Revolutionizing the battle against locally advanced breast cancer: A comprehensive insight into neoadjuvant radiotherapy.

Breast cancer (BC) constitutes one of the most pervasive malignancies affecting the female population. Despite progressive improvements in diagnostic and therapeutic technologies, leading to an increased detection of early stage BCs, locally advanced breast cancer (LABC) persists as a significant clinical challenge. Owing to its poor overall survival (OS) rate, elevated recurrence rate, and high potential for distant metastasis, LABC prominently impacts the comprehensive efficacy of BC treatments. Radiotherapy, encompassing preoperative, intraoperative, and postoperative modalities, is acknowledged as an effective strategy for mitigating BC metastasis and enhancing survival rates among patients. Nevertheless, the domain of preoperative neoadjuvant radiotherapy (NART) remains conspicuously underexplored in clinical studies. Available research suggests that NART can induce tumor volume reduction, provoke fibrotic changes in tumor and adjacent normal tissues, thereby mitigating intraoperative cancer propagation and enhancing the quality of life for LABC patients. This manuscript seeks to provide a review of contemporary research pertaining to LABC and its preoperative radiotherapy.

Perioperative Chemotherapy Could Not Improve the Prognosis of Gastric Cancer Patients With Mismatch Repair Deficiency: A Multicenter, Real-World Study.

INTRODUCTION: To date, the role of deficient mismatch repair (dMMR) remains to be proven in gastric cancer, and it is difficult to judge its value in clinical application. Our study aimed to investigate how MMR status affected the prognosis in patients with gastrectomy, as well as the efficacy of neoadjuvant chemotherapy and adjuvant chemotherapy in patients with dMMR with gastric cancer. MATERIALS AND METHODS: Patients with gastric cancer with certain pathologic diagnosis of dMMR or proficient MMR (pMMR) using immunohistochemistry from 4 high-volume hospitals in China were included. Propensity score matching was used to match patients with dMMR or pMMR in 1:2 ratios. Overall survival (OS) and progression-free survival (PFS) curves were plotted using the Kaplan-Meier method and compared statistically using the log-rank test. Univariate and multivariate Cox proportional hazards models based on hazard ratios (HRs) and 95% confidence intervals (CIs) were used to determine the risk factors for survival. RESULTS: In total, data from 6176 patients with gastric cancer were ultimately analyzed, and loss of expression of one or more MMR proteins was observed in 293 patients (293/6176, 4.74%). Compared to patients with pMMR, patients with dMMR are more likely to be older (≥66, 45.70% vs. 27.94%, P < .001), distal location (83.51% vs. 64.19%, P < .001), intestinal type (42.21% vs. 34.46%, P < .001), and in the earlier pTNM stage (pTNM I, 32.79% vs. 29.09%, P = .009). Patients with gastric cancer with dMMR showed better OS than those with pMMR before PSM (P = .002); however, this survival advantage was not observed for patients with dMMR after PSM (P = .467). As for perioperative chemotherapy, results of multivariable Cox regression analysis showed that perioperative chemotherapy was not an independent prognostic factor for PFS and OS in patients with dMMR with gastric cancer (HR = 0.558, 95% CI, 0.270-1.152, P = .186 and HR = 0.912, 95% CI, 0.464-1.793, P = .822, respectively). CONCLUSION: In conclusion, perioperative chemotherapy could not prolong the OS and PFS of patients with dMMR with gastric cancer.

The minimum number of examined lymph nodes was 24 for optimal survival of pathological T2-4 gastric cancer: a multi-center, hospital-based study covering 20 years of data.

