Single-Nucleotide Polymorphisms in LEP and LEPR Associated With Breast Cancer Risk: Results From a Multicenter Case-Control Study in Chinese Females.

BACKGROUND: Leptin (LEP) plays a physiological role through its specific receptor (LEPR) and is involved in the occurrence and development of breast cancer. Our current study aimed at determining the influence of single-nucleotide polymorphisms (SNPs) in the genes coding for LEP and LEPR on breast cancer risk. METHODS: In the present study, 963 breast cancer cases and 953 controls were enrolled. Five SNPs of LEP and two of LEPR were chosen to evaluate the correlation of selected SNPs with breast cancer susceptibility among women in northern and eastern China. Analyses were further stratified by body mass index (BMI), waist-hip rate (WHR), estrogen receptor, and progesterone receptor status. The expression patterns of risk variant-associated genes were detected by expression quantitative trait locus (eQTL) analysis with eQTLGen and The Cancer Genome Atlas database. RESULTS: There were significant differences between breast cancer cases and control groups in the menopausal status and family history of breast cancer. Two SNPs (rs1137101 and rs4655555) of the LEPR gene decreased overall breast cancer risk, and other five SNPs showed no significant association with breast cancer risk. rs1137101 (GA vs. GG; adjusted OR = 0.719, 95% CI = 0.578-0.894, p = 0.003) and rs4655555 (TT vs. AA; adjusted OR = 0.574, 95% CI = 0.377-0.873, p = 0.009) significantly decreased breast cancer risk after Bonferroni correction for multiple testing. In subgroup analyses, the GA and GA + AA genotypes of LEPR rs1137101 associated with decreased breast cancer risk in the subgroup of BMI ≤ 24 kg/m2 or WHR ≥ 0.85 after Bonferroni correction. Furthermore, we found that the expressions of rs4655555-associated gene LEPR and leptin receptor overlapping transcript (LEPROT) were upregulated in breast cancer tumor tissues compared with adjacent normal tissues, and a higher expression of LEPR in tumor tissues was correlated with poor prognosis of breast cancer patients using The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) data. CONCLUSION: Our study demonstrated that the polymorphisms rs1137101 and rs4655555 located in the LEPR gene decreased breast cancer risk in Chinese females, which might be a research-worthy bio-diagnostic marker and applied for early prediction and risk assessment of breast cancer.

XRCC5/6 polymorphisms and their interactions with smoking, alcohol consumption, and sleep satisfaction in breast cancer risk: A Chinese multi-center study.

BACKGROUND: X-ray repair cross-complementary 5 (XRCC5) and 6 (XRCC6) are critical for DNA repair. Few studies have assessed their association with breast cancer risk, and related gene-environment interactions remain poorly understood. This study aimed to determine the influence of XRCC5/6 polymorphisms on breast cancer risk, and their interactions with cigarette smoking, alcohol consumption, and sleep satisfaction. METHODS: The study included 1039 patients with breast cancer and 1040 controls. Four single-nucleotide polymorphisms of XRCC5 and two of XRCC6 were genotyped. Information about smoking, alcohol consumption, and sleep satisfaction was collected through questionnaires. Odds ratios (OR) and related 95% confidence intervals (95% CI) were assessed using unconditional logistic regression models. Gene-environment interactions were analyzed using logistic regression with multiplicative interaction models. RESULTS: XRCC5 rs16855458 was associated with increased breast cancer risk in the co-dominant (ptrend  = 0.003) and dominant (CA + AA vs. CC, OR = 1.29, 95% CI = 1.07-1.56, p = 0.008) genetic models after Bonferroni correction. The CG + GG genotype of XRCC6 rs2267437 was associated with an increased risk of estrogen receptor-negative/progesterone receptor-negative (ER-/PR-) breast cancer (CG + GG vs. CC: OR = 1.54, 95% CI = 1.12-2.13, p = 0.008) after Bonferroni correction. Moreover, an antagonistic interaction between XRCC5 rs16855458 and alcohol consumption (pinteraction  = 0.017), and a synergistic interaction between XRCC6 rs2267437 and sleep satisfaction were associated with breast cancer risk (pinteraction  = 0.0497). However, these interactions became insignificant after Bonferroni correction. CONCLUSION: XRCC5 rs16855458 was associated with breast cancer risk, and XRCC6 rs2267437 was associated with the risk of ER-/PR- breast cancer. Breast cancer risk associated with XRCC5 and XRCC6 polymorphisms might vary according to alcohol consumption and sleep satisfaction, respectively, and merit further investigation.

