Using Oncotype DX breast recurrence score® assay to define the role of neoadjuvant endocrine therapy in early-stage hormone receptor-positive breast cancer.

PURPOSE: The role of neoadjuvant endocrine therapy in the treatment of patients with early-stage, hormone receptor-positive (HR +) breast cancer is not well defined. Tools to better determine which patients may benefit from neoadjuvant endocrine therapy versus chemotherapy or upfront surgery remain an unmet need. METHODS: We assessed the rate of clinical and pathologic complete response (cCR, pCR) among a pooled cohort of patients with early-stage HR + breast cancer who had been randomized to neoadjuvant endocrine therapy or neoadjuvant chemotherapy in two earlier studies to understand better how outcomes varied by Oncotype DX Breast Recurrence Score® assay. RESULTS: We observed that patients with intermediate RS results had no statistically significant differences in pathologic outcomes at the time of surgery based on whether they received neoadjuvant endocrine therapy or neoadjuvant chemotherapy, suggesting that a subgroup of women with a RS 0-25 may omit chemotherapy without compromising outcomes. CONCLUSION: These data suggest that Recurrence Score® (RS) results may serve as a useful tool in treatment decision-making in the neoadjuvant setting.

Reduced effects of tendon vibration with increased task demand during active, cyclical ankle movements.

Tendon vibration can alter proprioceptive feedback, one source of sensory information which humans can use to produce accurate movements. However, the effects of tendon vibration during functional movement vary depending on the task. For example, ankle tendon vibration has considerably smaller effects during walking than standing posture. The purpose of this study was to test whether the effects of ankle tendon vibration are predictably influenced by the mechanical demands of a task, as quantified by peak velocity. Twelve participants performed symmetric, cyclical ankle plantar flexion/dorsiflexion movements while lying prone with their ankle motion unconstrained. The prescribed movement period (1, 3 s) and peak-to-peak amplitude (10°, 15°, 20°) were varied across trials; shorter movement periods or larger amplitudes increased the peak velocity. In some trials, vibration was continuously and simultaneously applied to the right ankle plantar flexor and dorsiflexor tendons, while the left ankle tendons were never vibrated. The vibration frequency (40, 80, 120, 160 Hz) was varied across trials. During trials without vibration, participants accurately matched the movement of their ankles. The application of 80 Hz vibration to the right ankle tendons significantly reduced the amplitude of right ankle movement. However, the effect of vibration was smaller during more mechanically demanding (i.e., higher peak velocity) movements. Higher vibration frequencies had larger effects on movement accuracy, possibly due to parallel increases in vibration amplitude. These results demonstrate that the effects of ankle tendon vibration are dependent on the mechanical demand of the task being performed, but cannot definitively identify the underlying physiological mechanism.

Biopanning Phage-Display Libraries on Small Tissue Sections Captured by Laser Capture Microdissection.

Phage-display technology has been widely used for developing tumor-targeting agents. Laser capture microdissection (LCM) has proven to be an accurate method to select specific cells from histological sections. Our goal was to develop a method to combine phage-display with LCM to obtain phage-displayed ligands that bind to selected cells in human solid tumors. Two panning strategies were evaluated and optimized. The first strategy was to pan on patient tissue mounted to LCM slides before LCM occurred. The poor panning output showed that phage did not tolerate the drying conditions during LCM. The second strategy was to pan on tumor cells from the patient tumor tissue that were isolated by LCM. The catapulted tumor cells were transferred to a filter unit which retained cells but allowed rinsing of unbound phage. Six commercially available filter units were evaluated and the one with the lowest nonspecific binding to phage was selected for the panning steps. The smallest number of cells (500) in which panning could be successfully accomplished was also determined. A micropipette system was developed to further decrease background by removing catapulted cells from the filter unit after panning was complete. This left behind nearly all background binding phage in the filter unit. This strategy led to the selection of individual phage antibody clones (5 out of 79 tested) specific for tumor cells of the patient's cancer tissue. Immunofluorescence staining on tumor tissues from the same patient showed that these clones have selective signals on tumor island cells, while the scFv library only showed low nonspecific signals on tumor tissues. We established a method of panning on a small number of LCM-captured solid tumor specimens. The quick identification of specific phage-displayed antibodies in the cancer tissue of human patients will greatly enhance the therapy and diagnosis of cancer.