INTRODUCTION: The current National Comprehensive Cancer Network (NCCN) guidelines recommend that at least 16 lymph nodes should be examined for gastric cancer patients to reduce staging migration. However, there is still debate regarding the optimal management of examined lymph nodes (ELNs) for gastric cancer patients. In this study, we aimed to develop and test the minimum number of ELNs that should be retrieved during gastrectomy for optimal survival in patients with gastric cancer. METHODS: We used the restricted cubic spline (RCS) to identify the optimal threshold of ELNs that should be retrieved during gastrectomy based on the China National Cancer Center Gastric Cancer (NCCGC) database. Northwest cohort, which sourced from the highest gastric cancer incidence areas in China, was used to verify the optimal cutoff value. Survival analysis was performed via Kaplan-Meier estimates and Cox proportional hazards models. RESULTS: In this study, 12,670 gastrectomy patients were included in the NCCGC cohort and 4941 patients in the Northwest cohort. During 1999-2019, the average number of ELNs increased from 17.88 to 34.45 nodes in the NCCGC cohort, while the number of positive lymph nodes remained stable (5-6 nodes). The RCS model showed a U-curved association between ELNs and the risk of all-cause mortality, and the optimal threshold of ELNs was 24 [Hazard ratio (HR) = 1.00]. The ELN ≥ 24 group had a better overall survival (OS) than the ELN < 24 group clearly (P = 0.003), however, with respect to the threshold of 16 ELNs, there was no significantly difference between the two groups (P = 0.101). In the multivariate analysis, ELN ≥ 24 group was associated with improved survival outcomes in total gastrectomy patients [HR = 0.787, 95% confidence interval (CI): 0.711-0.870, P < 0.001], as well as the subgroup analysis of T2 patients (HR = 0.621, 95%CI: 0.399-0.966, P = 0.035), T3 patients (HR = 0.787, 95%CI: 0.659-0.940, P = 0.008) and T4 patients (HR = 0.775, 95%CI: 0.675-0.888, P < 0.001). CONCLUSION: In conclusion, the minimum number of ELNs for optimal survival of gastric cancer with pathological T2-4 was 24.

Survival processing advantage demonstrated with virtual reality-based survival environment: A promising tool for survival processing research.

Many studies have been conducted to demonstrate the survival processing advantage (SPA) as an evolutionary-oriented memory effect. But few studies were conducted to demonstrate this effect in real-life or simulated survival environments. This study tested whether the SPA could be replicated in a survival virtual reality environment (VRE). In Experiment 1, the SPAs were measured in VREs (survival grasslands, survival battlefield, nonsurvival moving) in which Experiment 1A used the standard long instructions and Experiment 1B used the modified short instructions. In Experiment 2, the SPAs were measured again with the scenarios corresponding to the VREs used in Experiment 1A. All experiments demonstrated typical SPAs, suggesting that the survival VRE is a reliable tool in designing and delivering a survival situation. The potential problems of applying survival VRE to survival processing research are discussed at the end.

Comparison of Total and Nontotal Endoscopic Transaxillary Breast Augmentation Techniques: A Retrospective Study.

BACKGROUND: The aim of this retrospective study was to compare the clinical outcomes of total endoscopic transaxillary (TET) breast augmentation with those of non-TET (NTET) breast augmentation. For the purposes of this study, the term NTET refers to the combination of blunt dissection and endoscopic techniques, whereas TET did not involve blunt dissection. METHODS: We conducted a retrospective review of 119 consecutive cases of primary breast augmentation from May 1, 2020, to August 31, 2020. The primary outcomes were the number of drainage days and pain scores as assessed using the visual analog scale on the first postoperative day. The secondary outcomes were the daily drainage volume recorded during the postoperative drainage days, the presence of postoperative daily pain that required the administration of tramadol for relief, reoperation rate, and operative time. RESULTS: The number of drainage days was significantly lower in the TET group than in the NTET group (TET vs NTET: 2.56 ± 0.57 vs 3.78 ± 1.30 days, P = 0.000). The visual analog scale score on the first postoperative day was significantly lower in the TET group than in the NTET group (TET vs NTET: 4.96 ± 0.63 vs 5.93 ± 0.93, P = 0.000). CONCLUSIONS: We observed that the major outcomes of the TET group were more favorable than those of the NTET group. Based on our results, we recommend the avoidance of blunt dissection during endoscopic transaxillary breast augmentation. LEVEL OF EVIDENCE: III.

Oncological safety of reconstruction with autologous fat grafting in breast cancer patients: a systematic review and meta-analysis.

