Influential factors and prediction model of mammographic density among Chinese women.

ABSTRACT: To evaluate the characteristics and influential factors of breast density and establish a new model for predicting breast density in Chinese women, so as to provide a basis for breast cancer screening techniques and duration.A total of 9412 women who were selected from screening and intervention techniques for Breast and Cervical Cancer Project between April 2018 and June 2019 were enrolled in this study. Selected women were randomly assigned to training and validation sets in a ratio of 1:1. Univariable and multivariable analyzes were performed by Logistic regression model. Nomogram was generated according to the results of multivariate analysis. Calibration, area under curve (AUC) and akaike information criterion (AIC) were used for measuring accuracy of prediction model.There were 377 (4.0%) women in breast imaging reporting and data system (BI-RADS) A category, 2164 (23.0%) in B category, 5749 (61.1%) in C category and 1122 (11.9%) in D category. Age duration, educational attainment, history of benign diseases, breastfeeding history, menopausal status, and body mass index (BMI) were imputed as independent influential factors for breast density in multivariable analysis. The AUC and AIC of training and validation set were 0.7158, 0.7139, and 4915.378, 4998.665, respectively.This study indicated that age, educational attainment, history of benign breast disease, breastfeeding history, menopausal status and BMI were independent influential factors of breast density. Nomogram generated on the basis of these factors could relatively predict breast density, which in turn could be used for recommendations of breast cancer screening techniques.

Leptin-elicited PBX3 confers letrozole resistance in breast cancer.

Aberrant leptin signaling and overexpression of fibroblast growth factor receptor 1 (FGFR1) are both implicated in the pathogenesis of letrozole resistance in breast cancer (BCa), but it remains unknown whether these two pathways are involved in letrozole resistance in a coordinated manner. Here, we demonstrate that expression levels of the pre-B-cell leukemia homeobox transcription factor 3 (PBX3), a pioneer factor that governs divergent biological processes, were significantly upregulated in letrozole-resistant BCa cells and tissues, and this upregulation correlated to a poorer progression-free survival in patients. By leveraging a patient-derived xenograft model with pharmacological approaches, we demonstrated that leptin activated PBX3 expression in a STAT3 (signal transducer and activator of transcription 3)-dependent manner. Our loss- and gain-of-function study further showed that PBX3 attenuated response to letrozole by potentiating BCa cell survival and anchorage-independent growth in BCa cells. By profiling BCa cells with ectopic PBX3 expression, we revealed that PBX3 conferred letrozole resistance via transactivation of the FGFR1 signaling, and this molecular event must coordinate a synergistic transcription activation programs through interacting with MTA1-HDAC2 (metastasis associated 1-histone deacetylase 2) complex. Overall, the available data reveal a novel role of leptin/PBX3 cascade linking energy homeostasis (i.e. hyperleptinemia) and endocrine therapy failure (i.e. letrozole resistance) in BCa.

A nomogram for predicting cancer-specific survival in different age groups for operable gastric cancer: a population-based study.

BACKGROUND: The age thresholds for differentiating young and elderly patients are still under debate. This study aimed to evaluate the cut-off age for differentiating patients along with the prognostic value of age for operable gastric cancer (GC). METHODS: Patients diagnosed with resected gastric adenocarcinoma were identified from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database (training cohort and internal validation cohort) and Liaoning Cancer Hospital (external validation cohort). Kaplan-Meier plots were used to compare cancer-specific survival (CSS) across different age groups. Univariate and multivariate analysis was conducted using a Cox regression model. Predictive ability of the nomogram was determined by the Harrell's concordance index (C-index), calibration curves, and Akaike's Information Criterion (AIC). RESULTS: A total of 17,339 patients with GC were included. According to the univariate analysis results, CSS was similar among patients aged 20-69 years old, started to worsen for patients over the age of 70, and was the worst for patients older than 79 years in the training cohort. Thus, we further divided the age groups into 20-69, 70-79, and >79, and multivariate analysis showed that patients above 70 years of age had worse CSS. The nomogram was established based on the results of the multivariate analysis. The C-indexes for the training, internal, and external validation cohorts were 0.7531, 0.7344, and 0.7431, respectively. CONCLUSIONS: This study showed that age had a relative predictive ability for CSS, 70 years should be the cut-off age, and age ≥70 years is an independent prognostic risk factor for GC patients who undergo surgery. These data highlight the importance of individualized treatment to improve the prognosis of patients with GC.

Clinicopathological features and prognostic analysis of signet ring cell gastric carcinoma: a population-based study.

BACKGROUND: The impact of signet ring cell carcinoma (SRC) on gastric cancer patients' prognosis remains controversial. The aim of this study was to evaluate the clinicopathological characteristics and prognosis of SRC carcinoma and adenocarcinoma (AC) in patients with gastric cancer (GC). METHODS: An electronic search of SRC and AC cases from 2004 to 2015 was conducted within the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database. According to histological type, AC patients were divided into two groups: well- and moderately differentiated (WMD) and, poorly differentiated adenocarcinoma (PD). Kaplan-Meier (KM) curves were used to compare 5-year overall survival (OS), Univariate, and multivariable analysis were performed by Cox regression model. RESULTS: We identified 29,851 gastric cancer patients, among whom 16,482 were in the M0 group and 13,369 were in the M1 group. SRC patients had younger age distribution and were more seen in women. SRC was more likely to be found in advanced T and N stage, and with more distant metastasis. The most common metastatic site was bone-in SRC, while the most common site was the liver for WMD and PD. In the M0 group, multivariable analyses demonstrated that SRC had a similar survival rate with WMD and PD in stage I, and with the stage increasing, the overall survival of SRC was worse than that of WMD. Meanwhile, in the M1 group, SRC had an even worse prognosis than PD. CONCLUSIONS: SRC was significantly different from AC in its clinicopathologic characteristics. Although the prognosis of SRC was similar to AC in the early stage, it had a more inferior prognostic impact with the progression of the disease. Different therapeutic regimens and imaging evaluations should be applied according to the histological types of gastric cancer.