HER2-low heterogeneity between primary and paired recurrent/metastatic breast cancer: Implications in treatment and prognosis.

BACKGROUND: With the largest sample size to date, the authors' objective was to investigate the incidence of primary-to-metastatic human epidermal growth factor 2 (HER2) conversion and the predictors for such conversion. Moreover, no previous studies have evaluated the prognosis of patients who have negative HER2 expression (HER2-0) versus low HER2 expression (HER2-low) when HER2 status was assessed based on all recurrent/metastatic lesions. METHODS: The authors included 1299 patients who had available HER2 status of primary breast tumors and paired recurrent/metastatic lesions at Fudan University Shanghai Cancer Center and West China Hospital. RESULTS: In total, 370 patients (28.5%) experienced primary-to-metastatic HER2 conversion. Intrapatient intermetastasis spatial heterogeneity and temporal heterogeneity of HER2 were detected. When assessing HER2 based on recurrent/metastatic tumors, patients who had HER2-0 tumors had significantly shorter overall survival than those who had HER2-low tumors in the overall population and in the estrogen receptor (ER)-negative subgroup. However, when assessing HER2 based on primary tumors, there was no difference in overall survival between patients who had HER2-0 versus HER2-low tumors. Moreover, patients who had tumors that converted from HER2-0 to HER2-low had longer overall survival than those who had consistent HER2-0 status in the ER-negative subgroup. By combining four predictors (ER status, Ki67 index, biopsy site, and disease-free interval), the authors established the first prediction tool to estimate the probability of HER2-0 tumors converting to HER2-low/positive tumors. CONCLUSIONS: Intrapatient primary-to-metastatic and intermetastatic HER2 heterogeneity were observed in this large-scale cohort study. When evaluating HER2 based on recurrent/metastatic tumors, an overall survival difference was observed between patients who had HER2-0 versus HER2-low, recurrent/metastatic breast tumors. The developed prediction tool might help clinicians screen out patients with primary HER2-0 tumors that have a high probability of HER2 status conversion and recommend them for re-biopsy, thus helping to screen out candidate patients for trastuzumab deruxtecan treatment.

Is postmastectomy radiotherapy necessary for breast cancer patients with clinically node-positive downstaging to ypN0 after neoadjuvant chemotherapy?

PURPOSE: The significance of postmastectomy radiotherapy (PMRT) in breast cancer patients who initially have clinically node-positive (cN +) status but achieve downstaging to ypN0 following neoadjuvant chemotherapy (NAC) remains uncertain. This study aims to assess the impact of PMRT in this patient subset. METHODS: Patients were enrolled from West China Hospital, Sichuan University from 2008 to 2019. Overall survival (OS), Locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and breast cancer-specific survival (BCSS) were estimated using the Kaplan-Meier method and assessed with the log-rank test. The impact of PMRT was further analyzed by the Cox proportional hazards model. Propensity score matching (PSM) was performed to reduce the selection bias. RESULTS: Of the 333 eligible patients, 189 (56.8%) received PMRT, and 144 (43.2%) did not. At a median follow-up period of 71 months, the five-year LRFS, DMFS, BCSS, and OS rates were 99.1%, 93.4%, 96.4%, and 94.3% for the entire cohort, respectively. Additionally, the 5-year LRFS, DMFS, BCSS, and OS rates were 98.9%, 93.8%, 96.7%, and 94.5% with PMRT and 99.2%, 91.3%, 94.9%, and 92.0% without PMRT, respectively (all p-values not statistically significant). After multivariate analysis, PMRT was not a significant risk factor for any of the endpoints. When further stratified by stage, PMRT did not show any survival benefit for patients with stage II-III diseases. CONCLUSION: In the context of comprehensive treatments, PMRT might be exempted in ypN0 breast cancer patients. Further large-scale, randomized controlled studies are required to investigate the significance of PMRT in this patient subset.

miR-942-5p Regulates Proliferation, Invasion and EMT of Trophoblast Cells in Gestational Diabetes by Targeting the CEBPA.