To evaluate the oncological safety of autologous fat grafting and its effect on disease-free survival and local recurrence in breast cancer patients with autologous fat grafting (AFG) reconstruction. A literature search was performed using the Pubmed, Medline, Web of Science, and Cochrane libraries from January 2011 to March 2020, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to identify all relevant studies involving the application of autologous fat grafting in breast cancer reconstruction procedures. The primary outcome of the meta-analysis was a difference in incidence rates of locoregional recurrence and disease-free survival (DFS) between patients who had autologous fat grafting and controls. A total of 11 studies were included. Eight studies reported local-regional recurrences (LRR) and five studies reported disease-free survival (DFS) in 5,886 patients. Our meta-analysis of all included studies about survival outcomes showed AFG was not associated with increased LRR and DFS. Pooled hazard ratios (HRs) (95% CIs) for LRR and DFS were 1.26 (0.90-1.76) and 1.27 (0.96-1.69), respectively. According to the published literature, autologous fat grafting did not result in an increased rate of LRR and DFS in patients with breast cancer. Autologous fat grafting can, therefore, be performed safely in breast reconstruction after breast cancer.

Evaluation of a beneficial effect of adjuvant chemotherapy in patients with stage I triple-negative breast cancer: a population-based study using the SEER 18 database.

PURPOSE: To evaluate the effect of adjuvant chemotherapy on improving the prognosis of patients with stage I triple-negative breast cancer (TNBC). METHODS: TNBC patients diagnosed in the SEER 18 database from 2010 to 2015 were included. Kaplan-Meier plots and log-rank tests were used to compare the differences in breast cancer-specific survival (BCSS) and overall survival (OS) between subgroups of variables. A Cox proportional hazard model was used to determine the prognostic factors affecting BCSS and OS. RESULTS: A total of 9256 patients were enrolled in this study. Among these patients, 380 died from breast cancer, and 703 died from all causes. Patients who received chemotherapy had significantly better BCSS and OS than those who did not receive chemotherapy for stage T1cN0M0 (BCSS, hazard ratio (HR) = 0.68, 95% confidence interval (CI) 0.51-0.90; OS, HR = 0.54, 95% CI 0.44-0.67) and stage IB (BCSS, HR = 0.39, 95% CI 0.16-0.95; OS, HR = 0.41, 95% CI 0.19-0.87) disease. Patients who received chemotherapy did not have significantly better BCSS or OS than those who did not receive chemotherapy for stage T1aN0M0 or T1bN0M0 disease. The patients who received chemotherapy in the poorly differentiated and undifferentiated groups had better BCSS (HR = 0.68, 95% CI 0.52-0.88) and OS (HR = 0.54, 95% CI 0.44-0.66) than the patients who did not receive chemotherapy. CONCLUSION: According to current clinical guidelines, patients with stage T1bN0M0 TNBC are probably overtreated. The prognosis of these patients with stage T1aN0M0 or T1bN0M0 disease is good enough that adjuvant chemotherapy cannot improve it further.

Impact of Locoregional Treatment on Prognosis of de novo Stage IV Breast Cancer: A Retrospective Long-Term Study of Chinese Population.

OBJECTIVES: This study aimed to evaluate the impact of locoregional resection and radiotherapy on the prognosis of Chinese women with stage IV breast cancer. METHODS: The retrospective study included Chinese patients with de novo stage IV breast cancer in National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, between January 1, 2001, and December 31, 2016. The patients were classified into surgery and nonsurgery groups. Overall survival (OS) and distant progression-free survival (DPFS) were evaluated at the last follow-up. RESULTS: Of the 157 patients, 66 (42.0%) underwent surgery and 52 (33.1%) received locoregional radiotherapy. The follow-up time ranged from 3 to 180 months. The median patient follow-up was 54.5 months. The patients in the surgery group had longer 5-year OS and 5-year DPFS compared with the patients in the nonsurgery group. DPFS was also significantly longer in patients who received radiotherapy. Two factors proved to be associated with survival: response to systemic therapy and surgical treatment. Multivariate analysis also showed that the progestogen receptor status significantly influenced the DPFS. CONCLUSION: Locoregional surgery and radiotherapy of primary tumor might be beneficial for Chinese patients with stage IV breast cancer. It proposed that surgical resection for selected stage IV breast cancer patients.

