Node-positive Tumors Research Articles

Induction Therapy Is Not Associated With Improved Survival in Large cT4 N0 Non-Small Cell Lung Cancers

BackgroundThe eighth edition of the staging manual for non-small cell lung cancer reclassified tumors >7 cm as stage IIIA (T4 N0); previously, such tumors without nodal disease were considered stage IIB (T3 N0). This study tested the hypothesis that induction chemotherapy for these stage IIIA patients does not improve survival compared with primary surgery. MethodsThe National Cancer Database was queried for patients with non-small cell lung cancer with tumor size >7 cm who underwent surgical resection from 2010 to 2015. Patients with clinically node-positive disease or tumor invasion of major structures were excluded. Patients undergoing induction chemotherapy followed by surgical resection (IC group) were compared with patients undergoing primary surgery (PS group). Propensity score matching was performed. ResultsIn total, 1610 patients with cT4 N0 disease on the basis of tumor size >7 cm and no tumor invasion underwent surgical resection: 1346 (83.6%) comprised the PS group and 264 (16.4%) the IC group. After propensity score matching, the IC group had a higher rate of pN0 (78.4% vs 66.0%; P < .001) and less lymphovascular invasion (13.9% vs 26.3%; P < .001), but longer postoperative stays (6 days vs 5 days; P < .001) and higher 30-day mortality (3.5% vs 0%; P = .002). Median 5-year survival was similar between the IC and PS groups (53.5% vs 62.2%; P = .075), and IC was not independently associated with survival (hazard ratio, 1.45; P = .146). ConclusionsPatients with cT4 N0 non-small cell lung cancer on the basis of tumor size >7 cm and no tumor invasion of major structures have similar overall survival with either induction chemotherapy or primary surgery. Induction chemotherapy should not be routinely given for this subset of stage IIIA patients.

Resection of Non-Functional Pancreatic Neuroendocrine Neoplasms-A Single-Center Retrospective Outcome Analysis.

Surgery remains the only curative treatment of pancreatic neuroendocrine neoplasms (pNEN). Here, we report the outcome after surgery for non-functional pNEN at a European Neuroendocrine Tumor Society (ENETS) center in Germany between 2000 and 2019; cases were analyzed for surgical (Clavien–Dindo classification; CDc) and oncological outcomes. Forty-nine patients (tumor grading G1 n = 25, G2 n = 22, G3 n = 2), with a median age of 56 years, were included. Severe complications (CDc ≥ grade 3b) occurred in 11 patients (22.4%) and type B/C pancreatic fistulas (POPFs) occurred in 5 patients (10.2%); in-hospital mortality was 2% (n = 1). Six of seven patients with tumor recurrence (14.3%) had G2 tumors in the pancreatic body/tail. The median survival was 5.7 years (68 months; [1–228 months]). Neither the occurrence (p = 0.683) nor the severity of complications had an influence on the relapse behavior (p = 0.086). This also applied for a POPF (≥B, p = 0.609). G2 pNEN patients (n = 22) with and without tumor recurrence had similar median tumor sizes (4 cm and 3.9 cm, respectively). Five of the six relapsed G2 patients (83.3%) had tumor-positive lymph nodes (N+); all G2 pNEN patients with recurrence had initially been treated with distal pancreatic resection. Pancreatic resections for pNEN are safe but associated with relevant postoperative morbidity. Future studies are needed to evaluate suitable resection strategies for G2 pNEN.

Relationship Between Breast and Axillary Pathologic Complete Response in Women Receiving Neoadjuvant Chemotherapy for Breast Cancer.