Relationship Between Lifestyle Habits and Health-Related Quality of Life of Recently Diagnosed Breast Cancer Patients: A Comparison Between Younger and Older Women in China.

Objective: The aim of this study was to evaluate the relationship between lifestyle habits and health-related quality of life (HRQoL) among different ages who were initially diagnosed with breast cancer (within the first 2 weeks) and to determine the contribution of lifestyle habits factors on HRQoL. Methods: Patients with breast cancer were recruited from 22 hospitals in 11 provinces or municipalities in northern and eastern China. The Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) was used to measure HRQoL. Chi-square test, ANOVA, and multivariable generalized linear models were conducted to identify the differences in HRQoL between two age groups (age <50 years and ≥50 years) and to evaluate the contribution of lifestyle habits factors on HRQoL of patients with breast cancer. Results: About 1,199 eligible patients with breast cancer were used for analysis. Younger women (aged <50 years) appeared to show lower scores than older women (aged ≥50 years) in HRQoL subscales, including emotional well-being (p = 0.003), functional well-being (p = 0.006), breast cancer subscale (p = 0.038), and FACT-B Total scores (p = 0.028). Tea and alcohol consumption and being very satisfied with sleep and current life were the strongest predictors of higher HRQoL in younger group. Meanwhile, no coffee consumption, frequent participation in physical activities, high sleep satisfaction, and current life satisfaction were the key predictors of higher HRQoL in older women with breast cancer. Conclusion: The relationship of the nine lifestyle habit items with HRQoL differed among younger and older women. The associated variable of low HRQoL can help clinicians take intervention early in order to improve the prognosis of patients with breast cancer.

Association of PTPN1 polymorphisms with breast cancer risk: A case-control study in Chinese females.

BACKGROUND: Breast cancer (BC) risk, development, and prognosis were closely related to obesity, diabetes mellitus, and metabolic syndrome. Protein tyrosine phosphatase, non-receptor type 1 (PTPN1) located on chromosome 20q13, could negatively regulate insulin and leptin signaling. In this study, we determined the association of PTPN1 polymorphisms with BC risk. METHODS: We analyzed the distribution of 11 selected PTPN1 single nucleotide polymorphisms in Chinese female patients with BC (n = 953) and healthy controls (n = 963) based on a multicenter case-control study. The association of PTPN1 genotypes and haplotypes frequencies with BC risk were determined by logistic regression analysis. Analyses were further stratified by body mass index (BMI), waist-hip rate (WHR), diabetes mellitus history, and fasting plasma glucose level. The eQTL (expression Quantitative Trait Loci) analysis for PTPN1 was conducted by GTEx database. RESULTS: There were significant differences between BC cases and control groups in menopausal status, number of births, and BMI. Four single nucleotide polymorphisms (SNPs; rs3215684, rs3787345, rs718049, and rs718050) decreased overall BC risk, and other seven SNPs showed no significant association with BC risk. In multivariate analysis, BMI and rs3215684 DT + DD genotype were identified as independent risk factors for BC, and mutated genotypes of rs3215684 were correlated with increased PTPN1 expression. There are no haplotypes showed different frequencies between cases and controls. In the stratified analysis, rs2206656 showed a significant association with decreased BC risk in the subgroup of BMI ≤ 24 kg/m 2 , while rs3215684 and rs718049 showed lower BC risk in the subgroup of WHR > 0.85. Seven SNPs showed lower BC risk in the subgroup with diabetes mellitus history and/or fasting plasma glucose level ≥ 7 mM, while rs754118 decreased BC risk in the subgroup of fasting plasma glucose level < 7 mM. CONCLUSION: Our findings suggest that PTPN1 SNPs associated with BC susceptibility in Chinese females, which also suggested a novel mechanism between obesity, diabetes mellitus, and BC risk.

