Comparison of comfort and complications of Implantable Venous Access Port (IVAP) with ultrasound guided Internal Jugular Vein (IJV) and Axillary Vein/Subclavian Vein (AxV/SCV) puncture in breast cancer patients: a randomized controlled study.

BACKGROUND: Axillary vein/subclavian vein (AxV/SCV) and Internal jugular vein (IJV) are commonly used for implantable venous access port (IVAP) implantation in breast cancer patients for chemotherapy. Previous research focused on comparison of complications while patient comfort was ignored. This study aims to compare patient comfort, surgery duration and complications of IVAP implantation between IJV and AxV/SCV approaches. METHODS: Two hundred forty-eight breast cancer patients were enrolled in this randomized controlled study from August 2020 to June 2021. Patients scheduled to undergo IVAP implantation were randomly and equally assigned to receive central venous catheters with either AxV /SCV or IJV approaches. All patients received comfort assessment using a comfort scale table at day 1, day 2 and day 7 after implantation. Patient comfort, procedure time of operation as well as early complications were compared. RESULTS: Patient comfort was significantly better in the AxV/SCV group than that of IJV group in day 1 (P < 0.001), day 2 (P < 0.001) and day 7(P = 0.023). Procedure duration in AxV/SCV group was slightly but significantly shorter than IJV group (27.14 ± 3.29 mins vs 28.92 ± 2.54 mins, P < 0.001). More early complications occurred in AxV/SCV group than IJV group (11/124 vs 2/124, P = 0.019). No difference of complications of artery puncture, pneumothorax or subcutaneous hematoma between these two groups but significantly more catheter misplacement in AxV/SCV group than IJV group (6/124 vs 0/124, P = 0.029). Absolutely total risk of complications was rather low in both groups (8.87% in AxV/SCV group and 1.61% in IJV group). CONCLUSIONS: Our study indicates that patients with AxV/SCV puncture have higher comfort levels than IJV puncture. AxV/SCV puncture has shorter procedure duration but higher risk of early complications, especially catheter misplacement. Both these two approaches have rather low risk of complications. Consequently, our study provides an alternative choice for breast cancer patients to reach better comfort.

Associations of Epstein-Barr Virus DNA in PBMCs and the Subtypes with Breast Cancer Risk.

Objective: Epstein-Barr virus (EBV) has been found to be implicated in the development of breast cancer. The purpose of the present study was to identify the associations of EBV DNA and the subtypes in peripheral blood mononuclear cells (PBMCs) with the risk of breast cancer. Material and Methods: A case-control study with 671 breast cancer cases and 859 age-matched controls was conducted in Guangzhou, China. Face-to-face interviews were performed and blood samples were collected immediately after admission to the hospital for patients or after the interview for controls. EBV DNA in PBMCs and the subtypes were detected using Polymerase Chain Reaction (PCR) and restricted fragment length polymorphisms (RFLP). IgA antibodies against EBV VCA-p18 and EBNA-1 were examined using commercial enzyme-linked immunosorbent assay kits. Unconditional logistic regression analysis was applied to evaluate the associations of the DNA positivity and subtypes of EBV with the risk of breast cancer. Results: Among the 1530 subjects, 164 cases (24.4 %) and 206 controls (24.0 %) were positive for EBV DNA in PBMCs and no significant difference occurred between cases and controls. The presence of EBV DNA was related to the positivity of EBV IgA antibodies. Of the DNA positive samples, 71 cases and 109 controls for F/f subtype and 58 cases and 112 controls for C/D subtype were successfully obtained. The D subtype was associated with an increased breast cancer risk compared with the C subtype [OR (95% CI): 2.86 (1.25~6.53)]. We did not find an association of the F/f polymorphism with breast cancer risk. Conclusions: The present study suggested that the presence of EBV DNA in PBMCs may not be an appropriate biomarker for breast cancer risk. The subtype D of EBV was likely to be related to breast tumorigenesis.