We aim to delineate the relationship between breast and axillary pathologic complete response (pCR) in patients receiving neoadjuvant chemotherapy for breast cancer. We performed a retrospective cohort study of patients with clinical T1-4N0-3M0 breast cancerreceiving neoadjuvant chemotherapy followed by surgical therapy at Sunnybrook Health Sciences Centre in Toronto, Canada between 2014 and 2019.Clinicopathologic data were abstracted from the electronic medical record. Women were stratified into receptor subtypes as follows: hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-), HR+/HER2+, HR-/HER2+ and HR-/HER2- (triple negative) and compared with Fisher's exact test.Our primary outcome was to assess the positive predictive value of breast pCR for determining axillary pCR, and vice versa. There were 374 breast cancers, with 109 (29.1%) achieving breast pCR (ypT0/Tis). Amongst node-positive tumours achieving breast pCR, rates of associated axillary pCR (ypN0/0i+) were as follows: HR+/HER2- (2/6, 33.3%), HR+/HER2+ (12/13, 92.3%), HR-/HER2+ (15/17, 88.2%) and triple negative (15/17, 88.2%) (P = 0.02).Conversely, amongst node-positive tumours achieving axillary pCR, rates of associated breast pCR were: HR+/HER2- (2/10, 20.0%), HR+/HER2+ (12/23, 52.2%), HR-/HER2+ (15/24, 62.5%) and triple negative (15/26, 57.7%) (P = 0.1). Breast pCR is a strong predictor of axillary pCR in women with HER2-positive and triple-negative breast cancers.Conversely, axillary pCR is a modest predictor of breast pCR for these subtypes.There is a poor relationship between breast and axillary pCR in women with hormone receptor-positive disease.These data may inform future de-escalation of surgery in women with HER2-positive and triple-negative disease.

Postmastectomy radiation therapy and survival outcome in older patients with T1-2N1 breast cancer

BackgroundThe prognostic impact of postmastectomy radiation therapy (PMRT) on contemporary older patients with T1-2N1 breast cancer is unclear. We aimed to investigate the effect of PMRT in this setting. MethodsLeveraging the Surveillance, Epidemiology, and End Results (SEER) program data from 2004 to 2015, 7052 patients aged 70 years or older with T1-2N1 breast cancer were identified for this propensity-matched analysis. Fine and Gray competing risks regression was conducted to explore the correlation between PMRT and breast cancer-specific survival, in subgroups defined by tumor size and positive lymph nodes. ResultsThe median follow-up was 60.1 months (interquartile range, 28.0 to 87.0). Among propensity-matched patients, multivariate analysis identified an association between PMRT and decreased breast cancer mortality (BCM; HR 0.637; 95 % CI 0.436–0.931; P = 0.020) in patient subset with three positive nodes and tumors 2–5 cm in size, and this benefit was limited to patients with three positive nodes and tumors 2–5 cm in size who did not receive chemotherapy. In patient subsets who received chemotherapy, no association between PMRT and BCM was found. ConclusionPMRT was not associated with BCM in older patients with T1-2N1 breast cancer who received chemotherapy. The benefit of PMRT was limited to those with three positive nodes and tumors 2–5 cm in size who did not receive chemotherapy.

Clinicopathological Prognostic Factors Influencing Survival Outcomes of Vulvar Cancer.

Background:The prognostic factors for survival in squamous cell carcinoma (SCCA) of vulva cancer such as groin node involvement, postmenopausal status, tumor size, margin status, tumor grade, lymph vascular space invasion (LVSI) were reported in the past. However, with limited data from Southeast - Asian population, the present study was conducted to evaluate the clinicopathological prognostic factors for survival outcomes of this disease after treatment with surgery.Methods:All SCCA vulva cancer patients who underwent surgery between January 2006 and December 2017 were reviewed. The clinicopathological factors were analyzed to identify the prognostic factors for the progression-free survival (PFS) and overall survival (OS) using the Kaplan- Meier method and Cox-Proportional Hazard model. Results:One hundred twenty-five patients were recruited. The independent poor prognostic factors for PFS were groin node-positive and pathologic tumor diameter of more than 25 mm. Whereas postmenopausal status and groin node positive were independent poor prognostic factors for OS. Conclusion:Groin node-positive was the only one independent poor prognostic factor for both PFS and OS. In addition, the tumor diameter longer than 25 mm. was independent poor prognostic factors for PFS while postmenopausal status was independent poor prognostic factors for OS. Special adjuvant treatment for patients with these factors should be further investigated.

Occupational Radiation Exposure of Radiopharmacy, Nuclear Medicine, and Surgical Personnel During Use of [99mTc]Tc-PSMA-I&S for Prostate Cancer Surgery.