A case-control study on risk factors of breast cancer in Han Chinese women.

This study aimed to investigate risk factors associated with breast cancer among Han Chinese women in northern and eastern China. A matched case-control study involving 1489 patients with breast cancer and 1489 controls was conducted across 21 hospitals in 11 provinces in China, from April 2012 to April 2013. We developed a structured questionnaire to record information from face-to-face interviews with participants. Student's t-tests, Pearson's chi-square tests, and univariate and multivariate conditional logistic regression analyses were used to identify variables with significant differences between the case and control groups. Ten variables were identified (P<0.05): location, economic status, waist-to-hip ratio, menopause, family history of breast cancer, present life satisfaction, sleep satisfaction, milk products, behavior prevention scores, and awareness of breast cancer. We identified a comprehensive range of factors related to breast cancer, among which several manageable factors may contribute to breast cancer prevention. Further prospective studies concerning psychological interventions, sleep regulation, health guidance, and physical exercise are required. A screening model for high-risk populations should be put on the agenda.

Distinct Effects of Body Mass Index and Waist/Hip Ratio on Risk of Breast Cancer by Joint Estrogen and Progestogen Receptor Status: Results from a Case-Control Study in Northern and Eastern China and Implications for Chemoprevention.

BACKGROUND: Obesity is a consideration in the pharmacologic intervention for estrogen receptor (ER) positive (ER+) breast cancer risk. Body mass index (BMI) and waist/hip ratio (WHR) have demonstrated different effects on breast cancer risk in relation to estrogen receptor (ER) status, but the results have been inconsistent. Furthermore, the situation in Chinese women remains unclear. MATERIALS AND METHODS: We conducted a case-control study including 1,439 breast cancer cases in Northern and Eastern China. Both ER and progesterone receptor (PR) statuses were available for 1,316 cases. Associations between body size-related factors and breast cancer risk defined by receptor status were assessed by multiple polytomous unconditional logistic regression analysis. RESULTS: Body mass index and WHR were positively associated with overall breast cancer risk. Body mass index was positively associated with both ER+/PR positive (PR+) and ER negative (ER-)/PR negative(PR-) subtype risks, although only significantly for ER+/PR+ subtype. Waist-hip ratio was only positively correlated with ER-/PR- subtype risk, although independent of BMI. Body mass index was positively associated with risk of ER+/PR+ and ER-/PR- subtypes in premenopausal women, whereas WHR was inversely correlated with ER+/PR- and positively with ER-/PR- subtype risks. Among postmenopausal women, WHR >0.85 was associated with increased risk of ER-/PR- subtype. CONCLUSION: Both general and central obesity contribute to breast cancer risk, with different effects on specific subtypes. General obesity, indicated by BMI, is more strongly associated with ER+/PR+ subtype, especially among premenopausal women, whereas central obesity, indicated by WHR, is more specific for ER-/PR- subtype, independent of menopausal status. These results suggest that different chemoprevention strategies may be appropriate in selected individuals. IMPLICATIONS FOR PRACTICE: The results of this study suggest that general and central obesity may play different roles in different breast cancer subtypes, supporting the hypothesis that obesity affects breast carcinogenesis via complex molecular interconnections, beyond the impact of estrogens. The results also imply that different chemoprevention strategies may be appropriate for selected individuals, highlighting the need to be particularly aware of women with a high waist/hip ratio but normal body mass index. Given the lack of any proven pharmacologic intervention for estrogen receptor negative breast cancer, stricter weight-control measures may be advised in these individuals.

Tumor suppressor p53 induces miR-15a processing to inhibit neuronal apoptosis inhibitory protein (NAIP) in the apoptotic response DNA damage in breast cancer cell.

