Predicted sensitivity to endocrine therapy for stage II-III hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancer before chemo-endocrine therapy.

BACKGROUND: We proposed that a test for sensitivity to the adjuvant endocrine therapy component of treatment for patients with stage II-III breast cancer (SET2,3) should measure transcription related to estrogen and progesterone receptors (SETER/PR index) adjusted for a baseline prognostic index (BPI) combining clinical tumor and nodal stage with molecular subtype by RNA4 (ESR1, PGR, ERBB2, and AURKA). PATIENTS AND METHODS: Patients with clinically high-risk, hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2-) breast cancer received neoadjuvant taxane-anthracycline chemotherapy, surgery with measurement of residual cancer burden (RCB), and then adjuvant endocrine therapy. SET2,3 was measured from pre-treatment tumor biopsies, evaluated first in an MD Anderson Cancer Center (MDACC) cohort (n = 307, 11 years' follow-up, U133A microarrays), cut point was determined, and then independent, blinded evaluation was carried out in the I-SPY2 trial (n = 268, high-risk MammaPrint result, 3.8 years' follow-up, Agilent-44K microarrays, NCI Clinical Trials ID: NCT01042379). Primary outcome measure was distant relapse-free survival. Multivariate Cox regression models tested prognostic independence of SET2,3 relative to RCB and other molecular prognostic signatures, and whether other prognostic signatures could substitute for SETER/PR or RNA4 components of SET2,3. RESULTS: SET2,3 added independent prognostic information to RCB in the MDACC cohort: SET2,3 [hazard ratio (HR) 0.23, P = 0.004] and RCB (HR 1.77, P < 0.001); and the I-SPY2 trial: SET2,3 (HR 0.27, P = 0.031) and RCB (HR 1.68, P = 0.008). SET2,3 provided similar prognostic information irrespective of whether RCB-II or RCB-III after chemotherapy, and in both luminal subtypes. Conversely, RCB was most strongly prognostic in cancers with low SET2,3 status (MDACC P < 0.001, I-SPY2 P < 0.001). Other molecular signatures were not independently prognostic; they could effectively substitute for RNA4 subtype within the BPI component of SET2,3, but they could not effectively substitute for SETER/PR index. CONCLUSIONS: SET2,3 added independent prognostic information to chemotherapy response (RCB) and baseline prognostic score or subtype. Approximately 40% of patients with clinically high-risk HR+/HER2- disease had high SET2,3 and could be considered for clinical trials of neoadjuvant endocrine-based treatment.

Quantification of background enhancement in breast magnetic resonance imaging.

PURPOSE: To present a novel technique for measuring tissue enhancement in breast fibroglandular tissue regions on contrast-enhanced breast magnetic resonance imaging (MRI) aimed at quantifying the enhancement of breast parenchyma, also known as "background enhancement." MATERIALS AND METHODS: Our quantitative method for measuring breast MRI background enhancement was evaluated in a population of 16 healthy volunteers. We also demonstrate the use of our new technique in the case study of one subject classified as high risk for developing breast cancer who underwent 3 months of tamoxifen therapy. RESULTS: We obtained quantitative measures of background enhancement in all cases. The high-risk patient exhibited a 37% mean reduction in background enhancement with treatment. CONCLUSION: Our quantitative method is a robust and promising tool that may allow investigators to quantify and document the potential adverse effect of background enhancement on diagnostic accuracy in larger populations.

Utility of magnetic resonance imaging in the management of breast cancer: evidence for improved preoperative staging.