The aim of this study was to estimate and subsequently measure the occupational radiation exposure for all personnel involved in producing, administering, or performing imaging or surgery with [99mTc]Tc-PSMA-I&S, which has been introduced for identification of tumor-positive lymph nodes during salvage prostate cancer surgery. Methods: The effective dose was estimated and subsequently measured with electronic personal dosimeters for the following procedures and personnel: labeling and quality control by the radiopharmacy technologist, syringe preparation by the nuclear medicine laboratory technologist, patient administration by the nuclear medicine physician, patient imaging by the nuclear medicine imaging technologist, and robot-assisted laparoscopic salvage lymph node dissection attended by an anesthesiology technologist, scrub nurse, surgical nurse, and surgeon. The dose rate of the patient was measured immediately after administration of [99mTc]Tc-PSMA-I&S, after imaging, and after surgery. Results: The estimated dose per procedure ranged from 1.59 × 10-10 μSv (imaging technologist) to 9.74 μSv (scrub nurse). The measured effective dose ranged from 0 to 5 μSv for all personnel during a single procedure with [99mTc]Tc-PSMA-I&S. The highest effective dose was received by the scrub nurse (3.2 ± 1.3 μSv), whereas the lowest dose was measured for the surgical nurse (0.2 ± 0.5 μSv). If a single scrub nurse were to perform as many as 100 procedures with [99mTc]Tc-PSMA-I&S in a year, the total effective dose would be 320 μSv/y. Immediately after administration, the dose rate at 50 cm from the patient was 18.5 ± 1.6 μSv/h, which dropped to 1.8 ± 0.3 μSv/h after imaging the following day, reducing even further to 0.56 ± 0.33 μSv/h after surgery. Conclusion: The effective dose for personnel involved in handling [99mTc]Tc-PSMA-I&S is comparable to that of other 99mTc-radiopharmaceuticals and therefore safe for imaging and radioguided surgery.

Extreme weekly locoregional hypofractionated radiation in elderly women with non-metastatic breast cancer

Background and purposeBreast cancer locoregional (LR) radiation in the elderly requires careful consideration between the benefits of aggressive treatment and its potential toll on these patients. Extreme weekly LR hypofractionated radiation (HFRT), delivering >5 Gy per fraction, may be better suited in such a population. It represents a good compromise between RT omission and exhaustive daily radiation. This study aims to report the local and LR control rate as well as the acute and long-term side effects of the elderly patients treated with HFRT in our institution, and to compare these results to those from the literature. Materials and methodsWe conducted a retrospective study by reviewing medical records of elderly patients with breast cancer treated with adjuvant once-weekly LR HFRT between 2011 and 2020. Fifty patients presenting with primary non-metastatic node-positive breast tumors were included. Treatment outcomes including local/LR control and overall survival were reported. Early and late toxicity profiles were also assessed. ResultsAfter a median follow-up of 4.8 years, only one local recurrence in the chest wall occurred and there was no regional recurrence. The distant metastatic rate was 6%. The long-term recurrence-free survival rate was 80% at 5 years. The cause specific survival rate was 90% at 5 years. The overall survival rate was 69.4% and 55.5% at 3 and 5 years, respectively. There were 44 (88%) patients with Grade 1 or 2 early toxicity. There was no Grade 3 or higher acute toxicity registered. Late toxicity was mainly Grade 1 or 2 subcutaneous fibrosis, lymphoedema, and neuropathy except for one patient with Grade 3 fibrosis. ConclusionExtreme LR HFRT is well tolerated with good outcomes and is a good alternative for elderly and frail patients. Our results confirm the efficacy and safety of such a regimen. Further randomized trials assessing both oncologic outcome and toxicity profile are justified.

Epithelial-mesenchymal plasticity and lymph node metastases in invasive breast carcinoma of no special type

Background: Breast cancer is the commonest cancer among women with distant metastases being the leading cause of mortality. Epithelial-mesenchymal plasticity (EMP) is a proposed mechanism involved in establishment of metastasis. E-cadherin and vimentin can be used as epithelial and mesenchymal markers, respectively, to identify EMP. Aims: To compare E-cadherin and vimentin expressions between node-negative and node-positive invasive breast carcinoma–no special type (IBC-NST) and their lymph node metastases. Methods: Forty node negative tumours and 44 axillary node positive tumours of IBC-NST with their metastatic lymph nodes were retrieved from patients who had undergone mastectomy at the Teaching Hospital, Peradeniya. Samples were subjected to dual immunohistochemical staining with anti-E-cadherin and anti-vimentin primary antibodies. Any cytoplasmic staining for vimentin and 70% or more of membranous staining for E-cadherin were taken as positive and cells counted in 10 high power fields. Intensity of staining was graded as high=3, moderate=2, low=1 and absent=0 by comparing with internal controls. Percentage of positive cells was multiplied by the intensity to obtain the immuno-score (IS) for both protein expressions. IS was compared using independent and paired t-test. Results and conclusions: A lower E-cadherin (p=0.001) and higher vimentin (p=0.008) expression was seen in node positive group compared to node negative group. A higher E-cadherin (p<0.001) and lower vimentin (p<0.001) expression was seen in lymph nodes compared to the corresponding primary tumours. A significant loss of epithelial properties and acquisition of mesenchymal properties in the node positive group indicates epithelial to mesenchymal transition of tumour cells, contributing to metastasis. In the lymph nodes, higher E-cadherin and lower vimentin expression suggests a reverse mechanism, i.e., mesenchymal to epithelial transition. These Results are suggestive of epithelial-mesenchymal plasticity of tumour cells in establishment of metastasis in IBC-NST.