Evaluation of menopausal status among breast cancer patients with chemotherapy-induced amenorrhea.

OBJECTIVE: In patients with chemotherapy-induced amenorrhea (CIA), the menopausal status is ambiguous and difficult to evaluate. This study aimed to establish a discriminative model to predict and classify the menopausal status of breast cancer patients with CIA. METHODS: This is a single center hospital-based study from 2013 to 2016. The menopausal age distribution and accumulated incidence rate of CIA are described. Multivariate models were adjusted for established and potential confounding factors including age, serum concentration of estradiol (E2) and follicle-stimulating hormone (FSH), feeding, pregnancy, parity, abortions, and body mass index (BMI). The odds ratio (OR) and 95% confidence interval (95% CI) of different risk factors were estimated. RESULTS: A total of 1,796 breast cancer patients were included in this study, among whom, 1,175 (65.42%) were premenopausal patients and 621 (34.58%) were post-menopause patients. Five hundred and fifty patients were included in CIA analysis, and a cumulative CIA rate of 81.64% was found in them. Age (OR: 1.856, 95% CI: 1.732-1.990), serum concentration of E2 (OR: 0.976, 95% CI: 0.972-0.980) and FSH (OR: 1.060, 95% CI: 1.053-1.066), and menarche age (OR: 1.074, 95% CI: 1.009-1.144) were found to be associated with the patients' menopausal status. According to multivariate analysis, the discriminative model to predict the menopausal status is Logit (P)=-28.396+0.536Age-0.014E2+0.031FSH. The sensitivities for this model were higher than 85%, and its specificities were higher than 89%. CONCLUSIONS: The discriminative model obtained from this study for predicting menstrual state is important for premenopausal patients with CIA. This model has high specificity and sensitivity and should be prudently used.

The Association Between Body Size and Breast Cancer in Han Women in Northern and Eastern China.

INTRODUCTION: Although obesity has been reported worldwide as a risk factor for breast cancer, there are still some inconsistencies regarding the association between obesity and breast cancer. Body mass index (BMI) is used most to assess the extent of obesity; however, the association of other body size characteristics, such as waist and hip circumference, with susceptibility to breast cancer in Chinese Han women needs to be better assessed. PATIENTS AND METHODS: Female Chinese Han patients (N = 2,800) were recruited from 21 hospitals in northern and eastern China from April 2012 to April 2013 for a case-control study. The significant differences of factors related to body size between the breast-cancer case and control groups were determined by Student's t test and chi-square tests. RESULTS: Premenopausal women with breast cancer had higher BMI and larger waist and hip circumferences (p = 2 × 10-4, <1 × 10-6, and 2 × 10-5, respectively). However, these body-size factors were not associated with postmenopausal breast cancer (p = .45, 0.32, and 0.12, respectively). BMI between 28 and 30 kg/m2 or greater than 32 kg/m2 was related to breast cancer incidence in the overall study population and in premenopausal women but not in the postmenopausal group. CONCLUSION: Obesity is significantly associated with breast cancer in Chinese Han premenopausal women but not in postmenopausal women. Thus, it is important to realize that weight control, as well as avoiding abdominal obesity, should be considered as one of the most effective methods of reducing breast cancer risk. IMPLICATIONS FOR PRACTICE: To better understand the characteristics and risk factors for breast cancer in Han women in northern and eastern China, a case-control study of 2,800 Chinese Han women was conducted. Obesity was significantly associated with breast cancer in Chinese Han premenopausal women but not in postmenopausal women. Consequently, controlling body weight and avoiding abdominal obesity should be considered as one of the most effective methods of reducing breast cancer susceptibility. However, the diversity between this study's finding among Chinese Han women and other data previously reported among European and American populations still needs further investigation.