PURPOSE: The staging and treatment for breast cancer are changing; there is an increase in the incidence of ductal carcinoma-in-situ, the use of fine-needle aspiration and stereotactic biopsy for diagnosis, and the use of neoadjuvant chemotherapy. Thus, there is a need for a tool to assess more precisely the extent of cancer in the breast before surgery. To better plan surgical and chemotherapeutic interventions, we evaluated high-resolution magnetic resonance imaging (MRI) as such a tool. PATIENTS AND METHODS: Fifty-seven patients with 58 cases of breast cancer were evaluated preoperatively with MRI using a technique called the triple-acquisition rapid gradient echo technique to maximize anatomic detail. Imaging results were compared with mammography and subsequent pathology results. RESULTS: Magnetic resonance imaging correctly identified residual or primary cancer in 55 of 58 cases and accurately predicted the extent of the cancer in 54 of 58 cases. The anatomic extent was more accurately defined with MRI compared with mammography (98% v 55%). Magnetic resonance imaging added the greatest value in cases of multifocal disease. CONCLUSION: By applying MRI selectively to patients with a known diagnosis of cancer and focusing on defining the extent of malignant lesions, we were able to obtain clear and accurate anatomic information. Our results suggest that MRI could provide very valuable information for preoperative planning and single-stage resection in breast cancer. Based on preliminary data from our series, MRI would be valuable as a staging tool in the preoperative setting even if the cost is in the range of $1,300 to $2,000. It is already significantly less than the target cost, so it is reasonable to refine this technique for clinical use to help plan the most appropriate surgical intervention and possibly reduce costs as well. A careful prospective study is warranted to validate our findings.

Magnetic resonance imaging for primary breast cancer management: current role and new applications.

Techniques for magnetic resonance (MR) imaging of the breast have been evolving over the past decade. The opportunities for integration of MR imaging into clinical breast cancer management and clinical research are increasing. In this paper, we will review the principles behind the creation of standard and MR images and use this as a platform to evaluate clinical studies and indications for the use and study of MR. In particular, we will focus on those areas where MR has the capability of changing care and/or improving our understanding of the biology of breast cancer. In addition, we will address areas where MR is not yet capable of adding value or where MR may lead to unnecessary procedures.

The value of relaxation times and density measurements in clinical MRI.

The hope that MRI relaxation time signatures would identify tissues, specifically, malignancies, has not been realized. This is due much less to measurement inaccuracies than to a large intrinsic variability and overlaps between malignancies and many benign pathologies. Neither has there been success in predicting relaxation times from basic tissue compositions. Nevertheless, MRI provides a qualitative measure of tissue hydration, and of flow, on the basis of relaxation times. Furthermore, pixel-by-pixel maps of relaxation times have proven useful in understanding the MRI process, in predicting the efficacy of untried techniques, and replace, in many circumstances, the need for acquisition of images with diverse sequencing parameters.

NMR in experimental cerebral edema: value of T1 and T2 calculations.

In an experimental investigation, the efficacy of nuclear magnetic resonance (NMR) relaxation times in measuring brain water was studied. Cerebral edema was induced in four dogs with a freeze lesion, which was produced by contact with a steel cylinder cooled in liquid nitrogen and placed on the exposed dural surface of the brain. NMR proton imaging was performed 2, 3, 6, or 24 hr after production of the lesion, at a field strength of 0.35 T, using multiparametric spin-echo (SE) technique. The animals were sacrificed immediately after imaging, and brain samples were analyzed for water content (wet-to-dry, microgravimetry). Correlation between water content, NMR imaging, and resulting T1, T2 relaxation times and mobile proton density values calculated with SE technique was performed. Brain sample analysis showed elevation of water content in the white matter subjacent to the lesion in all four dogs, rising at least 15% in each of the animals. NMR imaging detected the freeze lesion and subjacent vasogenic edema of the white matter in all animals. The 2 sec pulse interval SE technique was most sensitive in the detection of the abnormality, and provided optimal differentiation of gray and white matter. The second echo sampling (56 msec) was most sensitive to the detection of edema. The T1 and T2 relaxation values, as well as the mobile proton density values, were elevated in the normal gray matter and in the abnormal white matter when compared with normal white matter in any given animal.(ABSTRACT TRUNCATED AT 250 WORDS)

Technical aspects of breast magnetic resonance imaging.

The appropriate role for magnetic resonance imaging (MRI) as an adjunct technique to mammography in the detection, diagnosis, staging, and therapy management of breast cancer has been the subject of much current research. The clinical application determines the choice of imaging technique. Time restraints due to the rapid kinetics of contrast enhancement require that trade-offs be made between spatial and temporal resolution, with a resulting effect on sensitivity and specificity. This article discusses some general requirements and recommendations for breast MRI techniques, including dedicated radiofrequency coils, pulse sequence specifications and image quality considerations, fat-suppression techniques, methods of contrast administration, and image postprocessing and interpretation.

