Anastrozole satisfied the predefined criteria for equivalence to tamoxifen. Furthermore, we observed both a significant increase in TTP and a lower incidence of thromboembolic events and vaginal bleeding with anastrozole. These findings indicate that anastrozole should be considered as first-line therapy for postmenopausal women with advanced breast cancer.

Fulvestrant was at least as effective as anastrozole, with efficacy end points slightly favoring fulvestrant. Fulvestrant represents an additional treatment option for postmenopausal women with advanced breast cancer whose disease progresses on tamoxifen therapy.

No abstract

Background Tamoxifen is standard adjuvant treatment for postmenopausal women with hormone receptor-positive breast cancer. The benefit of adding chemotherapy and optimal timing of tamoxifen with chemotherapy are unknown. Methods We conducted a parallel randomized phase III trial in postmenopausal women with hormone receptor-positive, node-positive breast cancer to test whether disease-free survival (DFS) with cyclophosphamide, doxorubicin (AdriamycinR), and 5-fluorouracil (CAF) plus 5 years of tamoxifen was longer than with tamoxifen alone; and whether DFS with CAF followed by tamoxifen (CAF-T) was better than CAF plus concurrent tamoxifen (CAFT). Overall survival and toxicity were predefined, important secondary outcomes. Randomization was a 2:3:3 (T:CAF-T:CAFT) unblinded allocation and analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00929591. Findings Of 1558 women randomized, 1477 (95%) were eligible (tamoxifen, 361; CAF-T, 566; CAFT, 550). The combined CAF groups were superior to tamoxifen for the primary outcome of DFS (P=0.002), with adjusted Cox regression hazard ratio (HR) =0.76 (95% CI 0.64,0.91). CAF-T was marginally better than CAFT for DFS (P=0.055) with adjusted HR 0.84 (0.70,1.01). Ten-year DFS for CAF-T, CAFT, and T were 60%, 53%, and 48%, respectively. The planned secondary outcome, overall survival, showed a similar pattern of results, with combined CAF groups seem superior to tamoxifen [p=0.043, adjusted HR 0.83 (0.68,1.01)]. Neutropenia, stomatitis, thromboembolism, congestive heart failure and leukemia were more frequent with CAF than tamoxifen alone. Interpretation Chemotherapy with CAF plus tamoxifen resulted in longer survival over tamoxifen in endocrine-responsive, node-positive breast cancer, with greater benefit when tamoxifen followed CAF. Funding National Cancer Institute (NIH-USA).

Purpose To determine the optimal dose and schedule of anthracycline and taxane administration as adjuvant therapy for early-stage breast cancer. Patients and Methods A 2 × 2 factorial design was used to test two hypotheses: (1) that a novel continuous schedule of doxorubicin-cyclophosphamide was superior to six cycles of doxorubicin-cyclophosphamide once every 2 weeks and (2) that paclitaxel once per week was superior to six cycles of paclitaxel once every 2 weeks in patients with node-positive or high-risk node-negative early-stage breast cancer. With 3,250 patients, a disease-free survival (DFS) hazard ratio of 0.82 for each randomization could be detected with 90% power with two-sided α = .05. Overall survival (OS) was a secondary outcome. Results Interim analyses crossed the futility boundaries for demonstrating superiority of both once-per-week regimens and once-every-2-weeks regimens. After a median follow-up of 6 years, a significant interaction developed between the two randomization factors (DFS P = .024; OS P = .010) in the 2,716 patients randomly assigned in the original design, which precluded interpretation of the two factors separately. Comparing all four arms showed a significant difference in OS (P = .040) but not in DFS (P = .11), with all treatments given once every 2 weeks associated with the highest OS. This difference in OS seemed confined to patients with hormone receptor–negative/human epidermal growth factor receptor 2 (HER2) –negative tumors (P = .067), with no differences seen with hormone receptor–positive/HER2-negative (P = .90) or HER2-positive tumors (P = .40). Conclusion Patients achieved a similar DFS with any of these regimens. Subset analysis suggests the hypothesis that once-every-2-weeks dosing may be best for patients with hormone receptor–negative/HER2-negative tumors.