Intra-scanner repeatability of quantitative imaging features in a 3D printed semi-anthropomorphic CT phantom

ObjectivesRadiomics has shown to provide novel diagnostic and predictive disease information based on quantitative image features in study settings. However, limited data yielded contradictory results and important questions regarding the validity of the methods remain to be answered. The purpose of this study was to evaluate how clinical imaging techniques affect the stability of radiomics features by using 3D printed anthropomorphic CT phantom to test for repeatability and reproducibility of quantitative parameters. Methods48 PET/CT validated lymph nodes of prostate cancer patients (24 metastatic, 24 non-metastatic) were used as a template to create a customized 3D printed anthropomorphic phantom. We subsequently scanned the phantom five times with a routine abdominal CT protocol. Images were reconstructed using iterative reconstruction and two soft tissue kernels and one bone kernel. Radiomics features were extracted and assessed for repeatability and susceptibility towards image reconstruction settings using concordance correlation coefficients. ResultsOur analysis revealed 19 of 86 features (22 %) as highly repeatable (CCC ≥ 0.85) with low susceptibility towards image reconstruction protocols. Most features analyzed depicted critical non-repeatability with CCC’s < 0.75 even under entirely consistent imaging acquisition settings. Edge enhancing kernels result in higher variances between the scans and differences in repeatability and reproducibility were detected between PSMA-positive and negative lymph nodes with overall more stable features seen in tumor positive lymph nodes. ConclusionsBoth, repeatability and reproducibility play a crucial role in the validation process of radiomics features in clinical routine. This phantom study shows that most radiomics features in contrast to previous studies, including phantom and clinical, do not depict sufficient intra-scanner repeatability to serve as reliable diagnostic tools.

Audit of Lymph Node Sampling in Colorectal Carcinoma Resections-implication for Prognosis and Management

Aims: To review lymph node yield in colorectal carcinoma (CRC) resections and its associated factors in a Nigerian Teaching Hospital practice.&#x0D; Study design: This was a retrospective cross-sectional study.&#x0D; Place and duration of study: Department of Pathology, University College Hospital Ibadan Nigeria and colectomies from January 2014 to December 2018 were reviewed.&#x0D; Methodology: Surgical Pathology reports of CRC resections at the University College Hospital Ibadan over 5 years (2014-2018) were reviewed. Colectomy lengths, tumour location (colon/rectum), tumour size, comment on presence of lymph node (yes/no), lymph node count, presence of attached mesentery (yes/no), histological subtype, tumour grade, presence of tumour-positive node and count, and pT stage were documented. Fisher’s Exact test was employed to test the effects of these variables on presence of lymph node and tumour-positive node at histology using SPSS 20. Significance level was set at P &lt; .05.&#x0D; Results: Of 66 histology reports retrieved, 62 (93.9%) had comments on search for lymph nodes and attached mesentery was documented in 25 (37.9%). The median colectomy length and tumour size were 25cm (6cm-152cm) and 6.75cm (3-30cm) respectively. Lymph nodes were present in 52 (78.8%) specimens; 28 (53.8%) of these had tumour-positive lymph nodes. Adenocarcinoma NOS was the commonest histological subtype 53 (80.3%), mucinous carcinoma 12 (18.2%) and signet ring carcinoma 1 (1.5%). Eighteen, 9 and 1of adenocarcinoma NOS, mucinous carcinoma, and signet ring carcinoma respectively had tumour-positive lymph nodes. Finding of lymph node was significantly associated with comment on search for lymph node (p &lt; .01) while finding tumour-positive nodes was associated with histological subtype, presence of mesentery, late tumour stage and lymph node count ≥ 12 (p &lt; .05).&#x0D; Conclusion: If lymph nodes were present, more than likely there will be metastatic involvement. To increase Lymph node yield in CRC resections, submission of mesentery and search for lymph nodes is indicated. When nodes are absent, a mention is required for practice audit. It is imperative to include both clinical and grossing notes for lymph nodes to certify and guide precise staging of the cancer.

