecular markers in risk stratification of patients with node negative colon cancer and is therefore advised.

Adverse impact of tumor deposits in lymph node negative rectal cancer - a national cohort study.

PURPOSE: This study aimed to investigate the prognostic effect of tumor deposits (TDs) in lymph node negative rectal cancer. METHODS: Patients who had undergone surgery for rectal cancer with curative intention between 2011 and 2014 were extracted from the Swedish Colorectal Cancer Registry. Patients with positive lymph nodes, undisclosed TD status, stage IV disease, non-radical resections, or any outcome (local recurrence (LR), distant metastasis (DM) or mortality) within 90 days after surgery were excluded. TDs status was based on histopathological reports. Cox-regression analyses were used to examine the prognostic impact of TDs on LR, DM, and overall survival (OS) in lymph node-negative rectal cancer. RESULTS: A total of 5455 patients were assessed for inclusion of which 2667 patients were analyzed, with TDs present in 158 patients. TD-positive patients had a lower 5-year DM-free survival (72.8%, p < 0.0001) and 5-year overall survival (75.9%, p = 0.016), but not 5-year LR-free survival (97.6%) compared to TD-negative patients (90.2%, 83.1% and 95.6%, respectively). In multivariable regression analysis, TDs increased the risk of DM [HR 4.06, 95% CI 2.72-6.06, p < 0.001] and reduced the OS [HR 1.83, 95% CI 1.35-2.48, p < 0.001]. For LR, only univariable regression analysis was performed which showed no increased risk of LR [HR 1.88, 95% CI 0.86-4.11, p = 0.11]. CONCLUSION: TDs are a negative predictor of DM and OS in lymph node-negative rectal cancer and could be taken into consideration when planning adjuvant treatment.

MiR-640 and MiR-525-5p as Relapse-Associated MicroRNAs in Systematically Untreated Individuals with Low-Risk Primary Breast Cancer.

MicroRNAs have been suggested to be signatures for predicting recurrence in breast cancer. This study aimed to identify miR-640 and miR-525-5p as relapse-associated microRNAs in systematically untreated and lymph node negative patients with primary breast cancer. GEO datasets GSE126125 and GSE103161 were analyzed to find the differential microRNAs in primary breast cancer with and without relapse. Systematically untreated patients (n = 180) with low-risk primary breast cancer were selected in this independent validation set, and 48 patients developed relapse within 5 years. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to detect miR-640 and miR-525-5p expressions in tumor tissues. Based on the retrieved data from GSE126125, miR-640 and miR-525-5p expressions were significantly lower in tumors from patients with relapse compared to tumors from patients without relapse, accompanying by highly predictive potential to discriminate cases with and without relapse. The decreased miR-640 and miR-525-5p expressions were revealed in dead patients as compared to alive patients. In the independent validation set, patients with low expression of miR-640 and miR-525-5p showed poor outcome as compared to those with high expression. The receiver operating characteristic (ROC) curves of miR-640 and miR-525-5p for evaluation as diagnostic markers were depicted with the area under curves (AUCs) of 0.940 and 0.886, respectively. Tumors with larger size and higher grade had lower expression of miR-640 and miR-525-5p. MiR-640, miR-525-5p and histologic grade were significant predictors of relapse-free survival (RFS). Our study validated the values of miR-640 and miR-525-5p in predicting relapse of systematically untreated and lymph node negative patients with primary breast cancer.

Segmental and extended resections provide comparable survival for clinically node-negative splenic flexure cancer: a propensity score-matched analysis of the National Cancer Database.

PURPOSE: There is an ongoing debate regarding the extent of resection for splenic flexure tumors (SFT). The purpose of this study was to compare segmental and extended resections in terms of overall survival (OS) and pathologic outcomes. METHODS: Retrospective analysis of all patients surgically treated for SFT in the National Cancer Database (NCDB) for the period 2010-2019. Outcomes of segmental and extended resections were compared and a 1:1 propensity score matching was used to match for confounders. Primary outcome was OS. RESULTS: In total 3498/668,852 (0.5%) patients with clinical stage I-III splenic flexure adenocarcinoma in the NCDB were included. Of these, 1533 (43.8%) underwent segmental resection while 1965 (56.1%) underwent extended resection. After matching, mean OS was similar between the groups (92 vs 91 months; p = 0.94). When survival was stratified by clinical N stage, an 8-month survival benefit was shown in the extended resection group for clinical N-positive status (86 vs 78); however, this difference did not achieve statistical significance (p = 0.078). Median number of harvested lymph nodes was significantly lower in the segmental resection group (16 vs 17; p < 0.001) and the percentage of patients with fewer than 12 harvested nodes was significantly higher (18.4% vs 11.6%; p < 0.001). Length of stay was significantly shorter in the segmental resection group (5 vs 6 days; p = 0.027). There were no significant differences between the groups in terms of 30-day readmission or 30- or 90-day mortality. CONCLUSIONS: While segmental and extended resections were associated with similar OS for clinically node-negative SFT, there might be a survival benefit for extended resection in patients with clinical evidence of lymph node involvement.

