Immune pathogenesis of idiopathic granulomatous mastitis: from etiology toward therapeutic approaches.

Idiopathic granulomatous mastitis (IGM) is a noncancerous, chronic inflammatory disorder of breast with unknown causes, posing significant challenges to the quality of life due to its high refractoriness and local aggressiveness. The typical symptoms of this disease involve skin redness, a firm and tender breast mass and mastalgia; others may include swelling, fistula, abscess (often without fever), nipple retraction, and peau d'orange appearance. IGM often mimics breast abscesses or malignancies, particularly inflammatory breast cancer, and is characterized by absent standardized treatment options, inconsistent patient response and unknown mechanism. Definite diagnosis of this disease relies on core needle biopsy and histopathological examination. The prevailing etiological theory suggests that IGM is an autoimmune disease, as some patients respond well to steroid treatment. Additionally, the presence of concurrent erythema nodosum or other autoimmune conditions supports the autoimmune nature of the disease. Based on current knowledge, this review aims to elucidate the autoimmune-favored features of IGM and explore its potential etiologies. Furthermore, we discuss the immune-mediated pathogenesis of IGM using existing research and propose immunotherapeutic strategies for managing this condition.

Expanded indications for breast-conserving surgery with oncoplastic approaches compared to conventional approaches: a single-center retrospective comparative cohort study.

Background: Oncoplastic breast-conserving surgery (OPBS) is the evolution of conventional breast-conserving surgery (CBCS); however, data from studies comparing patients who received two surgical procedures are limited. A comparison of differences in terms of the patient characteristics, tumor-nipple distance, volume of resected breast tissue, tumor volume and postoperative breast appearance between patients undergoing OPBS and CBCS was carried out in this study, enhancing the evidence base for OPBS by widening indications and improving patient satisfaction. Methods: From January 2020 to April 2022, the Breast Center of West China Hospital conducted a retrospective comparative study involving 106 patients. Preoperative characteristics of patients were recorded, and the tumor-nipple distance, the volume of resected breast tissue, tumor volume and patient-reported esthetic outcomes measured by the Harris cosmetic scale were compared between patients who underwent OPBS and CBCS. Results: Each group had a median follow-up time of 2 months, ranging from 1 week to 6 months. The tumor-nipple distance was significantly shorter in patients receiving OPBS than in those receiving CBCS (2.98±1.42 vs. 3.85±1.78 cm, P=0.006). The rate of positive margin evaluated by intraoperative frozen section biopsy was significantly lower in OPBS group than in CBCS group (2/43, 4.65% vs. 11/63, 17.46%; P=0.048). The maximum diameter of resected tissue (7.80±2.29 vs. 6.75±1.87 cm, P=0.011) and volume of resected tissue (74.20±42.77 vs. 45.52±30.99 cm3, P<0.001) were significantly larger with OPBS. The tumor size, tumor volume (either clinically measured by ultrasound or pathologically measured), tumor location, and reoperation rate due to positive margins did not differ significantly between groups. Moreover, insignificant differences existed regarding patient satisfaction between two groups (87.30% vs. 81.40%). Conclusions: The OPBS strategy allowed extensive resections and expanded indications with equivalent cosmetic satisfaction and favorable oncological safety.

Circulating tumor cells in peripheral blood as a diagnostic biomarker of breast cancer: A meta-analysis.

Purpose: Studies have reported that breast cancer (BC) patients' circulating tumor cells (CTCs) have varying results for their diagnostic role. Thus, we conducted a meta-analysis to systematically assess the accuracy of CTCs in the diagnosis of BC. Methods: A meta-analysis was conducted to evaluate the overall accuracy of CTC detection. A pooled analysis of sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic advantage ratio (DOR) was used to measure diagnostic accuracy. In addition, the area under the summary receiver operating characteristic curve (AUC) was used to discriminate BC from non-BC. An analysis of the threshold effect was calculated using the Spearman correlation coefficient. We calculated the Q and I2 statistics to determine whether the studies were heterogeneous. Sensitivity analysis was performed by removing studies one by one. Publication bias was assessed by Deeks' funnel plot asymmetry test. Results: Studies from the PubMed, Cochrane Library, Embase, Web of Science, Wanfang, Vip, and CNKI databases were collected for diagnosing BC from January 2000 to April March 2023. Finally, 8 publications were retrieved in total containing 2014 cases involved in the study. Based on a random-effects model, it was found that the pooled SEN was 0.69 (0.55 - 0.80), SPE was 0.93 (0.60 - 0.99), PLR was 9.5 (1.4 - 65.9), NLR was 0.33 (0.23 - 0.48), DOR was 29 (4 - 205) and the AUC of the summary receiver operating characteristic (SROC) curve was 0.81 (0.77 - 0.84). Some heterogeneity was found in the article, but there was no threshold effect to account for it (P = 0.27). Deek's funnel plot asymmetry test indicated that no publication bias was observed in this meta-analysis (P = 0.52). Conclusion: The results of this meta-analysis confirmed that CTCs were an important component of noninvasive methods of confirming BC with SEN of 0.69 (0.55 - 0.80), SPE of 0.93 (0.60 - 0.99) and AUC of 0.81 (0.77 - 0.84).