76P The clinical survival benefit of postmastectomy radiotherapy patients screened form T1-2N1M0 breast cancer according to tumour size and the number of lymph nodes

The prognostic value of postmastectomy radiotherapy (PMRT) in T1-2N1 breast cancer patients remains controversial. The aim of this study was to evaluate the benefit of PMRT in overall survival (OS) of T1-2N1 breast cancer patients based on the combination of lymph node numbers and tumor size. We used data extracted from the Surveillance, Epidemiology, and End Results program. Women diagnosed as T1-2N1M0 breast cancet betweent 2004 and 2015 was abstracted. The primary outcome was overall survival. Multivariate Cox proportional hazard models were used to estimate the independent prognostic factors and to assess hazard ratios (HR) and their 95% confidence intervals (CI) with OS. Subgroup analysis of patients with different node positive number and tumor size were enrolled in our study. A total of 29366 patients included the final analysis, 20167 (68.7%) patients in no-PMRT group and 9199 (31.3%) patients in PMRT group. Multivariable Cox model analysis showed that radiotherapy could improve the overall survival (Hazard ratio [HR]0.89;95%CI 0.83-0.96, P=0.001) for T1-2N1 breast cancer patients. Subgroup analysis based on different tumor burden types showed that there was not all survival benefit to every subgroup. Analysis shows the benefits of PMRT are associated with exaltation in breast cancer overall survive rate among the patients with tumor size 4-5 cm and two or three positive lymph nodes respectively (HR 0.69; 95%CI 0.51-0.94; P=0.017or HR0.65; 95%CI 0.44-0.95; P= 0.027,separately). PMRT also has a beneficial effect for the patients with tumor size 2-3 cm and three positive lymph nodes (HR 0.61; 95%CI 0.48-0.78; P<0.001), but not in the others. The integration of tumor size and the number of positive lymph nodes status seems to be a reliable predictor of overall survival from radiotherapy, which may enable physician to make clinical decision more precisely and effectually about PMRT, especially in the low -risk breast cancer subgroup.

Suppression of Breast Cancer Progression by FBXL16 Via Oxygen-Independent Regulation of HIF1α Stability

Summary Triple-negative breast cancers (TNBCs) are characterized by high rates of recurrence and aggressiveness, and poor clinical outcomes. Deregulated E3 ligases are involved in breast cancer pathogenesis and progression, but the underlying mechanisms are unclear. Here, we found that F-box and leucine-rich repeat protein 16 (FBXL16) acts as a tumor suppressor in TNBC. Specifically, FBXL16 directly binds to HIF1α and induces its ubiquitination and degradation, regardless of the tumor microenvironment, resulting in blockade of the HIF1α-mediated epithelial-mesenchymal transition (EMT) and angiogenesis features of breast cancer. In TNBC, FBXL16 expression is downregulated by the p38/miR-135b-3p axis, and loss of FBXL16 expression restores HIF1α-mediated metastatic features of breast cancer. Low expression of FBXL16 is associated with high-grade and lymph node-positive tumors and poor overall survival of breast cancer. Together, these findings reveal a novel suppressive role of FBXL16 in regulating breast cancer progression and suggest that modulation of FBXL16 expression may offer a favorable strategy for treatment of patients with metastatic breast cancer, including TNBCs.