S100A14, a member of the EF-hand calcium-binding proteins, is overexpressed in breast cancer and acts as a modulator of HER2 signaling.

HER2 is overexpressed in 20­25% of breast cancers. Overexpression of HER2 is an adverse prognostic factor and correlates with decreased patient survival. HER2 stimulates breast tumorigenesis via a number of intracellular signaling molecules, including PI3K/AKT and MAPK/ERK.S100A14,one member of the S100 protein family, is significantly associated with outcome of breast cancer patients. Here, for the first time, we show that S100A14 and HER2 are coexpressed in invasive breast cancer specimens,andthere is a significant correlation between the expression levels of the two proteins by immunohistochemistry. S100A14 and HER2 are colocalized in plasma membrane of breast cancer tissue cells and breast cancer cell lines BT474 and SK-BR3. We demonstrate that S100A14 binds directly to HER2 by co-immunoprecipitation and pull-down assays. Further study shows that residues 956­1154 of the HER2 intracellular domain and residue 83 of S100A14 are essential for the two proteins binding.Moreover,we observe a decrease of HER2 phosphorylation, downstream signaling, and HER2-stimulated cell proliferation in S100A14-silenced MCF-7, BT474, and SK-BR3 cells. Our findings suggest that S100A14 functions as a modulator of HER2 signaling and provide mechanistic evidence for its role in breast cancer progression.

Trends in Radical Surgical Treatment Methods for Breast Malignancies in China: A Multicenter 10-Year Retrospective Study.

BACKGROUND: Incidence rates of breast cancer continue to rise in the People's Republic of China. The purpose of this study was to describe Chinese trends in radical surgical modalities and influential imaging and demographic factors for breast malignancies. MATERIALS AND METHODS: This study was a hospital-based, multicenter, 10-year (1999-2008), retrospective study. Descriptive statistical tests were used to illustrate information regarding radical surgical trends for the treatment of breast malignancies. Chi-square tests were used to assess effect of demographic factors in addition to imaging and pathological data on the specific surgical method. RESULTS: A total of 4,211 patients were enrolled in the survey. Among them, 3,335 patients with stage 0 to stage III disease undergoing mastectomy or breast-conserving surgery (BCS) were included in the final analysis. The rate of BCS increased from 1.53% in 1999 to 11.88% in 2008. The rate of mastectomy declined over this time period, from 98.47% in 1999 to 88.12% in 2008, with increasing use of diagnostic imaging methods and pathological biopsies. A significantly greater percentage of patients with office work, high education levels, unmarried status, younger age, and early pathological stages preferred BCS compared with mastectomy. CONCLUSION: Rates of mastectomy in China remain elevated due to diagnosis at higher stages; however, because of increased use of diagnostic imaging, improvement of biopsy methods, and patient education, rates of less invasive lumpectomy are increasing and rates of mastectomy have decreased in China. IMPLICATIONS FOR PRACTICE: In this study, 4,211 cases were collected from 1999 to 2008 through a multicenter retrospective study of varying geographic and socioeconomic areas to illustrate trends of surgeries in the People's Republic of China. The correlations between demographic and tumor characteristics and among methods of surgical treatment were explored. This study shows that the rate of breast-conserving surgery (BCS) increased and the rate of mastectomy declined over this time period with increasing use of diagnostic imaging methods and pathological biopsies. Patients with office work, high education levels, unmarried status, younger age, and early pathological stages preferred BCS compared with mastectomy in China.

Regulation of the microRNA 200b (miRNA-200b) by transcriptional regulators PEA3 and ELK-1 protein affects expression of Pin1 protein to control anoikis.