This study was aimed to investigate the functional role of miR-15a in breast cancer cells in response to DNA damage and to illustrate the possible potential underlying molecular mechanism(s). Human breast cancer cell lines MCF-7 cells and/or MDA-MB-231 cells were pre-treated with or without bleomycin. Cells were transfected with corresponding vectors. qRT-PCR was used to detect the expression of mRNA or miRNA, and immunoprecipitation and immunoblot analysis were performed to explore the status of protein association. Cell apoptosis was analyzed with flow cytometry. The results showed that neuronal apoptosis inhibitory protein (NAIP) was negatively regulated by p53 in MCF-7 cells, and NAIP expression was still high in bleomycin-treated MCF-7 cells. In addition, we observed that miR-15a expression was regulated by p53, and the effects of miR-15a on DNA damage was also mediated by p53. Furthermore, the results revealed that the cell apoptosis was mediated by miR-15a. Taken together, this study reveals that p53 negatively regulates NAIP expression by targeting miR-15a processing from primary into precursor miRNA in breast cancer.

miR-375 inhibits cancer stem cell phenotype and tamoxifen resistance by degrading HOXB3 in human ER-positive breast cancer.

Cancer stem cell (CSC) formation and epithelial-mesenchymal transition (EMT) are pivotal events in tumor cell invasion and metastasis. They have been shown to occur in resistance to tamoxifen. Moreover, microRNAs (miRNAs) have been associated with CSCs, EMT as well as tamoxifen resistance. Studying molecular mechanism of CSCs, EMT as well as tamoxifen resistance will help us to further understand the pathogenesis and progression of the disease and offer new targets for effective therapies. In the present study, we showed that miR-375 inhibits CSC traits in breast cancer MCF-7 cells. Bioinformatics analysis and experimental validation identified HOXB3 as a direct target of miR-375. Overexpressing miR-375 degraded HOXB3 mRNA in MCF-7 cells. Moreover, overexpression of HOXB3 induced formation of CSC phenotypes, EMT and tamoxifen-resistance as well as enhanced ability of migration and invasion in MCF-7 cells. Most ER-positive breast cancer-related deaths occur, because of resistance to standard therapies and metastasis, restoring miR-375 or targeting HOXB3 might serve as potential therapeutic approaches for the treatment of tamoxifen-resistant breast cancer.

MicroRNA-223 Increases the Sensitivity of Triple-Negative Breast Cancer Stem Cells to TRAIL-Induced Apoptosis by Targeting HAX-1.

Drug resistance remains a significant challenge in the treatment of triple-negative breast cancer (TNBC). Recent studies have demonstrated that this drug resistance is associated with a group of cells known as cancer stem cells (CSCs), which are believed to determine the sensitivity of tumor cells to cancer treatment. MicroRNAs (miRNAs) are small, non-coding RNAs that play significant roles in normal and cancer cells. MiR-223 reportedly acts as a tumor suppressor in a range of cancers. However, the role of miR-223 in TNBC, especially in triple-negative breast cancer stem cells (TNBCSCs), remains unknown. Here, we found that miR-223 expression was down-regulated in CD44+CD24-/low TNBCSCs compared with non-CSCs. Furthermore, we found that miR-223 overexpression resensitized TNBCSCs to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. The HAX-1 gene, which is located in the mitochondria and functions as an anti-apoptotic protein, was found to be directly regulated by miR-223 in MDA-MB-231 cells. We demonstrated that miR-223 overexpression promoted TRAIL-induced apoptosis through the mitochondria/ROS pathway. In conclusion, our results suggest that miR-223 increases the sensitivity of TNBCSCs to TRAIL-induced apoptosis by targeting HAX-1. Our findings have improved our understanding of the role of miR-223 in TNBC and may contribute to TNBC treatment.

A mini-review on factors and countermeasures associated with false-negative sentinel lymph node biopsies in breast cancer.