Polymorphisms in homologous recombination repair genes and the risk and survival of breast cancer.

BACKGROUND: Immunoglobulin (Ig)A antibody of Epstein-Barr virus (EBV) was found to associate with breast cancer (BC), whereas IgA positivity was related to a series of genetic markers in the genes of homologous recombination repair system (HRRs). We assessed the associations of the polymorphisms in HRR genes with the risk and survival of BC. METHODS: A case-control study was conducted with 1551 bc cases and 1605 age-matched healthy controls between October 2008 and March 2012 in the Guangzhou Breast Cancer Study (GZBCS), China, and the case population were followed up until 31 January 2016. Five single nucleotide polymorphisms of candidate genes in HRR system were genotyped. Odds ratios (ORs) and hazards ratios (HRs) were calculated using multivariate logistic regression and Cox proportional hazards regression to estimate the risk and prognostic effect, respectively. RESULTS: RFC1 rs6829064 (AA) was associated with an increased BC risk [OR = 1.35; 95% confidence interval (CI) = 1.06-1.73] compared to the wild genotype (GG). NRM rs1075496 (GT/TT versus GG) was associated with a worse progression-free survival (PFS) and the HR was 1.34 (95% CI = 1.01-1.78), particularly among advanced patients. LIG3 rs1052536 (CT/TT versus CC) was associated with a better PFS and the HR was 0.70 (95% CI = 0.53-0.93). However, RAD54L rs1710286 and RPA1 rs11078676 were not observed to be associated with either the risk or survival of BC. CONCLUSIONS: The findings of the present study suggest that the polymorphisms in HRR genes were associated with BC risk (RFC1 rs6829064) and prognosis (NRM rs1075496 and LIG3 rs1052536), whereas RAD54L rs1710286 and RPA1 rs11078676 had null associations with BC.

Modification effects of genetic polymorphisms in FTO, IL-6, and HSPD1 on the associations of diabetes with breast cancer risk and survival.

The contribution of diabetes to breast cancer remains uncertain among Chinese females, which may result from different genetic factors. We evaluated the associations of diabetes, combined with the polymorphisms in the genes of fat mass and obesity-associated gene (FTO), interleukin 6 (IL-6), and heat shock protein 60 (HSPD1), with breast cancer risk and survival in a Chinese Han population. The information on the history of diabetes was collected from 1551 incident breast cancer cases and 1605 age-frequency matched controls in Guangzhou, China. In total, 1168 cases were followed up. Diabetes was associated with both an increased risk of breast cancer [OR (95%CI): 1.67 (1.11, 2.52)] and a poor overall survival and progression free survival for breast cancer patients [HRs (95%CIs): 2.66 (1.10, 6.44) and 2.46 (1.29, 4.70), respectively]. IL-6 rs1800796 and HSPD1 rs2605039 had interactions with diabetes on breast cancer risk. Among women with CC genotype of IL-6 rs1800796 or GG genotype of HSPD1 rs2605039, diabetic individuals had a remarkably increased risk of breast cancer compared to non-diabetic women with ORs and 95%CIs of 2.53 (1.45, 4.41) and 6.40 (2.29, 17.87), respectively. GT/TT genotypes of HSPD1 rs2605039 was also associated with a better progression free survival for breast cancer patients [HR (95%CI): 0.70 (0.49, 0.99)]. Our results suggest that the contribution of diabetes to breast cancer risk might be modified by IL-6 rs1800796 and HSPD1 rs2605039. Diabetes and HSPD1 rs2605039 might also influence breast cancer prognosis.

Allelic expression imbalance polymorphisms in susceptibility chromosome regions and the risk and survival of breast cancer.