Objective: Gestational diabetes mellitus (GDM) is a prevalent metabolic disorder caused by abnormal glucose metabolism during pregnancy. Trophoblast dysfunction induced by hyperglycemia during pregnancy is the main factor leading to the development of GDM. In this study, we evaluated the expression of miR-942-5p in the placenta of patients with GDM and its regulation of trophoblast cell biological function. Methods: HTR-8/SVneo trophoblast cells were incubated with glucose to establish in vitro models, and miR-942-5p mimics transfected cells were added. The expression levels of miR-942-5p, CCAAT-enhancer-binding protein alpha (CEBPA) and N-cadherin in tissues and cells were detected by reverse-transcription quantitative polymerase chain reaction (RT-qPCR), protein blotting and immunohistochemistry (IHC). MTT, flow cytometry and Transwell assays were used to determine changes in cell proliferation, apoptosis and invasion. Dual-luciferase reporter assay and Pearson analysis were used to confirm the association between miR-942-5p and CEBPA. Results: miR-942-5p and N-cadherin were decreased in placental tissue and in human placental trophoblast cells (HTR-8/SVneo) exposed to high glucose (HG) conditions, while CEBPA was increased in placental tissue and HTR-8/SVneo exposed to HG conditions. Elevated levels of miR-942-5p suppressed apoptosis induced by HG and facilitated the proliferative and invasive capacities of HTR-8/SVneo. Mechanistically, we confirmed that miR-942-5p overexpression directly targeted CEBPA and suppressed CEBPA expression, while upregulating N-cadherin expression, which is involved in the EMT process of trophoblast cells and alleviated the dysfunction of trophoblast cells induced by HG in GDM. Conclusion: Overexpression of miR-942-5p promotes proliferation, invasion and EMT of trophoblast cells by targeting and negatively regulating CEBPA. These findings offer novel understanding regarding the treatment of GDM.

Visual SLAM for Unmanned Aerial Vehicles: Localization and Perception.

Localization and perception play an important role as the basis of autonomous Unmanned Aerial Vehicle (UAV) applications, providing the internal state of movements and the external understanding of environments. Simultaneous Localization And Mapping (SLAM), one of the critical techniques for localization and perception, is facing technical upgrading, due to the development of embedded hardware, multi-sensor technology, and artificial intelligence. This survey aims at the development of visual SLAM and the basis of UAV applications. The solutions to critical problems for visual SLAM are shown by reviewing state-of-the-art and newly presented algorithms, providing the research progression and direction in three essential aspects: real-time performance, texture-less environments, and dynamic environments. Visual-inertial fusion and learning-based enhancement are discussed for UAV localization and perception to illustrate their role in UAV applications. Subsequently, the trend of UAV localization and perception is shown. The algorithm components, camera configuration, and data processing methods are also introduced to give comprehensive preliminaries. In this paper, we provide coverage of visual SLAM and its related technologies over the past decade, with a specific focus on their applications in autonomous UAV applications. We summarize the current research, reveal potential problems, and outline future trends from academic and engineering perspectives.

Characteristics of DNA macro-alterations in breast cancer with liver metastasis before treatment.

BACKGROUND: Whole-genome doubling (WGD) has been observed in 30% of cancers, followed by a highly complex rearranged karyotype unfavourable to breast cancer's outcome. However, the macro-alterations that characterise liver metastasis in breast cancer(BC) are poorly understood. Here, we conducted a whole-genome sequencing analysis of liver metastases to explore the status and the time frame model of these macro-alterations in pre-treatment patients with metastatic breast cancer. RESULTS: Whole-genome sequencing was conducted in 11 paired primary tumours, lymph node metastasis, and liver metastasis fresh samples from four patients with late-stage breast cancer. We also chose five postoperative frozen specimens from patients with early-stage breast cancer before any treatment as control. Surprisingly, all four liver metastasis samples were classified as WGD + . However, the previous study reported that WGD happened in 30% of cancers and 2/5 in our early-stage samples. WGD was not observed in the two separate primary tumours and one lymph node metastasis of one patient with metastatic BC, but her liver metastasis showed an early burst of bi-allelic copy number gain. The phylogenetic tree proves her 4 tumour samples were the polyclonal origin and only one WGD + clone metastasis to the liver. Another 3 metastatic BC patients' primary tumour and lymph node metastasis experienced WGD as well as liver metastasis, and they all showed similar molecular time-frame of copy number(CN) gain across locations within the same patient. These patients' tumours were of monoclonal origin, and WGD happened in a founding clone before metastasis, explaining that all samples share the CN-gain time frame. After WGD, the genomes usually face instability to evolve other macro-alterations. For example, a greater quantity and variety of complex structural variations (SVs) were detected in WGD + samples. The breakpoints were enriched in the chr17: 39 Mb-40 Mb tile, which contained the HER2 gene, resulting in the formation of tyfonas, breakage-fusion-bridge cycles, and double minutes. These complex SVs may be involved in the evolutionary mechanisms of the dramatic increase of HER2 copy number. CONCLUSION: Our work revealed that the WGD + clone might be a critical evolution step for liver metastasis and favoured following complex SV of breast cancer.