MicroRNA (miRNA) 200s regulate E-cadherin by directly targeting ZEB1/ZEB2, which are transcriptional repressors of E-cadherin. Decreased expression of E-cadherin results in cancer cells losing interaction with the extracellular matrix and detaching from the primary tumor. Normally, cells will undergo anoikis after losing interaction with the extracellular matrix. Cancer cells must, therefore, possess the ability to resist anoikis during the process of metastasis. Here we show that miRNA-200b regulates anoikis by directly targeting the 3' UTR of Pin1 mRNA and regulating Pin1 expression at the translational level. We found that down-regulation of miRNA-200b promotes cancer cells survival during metastasis, and the homeless state of these cells resulted in decreased expression of miRNA-200b in the MCF-7 cell line. We also found that expression of miRNA-200b is down-regulated in human breast cancer during lymph node metastasis, which has a significant negative correlation with Pin1 expression. Two members of the ETS (E-26) family (PEA3 and ELK-1) regulate the expression of miRNA-200b. PEA3 promotes the expression of miRNA-200b, and ELK-1 is a transcriptional repressor of miRNA-200b. In addition, miRNA-200b regulates the activity of PEA3 and ELK-1 via the Pin1-pERK pathway and forms self-regulated feedback loops. This study characterizes the role of miRNA-200b in the regulation of anoikis and demonstrates the regulation of its own expression in the process of metastasis.

Design of p53-derived peptides with cytotoxicity on breast cancer.

The tumor suppressor p53 plays essential role in conserving stability by preventing genome mutation, which is inactivated naturally by its negative regulator MDM2. Thus, targeting p53-MDM2 protein-protein interaction has been raised as a new cancer therapy in the medicinal community. In the current study, we report a successful application of an integrative protocol to design novel p53-derived peptides with cytotoxicity on human breast cancer cells. A quantitative structure-activity relationship-improved statistical potential was used to evaluate the binding potency of totally 24,054 single- and dual-point mutants of p53 peptide to MDM2 in a high-throughput manner, from which 46 peptide mutants with high predicted affinity and typical helical feature were involved in a rigorous modeling procedure that employed molecular dynamics simulations and post-binding energy analysis to systematically investigate the structural, energetic and dynamic aspects of peptide interactions with MDM2. Subsequently, a biological analysis was performed on a number of promising peptide candidates to determine their cytotoxic effects on human breast cancer cell line MDF-7. Six dual-point mutants were found to have moderate or high activities with their IC50 values ranging from 16.3 to 137.0 µM, which are better than that of wild-type p53 peptide (IC50 = 182.6 µM) and close to that of classical anticancer agent cis-platin (IC50 = 4.3 µM). Further, the most active peptide ETFSDWWKLLAE was selected as parent to further derive new mutants on the basis of the structural and energetic profile of its complex with MDM2. Consequently, three triple-point mutants (LTFSDWWKLLAE, ESFSDWWKLLAE and ETFADWWKLLAE) were obtained, and their biological activities (IC50 = 15.1, 27.0 and 8.7 µM, respectively) were determined to be comparable or better than the parent (IC50 = 16.3 µM).

[Expression of Ki67 and clinicopathological features in breast cancer].

OBJECTIVE: To analyze the relationship between the expression level of Ki67 and clinicopathological features in breast cancer. METHODS: Data of 918 female patients with invasive ductal breast carcinoma treated in the Cancer Hospital, Chinese Academy of Medical Sciences from Jan. to Dec. 2010 were analyzed retrospectively. The correlation of Ki67 expression and other clinicopathological features in the breast cancer was analyzed. RESULTS: Among the 918 cases, the Ki67 index was 0.9% to 95% (mean value 27.8%). Taking the Ki67 index 14% as the boundary to divide the patients into two subgroups, 263 cases (28.6%) were ≤ 14%, and 655 cases (71.4%) were >14%. There were significant differences between the Ki67 expression and age, tumor size, axillary lymph nodes status, histological grade and the expressions of C-erbB-2, estrogen receptor (ER) and progesterone receptor (PR) (P < 0.05 for all). All the Ki67 indexes of Ki67 expression in luminal B (30.44%), HER-2 overexpression (36.77%) and triple negative (47.40%) subtypes were significantly higher than that in the luminal A subtype (21.36%)(P < 0.01). The expression level of Ki67 in triple-negative subtype (47.40%) was significantly higher than that in the non-triple-negative subtype (24.79%)(P < 0.001). CONCLUSIONS: Ki67 index is significantly correlated with the age, tumor TNM stage, axillary lymph node status, histological grading, ER status, PR status and HER-2 status. A high expression level of Ki67 is a poor prognostic factor for breast cancer. The expression level of Ki67 should be detected routinely and it may become a useful prognostic marker in the treatment of breast cancer.