Allelic expression imbalance (AEI) has been applied to indicate potential function of genetic variants. Combining earlier results from global differential allele-specific expression analysis and genome wide association studies (GWASs), we select the single nuclear polymorphisms (SNPs) exhibiting AEI phenomenon located in breast cancer susceptibility chromosome regions, and evaluate their associations with breast cancer risk and survival. We examined the genotypes of 10 AEI SNPs in 1551 incident breast cancer cases and 1605 age-frequency matched controls from Guangzhou, China. In total, 1168 cases were followed up. MUC16 rs2591592 (AT/AA vs. TT) was associated with an increased risk of premenopausal breast cancer (OR [95%CI]: 1.30 [1.07, 1.57]); SLAMF1 rs1061217 (CT/TT vs. CC) decreased the risk of breast cancer among overweight women (OR [95%CI]: 0.74 [0.57, 0.96]) but increased the risk among normal-weight women (OR [95%CI]: 1.15 [1.01, 1.39]); ZNF331 rs8109631 (AG/AA vs. GG) and CHRAC1 rs10216653 (GC/GG vs. CC) were associated with progression free survival among breast cancer patients with negative ER/PR status and higher clinical stage (HRs [95%CIs]: 2.39 [1.14, 5.00], 1.85 [1.03, 3.32], and 0.49 [0.30, 0.80], respectively). ZNF331 rs8109631 and CHRAC1 rs10216653 were further found to represent several functional SNPs through bioinformatic analysis. In conclusion, our findings demonstrated suggestive associations of AEI polymorphisms with breast cancer risk (MUC16 rs2591592 and SLAMF1 rs1061217) and prognosis (ZNF331 rs8109631 and CHRAC1 rs10216653). © 2016 Wiley Periodicals, Inc.

Genetic variants in EBV reactivation-related genes and the risk and survival of breast cancer.

Tumor susceptibility gene 101 (TSG101) and activating transcription factor 2 (ATF2) have been suggested to involve in the reactivation of EBV which has implications in the development and progression of breast cancer. Therefore, the polymorphisms of TSG101 and ATF2 may associate with breast cancer risk and prognosis. A case-control study with 1551 breast cancer cases and 1605 age-matched controls were conducted in Guangzhou, China. We have also successfully followed up 1168 cases until December 31, 2014. The variant allele of TSG101 rs2292179 was associated with a non-significant reduced risk of breast cancer, particularly among women with BMI < 24 (kg/m(2)) (P for interaction <0.05). For ATF2 rs3845744, the variant allele was also associated with a significantly reduced breast cancer risk [odds ratio (OR) (95 % confidence interval (CI)) 0.86 (0.74∼1.00)], and the association occurred among only postmenopausal women [OR (95 % CI) 0.69 (0.54∼0.88)] (P for interaction <0.05). Breast cancer risk was further reduced with the increasing numbers of the variant G alleles of the two polymorphisms (P for trend <0.05). We did not find an overall association of the two loci with breast cancer prognosis, while the hazard ratios of the two loci (AG/GG vs. AA) were significantly higher among postmenopausal women than premenopausal women (P = 0.046, 0.016 for TSG101 rs2292179 and ATF2 rs3845744, respectively). In summary, the variant alleles of TSG101 rs2292179 and ATF2 rs3845744 were associated with a reduced risk of breast cancer, particularly for subjects with BMI <24 (kg/m(2)) and postmenopausal women, respectively. The two SNPs and menopausal status may have a significant interaction on breast cancer progression.

Night-shift work, sleep duration, daytime napping, and breast cancer risk.