A prospective cohort study of clinical characteristics and outcomes in Chinese patients with estrogen receptor-negative/progesterone receptor-positive early breast cancer.

PURPOSE: This study aimed to examine the clinical characteristics and outcomes of patients with estrogen receptor-negative (ER-)/progesterone receptor-positive (PR+) early breast cancer. We also aimed to investigate the benefits of adjuvant endocrine therapy (ET) in this patient population. METHODS: Patients with early breast cancer diagnosed at West China Hospital were divided into the ER-/PR+, ER+, and ER-/PR- groups. The chi-square test was used to analyze differences in clinical and pathological features among the groups. Multivariable Cox and Fine-Gray regression models were used to compare mortality and locoregional recurrence (LRR)/distant recurrence (DR), respectively. We performed a subgroup analysis to determine which ER-/PR+ patients can benefit more from ET. RESULTS: From 2008 to 2020, we enrolled 443, 7104, and 2892 patients into the ER-/PR+, ER+, and ER-/PR- groups, respectively. The ER-/PR+ group showed more unfavorable clinical features and aggressive pathological characteristics than the ER+ group. The mortality, LRR, and DR rates were higher in the ER-/PR+ than in the ER+ group. Most clinical features and pathological characteristics were similar between the ER-/PR+ and ER-/PR- group and their outcomes were comparable. In the ER-/PR+ group, patients who received ET showed significantly lower LRR and mortality rates than those who did not; however, no difference was observed in DR. Subgroup analysis suggested that ER-/PR+ patients age ≥ 55 years, and postmenopausal status can benefit from ET. CONCLUSION: ER-/PR+ tumors have more aggressive pathological characteristics and more unfavorable clinical features than ER+ tumors. ET can reduce the LRR and mortality rates in ER-/PR+ patients. Postmenopausal and age ≥ 55 years ER-/PR+ patients can benefit from ET.

Global longitudinal strain assessment in contrast-enhanced echocardiography in breast cancer patients: a feasibility study.

BACKGROUND: Left ventricular global longitudinal strain (GLS) obtained from two-dimensional speckle-tracking echocardiography (2D-STE) can reflect cancer therapy-related cardiac dysfunction in breast cancer (BC) patients, however, the accuracy and reproducibility of 2D-STE are restricted due to poor image quality. METHODS: Between January 2019 and October 2021, 160 consecutive BC patients aged ≥ 18 years were recruited. The 160 BC patients (mean age: 48.41 ± 9.93 years, 100% women) underwent both 2D-STE and Contrast-enhanced echocardiography (CEcho), 125 of whom were included in the measurement of GLS. The intraclass correlation coefficient (ICC) was used to determine the intra- and inter-observer reproducibility of 2D-STE and CEcho-STE. Correlation (r) was calculated using Pearson correlation. Statistical significance was set at P < 0.05. RESULTS: Among 160 BC patients, more segments were recognized by CEcho-STE than by 2D-STE (2,771, 99.53% vs. 2,440, 84.72%). The left ventricular ejection fraction (LVEF) obtained by 2D was lower than CEcho (61.75 ± 6.59% vs. 64.14 ± 5.97%, P < 0.0001). The GLS obtained by 2D-STE was lower than CEcho-STE (-21.74 ± 2.77% vs. -26.79 ± 4.30%, P = 0.001). The ICC of the intraobserver and interobserver agreements in the CEcho-STE group was lower than that in the 2D-STE group. GLS measurements were in good agreement between the 2D-STE and CEcho-STE groups (r = 0.773). CONCLUSIONS: CEcho can overcome some imaging limitations and recognize more segments than 2D, which may provide an LVEF and GLS closer to the true value. Based on AutoStrain, CEcho-STE may serve as a complementary method for those with poor image quality.

A nomogram for predicting breast cancer specific survival in elderly patients with breast cancer: a SEER population-based analysis.