Effect of prophylactic central neck dissection following total thyroidectomy on surgical site wound infection, hematoma, and haemorrhage in subjects with clinically node-negative papillary thyroid carcinoma: A meta-analysis.

We performed a meta-analysis to evaluate the effect of prophylactic central neck dissection following total thyroidectomy on surgical site wound infection, hematoma, and haemorrhage in subjects with clinically node-negative papillary thyroid carcinoma. A systematic literature search up to April 2022 was performed and 3517 subjects with clinically node-negative papillary thyroid carcinoma at the baseline of the studies; 1503 of them were treated with prophylactic central neck dissection following total thyroidectomy, and 2014 were using total thyroidectomy. Odds ratio (OR) with 95% confidence intervals (CIs) were calculated to assess the effect of prophylactic central neck dissection following total thyroidectomy on surgical site wound infection, hematoma, and haemorrhage in subjects with clinically node-negative papillary thyroid carcinoma using the dichotomous method with a random or fixed-effect model. The prophylactic central neck dissection following total thyroidectomy subjects had a significantly lower surgical site wound infection (OR, 0.40; 95% CI, 0.20-0.78, P = .007) in subjects with clinically node-negative papillary thyroid carcinoma compared with total thyroidectomy. However, prophylactic central neck dissection following total thyroidectomy did not show any significant difference in hematoma (OR, 0.08; 95% CI, 0.43-2.71, P = .87), and haemorrhage (OR, 0.72; 95% CI, 0.26-1.97, P = .52) compared with total thyroidectomy in subjects with clinically node-negative papillary thyroid carcinoma. The prophylactic central neck dissection following total thyroidectomy subjects had a significantly higher surgical site wound infection, and no significant difference in hematoma, and haemorrhage compared with total thyroidectomy in subjects with clinically node-negative papillary thyroid carcinoma. The analysis of outcomes should be with caution because of the low number of studies in certain comparisons.

Cyclin D1 Serves as a Poor Prognostic Biomarker in Stage I Gastric Cancer.

TNM stage still serves as the best prognostic marker in gastric cancer (GC). The next step is to find prognostic biomarkers that detect subgroups with different prognoses in the same TNM stage. In this study, the expression levels of epidermal growth factor receptor (EGFR) and cyclin D1 were assessed in 96 tissue samples, including non-tumorous tissue, adenoma, and carcinoma. Then, the prognostic impact of EGFR and cyclin D1 was retrospectively investigated in 316 patients who underwent R0 resection for GC. EGFR positivity increased as gastric tissue became malignant, and cyclin D1 positivity was increased in all the tumorous tissues. However, there was no survival difference caused by the EGFR positivity, while the cyclin D1-postive group had worse overall survival (OS) than the cyclin D1-negative group in stage I GC (10-year survival rate (10-YSR): 62.8% vs. 86.5%, p = 0.010). In subgroup analyses for the propensity score-matched (PSM) cohort, there were also significant differences in the OS according to the cyclin D1 positivity in stage I GC but not in stage II and III GC. Upon multivariate analysis, cyclin D1 positivity was an independent prognostic factor in stage I GC. In conclusion, cyclin D1 may be a useful biomarker for predicting prognosis in stage I GC.

Benefit of adjuvant chemotherapy in node-negative T1a versus T1b and T1c triple-negative breast cancer.