Effect of adjuvant chemotherapy on the survival outcomes of elderly breast cancer: A retrospective cohort study based on SEER database.

BACKGROUND: Currently, the proportion of standard chemotherapy for elderly patients is much lower than that for young patients, with little evidence from clinical trials supporting the use of chemotherapy for elderly patients. The effectiveness of chemotherapy for the elderly suffering from breast cancer remains to be further verified. METHODS: A total of 75,525 female breast cancer patients aged 70 years or older were hereby identified, all from the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2010 to December 31, 2016. Kaplan-Meier analysis and multivariable Cox proportional model were performed to evaluate the effectiveness of chemotherapy on overall survival (OS) and breast cancer-specific survival (BCSS). Propensity score matching (PSM) (PSM ratio: 1:1, caliper: 0.2 standard deviation of propensity score) was applied to construct balanced cohorts with or without chemotherapy based on demographic and pathophysiological characteristics. RESULTS: A total of 33,177 eligible patients were included, with 5273 (15.89%) receiving chemotherapy. Through PSM, 8360 patients were successfully matched, and balances between groups were almost reached. In the matched data set, multivariable Cox analysis reveals that chemotherapy was associated with a 36% and 21% risk reduction on OS (HR = 0.64, 95% CI 0.58 to 0.71) and BCSS (HR = 0.79, 95% CI 0.69 to 0.91), respectively. Furthermore, subgroups with more adjacent lymph nodes involved by tumor, or nonluminal A, were inclined to benefit more from chemotherapy. Moreover, chemotherapy did not increase the chances of dying from heart disease. CONCLUSIONS: The present study provided evidence that chemotherapy may improve the prognosis of elderly breast cancer, especially for those subpopulations that benefit more from chemotherapy treatment.

Development and validation of nomograms for predicting survival in patients with de novo metastatic triple-negative breast cancer.

Metastatic triple-negative breast cancer (mTNBC) is a heterogeneous disease with a poor prognosis. Individualized survival prediction tool is useful for this population. We constructed the predicted nomograms for breast cancer-specific survival (BCSS) and overall survival (OS) using the data identified from the Surveillance, Epidemiology, and End Results database. The Concordance index (C-index), the area under the time-dependent receiver operating characteristic curve (AUC) and the calibration curves were used for the discrimination and calibration of the nomograms in the training and validation cohorts, respectively. 1962 mTNBC patients with a median follow-up was 13 months (interquartile range, 6-22 months), 1639 (83.54%) cases died of any cause, and 1469 (74.87%) died of breast cancer. Nine and ten independent prognostic factors for BCSS and OS were identified and integrated to construct the nomograms, respectively. The C-indexes of the nomogram for BCSS and OS were 0.694 (95% CI 0.676-0.712) and 0.699 (95% CI 0.679-0.715) in the training cohort, and 0.699 (95% CI 0.686-0.712) and 0.697 (95% CI 0.679-0.715) in the validation cohort, respectively. The AUC values of the nomograms to predict 1-, 2-, and 3-year BCSS and OS indicated good specificity and sensitivity in internal and external validation. The calibration curves showed a favorable consistency between the actual and the predicted survival in the training and validation cohorts. These nomograms based on clinicopathological factors and treatment could reliably predict the survival of mTNBC patient. This may be a useful tool for individualized healthcare decision-making.

Non-coding genome in small cell lung cancer between theoretical view and clinical applications.