BACKGROUND: The number of elderly patients diagnosed with breast cancer is increasing worldwide. However, treatment decisions for these patients are highly variable. Although researchers have identified the effects of surgery, radiotherapy, endocrine therapy, and chemotherapy in elderly patients with breast cancer, clinicians still struggle to make appropriate decisions for these patients. METHODS: We identified 75,525 female breast cancer patients aged ≥ 70 years in the Surveillance, Epidemiology, and End Results (SEER) database treated between January 1, 2010, and December 31, 2016. The patients were further divided into training and testing cohorts. The cumulative occurrence of breast cancer-specific deaths (BCSDs) and other cause-specific deaths (OCSD) was calculated using the cumulative incidence function. In the univariate analysis, risk factors were screened using the Fine-Gray model. In the multivariate analysis for competing risks, the sub-distribution hazard ratio with a 95% confidence interval for each independent predictor associated with BCSD was calculated for the construction of nomograms. Based on the above analyses, a competing risk nomogram was constructed to predict the probability of BCSD in the 1st, 3rd, and 5th years after treatment. During validation, the concordance index (C-index) was selected to quantify the predictive ability of the competing risk model. RESULTS: A total of 33,118 patients were included in this study, with 24,838 in the training group and 8,280 in the testing group. Age, race, marital status, cancer grade, tumor stage, node stage, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor--2 status, and treatment including surgery, radiation, and chemotherapy were used to establish a nomogram. The C-index of 0.852 (0.842-0.862) in the training cohort and 0.876 (0.868-0.892) in the testing cohort indicated satisfactory discriminative ability of the nomogram. Calibration plots showed favorable consistency between the nomogram predictions and actual observations in both the training and validation cohorts. CONCLUSIONS: Our study identified independent predictors of BCSD in elderly patients with breast cancer. A prognostic nomogram was developed and validated to aid clinical decision-making.

Impact of time to initiation of postoperative radiotherapy after neoadjuvant chemotherapy on the prognosis of breast cancer: A retrospective cohort study in China.

The optimal time to the initiation of postoperative radiotherapy (TTR) in breast cancer patients after neoadjuvant chemotherapy (NAC) and surgery is unclear. We explored the association between TTR and outcomes among breast cancer females to determine the optimal timing for radiotherapy. We included 1022 women with breast cancer who underwent NAC and surgery between 1997 and 2019. Patients were categorized into three groups based on the TTR: <8 weeks, 8 to 16 weeks and >16 weeks. We used Cox proportional hazards models and analyzed the hazard ratios (HRs) for breast cancer-specific mortality (BCSM) and all-cause mortality (ACM). The median TTR for the cohort was 97 days. Compared to patients with TTRs of 8 to 16 weeks, those with TTRs <8 weeks or >16 weeks had an increased risk of BCSM (HR, 2.59; 95% confidence interval [CI], 1.26-5.36 and HR, 2.01; 95% CI, 1.24-3.28, respectively) and ACM (HR, 2.32; 95% CI, 1.17-4.56 and HR, 1.92; 95% CI, 1.24-2.98, respectively) after adjusting for the confounders. Furthermore, at TTR of >16 weeks, each additional week of TTR was associated with a 3% increase in BCSM risk and 2% increase in ACM risk. Our findings suggest that patients who have undergone NAC and surgery show lower BCSM and ACM risks at TTR of 8 to 16 weeks compared to <8 weeks or >16 weeks.

Mammography radiomics features at diagnosis and progression-free survival among patients with breast cancer.

BACKGROUND: The associations between mammographic radiomics and breast cancer clinical endpoints are unclear. We aimed to identify mammographic radiomics features associated with breast cancer prognosis. METHODS: Nested from a large breast cancer cohort in our institution, we conducted an extreme case-control study consisting of 207 cases with any invasive disease-free survival (iDFS) endpoint <5 years and 207 molecular subtype-matched controls with >5-year iDFS. A total of 632 radiomics features in craniocaudal (CC) and mediolateral oblique (MLO) views were extracted from pre-treatment mammography. Logistic regression was used to identify iDFS-associated features with multiple testing corrections (Benjamini-Hochberg method). In a subsample with RNA-seq data (n = 96), gene set enrichment analysis was employed to identify pathways associated with lead features. RESULTS: We identified 15 iDFS-associated features from CC-view yet none from MLO-view. S(1,-1)SumAverg and WavEnLL_s-6 were the lead ones and associated with favourable (OR 0.64, 95% CI 0.42-0.87, P = 0.01) and poor iDFS (OR 1.53, 95% CI 1.31-1.76, P = 0.01), respectively. Both features were associated with eight pathways (primarily involving cell cycle regulation) in tumour but not adjacent normal tissues. CONCLUSION: Our findings suggest mammographic radiomics features are associated with breast cancer iDFS, potentially through pathways involving cell cycle regulation.

