Citations

Abstract Triple-negative breast cancers are an aggressive subtype of breast cancer with poor survival, but there remains little known about the etiologic factors that promote its initiation and development. Commonly inherited breast cancer risk factors identified through genome-wide association studies display heterogeneity of effect among breast cancer subtypes as defined by the status of estrogen and progesterone receptors. In the Triple Negative Breast Cancer Consortium (TNBCC), 22 common breast cancer susceptibility variants were investigated in 2,980 Caucasian women with triple-negative breast cancer and 4,978 healthy controls. We identified six single-nucleotide polymorphisms, including rs2046210 (ESR1), rs12662670 (ESR1), rs3803662 (TOX3), rs999737 (RAD51L1), rs8170 (19p13.1), and rs8100241 (19p13.1), significantly associated with the risk of triple-negative breast cancer. Together, our results provide convincing evidence of genetic susceptibility for triple-negative breast cancer. Cancer Res; 71(19); 6240–9. ©2011 AACR.

Abstract Background: BRCA1 and BRCA2 mutation carriers have a lifetime breast cancer risk of 40% to 80%, suggesting the presence of risk modifiers. We previously identified significant associations in genetic variants in the insulin-like growth factor (IGF) signaling pathway. Here, we investigate additional IGF signaling genes as risk modifiers for breast cancer development in BRCA carriers. Methods: A cohort of 1,019 BRCA1 and 500 BRCA2 mutation carriers were genotyped for 99 single-nucleotide polymorphisms (SNP) in 13 genes. Proportional hazards regression was used to model time from birth to diagnosis of breast cancer for BRCA1 and BRCA2 carriers separately. For linkage disequilibrium (LD) blocks with multiple SNPs, an additive genetic model was used. For an SNP analysis, no additivity assumptions were made. Results: Significant associations were found between risk of breast cancer and LD blocks in IGF2 for BRCA1 and BRCA2 mutation carriers (global P values of 0.009 for BRCA1 and 0.007 for BRCA2), HTRA1 for BRCA1 carriers (global P value of 0.005), and MMP3 for BRCA2 carriers (global P = 0.0000007 for BRCA2). Conclusions: We identified significant associations of genetic variants involved in IGF signaling. With the known interaction of BRCA1 and IGF signaling and the loss of PTEN in a majority of BRCA1 tumors, this suggests that signaling through AKT may modify breast cancer risk in BRCA1 carriers. Impact: These results suggest potential avenues for future research targeting the IGF signaling pathway in modifying risk in BRCA1and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev; 20(8); 1690–702. ©2011 AACR.

Abstract BACKGROUND: Ventral decompression with posterior stabilization is the preferred treatment for symptomatic irreducible basilar invagination. Endoscopic image-guided transcervical odontoidectomy (ETO) may allow for decompression with limited morbidity. OBJECTIVE: To describe the perioperative outcomes of patients undergoing anterior decompression of basilar invagination with the use of ETO. METHODS: Fifteen patients who had a follow-up of at least 16 months were retrospectively reviewed. Intraoperatively, the vertebral body of C2 was removed and the odontoid was resected in a “top-down” manner using endoscopic visualization and frameless stereotactic navigation. Posterior instrumented stabilization was subsequently performed. RESULTS: The average (± standard deviation) age of the patients was 42.6 ± 24.5 (range, 11–72) years. Postoperative complications occurred in 6 patients, including a urinary tract infection (n = 2), upper airway swelling (n = 2), dysphagia (n = 2), gastrostomy tube placement (n = 1), and an asymptomatic pseudomeningocele (n = 1). No patients required a tracheostomy, had bacterial meningitis, or developed a venous thromboembolic event; only 1 patient was intubated for more than 48 hours postoperatively. With a mean follow-up of 41.9 ± 14.4 (range, 16–59) months, myelopathy improved in all patients and no patient experienced late neurological deterioration. The mean modified Japanese Orthopedic Association (JOA) score increased from 11.2 ± 4.2 to 15.9 ± 1.4 (P = .002). Patients with a diagnosis other than rheumatoid arthritis or who had a higher preoperative JOA score had a significantly better postoperative neurological recovery (P = .005). CONCLUSION: ETO may be a valid treatment for patients with symptomatic irreducible basilar invagination that avoids some of the morbidity of transoral surgery and leads to long-term improvement in myelopathy.

AbstractFree light chains (FLCs) are the most commonly detected paraproteins in chronic lymphocytic leukemia (CLL). We examined the types of FLC abnormalities and prognostic utility of the FLC assay compared with standard prognostic biomarkers in a prospective cohort of 339 patients with newly diagnosed CLL. Three types of FLC abnormalities were identified: monoclonal elevated FLC (elevated κ and/or λ with abnormal FLC ratio), polyclonal elevated FLC (elevated κ and/or λ with normal FLC ratio), and ratio-only FLC abnormality (normal range κ and λ with abnormal FLC ratio). One hundred sixty-five patients (49%) had a FLC abnormality with approximately equal distribution among monoclonal elevation, polyclonal elevation, and ratio-only abnormality. All FLC abnormalities were associated with poor time to first treatment: monoclonal FLC (hazard ratio [HR], 4.99; 95% confidence interval [CI], 2.94-8.48), polyclonal FLC (HR, 2.40; 95% CI, 1.24-4.64), ratio-only FLC (HR, 2.57; 95% CI, 1.40-4.69). Monoclonal FLC and polyclonal FLC were associated with poor overall survival compared with patients with normal FLC. Results remained significant after adjusting for Rai stage. The FLC assay is a simple, widely available clinical test with similar prognostic utility as routinely used prognostic biomarkers for CLL. Among persons with FLC abnormalities, the type of abnormality affects prognostic significance.

There is controversy regarding the application of angioplasty to patients with multivessel disease in whom all significant stenoses are not dilated. We analyzed the outcomes of 286 patients with multivessel disease and prior successful angioplasty at a mean follow-up duration of 26.2 months. End points analyzed included death, myocardial infarction, late revascularization, and angina pectoris. After successful angioplasty, 127 patients had no residual stenoses of 70% or greater (group 1) and 159 patients had one or more residual stenoses of 70% or greater (group 2). Because there were significant differences in baseline risk factors between the two groups, a logistic regression model was used to make the necessary adjustments in the analysis. Adjusted estimates of the risk of death, death/myocardial infarction, or presence of angina pectoris did not differ between the two groups. Group 2 patients, however, had more coronary artery bypass surgery during follow-up, while those in group 1 had more second PTCA procedures. Results suggest that angioplasty can be safely applied to patients with multivessel disease, even when all significant stenoses are not dilated.