FOXD3‑AS1/miR‑128‑3p/LIMK1 axis regulates cervical cancer progression

Long non-coding RNA forkhead box D3 antisense RNA 1 (FOXD3-AS1) functions as an oncogenic regulator in several types of cancer, including breast cancer, glioma and cervical cancer. However, the effects and mechanisms underlying FOXD3-AS1 in cervical cancer (CC) are not completely understood. The present study aimed to investigate the biological functions and potential molecular mechanisms underlying FOXD3-AS1 in CC progression. Reverse transcription-quantitative PCR was performed to detect FOXD3-AS1, microRNA (miR)-128-3p and LIM domain kinase 1 (LIMK1) expression levels in CC tissues and cells. Immunohistochemical staining and western blotting were conducted to assess LIMK1 protein expression levels in CC tissues and cells, respectively. Cell Counting Kit-8 and BrdU assays were used to determine the role of FOXD3-AS1 in regulating cell proliferation. CC cell migration and invasion were assessed by performing Transwell assays. Dual-luciferase reporter assays were conducted to verify the binding between miR-128-3p and FOXD3-AS1. FOXD3-AS1 expression was significantly increased in CC tissues and cell lines compared with adjacent healthy tissues and normal cervical epithelial cells, respectively. High FOXD3-AS1 expression was significantly associated with poor differentiation of tumor tissues, increased tumor size and positive lymph node metastasis. FOXD3-AS1 overexpression significantly increased CC cell proliferation, migration and invasion compared with the negative control (NC) group, whereas FOXD3-AS1 knockdown resulted in the opposite effects compared with the small interfering RNA-NC group. Moreover, the results demonstrated that FOXD3-AS1 targeted and negatively regulated miR-128-3p, which indirectly upregulated LIMK1 expression. Therefore, the present study demonstrated that FOXD3-AS1 upregulated LIMK1 expression via competitively sponging miR-128-3p in CC cells, promoting CC progression.

Abstract PS10-07: Pathologic complete response and 3-year survival with or without pertuzumab using real-world data of stage II and III HER2-positive breast cancer

Abstract Background Pertuzumab greatly improves pathologic complete response (pCR) rates in early stage HER2-positive breast cancer. Long-term benefit of pertuzumab, however, is less well established, as follow-up of the NEOSPHERE and APHINITY trials did not show clear improvement in overall survival, although patients with high risk of recurrence (e.g. node positive) appeared to benefit. Since its long-term benefit remains uncertain, we compared outcome of patients treated with or without pertuzumab in a quasi-random experiment using real-world data. Methods We identified all patients with stage II-III HER2-positive breast cancer in the Netherlands treated with neoadjuvant trastuzumab containing chemotherapy between November 2013 and January 2016 from the nationwide Netherlands Cancer Registry. During this period, reimbursement of pertuzumab in the Netherlands was pending and pertuzumab was only available as trial medication for patients in 37 hospitals that participated in the TRAIN-2 study. This setting created a unique opportunity to compare two quasi-random cohorts of patients treated with or without pertuzumab. We used logistic regression analysis to evaluate the association between pertuzumab use and pCR (ypT0/is, ypN0) and Kaplan-Meier estimates and Cox regression analysis for the association with overall survival (OS). Multivariate analyses included age, cT-status, cN-status, hormone receptor (HR) status and grade. Multiple imputation was used to impute missing data for multivariate analysis. Results We identified 1,124 eligible patients of whom 453 (40%) had received pertuzumab. Baseline characteristics were comparable with and without pertuzumab: 61% of tumors were cT2, 22% cT3, 66% were node positive and 62% ER and/or PR-positive. Grade was missing for 17% in patients treated with and 46% in patients treated without pertuzumab and therefor imputed. PCR in breast and axilla could be determined in 1,091 patients. Pertuzumab use improved pCR rates (65% vs 41%, adjusted odds ratio [aOR] 3.01; 95% confidence interval [CI] 2.29-3.97; p&amp;lt;0.001). At a median follow-up of 59 months (IQR 53-66) 23 deaths had occurred in the pertuzumab group and 68 in the non-pertuzumab group (3-year OS 98% vs 95%; adjusted hazard ratio [aHR]: 0.61; 95% CI:0.38-1.00, p=0.048). Pertuzumab benefit appeared largest in ER/PR negative and cN+ tumors, although the number of events in each subgroup was too small for formal comparisons. Complete-case analysis showed similar aHRs, but with broader 95% confident intervals. Conclusion This real-world quasi-experiment confirms the efficacy of pertuzumab to achieve a pCR in stage II and III HER2-positive breast cancer. In addition, these data suggest a small absolute overall survival benefit with pertuzumab, most prominently in hormone receptor negative and node positive tumors. Despite the unique setting of two quasi-random cohorts treated with or without pertuzumab and very similar baseline characteristics, residual confounding cannot be fully excluded. Breast cancer specific evaluation and translational work including central revision of tumor grade for missing cases is pending. pCR (%)3-yr OS (%)Ptzno PtzPtzno PtzaHR (95%CI)Overall65%41%98%95%0.61 (0.38-1.00)HR-positive51%32%98%97%0.70 (0.36-1.33)HR-negative86%55%97%92%0.54 (0.26-1.13)cN071%46%99%100%0.54 (0.14-2.00)cN+62%38%97%93%0.65 (0.39-1.09) Citation Format: Anna van der Voort, Marte Liefaard, Mette van Ramshorst, Erik van Werkhoven, Astrid Scholten, Jelle Wesseling, Marie-Jeanne Vrancken Peeters, Linda de Munck, Gabe Sonke. Pathologic complete response and 3-year survival with or without pertuzumab using real-world data of stage II and III HER2-positive 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 PS10-07.