PTEN promoter methylation predicts 10-year prognosis in hormone receptor-positive early breast cancer patients who received adjuvant tamoxifen endocrine therapy.

PURPOSE: There remain a lack of biomarkers for endocrine therapy resistance in patients with breast cancer (BC), which is proving to be a great challenge. In vitro experiments have shown that downregulation of PTEN expression leads to resistance to tamoxifen (TAM) in BC cells. We aimed to investigate the predictive role of tumor PTEN promoter methylation and PTEN expression in long-term survival after TAM adjuvant therapy in patients with early-stage BC. METHODS: From 2001 to 2013, 105 patients with stage I-III BC who were treated with standardized adjuvant TAM for 5 years or until relapse in West China Hospital (WCH) were enrolled in this study. PTEN expression and DNA methylation of three specified sequences from the PTEN promoter in primary tumors were measured using immunohistochemistry and pyrosequencing. A cohort of 159 hormone receptor-positive patients receiving TAM treatment from The Cancer Genome Atlas (TCGA) database was used for verification. RESULTS: Median follow-up time for the WCH cohort was 141.7 months. The low, moderate, and high PTEN expression groups had differing 10-year disease-free survival (DFS) (42.3%, 55%, 81%, respectively, P = 0.027) and overall survival (OS) rates (65%, 84.2%, 90.5%, respectively, P = 0.027). Higher methylation levels of the second sequence (- 819 to - 787 bp), rather than the first (- 1143 to - 1107 bp) or third sequence (- 663 to - 593 bp), independently increased the risk of disease recurrence (hazard ratio = 2.60) and death (hazard ratio = 3.79) in the WCH cohort, according to multivariate Cox regression analysis. Importantly, out of the five CpG islands located within this sequence, only high methylation of the - 796 CpG island predicted shorter DFS and OS. In TCGA validation cohort, there was also a trend of higher methylation of the - 796 CpG island correlating with shorter disease-free intervals, with borderline significance (P = 0.057). CONCLUSION: Low PTEN expression and high methylation of its promoter (sequence - 819 to - 787 bp) in tissue predict poor DFS and OS in hormone receptor-positive early BC patients who received adjuvant TAM.

Association between age at initial diagnosis and post-metastasis mortality among women with recurrent metastatic breast cancer in China.

BACKGROUND: Little is known about whether age at initial diagnosis influences the prognosis of recurrent metastatic breast cancer (rMBC). Here, we analyzed the association between age at initial diagnosis and rMBC mortality in China. METHODS: A total of 1636 women diagnosed with rMBC between 1989 and 2020 at West China Hospital, Sichuan University were included in this study. The age at initial diagnosis was categorized as young (≤ 40 years), middle-aged (41-64 years) and elderly (≥ 65 years). Post-metastasis mortality was the primary outcome and its associated factors were analyzed by Cox proportional hazards models. RESULTS: During a median follow-up of 5.2 years after initial diagnosis of breast cancer, 620 deaths were identified. Compared with middle-aged patients, elderly patients had a 70% increased risk of post-metastasis mortality (95%CI, 1.24-2.33) after adjusting for demographics, tumor characteristics and treatment modes. Similarly, elderly patients were associated with a 75% increased risk of post-metastasis mortality (95%CI, 1.19-2.59) compared with young patients. Subgroup analyses also showed similar trends. CONCLUSION: Our findings suggest that in breast cancer, elderly patients at initial diagnosis face a higher risk of post-metastasis mortality.

Data-driven treatment pathways mining for early breast cancer using cSPADE algorithm and system clustering.