OBJECTIVES: Sleep habits vary among different countries, and sleep problems may cause various health problems. The aim of our study was to evaluate the separate and combined associations of night-shift work, sleep duration, and daytime napping with breast cancer risk among the Chinese population. METHODS: This study conducted face-to-face interviews with 712 women diagnosed with incident invasive breast cancer before treatment and 742 age-matched controls. Information on sleep habits, demographic characteristics, and suspected or established risk factors of breast cancer were collected from the two groups. Multivariate logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Night-shift work was associated with an increased risk of breast cancer [OR (95% CI): 1.34 (1.05-1.72)]. Compared to women with a sleep duration of 6.1-8.9 h/day, women who had shorter [(≤6.0 h/day) (OR (95% CI): 1.53 (1.10-2.12)] and longer (≥9.0 h/day) sleep duration [(OR (95% CI): 1.59 (1.17-2.17)] had an increased risk of breast cancer. In addition, daytime napping was associated with a reduced risk of breast cancer among night-shift workers [OR (95% CI): 0.57 (0.36-0.90)], but no association was found among women who never had night-shift work [OR (95% CI): 1.01 (0.75-1.35)] (P for interaction = 0.054). Night-shift work and longer sleep duration also synergistically increased breast cancer risk [OR (95% CI): 3.69 (1.94-7.02)] (P for interaction = 0.009). CONCLUSIONS: Sleep problems, including night-shift work, and shorter and longer sleep duration, are associated with an increased breast cancer risk. In particular, the combined effects of night-shift work with no daytime napping or longer sleep duration are greater than the independent effects.

Modified effect of urinary cadmium on breast cancer risk by selenium.

BACKGROUND: Previous experimental studies have shown an antagonistic interaction between cadmium and selenium. We explored the interaction between cadmium and selenium on human breast cancer risk. METHODS: A case-control study, enrolled 240 incident invasive breast cancer patients and 246 age-matched controls from 2 hospitals, was conducted in Guangzhou, China. Inductively coupled plasma mass spectrometry was used to examine urinary concentrations of cadmium and selenium. Association and interaction of the metal levels with breast cancer risk were tested using generalized additive and logistic regression models. RESULTS: As continuous variables, urinary cadmium [OR (95% CI): 1.16 (1.01-1.34)] but not selenium was significantly linearly associated with breast cancer risk. As tertiles, urinary cadmium did not significantly increase breast cancer risk; whereas women with the second tertile of selenium concentration had a significantly decreased risk of breast cancer as compared with those in the lowest tertile [OR (95% CI): 0.50 (0.30-0.81)]. Among the women with the lowest tertile of selenium, the highest tertile of cadmium significantly increased the risk of breast cancer [OR (95% CI): 2.83 (1.18-6.86)] compared to the lowest tertile of cadmium. A multiplicative interaction was found between tertiles of cadmium and selenium on breast cancer risk (P=0.018), particularly among postmenopausal women. CONCLUSIONS: These results suggested that the association of urinary cadmium with breast cancer risk was modified by urinary selenium.

Association of urinary cesium with breast cancer risk.

BACKGROUND: The aim of this study is to examine the association of urinary cesium with breast cancer risk. MATERIALS AND METHODS: We collected survey data and urine specimens from 240 women with incident invasive breast cancer before their treatment and 246 age-matched female controls between October 2009 and July 2010. Urinary concentrations of cesium were determined by inductively coupled plasma mass spectrometry. Interviews were conducted by face-to-face to obtain information on potential breast cancer risk factors. Logistic regression analysis was used to estimate the associations. RESULTS: Creatinine-adjusted levels [median (25th, 75th) ug/g] of cesium in cases and controls were 17.6 (13.1, 24.0) and 19.3 (15.3, 25.7), respectively. After adjustment for potential risk factors, women in the second and highest tertile of cesium showed a decreased risk of breast cancer in a dose-dependent manner as compared with those in the lowest tertile [ORs and 95% CIs: 0.75 (0.46- 1.22) and 0.50 (0.30-0.82), respectively]. This decrease was more evident in women with ER positive or localized clinical stage in an exploratory stratification analysis. CONCLUSIONS: These findings suggest that cesium may have anticancer efficacy and urinary cesium has potential as a biomarker for breast cancer risk assessment.

Association of physical activity and polymorphisms in FGFR2 and DNA methylation related genes with breast cancer risk.