Sentinel lymph node biopsy (SLNB) is a new surgical technique for local axillary lymph nodes (ALNs) of breast cancer. Large-scale clinical trials have confirmed that undergoing SLNB and ALN dissection (ALND) showed no significant difference for sentinel lymph node (SLN)-negative patients in terms of disease-free survival, overall survival and recurrence-free survival. However, false-negative results are still the main concern of physicians as well as patients who undergo SLNB instead of ALND. The American Society of Breast Surgeons established a task force to suggest acceptable standards for SLNB. In 2000, the task force recommended that the identification rate for SLNB be 85% or higher and the false-negative rate be 5% or lower. This review focuses on clinical factors (tumor volume, multifocal/multi-center cancers, neoadjuvant chemotherapy and skip metastasis), tracer techniques and pathological factors affecting SLNB and explores methods for reducing the false-negative rate.

Prospective study found that peripheral lymph node sampling reduced the false-negative rate of sentinel lymph node biopsy for breast cancer.

BACKGROUND: Although sentinel lymph node biopsy (SLNB) can accurately predict the status of axillary lymph node (ALN) metastasis, the high false-negative rate (FNR) of SLNB is still the main obstacle for the treatment of patients who receive SLNB instead of ALN dissection (ALND). The purpose of this study was to evaluate the clinical significance of SLNB combined with peripheral lymph node (PLN) sampling for reducing the FNR for breast cancer and to discuss the effect of "skip metastasis" on the FNR of SLNB. METHODS: At Shandong Cancer Hospital Affiliated to Shandong University between March 1, 2012 and June 30, 2015, the sentinel lymph nodes (SLNs) of 596 patients with breast cancer were examined using radiocolloids with blue dye tracer. First, the SLNs were removed; then, the area surrounding the original SLNs was selected, and the visible lymph nodes in a field of 3-5 cm in diameter around the center (i.e., PLNs) were removed, avoiding damage to the structure of the breast. Finally, ALND was performed. The SLNs, PLNs, and remaining ALNs underwent pathologic examination, and the relationship between them was analyzed. RESULTS: The identification rate of SLNs in the 596 patients was 95.1% (567/596); the metastasis rate of ALNs was 33.7% (191/567); the FNR of pure SLNB was 9.9% (19/191); and after the SLNs and PLNs were eliminated, the FNR was 4.2% (8/191), which was significantly decreased compared with the FNR before removal of PLNs (P = 0.028). According to the detected number (N) of SLNs, the patients were divided into four groups of N = 1, 2, 3, and ≥4; the FNR in these groups was 19.6, 9.8, 7.3, and 2.3%, respectively. For the patients with ≤2 or ≤3 detected SLNs, the FNR after removal of PLNs was significantly decreased compared with that before removal of PLNs (N ≤ 2: 14.0% vs. 4.7%, P = 0.019; N ≤ 3: 12.2% vs. 4.7%, P = 0.021), whereas for patients with ≥4 detected SLNs, the decrease in FNR was not statistically significant (P = 1.000). In the entire cohorts, the "skip metastasis" rate was 2.5% (15/596); the FNR caused by "skip metastasis" was 2.1% (4/191). CONCLUSIONS: The FNR of SLNB was associated with the number of SLNs. For patients with ≤3 detected SLNs, PLN sampling can reduce the FNR of SLNB to an acceptable level of less than 5%. Because of the existence of the "skip metastasis" and distinct metastasis patterns, the FNR of SLNB cannot be completely eliminated.

The Feasibility and Oncological Safety of Axillary Reverse Mapping in Patients with Breast Cancer: A Systematic Review and Meta-Analysis of Prospective Studies.