Small cell lung cancer (SCLC) is a highly aggressive cancer of the neuroendocrine system, characterized by poor differentiation, rapid growth, and poor overall survival (OS) of patients. Despite the recent advances in the treatment of SCLC recently, the 2-year survival rate of patients with the cancer is only 14-15%, occasioned by the acquired resistance to drugs and serious off-target effects. In humans, the coding region is only 2% of the total genome, and 20% of that is associated with human diseases. Beyond the coding genome are RNAs, promoters, enhancers, and other intricate elements. The non-coding regulatory regions, mainly the non-coding RNAs (ncRNAs), regulate numerous biological activities including cell proliferation, metastasis, and drug resistance. As such, they are potential diagnostic or prognostic biomarkers, and also potential therapeutic targets for SCLC. Therefore, understanding how non-coding elements regulate SCLC development and progression holds significant clinical implications. Herein, we summarized the recent discoveries on the relationship between the non-coding elements including long non-coding RNAs (lncRNA), microRNAs (miRNAs), circular RNA (circRNA), enhancers as well as promotors, and the pathogenesis of SCLC and their potential clinical applications.

Single-cell transcriptomic profiling unravels the adenoma-initiation role of protein tyrosine kinases during colorectal tumorigenesis.

The adenoma-carcinoma sequence is a well-accepted roadmap for the development of sporadic colorectal cancer. However, cellular heterogeneity in aberrant epithelial cells limits our understanding of carcinogenesis in colorectal tissues. Here, we performed a single-cell RNA sequencing survey of 54,788 cells from patient-matched tissue samples, including blood, normal tissue, para-cancer, polyp, and colorectal cancer. At each stage of carcinogenesis, we characterized cell types, transcriptional signatures, and differentially expressed genes of distinct cell populations. The molecular signatures of epithelial cells at normal, benign, and malignant stages were defined at the single-cell scale. Adenoma and carcinoma precursor cell populations were identified and characterized followed by validation with large cohort biopsies. Protein tyrosine kinases (PTKs) BMX and HCK were identified as potential drivers of adenoma initiation. Specific BMX and HCK upregulations were observed in adenoma precursor cell populations from normal and adenoma biopsies. Overexpression of BMX and HCK significantly promoted colorectal epithelial cell proliferation. Importantly, in the organoid culture system, BMX and HCK upregulations resulted in the formation of multilayered polyp-like buds protruding towards the organoid lumen, mimicking the pathological polyp morphology often observed in colorectal cancer. Molecular mechanism analysis revealed that upregulation of BMX or HCK activated the JAK-STAT pathway. In conclusion, our work improved the current knowledge regarding colorectal epithelial evolution during carcinogenesis at the single-cell resolution. These findings may lead to improvements in colorectal cancer diagnosis and treatment.

Nanoparticle-assisted axillary staging: an alternative approach after neoadjuvant chemotherapy in patients with pretreatment node-positive breast cancers.

PURPOSE: In order to achieve an optimized method of axillary staging after neoadjuvant chemotherapy (NAC) in breast cancer patients with pretreatment positive axillary lymph nodes, we evaluated the feasibility and accuracy of nanoparticle-assisted axillary staging (NAAS) which combines carbon nanoparticles with standard sentinel lymph node biopsy (SLNB) with radioisotope and blue dye. METHODS: Invasive breast cancer patients with pre-NAC positive axillary lymph nodes who converted to ycN0 and received surgeries from November 2020 to March 2021 were included. All patients underwent ipsilateral NAAS followed by axillary lymph node dissection. Detection rate (DR), false-negative rate (FNR), negative predictive value (NPV) and accuracy of axillary staging were calculated. RESULTS: Eighty of 136 (58.8%) breast cancer patients converted to ycN0 after NAC and received NAAS. The DR, NPV and accuracy was 95.0%, 93.3% and 97.4% for NAAS, respectively. And the FNR was 4.2% (2/48) for NAAS, which was lower than that of standard dual-tracer SLNB (SD-SLNB) (9.5%, 4/42). Pretreatment clinical T4 classification was a risk factor for detection failure in NAAS (p = 0.016). When patients with pretreatment inflammatory breast cancers were excluded from analysis, FNR dropped to 2.2% (1/45) for NAAS. CONCLUSION: NAAS revealed great performance in invasive breast cancer patients with pre-NAC positive axillary lymph nodes who converted to ycN0. The application of NAAS reached a better balance between more accurate axillary evaluation and less intervention. Trial registration Chictr.org.cn (ChiCTR2000039814). Registered Nov 11, 2020.