PURPOSE: Physical activity, a protective factor for breast cancer, increases the level of DNA methylation. Fibroblast growth factor receptor 2 (FGFR2), a confirmed breast cancer susceptibility gene, is predisposed to be methylated. Therefore, DNA methylation related genes, such as methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and DNA methyltransferase (DNMT), together with physical activity and FGFR2, may interact with each other to effect breast cancer risk. METHODS: A total of 839 incident breast cancer cases and 863 age-matched controls from Guangzhou, China were included in this study. We used questionnaires to assess physical activity in metabolic equivalent (MET)-h/week/year and a matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry platform to ascertain genotypes. Odds ratios (OR) and 95% confidence intervals (CI) were calculated from logistic regression models. RESULTS: Exercise activity and FGFR2 rs2981582 were confirmed to be associated with breast cancer risk, and were found to significantly interact (P for multiplicative and additive interactions = 0.045 and 0.021, respectively). Women who had CT/TT genotypes of FGFR2 rs2981582 and experienced exercise activity <3 MET-h/week/year had significantly increased risk (OR = 3.15, 95% CI = 2.28-4.35) compared to women with CC genotype and ≥ 3 MET-h/week/year. There was also a significant interaction between FGFR2 rs2981582 and MTHFR rs1801133 on breast cancer risk (P for multiplicative and additive interactions = 0.039 and 0.023, respectively). CONCLUSION: We found both a gene-environment (FGFR2-exercise activity) and a gene-gene (FGFR2-MTHFR) interaction on breast cancer risk. Our results suggest that environmental factors, such as physical activity, may be able to counteract genetic susceptibility to breast cancer.

Association of Epstein-Barr virus and passive smoking with the risk of breast cancer among Chinese women.

Reactivation of Epstein-Barr virus (EBV), as indexed by the higher immunoglobulin A (IgA) antibody titers, was reported to be associated with an increased risk of breast cancer. Passive smoking plays a role in host immune responses and may modify the association of EBV with breast cancer. We carried out a case-control study using data from 349 incident breast cancer cases and 500 age-matched controls in the Guangzhou Breast Cancer Study to investigate the interactions of EBV antibodies and passive smoking on breast cancer risk. A higher risk of breast cancer was observed in passive smokers who were seropositive for EBV viral capsid antigen IgA or nuclear antigen-1 IgA in serum compared with those with the seronegativity and no passive smoking [odds ratio 3.13 (95% confidence interval, 1.76-5.56)]. There was a significant linear trend for the risk of breast cancer from IgA seropositivity with passive smoking, only IgA seropositivity, only passive smoking, to seronegativity without passive smoking (P<0.001), but the interaction in either multiplicative or additive models was not significant. No significant association was found between passive smoking and EBV IgA seropositivity. The present study confirmed the associations of EBV IgA antibodies and passive smoking with the risk of breast cancer and suggested that there was no synergic action between passive smoking and EBV IgA seropositivity on the risk of breast cancer.

HER2-enriched tumors have the highest risk of local recurrence in Chinese patients treated with breast conservation therapy.

PURPOSE: The purpose of this study was to investigate the recurrence pattern and characteristics of patients based on the 2013 St. Gallen surrogate molecular subtypes after breast-conserving surgery (BCS) in Chinese women. METHODS: This retrospective analysis included 709 consecutive breast cancer patients undergoing BCS from 1999-2010 at our institution. Five different surrogate subtypes were created using combined expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2. Locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS) rates were calculated. RESULTS: The 5-year LRRFS, DMFS, and DFS rates were 90.5%, 88.2%, and 81.5%, respectively. Multivariate analysis revealed that young age, node-positive disease, and HER2 enrichment were independent prognostic factors in LRRFS patients. There was also an independent prognostic role of lymph node-positive disease in DMFS and DFS patients. Patients with luminal A tumors had the most favorable prognosis, with LRRFS, DMFS, and DFS rates of 93.2%, 91.5%, and 87.5% at 5 years, respectively. Conversely, HER-2-enriched tumors exhibited the highest rate of recurrence (27.5%) and locoregional recurrence (11.4%). CONCLUSION: Surrogate subtypes present with significant differences in RFS, DMFS, and LRRFS. Luminal A tumors have the best prognosis, whereas HER2-enriched tumors have the poorest.