PURPOSE: National comprehensive cancer network guidelines recommend delivery of adjuvant chemotherapy in node-negative triple-negative breast cancer (TNBC) if the tumor is > 1 cm and consideration of adjuvant chemotherapy for T1b but not T1a disease. These recommendations are based upon sparse data on the role of adjuvant chemotherapy in T1a and T1b node-negative TNBC. Our objective was to clarify the benefits of chemotherapy for patients with T1N0 TNBC, stratified by tumor size. METHODS: We performed a retrospective analysis of survival outcomes of TNBC patients at two academic institutions in the United States from 1999 to 2018. Primary tumor size, histology, and nodal status were based upon surgical pathology. The Kaplan-Meier plot and 5-year unadjusted survival probability were evaluated. RESULTS: Among 282 T1N0 TNBC cases, the status of adjuvant chemotherapy was known for 258. Mean follow-up was 5.3 years. Adjuvant chemotherapy was delivered to 30.5% of T1a, 64.7% T1b, and 83.9% T1c (p < 0.0001). On multivariable analysis, factors associated with delivery of adjuvant chemotherapy were tumor size and grade 3 disease. Improved overall survival was associated with use of chemotherapy in patients with T1c disease (93.2% vs. 75.2% p = 0.008) but not T1a (100% vs. 100% p = 0.3778) or T1b (100% vs. 95.8% p = 0.2362) disease. CONCLUSION: Our data support current guidelines indicating benefit from adjuvant chemotherapy in node-negative TNBC associated with T1c tumors but excellent outcomes were observed in the cases of T1a and T1b disease, regardless of whether adjuvant chemotherapy was delivered.

Definitive results of a phase III adjuvant trial comparing six cycles of FEC-100 to four cycles of AC in women with operable node-negative breast cancer: the NSABP B-36 trial (NRG Oncology).

PURPOSE: Results from adjuvant trials evaluating 6 cycles of epirubicin-based chemotherapy regimens suggested these programs may be more effective than 4 cycles of doxorubicin-based chemotherapy. METHOD: NSABP B-36 was a phase III clinical trial originally designed as a 2 × 2 factorial study comparing 6 cycles of 5-FU, epirubicin, and cyclophosphamide (FEC-100) to 4 cycles of conventional doxorubicin and cyclophosphamide (AC) with celecoxib or placebo. Shortly after activation, concerns regarding increased cardiovascular risks among selective COX-2 inhibitors resulted in a decision to remove the celecoxib/placebo from the trial. Women with histologically node-negative invasive breast cancer who had undergone primary surgery with a lumpectomy or total mastectomy were eligible. Primary endpoint was disease-free survival (DFS). RESULTS: Between May 2004 and July 2008, 2722 patients were enrolled. Administration of FEC-100 did not result in improvement in DFS compared to AC (HR 1.09; 95% CI 0.92-1.29, p value = 0.31). The effect of FEC-100 compared to AC on DFS was significantly different for receptor-positive (HR 1.32, 95% CI 1.05-1.66) compared to receptor-negative patients (HR 0.86, 95% CI 0.66-1.11) (treatment-by-receptor status interaction p value = 0.02). There was no statistically significant difference in the effect of treatment on overall survival (OS) with FEC-100 compared to AC (HR 1.06; 95% CI 0.84-1.35, p value = 0.61). Overall, Grade 3 and 4 adverse events were more frequent in the FEC-100 group. CONCLUSION: The results of B-36 do not support use of six-cycle anthracycline-based regimens in node-negative breast cancer. Prolongation of anthracycline-based therapy with FEC-100 does not improve DFS or OS, relative to AC for 4 cycles, and was associated with expected increases in toxicity. A statistically significant interaction between treatment and hormone receptor status favoring AC in hormone-receptor-positive breast cancers is consistent with the hypothesis that optimal duration of chemotherapy may be four cycles in these patients. Late cardiac events and deaths prior to recurrence or second cancer were infrequent on both arms, but slightly higher with FEC-100. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00087178.

Evaluating anthracycline + taxane versus taxane-based chemotherapy in older women with node-negative triple-negative breast cancer: a SEER-Medicare study.