The Evolution of Acquired Resistance to BRAFV600E kinase inhibitor Is Sustained by IGF1-Driven Tumor Vascular Remodeling.

As a hallmark of cancer, angiogenesis plays a pivotal role in carcinogenesis. However, the correlation between angiogenesis and the evolution of BRAFV600E kinase inhibitor‒acquired resistance is still poorly understood. In this study, we reported that the molecular signatures of angiogenesis were enriched in early on-treated biopsies but not in disease-progressed biopsies. The process of drug resistance development was accompanied by the remodeling of vascular morphology, which was potentially manipulated by tumor-secreted proangiogenic factors. Further transcriptomic dissection indicated that tumor-secreted IGF1 drove the vascular remodeling by activating the IGF1/IGF1R axis on endothelial cells and sustained the prompt regrowth of resistant tumor. Blockade of IGF1R with small molecules at an early stage of response disrupted vascular reconstruction and subsequently delayed tumor relapse. Our findings not only showed the correlation between IGF1-mediated tumor vascular remodeling and the development of acquired resistance to BRAFV600E kinase inhibitor but also provided a potential therapeutic strategy for the prevention of tumor relapse in clinical application.

Immune-based combination therapy for esophageal cancer.

Esophageal cancer (EC) is an aggressive malignancy raising a healthcare concern worldwide. Standard treatment options include surgical resection, chemotherapy, radiation therapy, and targeted molecular therapy. The five-year survival rate for all stages of EC is approximately 20%, ranging from 5% to 47%, with a high recurrence rate and poor prognosis after treatment. Immunotherapy has shown better efficacy and tolerance than conventional therapies for several malignancies. Immunotherapy of EC, including immune checkpoint inhibitors, cancer vaccines, and adoptive cell therapy, has shown clinical advantages. In particular, monoclonal antibodies against PD-1 have a satisfactory role in combination therapy and are recommended for first- or second-line treatments. Here, we present a systematic summary and analysis of immunotherapy-based combination therapies for EC.

Establishment of a tumor immune microenvironment-based molecular classification system of breast cancer for immunotherapy.

Antitumor immunotherapy can enable promising and durable responses following their clinical application. However, heterogeneity in the tumor immune microenvironment leads to differences in the individual response rates. In this study, we identified novel immune-related molecular subclasses of breast cancer using a non-negative matrix factorization analysis. We enrolled 4184 patients with breast cancer, including 1104 patients from The Cancer Genome Atlas as a training cohort and 3080 patients from another four independent datasets as validation cohorts. In the training cohort, 36.9% of patients who exhibited significantly higher immunocyte infiltration and enrichment of immune response-associated signatures were categorized into an immune class, which was confirmed by probing the expression of immunocyte markers (CD3, CD19, and CD163). Within the immune class, 53.3% of patients belonged to an immune-suppressed subclass, characterized by the activation of stroma-related signatures and immune-suppressive cells. The remaining patients in the immune class were allocated to an immune-activated subclass. The interferon-γ and granzyme B levels were higher in the immune-activated subclass, whereas the transforming growth factor-ß1 and programmed cell death-1 (PD-1) levels were higher in the immune-suppressed subclass. The established molecular classification system was recapitulated in validation cohorts. The immune-activated subclass was predicted to have a better response to anti-PD-1 immunotherapy. The immune-related subclasses were associated with differences in copy number alterations, tumor mutation burden, neoantigens, tumor-infiltrating lymphocyte enrichment, PD-1/programmed death-ligand 1 expression, mutation landscape, and various infiltration immunocytes. Overall, we established a novel immune-related molecular classification of breast cancer, which may be used to select candidate patients for immunotherapy.

In situ Adipogenesis in Biomaterials Without Cell Seeds: Current Status and Perspectives.