GeneSearch™ BLN Assay could replace frozen section and touch imprint cytology for intra-operative assessment of breast sentinel lymph nodes.

BACKGROUND: Breast cancer sentinel lymph node (SLN) biopsy has become a common procedure. The GeneSearch™ Breast Lymph Node Assay is a real-time reverse-transcriptase polymerase chain reaction assay for detecting nodal metastases larger than 0.2 mm. The trial is a prospective multi-center clinical trial conducted to validate the assay in China. METHODS: Four hundred and seventy-nine consecutive prospective patients were enrolled from six centers. SLNs were sectioned along the short axis into multiple blocks. Odd blocks were tested by the assay intra-operatively, and even blocks were assessed by post-operative histology. Six 4- to 6-µm-thick sections were taken every 150 µm per block. In addition, intra-operative histological assessments were performed on the even blocks of 214 patients by frozen section (FS) and all blocks of 156 patients by touch imprint cytology (TIC). RESULTS: A total of 1046 SLNs were excised. Overall performance of the assay compared to post-operative histology was accuracy of 91.4 %, sensitivity of 87.5 %, and specificity of 92.9 %. There were no significant differences in assay performance of each center. After a learning curve of about 10 cases, the assay could be performed in a median time of about 35 min. The sensitivity of the assay was similar to the FS (84.9 %, P = 0.885) and was significantly higher than the TIC (70.0 %, P = 0.007) while the specificity of all were comparable. CONCLUSION: The GeneSearch™ Breast Lymph Node Assay is an accurate and rapid intra-operative assay for breast SLNs and it can replace FS and TIC for application.

[Association between urinary cadmium and clinicopathological characteristics of breast cancer].

OBJECTIVE: The aim of this study was to investigate the association between urinary cadmium and clinicopathological characteristics of breast cancer. METHODS: The clinicopathological characteristics of 240 patients with breast cancer were obtained and urine specimens were collected from October 2009 to July 2010. The concentration of urinary cadmium was determined by inductively coupled plasma mass spectrometry (ICP-MS). χ(2) test and Wilcoxon rank sum test were used to analyze whether urinary cadmium is associated with clinicopathological characteristics of breast cancer. RESULTS: The median concentration of urine cadmium of 240 patients was 1.99 µg/g (25th percentile, 1.32 µg/g; 75th percentile, 2.88 µg/g). HER-2 positive rate, regional/distant metastasis rate, and advanced stage rate in patients with the highest tertile of cadmium concentration were significantly higher than those in the patients with second and lowest Cd tertiles (P = 0.042, P = 0.028 and P = 0.017, respectively), and 28.2% vs. 16.5% for HER-2 and 47.2% vs. 32.0% for regional/distant metastasis, respectively. There were still significant associations between urinary cadmium levels and these clinicopathological parameters after being adjusted in age by unconditional logistic regression model, respectively (P < 0.05). CONCLUSIONS: The results of this study suggest that urinary cadmium levels are associated with the HER-2 status, regional/distant metastasis status and stages of breast cancer, respectively. Cadmium may induce highly aggressive breast cancer in humans.

Effects of passive smoking on breast cancer risk in pre/post-menopausal women as modified by polymorphisms of PARP1 and ESR1.