OBJECTIVE: The axillary reverse mapping (ARM) technique has recently been developed to prevent lymphedema by preserving the arm lymphatic drainage during sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) procedures. The objective of this systematic review and meta-analysis was to evaluate the feasibility and oncological safety of ARM. METHODS: We searched Medline, Embase, Web of science, Scopus, and the Cochrane Library for relevant prospective studies. The identification rate of ARM nodes, the crossover rate of SLN-ARM nodes, the proportion of metastatic ARM nodes, and the incidence of complications were pooled into meta-analyses by the random-effects model. RESULTS: A total of 24 prospective studies were included into meta-analyses, of which 11 studies reported ARM during SLNB, and 18 studies reported ARM during SLNB. The overall identification rate of ARM nodes was 38.2% (95% CI 32.9%-43.8%) during SLNB and 82.8% (78.0%-86.6%) during ALND, respectively. The crossover rate of SLN-ARM nodes was 19.6% (95% CI 14.4%-26.1%). The metastatic rate of ARM nodes was 16.9% (95% CI 14.2%-20.1%). The pooled incidence of lymphedema was 4.1% (95% CI 2.9-5.9%) for patients undergoing ARM procedure. CONCLUSIONS: The ARM procedure was feasible during ALND. Nevertheless, it was restricted by low identification rate of ARM nodes during SLNB. ARM was beneficial for preventing lymphedema. However, this technique should be performed with caution given the possibility of crossover SLN-ARM nodes and metastatic ARM nodes. ARM appeared to be unsuitable for patients with clinically positive breast cancer due to oncological safety concern.

MicroRNA-145 inhibits growth and migration of breast cancer cells through targeting oncoprotein ROCK1.

MicroRNAs are small non-coding RNAs that may also function as oncogenes and tumor suppressor genes, as the abnormal expression of microRNAs is associated with various human tumors. MicroRNA-145 (miR-145) inhibits growth and increases chemo- or radiosensitivity in various cancers. However, the role of miR-145 in breast cancer progression remains unknown. In this study, miR-145 expression level was measured via quantitative real-time PCR in 88 pairs of human breast cancer tissues and adjacent normal tissues and in a panel of human breast cancer cell lines. Cell proliferation and cell migration were assessed by cell viability assay and transwell assay. Western blot was used to verify Rho-associated protein kinase 1 (ROCK1) as a novel target gene of miR-145. Our results showed that miR-145 was frequently downregulated in breast cancer tissues and cell lines. Overexpression of miR-145 in MCF-7 and BT-549 cell lines significantly inhibited cell proliferation, migration, and invasion in vitro. ROCK1 was identified as a target of miR-145, and ectopic expression of miR-145 downregulated ROCK1. Our findings indicate that miR-145 acts as a tumor suppressor and its downregulation in tumor tissues may contribute to the progression of breast cancer through a mechanism involving ROCK1, suggesting miR-145 as a potential new diagnostic and therapeutic target for the treatment of breast cancer.

[Expression of osteopontin splice variant and its clinical significance in gastric cancer].

OBJECTIVE: To investigate the expression of osteopontin (OPN) splice variant mRNA, including the three isoforms OPN-A, OPN-B, and OPN-C, to explore its correlation with clinicopathologic features in gastric cancer, and to elucidate their role in tumor invasion and distant metastasis of gastric cancer. METHODS: The expression of OPN-A, OPN-B and OPN-C mRNA were detected by real-time reverse transcriptase-polymerase chain reaction in 66 gastric cancer tissues. The relationship between the expression of OPN-A, OPN-B and OPN-C mRNA and clinicopathologic features of gastric cancer was analyzed. RESULTS: The expression of OPN-C mRNA in the gastric cancer tissue was 3.21-fold higher than that in peritumoral mucosal tissue, showing a significant difference between them (P < 0.001). OPN-C mRNA expression was correlated with the depth of tumor invasion, tumor diameter, lymph node meatastasis, distant meatastasis and had no correlation with differentiation grades. The low expression of OPN-C mRNA was correlated with long survival benefit (P = 0.03). The expression of OPN-A and OPN-B mRNA had no significant relationship with clinicopathologic features of gastric cancer. CONCLUSIONS: One of the isoform of osteopontin (OPN) OPN-C mRNA is overexpressed in gastric cancer. The overexpression of OPN-C mRNA may reflect the progression and is associated with the prognosis of gastric cancer. OPN-C mRNA may have value as a prognostic biomarker in gastric cancer. However, the expression of OPN-A and OPN-B are not correlated with the progression and metastasis of gastric cancer.

Associations of miR-146a and miR-146b expression and breast cancer in very young women.