For cosmetic and reconstructive purposes in the setting of small-volume adipose tissue damage due to aging, traumatic defects, oncological resections, and degenerative diseases, the current strategies for soft tissue replacement involve autologous fat grafts and tissue fillers with synthetic, bioactive, or tissue-engineered materials. However, they all have drawbacks such as volume shrinkage and foreign-body responses. Aiming to regenerate bioactive vascularized adipose tissue on biomaterial scaffolds, adipose tissue engineering (ATE) has emerged as a suitable substitute for soft tissue repair. The essential components of ATE include scaffolds as support, cells as raw materials for fat formation, and a tolerant local environment to allow regeneration to occur. The commonly loaded seeding cells are adipose-derived stem cells (ASCs), which are expected to induce stable and predictable adipose tissue formation. However, defects in stem cell enrichment, such as donor-site sacrifice, limit their wide application. As a promising alternative approach, cell-free bioactive scaffolds recruit endogenous cells for adipogenesis. In biomaterials without cell seeds, the key to sufficient adipogenesis relies on the recruitment of endogenous host cells and continuous induction of cell homing to scaffolds. Regeneration, rather than repair, is the fundamental dominance of an optimal mature product. To induce in situ adipogenesis, many researchers have focused on the mechanical and biochemical properties of scaffolds. In addition, efforts to regulate an angiogenic and adipogenic microenvironment in cell-free settings involve integrating growth factors or extracellular matrix (ECM) proteins onto bioactive scaffolds. Despite the theoretical feasibility and encouraging results in animal models, few of the reported cell-free biomaterials have been tested in humans, and failures of decellularized adipose tissues in adipogenesis have also been reported. In these cases, the most likely reason was the lack of supporting vasculature. This review summarizes the current status of biomaterials without cell seeds. Related mechanisms and influencing factors of in situ adipogenesis in cell-free biomaterials, dilemma in the development of biomaterials, and future perspectives are also addressed.

Combination of MAPK inhibition with photothermal therapy synergistically augments the anti-tumor efficacy of immune checkpoint blockade.

The combination of MAPK-targeted therapy and immune checkpoint blockade is one of the most promising regimens for patients with advanced melanoma. However, the synergistic efficacy of the combo regimen is still controversial in clinical trials. Here, we report that MAPK inhibition induced T-cell suppression within tumor microenvironment is mediated by attenuation of HSP27/HSP70 and deficiency of neoantigen presentation. To address this problem, we designed a photothermal-responsive on-demand controlled drug release gold nano-system to carry BRAF inhibitor. The nano-system can be specifically delivered into tumor cells rather than T-cells, and effectively transformed the optical energy into heat energy upon laser irradiation. Combination of photothermal and targeted therapy significantly promoted immunogenic cell death and T-cell infiltration. On top of this regimen, systematically administration of PD-1 antibody not only suppressed local-treated tumor but also inhibited abscopal tumor by enhancing generalized immune-related antitumor response. More importantly, the triple-combo regimen could efficiently convert immune "cold" tumors into "hot" ones. In conclusion, our research proves the advantage of photothermal-targeted-immune triple combinatorial regimen in treating tumors which are clinical unresectable multifocal and lack of T-cell infiltration.

[Research progress of adipose-derived stem cells in skin scar prevention and treatment].

OBJECTIVE: To review the research progress of adipose-derived stem cells (ADSCs) in skin scar prevention and treatment. METHODS: The related literature was extensively reviewed and analyzed. The recent in vitroand in vivo experiments and clinical studies on the role of ADSCs in skin scar prevention and treatment, and the possible mechanisms and biomaterials to optimize the effect of ADSCs were summarized. RESULTS: As demonstrated by in vitro and in vivo experiments and clinical studies, ADSCs participate in the whole process of skin wound healing and may prevent and treat skin scars by reducing inflammation, promoting angiogenesis, or inhibiting (muscle) fibroblasts activity to reduce collagen deposition through the p38/mitogen-activated protein kinase, peroxisome proliferator activated receptor γ, transforming growth factor ß 1/Smads pathways. Moreover, bioengineered materials such as hydrogel from acellular porcine adipose tissue, porcine small-intestine submucosa, and poly (3-hydroxybutyrate-co-hydroxyvalerate) scaffold may further enhance the efficacy of ADSCs in preventing and treating skin scars. CONCLUSION: Remarkable progress has been made in the application of ADSCs in skin scar prevention and treatment. While, further studies are still needed to explore the application methods of ADSCs in the clinic.

Distance Between the Tumour and Nipple as a Predictor of Axillary Lymph Node Involvement in Breast Cancer.

