Association of proinflammatory cytokines and chemotherapy-associated cognitive impairment in breast cancer patients: a multi-centered, prospective, cohort study.

BACKGROUND: Existing evidence suggests that proinflammatory cytokines play an intermediary role in postchemotherapy cognitive impairment. This is one of the largest multicentered, cohort studies conducted in Singapore to evaluate the prevalence and proinflammatory biomarkers associated with cognitive impairment in breast cancer patients. PATIENTS AND METHODS: Chemotherapy-receiving breast cancer patients (stages I-III) were recruited. Proinflammatory plasma cytokines concentrations [interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating factor, interferon-γ and tumor necrosis factor-α] were evaluated at 3 time points (before chemotherapy, 6 and 12 weeks after chemotherapy initiation). The FACT-Cog (version 3) was utilized to evaluate patients' self-perceived cognitive disturbances and a computerized neuropsychological assessment (Headminder) was administered to evaluate patients' memory, attention, response speed and processing speed. Changes of cognition throughout chemotherapy treatment were compared against the baseline. Linear mixed-effects models were applied to test the relationships of clinical variables and cytokine concentrations on self-perceived cognitive disturbances and each objective cognitive domain. RESULTS: Ninety-nine patients were included (age 50.5 ± 8.4 years; 81.8% Chinese; mean duration of education = 10.8 ± 3.3 years). Higher plasma IL-1ß was associated with poorer response speed performance (estimate: -0.78; 95% confidence interval (CI) -1.34 to -0.03; P = 0.023), and a higher concentration of IL-4 was associated with better response speed performance (P = 0.022). Higher concentrations of IL-1ß and IL-6 were associated with more severe self-perceived cognitive disturbances (P = 0.018 and 0.001, respectively). Patients with higher concentrations of IL-4 also reported less severe cognitive disturbances (P = 0.022). CONCLUSIONS: While elevated concentrations of IL-6 and IL-1ß were observed in patients with poorer response speed performance and perceived cognitive disturbances, IL-4 may be protective against chemotherapy-associated cognitive impairment. This study is important because cytokines would potentially be mechanistic mediators of chemotherapy-associated cognitive changes.

Association of common genetic variants with breast cancer risk and clinicopathological characteristics in a Chinese population.

Genome-wide association studies (GWAS) have identified various genetic susceptibility loci for breast cancer based mainly on European-ancestry populations. Differing linkage disequilibrium patterns exist between European and Asian populations, and thus GWAS-identified single nucleotide polymorphisms (SNPs) in one population may not be of significance in another population. In order to explore the role of breast cancer susceptibility variants in a Chinese population of Southern Chinese descent, we analyzed 22 SNPs for 1,191 breast cancer cases and 1,534 female controls. Associations between the SNPs and clinicopathological features were also investigated. In addition, we evaluated the combined effects of associated SNPs by constructing risk models. Eight SNPs were associated with an elevated breast cancer risk. Rs2046210/6q25.1 increased breast cancer risk via an additive model [per-allele odds ratio (OR) = 1.43, 95 % confidence interval (CI) = 1.26-1.62], and was associated with estrogen receptor (ER)-positive (per-allele OR = 1.39, 95 % CI = 1.20-1.61) and ER-negative (per-allele OR = 1.55, 95 % CI = 1.28-1.89) disease. Rs2046210 was also associated with stage 1, stage 2, and stage 3 disease, with per-allele ORs of 1.38 (1.14-1.68), 1.48 (1.25-1.74), and 1.58 (1.28-1.94), respectively. Four SNPs mapped to 10q26.13/FGFR2 were associated with increased breast cancer risk via an additive model with per-allelic risks (95 % CI) of 1.26 (1.12-1.43) at rs1219648, 1.22 (1.07-1.38) at rs2981582, 1.21 (1.07-1.36) at rs2981579, and 1.18 (1.04-1.35) at rs11200014. Variants of rs7696175/TLR1, TLR6, rs13281615/8q24, and rs16886165/MAP3K1 were also associated with increased breast cancer risk, with per-allele ORs (95 % CI) of 1.16 (1.00-1.34), 1.15 (1.02-1.29), and 1.15 (1.01-1.29), respectively. Five SNPs associated with breast cancer risk predominantly among ER-positive tumors (rs2981582/FGFR2, rs4415084/MRPS30, rs1219648/FGFR2, rs2981579/FGFR2, and rs11200014/FGFR2). Among our Chinese population, the risk of developing breast cancer increased by 90 % for those with a combination of 6 or more risk alleles, compared to patients with ≤3 risk alleles.

