With less cost and greater QALYs than WB-EBRT, IORT is the more valuable strategy. IORT offers a unique example of new technology that is less costly than the current standard of care option but offers similar efficacy. Even when considering the capital investment for the equipment ($425 K, low when compared with the investments required for robotic surgery or high-dose-rate brachytherapy), which could be recouped after 3-4 years conservatively, these results support IORT as a change in practice for treating early-stage invasive breast cancer.

The TARGIT-A Trial is an international randomized, prospective trial comparing intraoperative radiotherapy (IORT) for equivalence to external beam radiotherapy (EBRT) following lumpectomy for invasive breast cancer in selected low-risk patients; early results suggest that outcomes are similar. In addition to effectiveness data and cost considerations, the preferences of patients should help inform practice. This study was undertaken to explore and quantify preference in choosing between IORT and the current standard, EBRT. Eligible subjects were current or past candidates for breast-conserving surgery and radiation being seen at the University of California, San Francisco Breast Care Center. A trade-off technique varying the risk of local recurrence for IORT was used to quantify any additional accepted risk that these patients would accept to receive either treatment. Patients were first presented with a slideshow comparing EBRT with the experimental IORT option before being asked their preferences given hypothetical 10-year local recurrence risks. Patients were then given a questionnaire on demographic, social and clinical factors. Data from 81 patients were analyzed. The median additional accepted risk to have IORT was 2.3 % (-9 to 39 %), mean 3.2 %. Only 7 patients chose to accept additional risk for EBRT; 22 accepted IORT at no additional risk; and the remaining 52 chose IORT with some additional risk. Patients weigh trade-offs of risks and benefits when presented with medical treatment choices. Our results show that the majority of breast cancer patients will accept a small increment of local risk for a simpler delivery of radiation. Further studies that incorporate outcome and side effect data from the TARGIT-A trial clarify the expected consequences of a local recurrence, and include an expanded range of radiation options that could help guide clinical decision making in this area.

Genes that regulate osteoclast (OC) development and function in both physiologic and disease conditions remain incompletely understood. Shp2 (the Src homology-2 domain containing protein tyrosine phosphatase 2), a ubiquitously expressed cytoplasmic protein tyrosine phosphatase, is implicated in regulating M-CSF and receptor activator of nuclear factor-κB ligand (RANKL)-evoked signaling; its role in osteoclastogenesis and bone homeostasis, however, remains unknown. Using a tissue-specific gene knockout approach, we inactivated Shp2 expression in murine OCs. Shp2 mutant mice are phenotypically osteopetrotic, featuring a marked increase of bone volume (BV)/total volume (TV) (+42.8%), trabeculae number (Tb.N) (+84.1%), structure model index (+119%), and a decrease of trabecular thickness (Tb.Th) (-34.1%) and trabecular spacing (Tb.Sp) (-41.0%). Biochemical analyses demonstrate that Shp2 is required for RANKL-induced formation of giant multinucleated OCs by up-regulating the expression of nuclear factor of activated T cells, cytoplasmic 1 (Nfatc1), a master transcription factor that is indispensable for terminal OC differentiation. Shp2 deletion, however, has minimal effect on M-CSF-dependent survival and proliferation of OC precursors. Instead, its deficiency aborts the fusion of OC precursors and formation of multinucleated OCs and decreases bone matrix resorption. Moreover, pharmacological intervention of Shp2 is sufficient to prevent preosteoclast fusion in vitro. These findings uncover a novel mechanism through which Shp2 regulates osteoclastogenesis by promoting preosteoclast fusion. Shp2 or its signaling partners could potentially serve as pharmacological targets to regulate the population of OCs locally and/or systematically, and thus treat OC-related diseases, such as periprosthetic osteolysis and osteoporosis.