Two-month stop in mammographic screening significantly impacts on breast cancer stage at diagnosis and upfront treatment in the COVID era

IntroductionThe present analysis aims to evaluate the consequences of a 2-month interruption of mammographic screening on breast cancer (BC) stage at diagnosis and upfront treatments in a region of Northern Italy highly affected by the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) virus.MethodsThis retrospective single-institution analysis compared the clinical pathological characteristics of BC diagnosed between May 2020 and July 2020, after a 2-month screening interruption, with BC diagnosed in the same trimester of 2019 when mammographic screening was regularly carried out.ResultsThe 2-month stop in mammographic screening produced a significant decrease in in situ BC diagnosis (−10.4%) and an increase in node-positive (+11.2%) and stage III BC (+10.3%). A major impact was on the subgroup of patients with BC at high proliferation rates. Among these, the rate of node-positive BC increased by 18.5% and stage III by 11.4%. In the subgroup of patients with low proliferation rates, a 9.3% increase in stage III tumors was observed, although node-positive tumors remained stable. Despite screening interruption, procedures to establish a definitive diagnosis and treatment start were subsequently carried out without delay.ConclusionOur data showed an increase in node-positive and stage III BC after a 2-month stop in BC screening. These findings support recommendations for a quick restoration of BC screening at full capacity, with adequate prioritization strategies to mitigate harm and meet infection prevention requirements.

Recurrence and survival after standard versus oncoplastic breast-conserving surgery for breast cancer.

BackgroundOncoplastic techniques in breast-conserving surgery (BCS) are used increasingly for larger tumours. This large cohort study aimed to assess oncological outcomes after oncoplastic BCS (OPS) versus standard BCS.MethodsData for all women who had BCS in three centres in Stockholm during 2010–2016 were extracted from the Swedish National Breast Cancer Register. All patients with T2–3 tumours, all those receiving neoadjuvant treatment, and an additional random sample of women with T1 tumours were selected. Medical charts were reviewed for local recurrences and surgical technique according to the Hoffman–Wallwiener classification. Date and cause of death were retrieved from the Swedish Cause of Death Register.ResultsThe final cohort of 4178 breast cancers in 4135 patients was categorized into three groups according to surgical technique: 3720 for standard BCS, 243 simple OPS, and 215 complex OPS. Median duration of follow up was 64 (range 24–110) months. Node-positive and large tumours were more common in OPS than in standard BCS (P < 0.001). There were 61 local recurrences: 57 (1.5 per cent), 1 (0.4 per cent) and 3 (1.4 per cent) in the standard BCS, simple OPS and complex OPS groups respectively (P = 0.368). Overall, 297 patients died, with an unadjusted 5-year overall survival rate of 94.7, 93.1 and 92.6 per cent respectively (P = 0.350). Some 102 deaths were from breast cancer, with unadjusted 5-year cancer-specific survival rates of 97.9, 98.3 and 95.0 per cent respectively (P = 0.056).DiscussionOncoplastic BCS is a safe surgical option, even for larger node-positive tumours, with low recurrence and excellent survival rates.

Evaluation of axillary lymph node status after axillary dissection in patients with SLN negative or single SLN positive T1 and T2 breast cancer

Aim: The most substantial factor determining prognosis in breast cancer is axillary lymph node involvement. Therefore, axillary lymph node status should be evaluated correctly in the staging of the disease and determining the prognosis. In this study, we aim to evaluate the detection rate of metastatic lymph nodes after axillary dissection in patients with negative or single positive sentinel lymph nodes in early-stage breast cancer.Materials and Methods: We have included patients with sentinel lymph node biopsy and/or axillary dissection diagnosed with early-stage (T1 and T2) breast cancer between 2018 and 2019 in the study. We have evaluated tumor prognostic factors from patient files and the total number of lymph nodes and tumor positive lymph nodes from pathology paraffin specimens.Results: The study included 29 female patients with an average age of 56 (34-83). Breast-conserving surgery (BCS)+SLNB was performed in 15 patients and BCS+ AD in 11 patients and modified radical mastectomy (MRM) was performed in 3 patients. In 3 patients with positive surgical margin after BCS + SLN, although one patient was positive and the other two patients were negative in SLN, multiple metasatic lymph nodes were detected after axillary dissection due to the patients' request for axillary dissection. Patients were followed-up for an average of 26 months without recurrence or metastasis. Conclusion: Considering that there may be lymph node metastasis other than the sentinel lymph node in patients with SLNB negatives or single positive sentinel lymph node, we recommend more than one lymph node excision in addition to the stained lymph node.