Factors influencing patient decision-making between simple mastectomy and surgical alternatives.

Background: Despite similar survival rates, breast-conserving therapy (BCT) remains a distant second choice after simple mastectomy for patients with early-stage breast cancer in Singapore. Uptake of reconstruction after mastectomy is also low (18 per cent). The aim of this study was to explore the factors influencing a patient's choice for mastectomy when eligible for BCT, and why patients decline reconstruction after mastectomy. Methods: Patients from the National Cancer Centre Singapore, who were eligible for BCT but chose mastectomy without reconstruction, between December 2014 and December 2015 were included. An interviewer-administered questionnaire focusing on patients' reasons for choosing mastectomy over BCT and not opting for immediate breast reconstruction after mastectomy was used. Tumour characteristics were retrieved from medical records. Spearman's rank correlation coefficient, Mann-Whitney U and Kruskal-Wallis tests were used to analyse the correlation between the patient's self-rated influential factors and variables. Statistical significance was taken as P < 0·050. Results: Ninety-one patients were included (90·1 per cent response rate). The main reasons for choosing mastectomy over BCT were: fear of cancer recurrence (considered very important in 74 per cent), the perception that health outweighs breast retention (49 per cent) and the possibility of second surgery for margins (40 per cent). Key factors for rejecting immediate reconstruction after mastectomy were: patient-perceived 'old age' (very important in 53 per cent), concern about two sites of surgery (42 per cent) and financial cost (29 per cent). Given a second chance, 19·8 per cent of patients would undergo BCT instead of mastectomy. Conclusion: This study has identified the considerations that women in Singapore have when deciding on breast cancer surgery. Some perceptions need to be addressed for women to make a fully informed decision, especially as one-fifth regret their initial choice.

Low incidence of penetrating trauma in a high-volume tertiary center: 10-year mortality review.

BACKGROUND: Trauma morbidity and mortality outcome is better in high-volume trauma centers. However, there are few publications investigating the experience of high-volume centers with high non-trauma emergency load but seeing a relatively low incidence of trauma. The objective of this study is to review the presentation and outcomes for the low volume of patients presenting with penetrating injuries in a high-volume hospital. METHODS: Data were extracted from the Singapore General Hospital database between 1998 and 2007. There were 1,233 patients who sustained penetrating injuries and were brought to the hospital during the 10-year period. Of these, only 78 patients had injury severity score (ISS) values of 16 or more. In the same period, there were 1,270 patients with ISS > 15 who were admitted with blunt injury. SPSS 10.1 was used to conduct univariate and multivariate analyses to elucidate risk factors for mortality. RESULTS: Age, ISS, and trauma injury severity score (TRISS) were significant predictors of mortality. Gender and type of injury were not predictive of mortality. Mortality outcomes were independently predicted by age, TRISS, and ISS. The most common site of injury was the chest, followed closely by the head and neck. The abdomen/pelvis was the third most common site of injury. There was no significant difference in anatomical site injury pattern between the survivors and non-survivors. For both groups, chest injuries and head and neck injuries dominated, with maximal abdominal/pelvic injuries a distant third. CONCLUSION: With a trauma system in place, high-volume centers with a low volume of penetrating injury patients can still manage uncommon injuries without jeopardizing patient care.