Vascularity assessment of breast lesions with gadolinium-enhanced MR imaging.

Gadolinium-enhanced MR imaging techniques can be used to assess both breast tumor morphology and vascularity. Pharmacokinetic models can be used to extract physiological parameters related to tumor vascularity from signal intensity-time curves. This article describes an empirical method, using three-point high resolution MR imaging, that also provides assessment of tumor vascularity. These techniques appear to improve diagnostic specificity of breast MR imaging and provide a noninvasive method for tumor characterization that may have prognostic value.

Vascularity assessment of breast lesions with gadolinium-enhanced MR imaging.

Gadolinium-enhanced MR imaging of the breast can be used to characterize both tumor morphology and vascularity. An empirical three-point method using high resolution three-dimensional MR imaging that combines high spatial resolution with an estimate of tumor pharmacokinetics is described. This technique appears to improve diagnostic specificity of breast MR imaging and may provide a noninvasive method of tumor characterization of prognostic value.

Imaging techniques for breast MR imaging.

Specialized rf coils and pulse sequence techniques for contrast-enhanced breast imaging have been a focus of recent attention in MR imaging research. The imaging strategies for maximizing sensitivity and specificity involve trade-offs between spatial and temporal resolution. This article discusses these issues and others, such as considerations for coil design, fat suppression, patient positioning, motion artifact reduction, and methods for quantitative measurement of dynamic contrast enhancement.

Semi-automated analysis for MRI of breast tumors.

Magnetic resonance imaging (MRI) techniques have the potential to greatly improve breast cancer detection, diagnosis, and treatment. Currently, a major problem associated with breast MRI is the overwhelming amount of data acquired during an exam, and the time-intensive analysis required to evaluate the images. We have developed a software platform for semi-automated analysis to assess both the tumor extent and overall grade or severity based on our diagnostic criteria. In a test subset of over 50 patients, the automated program produced results more accurate overall than those measurements taken manually, with a reduction in time for analysis from approximately 45 minutes down to 5 minutes per patient study.

Loss mitigation in plasmonic solar cells: aluminium nanoparticles for broadband photocurrent enhancements in GaAs photodiodes.

We illustrate the important trade-off between far-field scattering effects, which have the potential to provide increased optical path length over broad bands, and parasitic absorption due to the excitation of localized surface plasmon resonances in metal nanoparticle arrays. Via detailed comparison of photocurrent enhancements given by Au, Ag and Al nanostructures on thin-film GaAs devices we reveal that parasitic losses can be mitigated through a careful choice of scattering medium. Absorption at the plasmon resonance in Au and Ag structures occurs in the visible spectrum, impairing device performance. In contrast, exploiting Al nanoparticle arrays results in a blue shift of the resonance, enabling the first demonstration of truly broadband plasmon enhanced photocurrent and a 22% integrated efficiency enhancement.

I-SPY 2: an adaptive breast cancer trial design in the setting of neoadjuvant chemotherapy.

I-SPY 2 (investigation of serial studies to predict your therapeutic response with imaging and molecular analysis 2) is a process targeting the rapid, focused clinical development of paired oncologic therapies and biomarkers. The framework is an adaptive phase II clinical trial design in the neoadjuvant setting for women with locally advanced breast cancer. I-SPY 2 is a collaborative effort among academic investigators, the National Cancer Institute, the US Food and Drug Administration, and the pharmaceutical and biotechnology industries under the auspices of the Foundation for the National Institutes of Health Biomarkers Consortium.

MRI methods for evaluating the effects of tyrosine kinase inhibitor administration used to enhance chemotherapy efficiency in a breast tumor xenograft model.