screening of patients with newly diagnosed cancer for hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV is not routine in oncology practice, and experts disagree about whether universal screening should be performed. OBJECTIVE To estimate the prevalence of HBV, HCV, and HIV infection among persons with newly diagnosed cancer. DESIGN, SETTING, AND PARTICIPANTS Multicenter prospective cohort study of patients with newly diagnosed cancer (ie, identified within 120 days of cancer diagnosis) at 9 academic and 9 community oncology institutions affiliated with SWOG (formerly the Southwest Oncology Group) Cancer Research Network, a member of the National Clinical Trials Network, with enrollment from August 29, 2013, through February 15, 2017. The data analysis was conducted using data available through August 17, 2017. MAIN OUTCOMES AND MEASURES The accrual goal was 3000 patients and the primary end point was the presence of HBV infection (previous or chronic), HCV infection, or HIV infection at enrollment. Patients with previous knowledge of infection as well as patients with unknown viral viral status were evaluated. RESULTS Of 3092 registered patients, 3051 were eligible and evaluable. Median (range) age was 60.6 (18.2-93.7) years, 1842 (60.4%) were female, 553 (18.1%) were black, and 558 (18.3%) were Hispanic ethnicity. Screened patients had similar clinical and demographic characteristics compared with those registered. The observed infection rate for previous HBV infection was 6.5% (95% CI, 5.6%-7.4%; n = 197 of 3050 patients); chronic HBV, 0.6% (95% CI, 0.4%-1.0%; n = 19 of 3050 patients); HCV, 2.4% (95% CI, 1.9%-3.0%; n = 71 of 2990 patients); and HIV, 1.1% (95% CI, 0.8%-1.6%; n = 34 of 3045). Among those with viral infections, 8 patients with chronic HBV (42.1%; 95% CI, 20.3%-66.5%), 22 patients with HCV (31.0%; 95% CI, 20.5%-43.1%), and 2 patients with HIV (5.9%; 95% CI, 0.7%-19.7%) were newly diagnosed through the study. Among patients with infections, 4 patients with chronic HBV (21.1%; 95% CI, 6.1%-45.6%), 23 patients with HCV (32.4%; 95% CI, 21.8%-44.5%), and 7 patients with HIV (20.6%; 95% CI, 8.7%-37.9%) had no identifiable risk factors. CONCLUSIONS AND RELEVANCE Results of this study found that a substantial proportion of patients with newly diagnosed cancer and concurrent HBV or HCV are unaware of their viral infection at the time of cancer diagnosis, and many had no identifiable risk factors for infection. Screening patients with cancer to identify HBV and HCV infection before starting treatment may be warranted to prevent viral reactivation and adverse clinical outcomes. The low rate of undiagnosed HIV infection may not support universal screening of newly diagnosed cancer patients.

Our results suggest an improved outcome for metastatic triple negative breast cancer patients compared to non-triple negative breast cancer patients when treated with cisplatin and gemcitabine combination chemotherapy.

Purpose Adherence to aromatase inhibitor (AI) therapy for early stage breast cancer is limited by AI-associated musculoskeletal symptoms (AIMSS). Duloxetine is FDA-approved for treatment of multiple chronic pain disorders. We hypothesized that treatment of AIMSS with duloxetine would improve average joint pain compared with placebo. Patients and Methods This randomized, double-blind, phase 3 trial included AI-treated postmenopausal women with early stage breast cancer and who had average joint pain of ≥4/10 that developed or worsened since AI therapy initiation. Patients were randomized 1:1 to duloxetine versus placebo for 13 weeks. The primary endpoint was average joint pain through 12 weeks, examined using multivariable linear mixed models, adjusted for stratification factors (baseline pain score 4–6 vs. 7–10 and prior taxane use). Clinically significant change in average pain was defined as a ≥2-point decrease from baseline. Results Of 299 enrolled patients, 127 duloxetine-treated and 128 placebo-treated patients were evaluable for the primary analysis. Average joint pain was 0.82 points lower for duloxetine-treated patients compared with placebo-treated patients by 12 weeks (95% CI −1.24 to −0.40, p=0.0002). Similar patterns were observed for worst joint pain, joint stiffness, pain interference, and functioning. Rates of adverse events (AEs) of any grade were higher for duloxetine-treated patients (78% vs 50%); grade 3 AEs were similar. Conclusion Treatment with duloxetine for AIMSS was superior to placebo among women with early stage breast cancer, although it resulted in more frequent low grade toxicities.