OBJECTIVES: Due to the multidimensional, multilayered, and chronological order of the cancer data, it was challenging for us to extract treatment paths. To determine whether the cSPADE algorithm and system clustering proposed in this study can effectively identify the treatment pathways for early breast cancer. METHODS: We applied data mining technology to the electronic medical records of 6891 early breast cancer patients to mine treatment pathways. We provided a method of extracting data from EMR and performed three-stage mining: determining the treatment stage through the cSPADE algorithm → system clustering for treatment plan extraction → cSPADE mining sequence pattern for treatment. The Kolmogorov-Smirnov test and correlation analysis were used to cross-validate the sequence rules of early breast cancer treatment pathways. RESULTS: We unearthed 55 sequence rules for early breast cancer treatment, 3 preoperative neoadjuvant chemotherapy regimens, three postoperative chemotherapy regimens, and 2 chemotherapy regimens for patients without surgery. Through 5-fold cross-validation, Pearson and Spearman correlation tests were performed. At the significance level of p < 0.05, all correlation coefficients of support, confidence and lift were greater than 0.89. Using the Kolmogorov-Smirnov test, we found no significant differences between the sequence distributions. CONCLUSIONS: We have proved that cSPADE algorithm combined system clustering is an effective technique for identifying temporal relationships between treatment modalities, enabling hierarchical and vertical mining of breast cancer treatment models. In addition, we confirmed the robustness of the results by cross-validation of these treatment pathway ordering rules. Through this method, the treatment path of early breast cancer patients can be revealed, and the real-world breast cancer treatment behaviour model can be evaluated, which can provide reference for the redesign and optimization of treatment path.

Public health insurance and cancer-specific mortality risk among patients with breast cancer: A prospective cohort study in China.

Little is known about how health insurance policies, particularly in developing countries, influence breast cancer prognosis. Here, we examined the association between individual health insurance and breast cancer-specific mortality in China. We included 7436 women diagnosed with invasive breast cancer between 2009 and 2016, at West China Hospital, Sichuan University. The health insurance plan of patient was classified as either urban or rural schemes and was also categorized as reimbursement rate (ie, the covered/total charge) below or above the median. Breast cancer-specific mortality was the primary outcome. Using Cox proportional hazards models, we calculated hazard ratios (HRs) for cancer-specific mortality, contrasting rates among patients with a rural insurance scheme or low reimbursement rate to that of those with an urban insurance scheme or high reimbursement rate, respectively. During a median follow-up of 3.1 years, we identified 326 deaths due to breast cancer. Compared to patients covered by urban insurance schemes, patients covered by rural insurance schemes had a 29% increased cancer-specific mortality (95% CI 0%-65%) after adjusting for demographics, tumor characteristics and treatment modes. Reimbursement rate below the median was associated with a 42% increased rate of cancer-specific mortality (95% CI 11%-82%). Every 10% increase in the reimbursement rate is associated with a 7% (95% CI 2%-12%) reduction in cancer-specific mortality risk, particularly in patients covered by rural insurance schemes (26%, 95% CI 9%-39%). Our findings suggest that underinsured patients face a higher risk of breast cancer-specific mortality in developing countries.

The Effect of Postmastectomy Radiotherapy on Breast Cancer Patients After Neoadjuvant Chemotherapy by Molecular Subtype.

BACKGROUND: The effect of postmastectomy radiotherapy (PMRT) on patient outcomes after neoadjuvant chemotherapy (NAC) remains controversial. We aimed to establish a model to identify the subsets benefiting from PMRT and to examine the effect of PMRT according to molecular subtype. PATIENTS AND METHODS: We retrospectively analyzed 1118 cT1-4cN0-3M0 breast cancer patients treated with NAC and mastectomy. A nomogram predicting locoregional recurrence (LRR) was established based on 418 unirradiated patients, and X-tile analysis was performed to divide the patients into two risk groups. The effect of PMRT on LRR, distant recurrence (DR), and breast cancer mortality (BCM) was estimated for patients with different molecular subtypes in two risk groups. RESULTS: A nomogram predicting LRR was developed using six factors: histologic classification, lymphovascular invasion, ypT stage, ypN stage, estrogen receptor status, and Ki-67 expression. Our study found that PMRT correlated with lower 5-year LRR, DR, and BCM rates for the high-risk group; however, no significant improvement in these endpoints was observed in the low-risk group. Among patients with high risk, subgroup analysis showed that LRR control was improved after PMRT for the human epidermal growth factor receptor 2 (HER2)-negative/hormone receptor (HR)-positive (HER2-/HR+), HER2-positive (HER2+)/HR+, and HER2-/HR-negative (HR-) subtypes, with hazard ratios of 0.113 (95% confidence [CI] 0.034-0.379; p < 0.001), 0.159 (95% CI 0.038-0.671; p = 0.017), and 0.243 (95% CI 0.088-0.676; p = 0.007), respectively, but not for the HER2+/HR- subtype (p = 0.468). CONCLUSIONS: We built a nomogram showing favorable risk quantification and patient stratification. Patients in the high-risk group benefited from PMRT, but patients in the low-risk group did not. PMRT may show different benefits for each molecular subtype.

