Patti O'Brien

Cyclophosphamide, Epirubicin, and Fluorouracil Versus Dose-Dense Epirubicin and Cyclophosphamide Followed by Paclitaxel Versus Doxorubicin and Cyclophosphamide Followed by Paclitaxel in Node-Positive or High-Risk Node-Negative Breast Cancer

PURPOSE Cyclophosphamide, epirubicin, and fluorouracil (CEF) and doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T) are commonly used adjuvant regimens in women with early breast cancer. In a previous trial in women with locally advanced breast cancer, 3 months of high-dose epirubicin and cyclophosphamide (EC) administered every 2 weeks (dose-dense) was equivalent to 6 months of CEF. We hypothesized that 3 months of paclitaxel after dose-dense EC (EC/T) would be superior to CEF or AC/T. METHODS After lumpectomy or mastectomy, women 60 years of age or younger with axillary node-positive or high-risk node-negative breast cancer were randomly assigned to receive CEF, EC/T, or AC/T for 6 months. This article reports the interim analysis for recurrence-free survival (RFS), which was planned after 227 recurrences. Results A total of 2,104 patients were enrolled. The median follow-up is 30.4 months. Hazard ratios for recurrence are as follows: AC/T versus CEF, 1.49 (95% CI, 1.12 to 1.99), P = .005; AC/T versus EC/T, 1.68 (95% CI, 1.25 to 2.27), P = .0006; and EC/T versus CEF, 0.89 (95% CI, 0.64 to 1.22), P = .46. Three-year RFS rates for CEF, EC/T, and AC/T are 90.1%, 89.5%, and 85.0%, respectively. There was more febrile neutropenia with CEF (22.3%) and EC/T (16.4%) compared with AC/T (4.8%), but more neuropathy with the last two regimens. CONCLUSION Three-weekly AC/T is significantly inferior to CEF or EC/T in terms of RFS. It is too early to detect any difference between CEF and dose-dense EC/T.

Models for Integrating Rehabilitation and Primary Care: A Scoping Study

OBJECTIVE To describe the scope and breadth of knowledge currently available regarding the integration of rehabilitation and primary care services. DATA SOURCES Peer-reviewed journals were searched using CINAHL, MEDLINE, and EBM Reviews for the years 1995 through 2007. This process identified 172 items. STUDY SELECTION To be considered for the subsequent review, the article had to describe a service delivery program that offered primary care and rehabilitation, or services specifically designed for people with chronic conditions/disabilities. Further, it had to be available in English or French. No methodological limitations were applied to screen for levels of evidence. DATA EXTRACTION Based on these criteria, 38 articles remained that pertained to both primary care and rehabilitation. These were reviewed, sorted, and categorized to discover commonalities and differences among the approaches used to integrating rehabilitation into primary care. DATA SYNTHESIS In consultation with the team of investigators, it was determined that there were 6 different models for providing primary health care and rehabilitation services in an integrated approach: clinic, outreach, self-management, community-based rehabilitation, shared care, and case management. In addition, a number of themes were identified across models that may act as either supports or impediments to the integration of rehabilitation services into primary care settings: team approach, interprofessional trust, leadership, communication, compensation, accountability, referrals, and population-based approach. CONCLUSIONS Rehabilitation providers interested in working in the primary care sector may be assisted in conceptualizing the benefits that they bring to the setting by considering these models and issues.

A four gene signature of chromosome instability (CIN4) predicts for benefit from taxanes in the NCIC-CTG MA21 clinical trial

Recent evidence demonstrated CIN4 as a predictive marker of anthracycline benefit in early breast cancer. An analysis of the NCIC CTG MA.21 clinical trial was performed to test the role of existing CIN gene expression signatures as prognostic and predictive markers in the context of taxane based chemotherapy. RNA was extracted from patients in cyclophosphamide, epirubicin and fluorouracil (CEF) and epirubicin, cyclophosphamide and paclitaxel (EC/T) arms of the NCIC CTG MA.21 trial and analysed using NanoString technology. After multivariate analysis both high CIN25 and CIN70 score was significantly associated with an increased in RFS (HR 1.76, 95%CI 1.07-2.86, p=0.0018 and HR 1.59, 95%CI 1.12-2.25, p=0.0096 respectively). Patients whose tumours had low CIN4 gene expression scores were associated with an increase in RFS (HR: 0.64, 95% CI 0.39-1.03, p=0.06) when treated with EC/T compared to patients treated with CEF. In conclusion we have demonstrated CIN25 and CIN70 as prognostic markers in breast cancer and that CIN4 is a potential predictive maker of benefit from taxane treatment.