PURPOSE: The possibility of axillary node metastasis via the lymphatics might be related to a cancer's location within the breast. Previous studies of this topic had small sample sizes, inaccuracies because of subjective differences, and the inability to depict the entire three-dimensional structure of the breast. Here, we aimed to improve upon these existing drawbacks by retrospectively analysing whether tumour location (quadrants) and tumour-nipple distance can predict axillary node positivity. PATIENTS AND METHODS: We identified 961 patients with invasive breast cancer between January 2000 and April 2016. The tumour-nipple distance was objectively measured intraoperatively and clinicopathological information was extracted from hospital database. The distance was measured radially from the nipple to the epicentre rather than the edge of tumour to obviate confounders resulting from tumour size variations. RESULTS: A total of 847 breast cancers (839 patients) met the eligibility criteria and were included in the statistical analysis. The tumour-nipple distance was smaller in node-positive patients (n = 307; 2.76 ± 2.07 cm) than in node-negative patients (n = 297; 3.41 ± 2.18 cm) (p < 0.001). Tumour-nipple distance was an independent predictor of axillary involvement on logistic regression analysis. However, no statistically significant relationship was detected between node positivity and breast quadrant tumour location. CONCLUSION: Tumour-nipple distance can be used to predict axillary lymph node metastasis and assist in surgical decision-making and therapy planning. However, exploratory studies are required to increase our understanding of the mechanism.

NUSAP1 promotes the metastasis of breast cancer cells via the AMPK/PPARγ signaling pathway.

BACKGROUND: The biological function and molecular mechanism of nucleolar spindle-associated protein 1 (NUSAP1) in breast cancer remain controversial, this study aimed to reveal the mechanism of NUSAP1 in breast cancer cell metastasis and survival. METHODS: The expression of NUSAP1 expression was evaluated by immunohistochemistry and quantitative real-time polymerase chain reaction (RT-qPCR) in breast tissue samples. The correlation of NUSAP1 expression with the clinicopathological parameters of the patients and overall survival (OS) was evaluated. The protein expression was detected by Western blotting, the cell proliferation was evaluated by Edu staining and MTT assay, migration and invasion were tested by transwell and migration assay. Female BALB/c nude mice models for tumor growth and metastasis of breast cancer were evaluated in vivo. RESULTS: NUSAP1 is up-regulated in multiple cancers and is associated with a poor prognosis in breast cancer patients. Further analysis of the Gene Expression Omnibus (GEO) database and our included patients revealed that NUSAP1 expression gradually increased with pathological changes in breast tissue. Cell function assays confirmed that NUSAP1 was related to the proliferation, migration, and invasion of breast cancer cells. In vivo, NUSAP1 promoted lung metastasis in nude mice. We found that the NUSAP1 protein can promote tumor proliferation and metastasis by activating the AMPK/PPARγ signaling pathway. CONCLUSIONS: Our findings show that NUSAP1 promotes breast cancer proliferation and metastasis by activating the AMPK/PPARγ signaling pathway.

Pattern of Time-to-Surgery in Patients With Breast Cancer at Different Stages of the COVID-19 Pandemic.

BACKGROUND: The management of cancer surgeries is under unprecedented challenges during the COVID-19 pandemic, and the breast cancer patients may face a time-delay in the treatment. This retrospective study aimed to present the pattern of time-to-surgery (TTS) and analyze the features of breast cancer patients under the different stages of the COVID-19 pandemic. METHODS: Patients who received surgeries for breast cancers at West China Hospital between February 15, 2020 and April 30, 2020 (the outbreak and post-peak stages), and between March 10, 2021 and May 25, 2021 (the normalization stage) were included. TTS was calculated as the time interval between the pathological diagnosis and surgical treatment of breast cancer patients. And the pandemic was divided into three stages based on the time when the patients were pathologically diagnosed and the severity of pandemic at that time point. TTS, demographic and clinicopathological features were collected from medical records. RESULTS: A total of 367 patients were included. As for demographic features, it demonstrated statistically significant differences in insurance type (p<0.001) and regular screening (p<0.001), as well as age (p=0.013) and menstrual status (p=0.004). As for clinicopathological features, axillary involvement (p=0.019) was a factor that differed among three stages. The overall TTS was 23.56 ± 21.39 days. TTS for patients who were diagnosed during the outbreak of COVID-19 were longer than those diagnosed during pandemic post-peak and normalization stage (p<0.001). Pandemic stage (p<0.001) and excision biopsy before surgery (OR, 6.459; 95% CI, 2.225-18.755; p=0.001) were markedly correlated with the TTS of patients. CONCLUSIONS: TTS of breast cancer patients significantly varied in different stages of the COVID-19 pandemic. And breast cancer patients' daily lives and disease treatments were affected by the pandemic in many aspects, such as health insurance access, physical screening and change of therapeutic schedules. As the time-delay may cause negative influences on patients' disease, we should minimize the occurrence of such time-delay. It is vital to come up with comprehensive measures to deal with unexpected situations in case the pandemic occurs.