OBJECTIVES: The association between passive smoking and breast cancer risk differs in pre- and post-menopausal women. We aimed to explore the modification effects of PARP1 rs1136410 and ESR1 rs2234693 on the association between passive smoking and breast cancer risk among pre- and post-menopausal women. DESIGN AND METHODS: A case-control study of 839 breast cancer cases and 863 controls was conducted. The gene-environment interactions were tested after adjusting for potential breast cancer risk factors with unconditional logistic regression models. RESULTS: We found that the effect of passive smoking was modified by the genotypes in both pre- and post-menopausal women, but in opposite directions. The combination of the TC/CC genotypes of ESR1 rs2234693 and passive smoking significantly increased the risk of breast cancer [OR (95%CI): 2.06 (1.39-3.05)] in pre-menopausal women. A significant association was observed between TT genotype and passive smoking [OR (95%CI): 2.40 (1.27-4.53)] in postmenopausal women. For PARP1 rs1136410, similar differential associations were observed, but the interactions were not significant. CONCLUSIONS: These results imply that the risk of breast cancer from passive smoking may be influenced by genetic factors, and that the association may differ depending on menopausal status.

[Interaction of body mass index and a polymorphism in gene of catalytic subunit of glutamate-cysteine ligase on breast cancer risk among Chinese women].

OBJECTIVE: To investigate the interaction of body mass index(BMI)and a single nucleotide polymorphism (SNP, rs17883901) in catalytic subunit of glutamate-cysteine ligase (GCLC) on breast cancer risk. METHODS: A total of 839 women with incident breast cancer and 863 age-matched controls without cancer were recruited at the same period in three affiliated hospitals of Sun Yat-sen University in Guangzhou from October 2008 to June 2010. GCLC rs17883901 was genotyped by MALDI-TOF-MS. Binary unconditional logistic regression was applied to calculate odds ratios and 95% confidence intervals. RESULTS: The difference of present BMI and BMI at age 20 was not statistically significant between cases and controls, either as the genotypes of GCLC. No association was found between BMI at present and premenopausal or postmenopausal breast cancer risk. But we found that women who had a BMI at age 20 of 18.5 to 22.9 had a marginally decreased risk of premenopausal breast cancer [OR and 95%CI:0.69(0.48, 1.00)]. Among women with CT/TT genotypes, whose present BMI was greater than 25 had a increased risk [OR and 95%CI:1.91(1.09, 3.36)] of breast cancer and a decreased risk [OR and 95%CI:0.56 (0.31,0.99)] with a BMI at age 20 of 18.5 to 22.9. There was a interaction between GCLC gene(rs17883901)and BMI at present in breast cancer risk (P = 0.043), which was not found between rs17883901 and BMI at age 20. CONCLUSION: Our findings indicate BMI at age 20 may be a protective factor of premenopausal breast cancer, while no association appears between GCLC(rs17883901) and breast cancer. Obesity at present may significantly increase the risk of breast cancer among women with CT/TT genotypes of GCLC (rs17883901).

Joint effects of febrile acute infection and an interferon-γ polymorphism on breast cancer risk.

BACKGROUND: There is an inverse relationship between febrile infection and the risk of malignancies. Interferon gamma (IFN-γ) plays an important role in fever induction and its expression increases with incubation at fever-range temperatures. Therefore, the genetic polymorphism of IFN-γ may modify the association of febrile infection with breast cancer risk. METHODOLOGY AND PRINCIPAL FINDINGS: Information on potential breast cancer risk factors, history of fever during the last 10 years, and blood specimens were collected from 839 incident breast cancer cases and 863 age-matched controls between October 2008 and June 2010 in Guangzhou, China. IFN-γ (rs2069705) was genotyped using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry platform. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated using multivariate logistic regression. We found that women who had experienced ≥1 fever per year had a decreased risk of breast cancer [ORs and 95% CI: 0.77 (0.61-0.99)] compared to those with less than one fever a year. This association only occurred in women with CT/TT genotypes [0.54 (0.37-0.77)] but not in those with the CC genotype [1.09 (0.77-1.55)]. The association of IFN-γ rs2069705 with the risk of breast cancer was not significant among all participants, while the CT/TT genotypes were significantly related to an elevated risk of breast cancer [1.32 (1.03-1.70)] among the women with <1 fever per year and to a reduced risk of breast cancer [0.63 (0.40-0.99)] among women with ≥1 fever per year compared to the CC genotype. A marked interaction between fever frequencies and the IFN-γ genotypes was observed (P for multiplicative and additive interactions were 0.005 and 0.058, respectively). CONCLUSIONS: Our findings indicate a possible link between febrile acute infection and a decreased risk of breast cancer, and this association was modified by IFN-γ rs2069705.

