Iulia Cristina Tudor

Impact of Preoperative Anemia on Outcome in Patients Undergoing Coronary Artery Bypass Graft Surgery

Background— The risk of preoperative anemia in patients undergoing heart surgery has not been described precisely. Specifically, the impact of low hemoglobin per se or combined with other risk factors on postoperative outcome is unknown. Thus, we determined the effects of low preoperative hemoglobin and comorbidities on postoperative adverse outcomes in patients with coronary artery bypass graft in a large comprehensive multicenter study. Methods and Results— The Multicenter Study of Perioperative Ischemia investigated 5065 patients with coronary artery bypass graft at 70 institutions worldwide, collecting ≈7500 data points per patient. In 4804 patients who received no preoperative transfusions, we determined the association between lowest preoperative hemoglobin levels and in-hospital cardiac and noncardiac morbidity and mortality and the impact of concomitant risk factors, assessed by EuroSCORE, on this effect. In patients with EuroSCORE <4 (n=2054), only noncardiac outcomes were increased, whereas patients with EuroSCORE ≥4 (n=2750) showed an increased incidence of all postoperative events, starting at hemoglobin <11 g/dL. Low preoperative hemoglobin was an independent predictor for noncardiac (renal>cerebral; P<0.001) outcomes, whereas the increase in cardiac events was due to other factors associated with preoperative anemia. Conclusions— Anemic patients undergoing cardiac surgery have an increased risk of postoperative adverse events. Importantly, the extent of preexisting comorbidities substantially affects perioperative anemia tolerance. Therefore, preoperative risk assessment and subsequent therapeutic strategies, such as blood transfusion, should take into account both the individual level of preoperative hemoglobin and the extent of concomitant risk factors.

Central Nervous System Metastases in Patients with HER2-Positive Metastatic Breast Cancer: Incidence, Treatment, and Survival in Patients from registHER

Purpose: registHER is a prospective, observational study of 1,023 newly diagnosed HER2-positive metastatic breast cancer (MBC) patients. Experimental Design: Baseline characteristics of patients with and without central nervous system (CNS) metastases were compared; incidence, time to development, treatment, and survival after CNS metastases were assessed. Associations between treatment after CNS metastases and survival were evaluated. Results: Of the 1,012 patients who had confirmed HER2-positive tumors, 377 (37.3%) had CNS metastases. Compared with patients with no CNS metastases, those with CNS metastases were younger and more likely to have hormone receptor–negative disease and higher disease burden. Median time to CNS progression among patients without CNS disease at initial MBC diagnosis (n = 302) was 13.3 months. Treatment with trastuzumab, chemotherapy, or surgery after CNS diagnosis was each associated with a statistically significant improvement in median overall survival (OS) following diagnosis of CNS disease (unadjusted analysis: trastuzumab vs. no trastuzumab, 17.5 vs. 3.8 months; chemotherapy vs. no chemotherapy, 16.4 vs. 3.7 months; and surgery vs. no surgery, 20.3 vs. 11.3 months). Although treatment with radiotherapy seemed to prolong median OS (13.9 vs. 8.4 months), the difference was not significant (P = 0.134). Results of multivariable proportional hazards analyses confirmed the independent significant effects of trastuzumab and chemotherapy (HR = 0.33, P < 0.001; HR = 0.64, P = 0.002, respectively). The effects of surgery and radiotherapy did not reach statistical significance (P = 0.062 and P = 0.898, respectively). Conclusions: For patients with HER2-positive MBC evaluated in registHER, the use of trastuzumab, chemotherapy, and surgery following CNS metastases were each associated with longer survival. Clin Cancer Res; 17(14); 4834–43. ©2011 AACR.

Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation

BACKGROUND The poly(adenosine diphosphate‐ribose) inhibitor talazoparib has shown antitumor activity in patients with advanced breast cancer and germline mutations in BRCA1 and BRCA2 (BRCA1/2). METHODS We conducted a randomized, open‐label, phase 3 trial in which patients with advanced breast cancer and a germline BRCA1/2 mutation were assigned, in a 2:1 ratio, to receive talazoparib (1 mg once daily) or standard single‐agent therapy of the physicians choice (capecitabine, eribulin, gemcitabine, or vinorelbine in continuous 21‐day cycles). The primary end point was progression‐free survival, which was assessed by blinded independent central review. RESULTS Of the 431 patients who underwent randomization, 287 were assigned to receive talazoparib and 144 were assigned to receive standard therapy. Median progressionfree survival was significantly longer in the talazoparib group than in the standardtherapy group (8.6 months vs. 5.6 months; hazard ratio for disease progression or death, 0.54; 95% confidence interval [CI], 0.41 to 0.71; P<0.001). The interim median hazard ratio for death was 0.76 (95% CI, 0.55 to 1.06; P = 0.11 [57% of projected events]). The objective response rate was higher in the talazoparib group than in the standard‐therapy group (62.6% vs. 27.2%; odds ratio, 5.0; 95% CI, 2.9 to 8.8; P<0.001). Hematologic grade 3‐4 adverse events (primarily anemia) occurred in 55% of the patients who received talazoparib and in 38% of the patients who received standard therapy; nonhematologic grade 3 adverse events occurred in 32% and 38% of the patients, respectively. Patient‐reported outcomes favored talazoparib; significant overall improvements and significant delays in the time to clinically meaningful deterioration according to both the global health status‐quality‐of‐life and breast symptoms scales were observed. CONCLUSIONS Among patients with advanced breast cancer and a germline BRCA1/2 mutation, single‐agent talazoparib provided a significant benefit over standard chemotherapy with respect to progression‐free survival. Patient‐reported outcomes were superior with talazoparib. (Funded by Medivation [Pfizer]; EMBRACA ClinicalTrials.gov number, NCT01945775.)

Androgen Receptor Immunohistochemistry as a Companion Diagnostic Approach to Predict Clinical Response to Enzalutamide in Triple-Negative Breast Cancer

PurposeThe androgen receptor (AR) is increasingly recognized as a potential biomarker for identifying a subset of patients with possible hormonally driven triple-negative breast cancer (TNBC). However, its performance as a companion diagnostic remains elusive. Thus, we evaluated AR expression by immunohistochemistry in patients with advanced TNBC before treatment with the AR inhibitor enzalutamide.MethodsWe optimized and validated immunohistochemistry assays in breast and prostate cancer cell lines and tissues using two commercial AR monoclonal antibodies (SP107 and AR441). AR expression was then examined in patients with advanced TNBC enrolled in a phase II study of enzalutamide (ClinicalTrials.gov identifier: NCT01889238) on archived or fresh tissue before treatment. Association with clinical response was assessed by sensitivity, specificity, positive predictive value (PPV), drop-out rate, and survival.ResultsAR expression was detected in 80% and 63% of breast cancer tissue using SP107 and AR441, respec...