PURPOSE: To evaluate whether quantitative MRI parameters are sensitive to the effects of the tyrosine kinase inhibitor gefitinib and can discriminate between two different treatment protocols. MATERIALS AND METHODS: Untreated mice with BT474 breast tumor xenografts were characterized in a preliminary study. Subsequently, tumor volume, apparent diffusion coefficient (ADC), transendothelial permeability (K(ps)), and fractional plasma volume (fPV) were measured in three groups of mice receiving: 1) control vehicle for 10 days, or gefitinib as 2) a single daily dose for 10 days or 3) a 2-day pulsed dose. RESULTS: Gefitinib treatment resulted in significant tumor growth inhibition (pulsed: 439 +/- 93; daily: 404 +/- 53; control: 891 +/- 174 mm(3), P < 0.050) and lower cell density (pulsed: 0.15 +/- 0.01, daily: 0.17 +/- 0.01, control: 0.24 +/- 0.01, P < 0.050) after 9 days. Tumor ADC increased in treated groups but decreased in controls (P > 0.050). Tumor K(ps) decreased with pulsed treatment but rebounded afterwards and increased with daily treatment (P > 0.050). Tumor fPV increased in both treated groups, decreasing afterwards with pulsed treatment (P > 0.050). CONCLUSION: Quantitative MRI can provide a sensitive measure of gefitinib-induced tumor changes, potentially distinguish between treatment regimens, and may be useful for determining optimal treatment scheduling for enhancing chemotherapy delivery.

The development and use of SPIO Lycra compression bracing in children with neuromotor deficits.

The use of flexible compression bracing in persons with neuromotor deficits offers improved possibilities for stability and movement control without severely limiting joint movement options. At the Children's Therapy Center in Kent, Washington, this treatment modality has been explored with increasing application in children with moderate to severe cerebral palsy and other neuromotor deficits over the past 6 years, with good success. Significant functional improvements using Neoprene shoulder/trunk/hip Bracing led us to experiment with much lighter compression materials. The stabilizing pressure input orthosis or SPIO bracing system (developed by Cheryl Allen, parent and Chief Designer, and Nancy Hylton, PT) is custom-fitted to the stability, movement control and sensory deficit needs of a specific individual. SPIO bracing developed for a specific child has often become part of a rapidly increasing group of flexible bracing options which appear to provide an improved base of support for functional gains in balance, dynamic stability, general and specific movement control with improved postural and muscle readiness. Both deep sensory and subtle biomechanical factors may account for the functional changes observed. This article discusses the development and current use of flexible compression SPIO bracing in this area.

Information processing in magnetic resonance imaging.

Techniques of image processing have been developed for the extraction of information from magnetic resonance images. The response of nuclei to a sequence of magnetic stimulations has been modeled and used to predict the effects of changing magnetic resonance parameters on signal intensity. This allows the calculation of new images from a small set of acquired data without additional acquisition. These images can be used to predict the results of new imaging techniques before actual implementation and to simulate the effects of parameter variations which are unfeasible or impractical, such as variable field strength. New forms of representation, for example, a tissue type map in which each homogeneous tissue category has been identified and labeled, can be used for more direct interpretation.

Challenges to interpretation of breast MRI.

This review describes the current knowledge and challenges of lesion interpretation with MRI of the breast according to different image interpretation strategies. Particular emphasis is given to patient- and tumor-related factors that influence image interpretation. The impacts of the menstrual cycle, prior surgery, radiation therapy, and chemotherapy are summarized. Particular enhancement features of ductal carcinoma in situ (DCIS) or invasive lobular carcinoma are described. Finally, an adequate diagnosis at MRI of the breast should take into account the results of the patient's history, physical examination, and all imaging tests performed before MRI. J. Magn. Reson. Imaging 2001;13:821-829.

Integration of breast imaging into cancer management.

This article reviews the use of breast imaging for screening, diagnosis, and staging. Its focus is on the ways in which imaging techniques can most effectively be integrated into clinical management.

Impact of section doubling on MR angiography.

To improve the quality of projection angiograms generated from three-dimensional magnetic resonance (MR) angiography data, the authors applied voxel shifting to create intermediate sections ("section doubling") prior to maximum intensity projection. To date, the authors have processed MR angiography studies with and without section doubling in 20 cases. Section doubling resulted in improved vessel contrast and delineation of continuity (especially of small vessels) in all cases.