Targeted delivery of PLK1-siRNA by ScFv suppresses Her2+ breast cancer growth and metastasis.

A major obstacle to developing small interfering RNAs (siRNAs) as cancer drugs is their intracellular delivery to disseminated cancer cells. Fusion proteins of single-chain fragmented antibodies (ScFvs) and positively charged peptides deliver siRNAs into specific target cells. However, the therapeutic potential of ScFv-mediated siRNA delivery has not been evaluated in cancer. Here, we tested whether Polo-like kinase 1 (PLK1) siRNAs complexed with a Her2-ScFv-protamine peptide fusion protein (F5-P) could suppress Her2(+) breast cancer cell lines and primary human cancers in orthotopic breast cancer models. PLK1-siRNAs transferred by F5-P inhibited target gene expression, reduced proliferation, and induced apoptosis of Her2(+) breast cancer cell lines and primary human cancer cells in vitro without triggering an interferon response. Intravenously injected F5-P/PLK1-siRNA complexes concentrated in orthotopic Her2(+) breast cancer xenografts and persisted for at least 72 hours, leading to suppressed PLK1 gene expression and tumor cell apoptosis. The intravenously injected siRNA complexes retarded Her2(+) breast tumor growth, reduced metastasis, and prolonged survival without evident toxicity. F5-P-mediated delivery of a cocktail of PLK1, CCND1, and AKT siRNAs was more effective than an equivalent dose of PLK1-siRNAs alone. These data suggest that F5-P could be used to deliver siRNAs to treat Her2(+) breast cancer.

A prospective, multicenter, controlled, observational study to evaluate the efficacy of a patient support program in improving patients' persistence to adjuvant aromatase inhibitor medication for postmenopausal, early stage breast cancer.

Since the rate of persistence to adjuvant endocrine therapy such as 5-year aromatase inhibitors (AI) would decrease over time in patients with hormone-sensitive breast cancer, it is necessary to investigate if a patient support program could modify patients' beliefs and improve their persistence to AI treatment. This was a prospective, multicenter, controlled, observational study to evaluate the efficacy of a patient support program in improving postmenopausal patients' persistence to adjuvant AI medication for early stage breast cancer (NCT00769080). The primary objective was to compare the rates of 1-year persistence to upfront adjuvant AI for patients in the two observational arms (standard treatment group and standard treatment plus patient support program group). In this study, 262 patients were enrolled in the standard treatment group and 241 patients in the standard treatment plus patient support program group. The mean 1-year persistence rates were 95.9 and 95.8% for the standard treatment group and the standard treatment plus patient support program group, respectively (P=0.95). The mean times to treatment discontinuation were 231.2 days in the standard treatment group and 227.8 days in the standard treatment plus patient support program group, with no statistically significant difference between the two groups (P=0.96). There was also no statistically significant difference in the reason for treatment discontinuation (P=0.32). There was a significant relationship between the patient centered care questionnaire and poor persistence (odds ratio=3.9; 95% CI, 1.1-13.7; P=0.035), suggesting that the persistence rate of patients with whom the doctor always or usually spends time is greater than that of patients with whom the doctor sometimes or never spends time. Patients' persistence to adjuvant AI medication for postmenopausal, early stage breast cancer is relatively high in the first year and is not significantly increased by adding a patient support program to standard treatment.