BACKGROUND: MicroRNAs (miRNA) expression profiles might be useful novel biomarkers for tumor diagnostic and histological characterization. OBJECTIVE: Associations of miR-146 expression and breast cancer in very young women needed to be elucidated. METHODS: We investigated expressions of miR-146a, miR-146b and IL-6 in tissues between 120 young women with primary breast cancer and 130 patients with breast fibroadenoma by RT-PCR. The associations between the expression of miR-146, IL-6 and clinical parameters of breast cancer were analyzed. RESULTS: Levels of miR-146a and miR-146b in breast cancer tissues were lower while level of IL-6 was higher compared to the fibroadenoma tissues and pericancerous breast tissues (P< 0.05). Positive associations were found between levels of miR-146a/b and IL-6 in breast cancer tissues and ER-PgR-, HER2/neu-, Ki-67 index ≥ 20%, tumor size > 2 cm, positive distant metastasis and lymph node metastasis, advanced clinical TNM stages (III-IV) and basal-like phenotype (P< 0.05). CONCLUSION: Down-regulations of miR-146a and miR-146b expression in breast tissues were related to development and deterioration of breast cancer. miR-146a and miR-146b might act as potential biomarkers for young women with breast cancer.

Evaluation of hormone receptor, human epidermal growth factor receptor-2 and Ki-67 with core needle biopsy and neoadjuvant chemotherapy effects in breast cancer patients.

BACKGROUND: We investigated the reliability of core needle biopsy (CNB) in evaluating the status of hormone receptor (HR), human epidermal growth factor receptor (HER)-2, and Ki-67 status, and the effect of neoadjuvant chemotherapy (NAC) on the expression of these immunohistochemical markers. METHODS: Among 177 patients with breast adenocarcinoma, 95 patients underwent NAC and the remaining 82 patients made up the control group. Immunohistochemistry (IHC) was used to evaluate the expression status of estrogen receptor (ER), progesterone receptor (PR), HER-2, and Ki-67 in the specimens obtained by surgical excision or CNB. RESULTS: In the control group, the expression of ER, PR, HER-2, and Ki-67 was highly consistent between samples from surgical excision or CNB (all r > 0.8, P < 0.05). In the NAC group, the proportions of samples with changes in ER, PR, HER-2, and Ki-67 expression were 12.7%, 24.1%, 5.1%, and 38.0%, respectively; the figures in the control group were 2.4%, 4.9%, 2.4%, and 7.3%, respectively, which significantly differed in ER, PR, and Ki-67 (P < 0.05), but not HER-2 (P > 0.05). In the NAC group, pre- and post-treatment ER(+) rates did not significantly differ (P > 0.05), although PR(+) and high Ki-67 expression rates did significantly differ (P < 0.05). CONCLUSION: Neither CNB nor surgical excision samples gave highly consistent results in HR, HER-2, and Ki-67 status. NAC can alter HR and Ki-67 status in breast adenocarcinoma patients. NAC decreased PR(+) rate and Ki-67 expression. The mean ER(+) rate exhibited a decreasing, but insignificant trend after NAC treatment. NAC had no significant effect on HER-2 expression.

Metastases of basal-like breast invasive ductal carcinoma to the endometrium: A case report and review of the literature.

We present a case of single endometrial metastasis from breast invasive ductal cancer. This case was unique because the immunohistochemical staining was negative for human epidermal growth factor receptor 2/neu and estrogen and progesterone receptors, and positive for cytokeratin 5/6 and epidermal growth factor receptor in the primary and metastatic tumor cells. No gross evidence of tumor was observed in other sites. We identified 12 cases of metastases to the endometrium from breast carcinoma from series and case reports in the literature between 1985 and 2014. This review indicated that hormone receptor-positive invasive lobular breast cancer cells are more likely to metastasize to the endometrium than other cell types in patients over 50 years of age.

Novel nanosystem to enhance the antitumor activity of lapatinib in breast cancer treatment: Therapeutic efficacy evaluation.