The safety parameters of the study on intraductal cytotoxic agent delivery to the breast before mastectomy.

BACKGROUND: Intraductal administration of cytotoxic agents has been shown to inhibit the development of breast cancer in animal models. The object of this study was to demonstrate the safety of intraductal delivery cytotoxic agents in patients prior to mastectomy. This method is hopeful to be developed as a chemoprevention approach in patients with pre-malignant or non-invasive ductal lesions to prevent breast cancer which will be further developed. METHODS: TWO DRUGS, PEGYLATED LIPOSOMAL DOXORUBICIN (PLD) AND CARBOPLATIN WERE ADMINISTERED AT THREE DOSE LEVELS (PLD: 10, 20, 50 mg and carboplatin 60, 120, 300 mg). There were five subjects in each group with 15 subjects treated with each drug once. Venous blood samples were obtained for pharmacokinetic analysis. The breast was removed surgically 2-5 days post administration and the treated ducts were marked to enable identification on pathological evaluation. RESULTS: Intraductal administration was generally well-tolerated with mild, transient breast discomfort. In the carboplatin arm, three women at the 300 mg dose experienced mild nausea and vomiting. In the PLD arm most women had mild erythema and swelling of the breast over the 72 hours following the drug administration. Patients receiving the 50 mg dose experienced local erythema until the time of surgery. Pharmacokinetic analysis showed that carboplatin rapidly entered systemic circulation with an early peak time (Tmax ~30 min) with a corresponding plasma ultrafiltrate area under the curve (AUC) consistent with the Calvert Formula using estimated glomerular filtration rate (GFR). Total plasma doxorubicin had delayed peak concentration times (Tmax >48 hours) with a linear dose response and peak concentrations substantially lower than expected from equivalent intravenous injection dosing. No doxorubicinol metabolite was detected in the plasma. CONCLUSIONS: This study demonstrates that cytotoxic drugs can be safely administered into breast ducts with minimal toxicity.

Unveiling Intricacies of DIEP Breast Reconstruction Post Early Breast Cancer: A Deep Dive into a Case of Unforeseen Complications.

In the vast expanse of restorative surgical procedures, the Deep Inferior Epigastric Perforator (DIEP) flap, originating from the inferior epigastric artery, has emerged as the preferred method of breast reconstruction, attributable to its myriad advantages. The technique provides reliable vascular supply, robust tissue volume for excision, minimal invasiveness to the donor site, with direct closure and concealment of the said site. This paper embarks on an elaborate elucidation of the DIEP surgical procedure, pivoting on the analytical exploration of a particular instance where necrosis of the skin flap occurred following immediate DIEP breast reconstruction in a patient diagnosed with early-stage breast cancer. This patient had previously undergone Nipple Areola Complex Sparing Mastectomy (NSM). We endeavor to extrapolate insights from this singular case of post-NSM DIEP breast reconstruction failure and correlate our findings with current literature dedicated to similar instances of surgical failure in DIEP breast reconstruction.

Prognostic impact of oral microbiome on survival of malignancies: a systematic review and meta-analysis.