PURPOSE: Adjuvant chemotherapy reduces recurrence in early-stage triple-negative breast cancer (TNBC). However, data are lacking evaluating anthracycline + taxane (ATAX) versus taxane-based (TAX) chemotherapy in older women with node-negative TNBC, as they are often excluded from trials. The purpose of this study was to evaluate the effect of adjuvant ATAX versus TAX on cancer-specific (CSS) and overall survival (OS) in older patients with node-negative TNBC. PATIENTS AND METHODS: Using the SEER-Medicare database, we selected patients aged ≥ 66 years diagnosed with Stage T1-4N0M0 TNBC between 2010 and 2015 (N = 3348). Kaplan-Meier survival curves and adjusted Cox proportional hazards models were used to estimate 3-year OS and CSS. Multivariant Cox regression analysis was used to identify independent factors associated with use of ATAX compared to TAX. RESULTS: Approximately half (N = 1679) of patients identified received chemotherapy and of these, 58.6% (N = 984) received TAX, 25.0% (N = 420) received ATAX, and 16.4% (N = 275) received another regimen. Three-year CSS and OS was improved with any adjuvant chemotherapy from 88.9 to 92.2% (p = 0.0018) for CSS and 77.2% to 88.6% for OS (p < 0.0001). In contrast, treatment with ATAX compared to TAX was associated with inferior 3-year CSS and OS. Three-year CSS was 93.7% with TAX compared to 89.8% (p = 0.048) for ATAX and OS was 91.0% for TAX and 86.4% for ATAX (p = 0.032). CONCLUSION: While adjuvant chemotherapy was associated with improved clinical outcomes, the administration of ATAX compared to TAX was associated with inferior 3-year OS and CSS in older women with node-negative TNBC. The use of adjuvant ATAX should be considered carefully in this patient population.

Impact of adjuvant chemotherapy on T1N0M0 breast cancer patients: a propensity score matching study based on SEER database and external cohort.

BACKGROUND: There is no clear consensus on the benefits of adjuvant chemotherapy for tumor-node-metastasis (TNM) stage T1 (T1N0M0) breast cancer (BC). Our study investigated the effects of adjuvant chemotherapy on T1N0M0 BC patients. METHODS: Seventy-five thousand one hundred thirty-nine patients diagnosed with T1N0M0 BC were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate Cox analyses were performed to investigate the effects of adjuvant chemotherapy on T1a, T1b, and T1cN0M0 BC, including various tumor grades, and four molecular subtypes. Propensity score matching (PSM) was used to eliminate confounding factors and further compare the results between adjuvant chemotherapy and no adjuvant chemotherapy. Additionally, 545 T1N0M0 BC patients treated at the Northern Jiangsu People's Hospital were included as an independent external validation cohort. Univariate and multivariate Cox analyses were used to confirm the effects of adjuvant chemotherapy in T1a, T1b, and T1cN0M0 BC. Survival curves for the different tumor grades and molecular subtypes were plotted using the Kaplan-Meier method. RESULTS: Adjuvant chemotherapy demonstrated a statistically significant improvement in overall survival (OS) in T1b and T1c BC, but not in T1a BC. Within T1b BC, adjuvant chemotherapy was found to have effects on grade III, and hormone receptor + (HoR +)/human epidermal growth factor receptor 2 + (HER2 +), HoR-/HER2 + , and HoR-/HER2- molecular subtypes, respectively. Adjuvant chemotherapy was beneficial to OS for grade II/III and T1c BC. Identical results were obtained after PSM. We also obtained similar results with external validation cohort, except that adjuvant chemotherapy made a difference in grade II and T1b BC of the external validation dataset. CONCLUSIONS: Partial T1N0M0 BC patients with grade III T1bN0M0, patients with tumor grade II and III T1cN0M0, and excluding those with HoR + /HER2- subtype tumors, could obtain OS benefits from adjuvant chemotherapy.

Declining use of inguinofemoral lymphadenectomy in the treatment of clinically negative, pathologic node positive vulvar cancer.