Cost-effectiveness of different surgical treatment approaches for early breast cancer: a retrospective matched cohort study from China.

BACKGROUND: Both breast-conserving surgery and breast reconstruction surgery are less popular in China, although they can improve patients' quality of life. The main reason comes from the economy. There is currently no economic evaluation of different surgical treatment options for early breast cancer. Our study aims to assess the economic impact and long-term cost-effectiveness of different surgical treatments for early breast cancer. The surgical approaches are including mastectomy (MAST), breast-conserving therapy (BCT), and mastectomy with reconstruction (MAST+RECON). METHODS: Based on demographic data, disease-related information and other treatments, we applied propensity score matching (PSM) to perform 1: 1 matching among patients who underwent these three types of surgery in the tertiary academic medical center from 2011 to 2017 to obtain a balanced sample of covariates between groups. A Markov model was established. Clinical data and cost data were obtained from the medical records. Health utility values were derived from clinical investigations. Strategies were compared using an incremental cost-effectiveness ratio (ICER). RESULTS: After PSM, there were 205 cases in each group. In the matched data set, the distribution of covariates was fully balanced. The total cost of MAST, MAST+RECON and BCT was $37,392.84, $70,556.03 and $82,330.97, respectively. The quality-adjusted life year (QALYs) were 17.11, 18.40 and 20.20, respectively. Compared with MAST, MAST+RECON and BCT have an ICER of $25,707.90/QALY and $14,543.08/QALY, respectively. The ICER of BCT vs. MAST was less than the threshold of $27,931.04. The reliability and stability of the results were confirmed by Monte Carlo simulation and sensitivity analysis. CONCLUSIONS: We believe that in the context of the limited resources in China, after comparing the three surgical approaches, BCT is the more cost-effective and preferred solution.

Treatment patterns and outcomes in older women with early breast cancer: a population-based cohort study in China.

BACKGROUND: Despite the proportion of elderly breast cancer patients has been consistently increasing, the optimal treatment modalities for this population have not been well explored. We summarized the treatment outcomes of these patients in our hospital. METHODS: Older patients with early breast cancer were identified from the Breast Cancer Information Management System at West China Hospital, Sichuan University (2000-2019). We compared tumor characteristics and treatment outcomes between the older group (65-74 years old) and the elderly group (≥75 years old). The Kaplan-Meier and Cox regression analysis were conducted to determine significant prognostic factors. RESULTS: In total, 1094 patients were included. The median follow-up time for this cohort was 59 months. The majority of patients underwent surgery and benefited from surgical treatment. Elderly group patients were less likely to receive adjuvant chemotherapy or postmastectomy radiotherapy (PMRT) compared to the older group. However, adjuvant chemotherapy was associated with improved overall survival (OS) (hazard ratio [HR] 0.521, 95% confidence interval [CI] 0.284-0.955, P = 0.035). Subgroup analysis revealed that patients with grade III disease best benefited from adjuvant chemotherapy. PMRT offered a significant improvement in local disease control, but not in OS. Furthermore, endocrine therapy improved the OS of HR-positive patients (HR 0.440, 95%CI 0.261-0.741, P = 0.002), especially for cases aged 65-74 years. Also, receipt of trastuzumab in HER2-positive patients was associated with better OS (HR 0.168, 95%CI 0.029-0.958, P = 0.045). CONCLUSIONS: Our findings suggest that surgery, adjuvant chemotherapy, endocrine and targeted therapy are associated with improved OS in older breast cancer patients. Moreover, clinicopathological characteristics should be comprehensively considered when making treatment decisions for these patients.

Long-term excess body fat in adulthood and the risk of pre- and postmenopausal breast cancer in Chinese women.

PURPOSE: This study aimed to investigate the association between long-term excess body fat and breast cancer risk by studying adult weight gain together with the subsequent weight fluctuations. METHODS: Weight gain measure in three different time periods in adulthood of 1500 participants was collected in a case-control study of Western China. Logistic regression models were used to estimate odds ratios and 95% CIs. RESULTS: The increased risk of postmenopausal BC was associated with adult weight gain at 5 years and at 10 years before enrollment (OR 1.24, 95% CI 1.03-1.49 per 5 kg increase; OR 1.40, 95% CI 1.14-1.70 per 5 kg increase) but was not associated with adult weight gain at enrollment (OR 0.97, 95% CI 0.81-1.16 per 5 kg increase). Only a positive association was observed in premenopausal women who had gained > 5.0 kg at 10 years before enrollment (OR 1.61, 95% CI 1.10-2.35). Women who had gained > 5.0 kg at 10 years before enrollment and continued to gain during the subsequent 5 years had the highest postmenopausal BC risk (OR 3.34, 95% CI 1.58-7.08). CONCLUSION: Adult weight gain at 5 years and 10 years before enrollment are more closely associated with postmenopausal BC risk than adult weight gain at enrollment in Western China. Controlling body weight as early as possible throughout adulthood to keep weight gain not more than 5.0 kg is particularly necessary for Chinese women.