BACKGROUND: Recent studies have shown that there exists a significant correlation between oral microbiome and the occurrence of malignancies. However, the prognostic significance of oral microbiome for cancer patients remains unclear. The purpose of this meta-analysis is to evaluate the impact of oral microbiome on the survival of patients with malignant neoplasms. METHODS: We conducted a thorough literature search of PubMed, Embase, and Cochrane Library databases until September 2022. The hazard ratio (HR) with a corresponding 95% confidence interval (CI) was analyzed using Review Manager 5.4 software for survival outcomes, including overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS), and disease-free survival (DFS). RESULTS: A total of 15 studies, covering 5191 samples with various types of cancers, were selected based on specified inclusion and exclusion criteria. In both univariate and multivariate analysis, patients with low diversity of the oral microbiome, or those with Fusobacterium-high/positive, or P. gingivalis positive in cancer tissue displayed poorer OS (univariate HR = 1.74; 95% CI 1.15-2.62; P = 0.009; multivariate HR = 1.56; 95% CI 1.07-2.27; P = 0.02), DSS (univariate HR = 2.06; 95% CI 1.50-2.84; P < 0.00001; multivariate HR = 1.80; 95% CI 1.48-2.20; P < 0.00001), and PFS/DFS (univariate HR = 2.00; 95% CI 1.12-3.58; P = 0.002; multivariate HR = 1.78; 95% CI 1.05-3.02; P = 0.003). Subgroup analysis revealed that Fusobacterium positive or high abundance in cancer tissues was associated with poor OS in multivariate analysis but had no statistical differences in PFS or DFS in univariate and multivariate analysis. Additionally, P. gingivalis positive in cancer tissue was also associated with worse OS. CONCLUSIONS: Our meta-analysis suggests that the composition of the oral microbiome may play a significant role in predicting survival outcomes for cancer patients.

Prognosis prediction and risk stratification of breast cancer patients based on a mitochondria-related gene signature.

As the malignancy with the highest global incidence, breast cancer represents a significant threat to women's health. Recent advances have shed light on the importance of mitochondrial function in cancer, particularly in metabolic reprogramming within tumors. Recognizing this, we developed a novel risk signature based on mitochondrial-related genes to improve prognosis prediction and risk stratification in breast cancer patients. In this study, transcriptome data and clinical features of breast cancer samples were extracted from two sources: the TCGA, serving as the training set, and the METABRIC, used as the independent validation set. We developed the signature using LASSO-Cox regression and assessed its prognostic efficacy via ROC curves. Furthermore, the signature was integrated with clinical features to create a Nomogram model, whose accuracy was validated through clinical calibration curves and decision curve analysis. To further elucidate prognostic variations between high and low-risk groups, we conducted functional enrichment and immune infiltration analyses. Additionally, the study encompassed a comparison of mutation landscapes and drug sensitivity, providing a comprehensive understanding of the differing characteristics in these groups. Conclusively, we established a risk signature comprising 8 mitochondrial-related genes-ACSL1, ALDH2, MTHFD2, MRPL13, TP53AIP1, SLC1A1, ME3, and BCL2A1. This signature was identified as an independent risk predictor for breast cancer patient survival, exhibiting a significant high hazard ratio (HR = 3.028, 95%CI 2.038-4.499, P < 0.001). Patients in the low-risk group showed a more favorable prognosis, with enhanced immune infiltration, distinct mutation landscapes, and greater sensitivity to anti-tumor drugs. In contrast, the high-risk group exhibited an adverse trend in these aspects. This risk signature represents a novel and effective prognostic indicator, suggesting valuable insights for patient stratification in breast cancer.

[Analysis of influencing factors to metastasis in sentinel lymph nodes and non-sentinel lymph nodes in breast cancer].

OBJECTIVE: To explore the relevant factors influencing sentinel and non-sentinel lymph node (SLNM, NSLNM) metastases in breast cancer. METHODS: The clinicopathological data of 283 women with breast cancer who underwent sentinel lymph node biopsy from July 2010 to August 2011 in the Cancer Institute and Hospital at Chinese Academy of Medical Sciences were reviewed retrospectively, and the relevant factors affecting sentinel and non-sentinel lymph node metastases were analyzed. RESULTS: Univariate analysis showed that age, menopause status, tumor size, pathological type and intravascular tumor thrombus were associated with SLNM metastasis (all P < 0.05). Multivariate analysis showed that age, tumor size and intravascular tumor thrombus were associated with SLNM (all P < 0.05) . No risk factors were found in either univariate or multivariate analysis of NSLNM. CONCLUSIONS: Age, tumor size and intravascular tumor thrombus are independent influencing factors associated with SLNM, and age is a protective factor. Whether ER, pathological type and pathological grade are associated with SLNM or not is still controversial.