PURPOSE: The management of vulvar cancer with clinically negative groin lymph nodes but with positive sentinel lymph node biopsy (SLNB) is controversial, with options including inguinofemoral lymphadenectomy (IFL) and/or adjuvant chemotherapy and radiotherapy. We used the National Cancer Database (NCDB) to examine trends in the management of clinically node negative, pathologically node positive (cN-/pN+) patients. METHODS: The NCDB was used to identify cN-/pN+ vulvar cancer patients. Demographic and clinical data were compared with chi-squared and Wilcoxon rank-sum tests. OS was analyzed with the Kaplan-Meier method and log-rank test. Cox proportional hazards regression was used to determine factors associated with OS. RESULTS: A total of 885 cN-/pN+ vulvar cancer patients were identified between 2012 and 2016, during which the rate of SLNB alone increased from 3.6% to 11.7%, while the rate of IFL +/- SLNB decreased from 89.7% to 78.1% (p < 0.05). Radiation was used in 68.5% and 64.6% of the SLNB-alone and IFL +/- SLNB cohorts, respectively, with chemoradiation in 37.1% and 33.6%, respectively. OS was not different between patients who received SLNB-alone vs. IFL +/- SLNB (p = 0.644). Receipt of chemotherapy and radiation was associated with improved OS (p < 0.001). CONCLUSIONS: Among cN-/pN+ vulvar cancer patients in the NCDB, the practice of performing IFL decreased over time as SLNB-alone became more common and the majority received radiation +/- chemotherapy. There was no difference in OS between SLNB-alone vs. IFL +/- SLNB. Patients treated with adjuvant chemoradiation had improved survival. Whether the favorable outcomes in the SLNB-alone cohort may be attributed to radiotherapy dose escalation or use of chemotherapy warrants further study.

Critical Review of the Current Evidence on Sentinel Node Biopsy in Oral Cancer.

PURPOSE OF REVIEW: With contemporary surgery of the cN0 neck in early oral cancer becoming more selective, sentinel node biopsy (SNB) is gaining popularity as a possible alternate option to elective neck dissection (END). This review attempts to critically appraise the current evidence and highlight pertinent arguments for the use of SNB in early oral cancers. RECENT FINDINGS: Based on the recent randomized trials, it is imperative to perform an END at the time of primary resection in cN0 oral cancers. The much criticized false negative rate of SNB can be argued to be equal to the regional failure rate after END for pN0 necks, possibly making a case for SNB due to the reduction in number of neck dissections. There still lies ambiguity on the technique, protocols, and benefit of SNB over END. The role of extended histopathological techniques and the implications of micrometastasis and isolated tumor cells for treatment intensification remain questionable. Currently, SNB is an intermediary between routine imaging and END that needs to evolve before it can become a practice changing alternative to END itself. More efforts are needed in standardizing the protocols for SNB.

Androgen receptor expression and its prognostic value in T1N0 luminal/HER2- breast cancer.

Purpose: The authors aimed to evaluate the prognostic and predictive value of androgen receptor (AR) expression in patients with luminal/human EGFR2 negative (HER2-) T1N0 breast cancer. Methods: The cohort in this retrospective study comprised 471 patients with luminal/HER2- T1N0 breast cancer who had undergone surgery between 2013 and 2017 in the authors' center. Results: AR+ tumors were associated with favorable characteristics. AR+ patients had better 5-year recurrence-free survival rates and the risk of recurrence was greater for AR- than for AR+ patients. AR- status predicted the failure of adjuvant endocrine therapy with aromatase inhibitors and of adjuvant chemotherapy with docetaxel plus cyclophosphamide. Conclusion: AR+ expression is significantly related to a better prognosis. AR expression may be an additional biomarker for both endocrine and chemotherapy responsiveness.

Adjuvant treatment with paclitaxel plus trastuzumab for node-negative breast cancer: real-life experience.

Background: In node-negative HER2-overexpressed breast cancers, adjuvant paclitaxel plus trastuzumab treatment is a successful de-escalation approach with excellent survival outcomes. Methods: All patients with HER2+ breast cancer treated in our centers were retrospectively reviewed. Results: We analyzed 173 patients who were treated with adjuvant paclitaxel plus trastuzumab. The mean tumor size was 2.2 cm. There were eight invasive disease events or death: four distant recurrences (2.3%), three locoregional recurrences (1.7%) and one death without documented recurrence after a 52 month follow-up. The 3-year disease-free survival and recurrence-free interval rate was 96.6%. Conclusion: This real-life experience with adjuvant paclitaxel plus trastuzumab demonstrated few distant recurrences and is compatible with the APT trial findings.

Lay abstract In oncology practice, there have been some efforts to avoid the toxicity of combination chemotherapies and reduce the amount of treatment given in recent decades. These strategies have been studied especially for patients with a specific subtype of early-stage breast cancer. We present the results from patients treated in our centers and discuss them in relation to the literature.

Sentinel Lymph Node Removal After Neoadjuvant Chemotherapy in Clinically Node-Negative Patients: When to Stop?

