Background This systematic review is an update of evidence since the 2002 U.S. Preventive Services Task Force (USPSTF) recommendation on breast cancer screening. Purpose To determine the effectiveness of mammography screening in decreasing breast cancer mortality among average-risk women age 40 to 49 and 70 and older; the effectiveness of clinical breast examination (CBE) and breast self examination (BSE); and harms of screening. Data Sources Cochrane Controlled Trials Registry and Database of Systematic Reviews (4th Quarter 2008), MEDLINE® (January 2001 to December 2008), reference lists, and Web of Science® for published studies; Breast Cancer Surveillance Consortium for screening mammography data. Study Selection Randomized controlled trials with breast cancer mortality outcomes for screening effectiveness; multiple study designs and data sources for harms. Data Extraction Investigators abstracted relevant data and rated study quality using established criteria. Data Synthesis Mammography screening reduces breast cancer mortality by 15% for women age 39 to 49 (relative risk 0.85; 95% CrI 0.75 to 0.96; 8 trials); data are lacking for age ≥70. Radiation exposure from mammography is low. Patient adverse experiences are common, transient, and do not impact screening practices. Estimates of overdiagnosis vary from 1% to 10%. Younger women have more false positive mammograms and additional imaging, but fewer biopsies than older women. Trials of CBE are ongoing; for BSE, trials showed no reductions in mortality but increased benign biopsies. Limitations Studies of older women, digital mammography, and MRI are lacking. Conclusions Mammography screening reduces breast cancer mortality for women age 39 to 69; data are insufficient for older women. False positive mammograms and additional imaging are common. No benefit has been shown for CBE or BSE.

Targeted exercise training could reduce risk factors for fracture and obesity-related diseases that increase from breast cancer treatment, but has not been sufficiently tested. We hypothesized that progressive, moderate-intensity resistance + impact training would increase or maintain hip and spine bone mass, lean mass and fat mass and reduce bone turnover compared to controls who participated in a low-intensity, non-weight bearing stretching program. We conducted a randomized, controlled trial in 106 women with early stage breast cancer who were >1 year post-radiation and/or chemotherapy, ≥50 years of age at diagnosis and postmenopausal, free from osteoporosis and medications for bone loss, resistance and impact exercise naïve, and cleared to exercise by a physician. Women were randomly assigned to participate in 1 year of thrice-weekly progressive, moderate-intensity resistance + impact (jump) exercise or in a similar frequency and length control program of progressive, low-intensity stretching. Primary endpoints were bone mineral density (BMD; g/cm2) of the hip and spine and whole body bone-free lean and fat mass (kg) determined by DXA and biomarkers of bone turnover—serum osteocalcin (ng/ml) and urinary deoxypyrodiniline cross-links (nmol/mmolCr). Women in the resistance + impact training program preserved BMD at the lumbar spine (0.47 vs. −2.13%; P = 0.001) compared to controls. The resistance + impact group had a smaller increase in osteocalcin (7.0 vs. 27%, P = 0.03) and a larger decrease in deoxypyrodinoline (−49.9 vs. −32.6%, P = 0.06) than controls. Increases in lean mass from resistance + impact training were greatest among women currently taking aromatase inhibitors compared to controls not on this therapy (P = 0.01). Our combined program of resistance + impact exercise reduced risk factors for fracture among postmenopausal breast cancer survivors (BCS) and may be particularly relevant for BCS on aromatase inhibitors (AIs) because of the additional benefit of exercise on muscle mass that could reduce falls.

Axillary LR after SLN biopsy, with or without ALND, is a rare event, and this low relapse rate supports wider use of SLN biopsy for breast cancer staging. There is a low-risk subset of SLN-positive patients in whom completion ALND may not be required.

Shutter-speed pharmacokinetic analysis of [Dynamic-Contrast-Enhanced] DCE-MRI data allows evaluation of equilibrium inter-compartmental water interchange kinetics. The process measured here – transcytolemmal water exchange – is characterized by the mean intracellular water molecule lifetime (τi). The τi biomarker is a true intensive property not accessible by any formulation of the tracer pharmacokinetic paradigm, which inherently assumes it effectively zero when applied to DCE-MRI. We present population-averaged in vivo human breast whole tumor τi changes induced by therapy, along with those of other pharmacokinetic parameters. In responding patients, the DCE parameters change significantly after only one neoadjuvant chemotherapy cycle: while Ktrans [measuring mostly contract agent (CA) extravasation] and kep [CA intravasation rate constant] decrease, τi increases. However, high-resolution, (1 mm)2, parametric maps exhibit significant intra-tumar heterogenity, which is lost by averaging. A typical 400 ms τi value means a trans-membrane water cycling flux of 1013 H2O molecules/s/cell for a 12 µm diameter cell. Analyses of intra-tumor variations (and therapy-induced changes) of τi in combination with concomitant changes of Ve [extracellular volume fraction] inducate the former are dominated by alterations of the equilibrium cell membrane water permeability coefficient, Pw, not of cell size. These can be interpreted in light of literature results showing τi changes are dominated by a Pw(active) component that reciprocally reflects the membrane driving P-type ATPase ion pump turnover. For mammalian cells, this is the Na+,K+-ATPase pump. These results promise the potential to discriminate metabolic and microenvironmental states of regions within tumors in vivo, and their changes with therapy.

The ability of cancer cells to evade apoptosis may permit survival of a recombinant vaccinia lacking antiapoptotic genes in cancer cells compared with normal cells. We have explored the deletion of two vaccinia virus host range/ antiapoptosis genes, SPI-1 and SPI-2, for their effects on the viral replication and their ability to induce cell death in infected normal and transformed cells in vitro. Indeed, in three paired normal and transformed cell types, the SPI-1 and SPI-2 gene-deleted virus (vSP) preferentially replicates in transformed cells or p53-null cells when compared with their normal counterparts. This selectivity may be derived from the fact that vSP-infected normal cells died faster than infected cancer cells. A fraction of infected cells died with evidence of necrosis as shown by both flow cytometry and detection of high-mobility group B1 protein released from necrotic cells into the culture supernatant. When administered to animals, vSP retains full ability to replicate in tumor tissues, whereas replication in normal tissues is greatly diminished. In a model of viral pathogenesis, mice treated with vSP survived substantially longer when compared with mice treated with the wild-type virus. The mutant virus vSP displayed significant antitumoral effects in an MC38 s.c. tumor model in both nude (P < 0.001) and immunocompetent mice (P < 0.05). We conclude that this recombinant vaccinia vSP shows promise for oncolytic virus therapy. Given its enhanced tumor selectivity, improved safety profile, and substantial oncolytic effects following systemic delivery in murine models, it should also serve as a useful vector for tumor-directed gene therapy. (Cancer Res 2005; 65(21): 9991-8)