Repression of miR-135b-5p promotes metastasis of early-stage breast cancer by regulating downstream target SDCBP.

Metastasis is an essential event for breast cancer (BC) progression even after initial surgery. The identification of patients with a high probability of metastasis at an early stage is particularly important in clinical practice and requires individualized treatment or early prevention. A retrospective study of 242 cases of ductal carcinoma in situ with microinvasion (DCIS-Mi), the first stage of invasive BC, was performed in this follow-up analysis. Of all patients, 8 developed metastases, and they were all included for further mechanistic studies with control group of 24 DCIS-Mi by matched-pair designing. By screening DCIS-Mi with different prognoses, we found that the DCIS-Mi that metastasized had significantly lower miR-135b-5p expression than the DCIS-Mi that did not. The function of miR-135b-5p was studied in vitro and in vivo invasion and metastasis assays. We also validated a novel target gene for miR-135b-5p, syndecan binding protein (SDCBP), and assessed the functional consequences of SDCBP by invasion assays. By checking different BC cell lines, a strong inverse correlation between miR-135b-5p and SDCBP expression was recorded. For the functional study, the inhibition of miR-135b-5p was accompanied by increased BC cell growth, epithelial-mesenchymal transition (EMT), migration and invasion in vitro. Interestingly, silencing SDCBP can reverse miR-135b-5p-dependent EMT and proliferation. In vivo studies demonstrated that the newly revealed miR-135b-5p/SDCBP axis increased cell proliferation, invasion and malignant transformation, as well as promoted metastasis in a xenograft tumor mouse model. Thus, our clinical patient cohort and functional data suggest that miR-135b-5p/SDCBP is a crucial determinant of BC metastasis at a very early stage. Our results may shed light on the importance of miR-135b-5p molecular diagnosis and prognosis, as well as the early prevention of BC for metastasis.

A multiple breast cancer stem cell model to predict recurrence of T1-3, N0 breast cancer.

BACKGROUND: Local or distant relapse is the key event for the overall survival of early-stage breast cancer after initial surgery. A small subset of breast cancer cells, which share similar properties with normal stem cells, has been proven to resist to clinical therapy contributing to recurrence. METHODS: In this study, we aimed to develop a prognostic model to predict recurrence based on the prevalence of breast cancer stem cells (BCSCs) in breast cancer. Immunohistochemistry and dual-immunohistochemistry were performed to quantify the stem cells of the breast cancer patients. The performance of Cox proportional hazard regression model was assessed using the holdout methods, where the dataset was randomly split into two exclusive sets (70% training and 30% testing sets). Additionally, we performed bootstrapping to overcome a possible biased error estimate and obtain confidence intervals (CI). RESULTS: Four groups of BCSCs (ALDH1A3, CD44+/CD24-, integrin alpha 6 (ITGA6), and protein C receptor (PROCR)) were identified as associated with relapse-free survival (RFS). The correlated biomarkers were integrated as a prognostic panel to calculate a relapse risk score (RRS) and to classify the patients into different risk groups (high-risk or low-risk). According to RRS, 67.81 and 32.19% of patients were categorized into low-risk and high-risk groups respectively. The relapse rate at 5 years in the low-risk group (2.67, 95% CI: 0.72-4.63%) by Kaplan-Meier method was significantly lower than that of the high-risk group (19.30, 95% CI: 12.34-26.27%) (p <  0.001). In the multiple Cox model, the RRS was proven to be a powerful classifier independent of age at diagnosis or tumour size (p <  0.001). In addition, we found that high RRS score ER-positive patients do not benefit from hormonal therapy treatment (RFS, p = 0.860). CONCLUSION: The RRS model can be applied to predict the relapse risk in early stage breast cancer. As such, high RRS score ER-positive patients do not benefit from hormonal therapy treatment.