The present study was performed to investigate the therapeutic performance of polymer-lipid hybrid nanoparticles towards the delivery of lapatinib (LPT) in breast cancers. We have successfully developed the lapatinib-loaded polymer-lipid hybrid nanosystem and showed its therapeutic potential in in vitro and in vivo models of breast cancer. The nanoformulations consisted of a polymeric core (poly[lactide-co-glycolide]-D-a-tocopheryl polyethylene glycol 1000 succinate [PLGA-TPGS]), which was then enveloped by a PEGylated lipid layer (DSPE-PEG) (PLPT) to maintain the structural integrity. The PLPT formulation controlled the drug release in pH 7.4 conditions and accelerated the release at pH 5.5 conditions. The PLPT showed a remarkable cellular internalization and efficiently killed the MCF-7 cancer cells in a time- and concentration-dependent manner. Moreover, LPT-loaded nanoparticles effectively induced apoptosis of cancer cells than compared to free LPT. Pharmacokinetic data suggested that nanoparticles could significantly enhance the blood circulation time of LPT by reducing the uptake by a reticuloendothelial system (RES). The prolonged blood circulation of PLPT could allow the preferential accumulation of drug in the tumor tissues. Importantly, PLPT significantly reduced the tumor burden of cancerous mice and effectively controlled the tumor cell proliferation. TUNEL assay further showed a greater apoptosis of tumor tissues in the PLPT treated mice group. Our results suggest that the use of a hybrid system may allow a decrease in the dosage regimen without the loss of therapeutic effect. Overall, lapatinib-loaded hybrid nanoparticles hold great potential for achieving an optimal therapeutic effect in breast cancer treatment. The present anticancer drug delivery system could be potentially applied for the treatment of other cancers.

Circulating High-Molecular-Weight (HMW) Adiponectin Level Is Related with Breast Cancer Risk Better than Total Adiponectin: A Case-Control Study.

The level of total adiponectin, a mixture of different adiponectin forms, has been reported associated with breast cancer risk with inconsistent results. Whether the different forms play different roles in breast cancer risk prediction is unclear. To examine this, we measured total and high molecular weight (HMW) adiponectin in a case-control study (1167 sets). Higher circulating HMW adiponectin was negatively associated with breast cancer risk after adjusting for menopausal status and family history of breast cancer (P=0.024). We analyzed the relationship between adiponectin and breast cancer risk in 6 subgroups. Higher circulating HMW adiponectin was also negatively associated with breast cancer risk (P=0.020, 0.014, 0.035) in the subgroups of postmenopausal women, negative family history of breast cancer, BMI>=24.0. Total adiponectin was positively associated with breast cancer (P=0.028) in the subgroup of BMI<=24.0. Higher HMW/total adiponectin ratio was negatively associated with breast cancer (P=0.019) in the subgroup of postmenopausal women. Interestingly, in the subgroup of women with family history of breast cancer, higher circulating total and HMW adiponectin were positively associated with breast cancer risk (P=0.034, 0.0116). This study showed different forms of circulating adiponectin levels might play different roles in breast cancer risk. A higher circulating HMW adiponectin is associated with a decreased breast cancer risk, especially in postmenopausal, without family history of breast cancer or BMI>=24.0 subgroups, whereas higher circulating HMW adiponectin levels is a risk factor in women with a family history of breast cancer. Further investigation of different forms of adiponectin on breast cancer risk is needed.

Metastasis of breast cancer to renal cancer: report of a rare case.

Tumor-to-tumor metastasis (TTM) is a rare phenomenon. We present a case of an invasive ductal carcinoma (IDC) of the breast metastasizing to a clear cell renal cell carcinoma (RCC). Breast cancer (BC) metastasis to the RCC is rarely reported, especially in resected kidney tumor. In several cases reported, IDC was the exclusively histologic type of BC metastasized to RCC. It seems that the different molecular type of IDC doesn't affect the metastatic tendencies to RCC. TTM was an indicator of diffuse disease. For any patient with a history of breast cancer, especially with multi-organs metastasis, resection of kidney tumor should be carefully considered.