BACKGROUND: The maximum number of sentinel lymph nodes (SLN) to be resected to accurately stage the axilla in patients undergoing neoadjuvant chemotherapy (NAC) for the treatment of clinically node-negative (cN0) breast cancer has not been determined. We sought to determine the sequence of removal of the positive SLNs in this patient population. METHODS: All patients aged ≥ 18 years diagnosed with cN0 invasive breast cancer who received NAC and underwent SLN surgery at Mayo Clinic Rochester between September 2008 and September 2018 were identified. Univariate analysis was performed to compare factors associated with positive nodes and where the first positive node was in the sequence of removal of the SLNs. RESULTS: We identified 446 cancers among 440 patients with a median age of 51 (IQR: 43, 61) years. At surgery, 381 (85.4%) cancers were pathologically node (ypN) negative and 65 (14.6%) were pN + . The number of nodes removed was similar for both patients with ypN0 and ypN + disease, with a median number of SLNs removed of 2.0 (IQR: 2.0, 3.0). Of all patients with a positive node, the first positive node was most commonly the 1st node removed (75.4%), and was identified by the 3rd SLN removed in all cases. CONCLUSIONS: Among cN0 patients treated with NAC, if a positive SLN is present, it is most commonly identified as the 1st sentinel node removed by the surgeon, and was identified by the 3rd sentinel node in our series. This suggests that once 3 SLNs have been resected, removal of additional sentinel lymph nodes does not add diagnostic value.

Multicenter retrospective study on the use of Curebest™ 95GC Breast for estrogen receptor-positive and node-negative early breast cancer.

BACKGROUND: The benefits of postoperative chemotherapy in patients with estrogen receptor (ER)-positive breast cancer remain unclear. The use of tumor grade, Ki-67, or ER expression failed to provide an accurate prognosis of the risk of relapse after surgery in patients. This study aimed to evaluate whether a multigene assay Curebest™ 95GC Breast (95GC) can identify the risk of recurrence and provide more insights into the requirements for chemotherapy in patients. METHODS: This single-arm retrospective multicenter joint study included patients with ER-positive, node-negative breast cancer who were treated at five facilities in Japan and had received endocrine therapy alone as adjuvant therapy. The primary lesion specimens obtained during surgery were analyzed using the 95GC breast cancer multigene assay. Based on the 95GC results, patients were classified into low-risk (95GC-L) and high-risk (95GC-H) groups. RESULTS: The 10-year relapse-free survival rates were 88.4 and 59.6% for the 95GC-L and 95GC-H groups, respectively. Histologic grade, Ki-67, and PAM50 exhibited a significant relationship with the 95GC results. The segregation into 95GC-L and 95GC-H groups within established clinical factors can identify subgroups of patients using histologic grade or PAM50 classification with good prognosis without receiving chemotherapy. CONCLUSIONS: Based on the results of our retrospective study, 95GC could be used to evaluate the long-term prognosis of ER-positive, node-negative breast cancer. Even though further prospective validation is necessary, the inclusion of 95GC in clinical practice could help to select optimal treatments for breast cancer patients and identify those who do not benefit from the addition of chemotherapy, thus avoiding unnecessary treatment.

Optimal examined lymph node count in node-negative colon cancer should be determined.

Background: We aimed to investigate the association between optimal examined lymph node (ELNs) and overall survival to determine the optimal cutoff point. Methods: Cox models and locally weighted scatterplot smoothing were used to fit hazard ratios and explore an optimal cutoff point based on the Chow test. Results: Overall survival increased significantly with the corresponding increase in the number of ELNs after adjusting for covariates. In Chow's test, the optimal cutoff point for node-negative colon cancer was 15, which was validated in both cohorts after controlling for confounders (Surveillance, Epidemiology, and End Results database: hazard ratio: 0.701, p < 0.001; single-center: HR: 0.563; p = 0.031). Conclusions: We conservatively suggest that the optimal number of ELNs for prognostic stratification is 15 in node-negative colon cancer.

Lay abstract Over the past 20 years, the number of examined lymph nodes (ELNs) has been an important indicator to accurately assess lymph node metastasis, and therefore, many studies have focused on exploring an optimal cutoff point to prevent missed detection of positive lymph nodes. However, in recent years, ELNs has been considered to play other key roles. In the current study, ELNs were deemed an important prognostic factor, and the minimum number of ELNs was recommended to be 15 in node-negative colon cancer via rigorous statistical methods and a large sample of data.