Hemodialysis access-related bloodstream infections are a significant cause of morbidity and mortality in children maintained on hemodialysis. The rates of these infections are highly variable in ...large part due to the inconsistent definitions used to diagnose these infections and the failure to clearly delineate between primary and access-related bloodstream infections. Although standard treatment of catheter-related bloodstream infections routinely includes removal of the catheter, this therapeutic maneuver is difficult to implement in hemodialysis patients who require that access for life-sustaining dialysis and in children in whom sites for vascular access may be limited. The following case seeks to highlight the importance of this distinction as well as the unique aspects of treating access-related infections in pediatric hemodialysis patients. The case discussion will also review efforts to minimize the risk for these infections.
Given the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified ...set of breast cancer patients.
We performed genome-wide association analyses within 15 subgroups of breast cancer patients based on prognostic factors, including hormone receptors, tumor grade, age, and type of systemic treatment. Analyses were based on 91,686 female patients of European ancestry from the Breast Cancer Association Consortium, including 7531 breast cancer-specific deaths over a median follow-up of 8.1 years. Cox regression was used to assess associations of common germline variants with 15-year and 5-year breast cancer-specific survival. We assessed the probability of these associations being true positives via the Bayesian false discovery probability (BFDP < 0.15).
Evidence of associations with breast cancer-specific survival was observed in three patient subgroups, with variant rs5934618 in patients with grade 3 tumors (15-year-hazard ratio (HR) 95% confidence interval (CI) 1.32 1.20, 1.45, P = 1.4E-08, BFDP = 0.01, per G allele); variant rs4679741 in patients with ER-positive tumors treated with endocrine therapy (15-year-HR 95% CI 1.18 1.11, 1.26, P = 1.6E-07, BFDP = 0.09, per G allele); variants rs1106333 (15-year-HR 95% CI 1.68 1.39,2.03, P = 5.6E-08, BFDP = 0.12, per A allele) and rs78754389 (5-year-HR 95% CI 1.79 1.46,2.20, P = 1.7E-08, BFDP = 0.07, per A allele), in patients with ER-negative tumors treated with chemotherapy.
We found evidence of four loci associated with breast cancer-specific survival within three patient subgroups. There was limited evidence for the existence of associations in other patient subgroups. However, the power for many subgroups is limited due to the low number of events. Even so, our results suggest that the impact of common germline genetic variants on breast cancer-specific survival might be limited.
Breast cancer metastasis accounts for most of the deaths from breast cancer. Identification of germline variants associated with survival in aggressive types of breast cancer may inform understanding ...of breast cancer progression and assist treatment. In this analysis, we studied the associations between germline variants and breast cancer survival for patients with distant metastases at primary breast cancer diagnosis. We used data from the Breast Cancer Association Consortium (BCAC) including 1062 women of European ancestry with metastatic breast cancer, 606 of whom died of breast cancer. We identified two germline variants on chromosome 1, rs138569520 and rs146023652, significantly associated with breast cancer-specific survival (P = 3.19 × 10
and 4.42 × 10
). In silico analysis suggested a potential regulatory effect of the variants on the nearby target genes SDE2 and H3F3A. However, the variants showed no evidence of association in a smaller replication dataset. The validation dataset was obtained from the SNPs to Risk of Metastasis (StoRM) study and included 293 patients with metastatic primary breast cancer at diagnosis. Ultimately, larger replication studies are needed to confirm the identified associations.
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