Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer.

PURPOSE: The objective of this study was to determine whether the addition of trastuzumab to chemotherapy in the neoadjuvant setting could increase pathologic complete response (pCR) rate in patients with human epidermal growth factor receptor 2 (HER2) -positive disease. PATIENTS AND METHODS: Forty-two patients with HER2-positive disease with operable breast cancer were randomly assigned to either four cycles of paclitaxel followed by four cycles of fluorouracil, epirubicin, and cyclophosphamide or to the same chemotherapy with simultaneous weekly trastuzumab for 24 weeks. The primary objective was to demonstrate a 20% improvement in pCR (assumed 21% to 41%) with the addition of trastuzumab to chemotherapy. The planned sample size was 164 patients. RESULTS: Prognostic factors were similar in the two groups. After 34 patients had completed therapy, the trial's Data Monitoring Committee stopped the trial because of superiority of trastuzumab plus chemotherapy. pCR rates were 25% and 66.7% for chemotherapy (n = 16) and trastuzumab plus chemotherapy (n = 18), respectively (P = .02). The decision was based on the calculation that, if study continued to 164 patients, there was a 95% probability that trastuzumab plus chemotherapy would be superior. Of the 42 randomized patients, 26% in the chemotherapy arm achieved pCR compared with 65.2% in the trastuzumab plus chemotherapy arm (P = .016). The safety of this approach is not established, although no clinical congestive heart failure was observed. A more than 10% decrease in the cardiac ejection fraction was observed in five and seven patients in the chemotherapy and trastuzumab plus chemotherapy arms, respectively. CONCLUSION: Despite the small sample size, these data indicate that adding trastuzumab to chemotherapy, as used in this trial, significantly increased pCR without clinical congestive heart failure.     

A Physiological Profile of Four Wheelchair Marathon Racers

A profile of four wheelchair marathon racers (WMRs) is presented including an athletic history, dietary habits, maximal oxygen uptake, and average race pace oxygen uptake (Vo₂) values. These values were compared with those of able-bodied marathon runners matched for age and race time. The WMRs had lower Vo₂ max, maximal heart rates, and higher respiratory exchange ratios, and they used a higher percentage of their Vo₂ max and maximal heart rate at race pace. The authors suggest that a high degree of training is required to perform the grueling marathon.     

Advancing equity,diversity, and inclusion in the American College of Neuropsychopharmacology (ACNP): advances,challenges, and opportunities to accelerate progress

It is increasingly accepted that higher levels of excellence and innovation in research can be achieved by organizations that promote equity, diversity, and inclusion across several domains including ethnicity and gender. The purpose of this commentary is to provide an overview of the methods used to increase diversity within ACNP, as well as recommendations for accelerating progress. Annual membership surveys confirm increases in female membership and leadership positions, slower but encouraging signals for “Asian” and “Hispanic” members, and less progress for African American and other ethnic populations. Meetings have become visibly more diverse, due in part to ethnic minority travel awards and apparently increasing diversity among guest attendees. Evidence of increasing inclusion includes well-attended networking events and minority-relevant programming, active communications about diversity-related events and resources, and strong statements by ACNP leadership that embrace diversity as a core value and support collaboration among key committees and task forces to identify and implement pro-inclusion and diversity-enhancing efforts. We believe ACNP can accelerate progress with more scientifically valid approaches to assessing diversity and inclusion. The current membership survey includes five outmoded ethnic options and postmeeting surveys that are not designed to assess inclusion efforts and consequences. Measures should be developed that better characterize diversity and assess efforts to reduce the barriers that exist for potential non-White populations (e.g., annual membership and meeting attendance costs). Increased collaboration with NIH and other organizations that are committed to these same goals may also contribute to acceleration of progress by ACNP and other scientific organizations.Subject terms: Medical research, Neuroscience     

Occupational exposure to diesel engine exhaust and serum cytokine levels

The International Agency for Research on Cancer has classified diesel engine exhaust (DEE) as a human lung carcinogen. Given that inflammation is suspected to be an important underlying mechanism of lung carcinogenesis, we evaluated the relationship between DEE exposure and the inflammatory response using data from a cross‐sectional molecular epidemiology study of 41 diesel engine testing workers and 46 unexposed controls. Repeated personal exposure measurements of PM_2.5 and other DEE constituents were taken for the diesel engine testing workers before blood collection. Serum levels of six inflammatory biomarkers including interleukin (IL)‐1, IL‐6, IL‐8, tumor necrosis factor (TNF)‐α, macrophage inflammatory protein (MIP)‐1β, and monocyte chemotactic protein (MCP)‐1 were analyzed in all subjects. Compared to unexposed controls, concentrations of MIP‐1β were significantly reduced by ～37% in DEE exposed workers (P < 0.001) and showed a strong decreasing trend with increasing PM_2.5 concentrations in all subjects (P_trend < 0.001) as well as in exposed subjects only (P_trend = 0.001). Levels of IL‐8 and MIP‐1β were significantly lower in workers in the highest exposure tertile of PM_2.5 (>397 µg/m³) compared to unexposed controls. Further, significant inverse exposure‐response relationships for IL‐8 and MCP‐1 were also found in relation to increasing PM_2.5 levels among the DEE exposed workers. Given that IL‐8, MIP‐1β, and MCP‐1 are chemokines that play important roles in recruitment of immunocompetent cells for immune defense and tumor cell clearance, the observed lower levels of these markers with increasing PM_2.5 exposure may provide insight into the mechanism by which DEE promotes lung cancer. Environ. Mol. Mutagen. 59:144–150, 2018. © 2017 Wiley Periodicals, Inc.