Prognostic significance of transforming growth factor β receptor II in clinical stage III breast cancer patients - a pilot study.

Transforming growth factor-β (TGFβ) has a dual function in breast cancer, having a tumor suppressor activity in early carcinomas while enhancing tumor metastasis in advanced breast carcinoma. Consequently, the prognostic role of TGFβ and its signaling cascade in breast cancer remain unclear. To investigate the relationship between TβRII expression, clinic-pathological characteristics, and prognostic significance of TβRII expression in clinical stage III breast cancer. Biopsy from the primary tumor was obtained from 30 newly diagnosed clinical stage III breast cancer patients before receiving any therapy. Expression of TβRII, ER, PR, Her2 and Ki-67 was assessed by immunohistochemistry. TβRII expression was positive in 66.7% of cases and was significantly associated with advanced nodal stage and distant metastases. After a median follow up of 42.3 months, TβRII was associated with poor disease-free survival and it was an independent factor for predicting the poor outcome for breast cancer patients, especially in node positive tumors, ER/PR positive and Her2-negative tumors. These findings suggest the usage of therapeutic drugs that target TGFβ in advanced breast cancer patients may be effective. Nevertheless, blockage of the tumor promoting and sparing of the tumor suppressor effect of TGFβ pathway should be taken into consideration. We suggest that these therapies might have more benefit in ER and PR positive tumors.

Age-related transcriptome changes in melanoma patients with tumor-positive sentinel lymph nodes.

Age is an important factor for determining the outcome of melanoma patients. Sentinel lymph node (SLN) status is also a strong predictor of survival for melanoma. Paradoxically, older melanoma patients have a lower incidence of SLN metastasis but a higher mortality rate when compared with their younger counterparts. The mechanisms that underlie this phenomenon remain unknown. This study uses three independent datasets of RNA samples from patients with melanoma metastatic to the SLN to identify age-related transcriptome changes in SLNs and their association with outcome. Microarray was applied to the first dataset of 97 melanoma patients. NanoString was performed in the second dataset to identify the specific immune genes and pathways that are associated with recurrence in younger versus older patients. qRT-PCR analysis was used in the third dataset of 36 samples to validate the differentially expressed genes (DEGs) from microarray and NanoString. These analyses show that FOS, NR4A, and ITGB1 genes were significantly higher in older melanoma patients with positive SLNs. IRAK3- and Wnt10b-related genes are the major pathways associated with recurrent melanoma in younger and older patients with tumor-positive SLNs, respectively. This study aims to elucidate age-related differences in SLNs in the presence of nodal metastasis.

Nomograms for predicting overall and recurrence-free survival after trimodality therapy for esophageal adenocarcinoma.

Locally advanced esophageal carcinoma is treated with neoadjuvant chemoradiation and esophagectomy. Patients may still experience recurrence and death despite undergoing potentially curative trimodality therapy. This study describes predictive nomograms for recurrence-free (RFS) and overall survival (OS) after the completion of trimodality therapy. A total of 215 patients with esophageal adenocarcinoma underwent trimodality therapy from September 2010 to April 2018. Multivariate Cox proportional hazards regression models were used to create nomograms for OS and RFS. Kaplan-Meier survival curves were calculated for OS and RFS comparing high-risk and low-risk cohorts. On multivariate analysis, clinical N-stage, tumor differentiation, tumor regression grade, anastomotic leak, body mass index, age, and number of lymph nodes removed were predictive variables for overall survival. Clinical N-stage, tumor differentiation, tumor regression grade, anastomotic leak, age, and positive lymph nodes were significant predictors of RFS in a multivariate model. The nomogram for OS had good predictive ability (Harrell's Concordance index [C-index]: 0.71 [95% confidence interval {CI}: 0.66-0.76]). The nomogram for RFS also performed well (C-index: 0.70 [95% CI: 0.65-0.74]). Our nomograms can accurately predict OS and RFS after trimodality therapy and may provide guidance regarding adjuvant therapy and surveillance.