Redefining Criteria to Ensure Adequate Sentinel Lymph Node Biopsy With Dual Tracer for Breast Cancer.

BACKGROUND: For sentinel lymph node biopsy (SLNB) in patients with breast cancer, the dual tracer of blue dye and radioisotope with the 10% rule that all nodes with radioactive count of 10% or more of the hottest node ex vivo should be removed is widely accepted. However, the cut-off point of radioactivity is being questioned for possibly excessive removal of negative nodes. METHODS: To compare different percentile rules and optimize the criteria for identifying SLNs, we established a database which prospectively collected the radioactivity, status of blue dye and the pathological results of each SLN in breast cancer patients who successfully underwent SLNB with a combination of methylene blue and radioisotope. RESULTS: A total of 2,529 SLNs from 1,039 patients were identified from August 2010 to August 2019. 16.4% (414/2,529) positive nodes were removed at a cost of 83.6% (2115/2,529) negative nodes removed excessively. Up to 17.9% (375/2,115) negative nodes were removed as radioactively hot nodes without blue staining. By gradually increasing the threshold by each 10%, the number of negative nodes identified reduced by 18.2% (385/2,115) with only three node-positive patients (1.0%) missed to be identified using the "40% + blue" rule. In patients with ≥ 2 SLNs removed, 12.3% (238/1,942) negative nodes avoided unnecessary removal with only 0.8% (2/239) positive patients missed with the "hottest two + blue" rule. CONCLUSIONS: Our data indicated that the "40% + blue" rule or the "hottest two + blue" rule for SLNB with the dual tracer of blue dye and radioisotope may be considered as a potential alternative rule to minimize extra nodes resected. Nonetheless, it should be validated by prospective trials with long-term follow-up.

Predicting Survival Benefit of Sparing Sentinel Lymph Node Biopsy in Low-Risk Elderly Patients With Early Breast Cancer: A Population-Based Analysis.

Objective: The application of sentinel lymph node biopsy (SLNB) in elderly patients with early breast cancer remains somewhat controversial. This study aimed to establish individualized nomograms to predict survival outcomes of elderly patients with and without SLNB and find out which patients could avoid SLNB. Methods: A total of 39,962 ≥70-year-old patients diagnosed with T1-T2 breast cancer in 2010-2015 were included from the Surveillance, Epidemiology, and End Results (SEER) program and were divided into the training set (n = 29,971) and the validation set (n = 9,991). Axillary surgery was not specified in the SEER database, and we defined removing one to five lymph nodes as SLNB. Survival analysis was performed using the Kaplan-Meier plot and log-rank test. Multivariate Cox analysis was utilized to identify risk factors for overall survival (OS) and breast-cancer-specific survival (BCSS). Nomograms and a risk stratification model were constructed. Results: In the training set, patients with SLNB had better OS (adjusted HR 0.57, P < 0.001) and BCSS (adjusted HR 0.55, P < 0.001) than patients without SLNB. Multivariate COX analysis identified age, marital status, grade, subtype, T stage, and radiation as independent risk factors for OS and BCSS in both SLNB and non-SLNB groups (all P < 0.05). They were subsequently incorporated to establish nomograms to predict 3- and 5-year OS and BCSS for patients with or without SLNB. The concordance index ranged from 0.687 to 0.820, and calibration curves in the internal set and external set all demonstrated sufficient accuracies and good predictive capabilities. Further, we generated a risk stratification model which indicated that SLNB improved OS and BCSS in high-risk group (OS: HR 0.49, P < 0.001; BCSS: HR 0.54, P < 0.001), but not in the low-risk group (all P > 0.05). Conclusion: Well-validated nomograms and a risk stratification model were constructed to evaluate survival benefit from SLNB in elderly patients with early-stage breast cancer. SLNB was important for patients in the high-risk group but could be omitted in the low-risk group without sacrificing survival. This study could assist clinicians and elderly patients to weigh the risk-benefit of SLNB and make individualized decisions. We look forward to more powerful evidence from prospective trials.