Advances in Breast Imaging with Current Screening Recommendations and Controversies.

In the last several decades, breast imaging has undergone transformation. Technological advances in mammography and ultrasound and the development and increased availability of imaging modalities used in supplemental screening and diagnostic settings, including tomosynthesis and breast MRI, have allowed for improved breast cancer detection and diagnosis. Image-guided core breast biopsies have largely replaced fine needle aspirations. This article discusses the current status of breast imaging in the screening and diagnostic settings and is intended to inform the referring physician of why and how common studies and procedures are performed in the breast imaging clinic.

Combination of Eribulin and Aurora A Inhibitor MLN8237 Prevents Metastatic Colonization and Induces Cytotoxic Autophagy in Breast Cancer.

Recent findings suggest that the inhibition of Aurora A (AURKA) kinase may offer a novel treatment strategy against metastatic cancers. In the current study, we determined the effects of AURKA inhibition by the small molecule inhibitor MLN8237 both as a monotherapy and in combination with the microtubule-targeting drug eribulin on different stages of metastasis in triple-negative breast cancer (TNBC) and defined the potential mechanism of its action. MLN8237 as a single agent and in combination with eribulin affected multiple steps in the metastatic process, including migration, attachment, and proliferation in distant organs, resulting in suppression of metastatic colonization and recurrence of cancer. Eribulin application induces accumulation of active AURKA in TNBC cells, providing foundation for the combination therapy. Mechanistically, AURKA inhibition induces cytotoxic autophagy via activation of the LC3B/p62 axis and inhibition of pAKT, leading to eradication of metastases, but has no effect on growth of mammary tumor. Combination of MLN8237 with eribulin leads to a synergistic increase in apoptosis in mammary tumors, as well as cytotoxic autophagy in metastases. These preclinical data provide a new understanding of the mechanisms by which MLN8237 mediates its antimetastatic effects and advocates for its combination with eribulin in future clinical trials for metastatic breast cancer and early-stage solid tumors. Mol Cancer Ther; 15(8); 1809-22. ©2016 AACR.

Comparison between Ultrasound and Pathologic Status of Axillary Lymph Nodes in Clinically Node-negative Breast Cancer Patients.

Sentinel lymph node biopsy (SLNB) is the standard of care for axillary staging in clinically node-negative breast cancer patients. Ultrasound (US) has shown promise when used to assess axillary lymph nodes preoperatively, thus aiding surgical decision making. We examined the correlation between preoperative US and SLNB results to further clarify the role of US in clinicopathologic staging of breast cancer when the axilla is clinically negative on physical examination. Our institutional cancer registry was used to identify clinically node-negative patients diagnosed with breast cancer from January 1, 2009 to December 31, 2012. Variables including age, body mass index, date of surgery, date of diagnosis, US results, US-directed biopsy results, SLNB results, and final pathology were recorded. Incomplete charts were excluded. In all, 249 patients were included. Sensitivity/specificity of US in the clinically negative axilla were 7.4 per cent and 91.8 per cent, respectively. The false-positive rate was 80 per cent, whereas the negative predictive value was 78 per cent. The effect of time from diagnosis/US to SLNB, interpreting radiologist, year in which US was performed, and body mass index were not statistically significant. US in the clinically node-negative patient, although useful when it leads to a positive needle biopsy result, is unlikely to replace SLNB owing to its low sensitivity and a high false-positive rate. Further prospective study into the role of US in the evaluation of the clinically negative axilla is warranted.

Radiation exposure from diagnostic procedures in patients with newly diagnosed breast cancer.

Radiation exposure is associated with an increased risk of secondary cancers. Knowing the approximate radiation exposure from diagnostic procedures in the œrst year after a breast cancer diagnosis could help educate patients and allow physicians to monitor them more closely for potential risks.

3-D visualization and non-linear tissue classification of breast tumors using ultrasound elastography in vivo.

The goal of the study described here was to introduce new methods for the classification and visualization of human breast tumors using 3-D ultrasound elastography. A tumor's type, shape and size are key features that can help the physician to decide the sort and extent of necessary treatment. In this work, tumor type, being either benign or malignant, was classified non-invasively for nine volunteer patients. The classification was based on estimating four parameters that reflect the tumor's non-linear biomechanical behavior, under multi-compression levels. Tumor prognosis using non-linear elastography was confirmed with biopsy as a gold standard. Three tissue classification parameters were found to be statistically significant with a p-value < 0.05, whereas the fourth non-linear parameter was highly significant, having a p-value < 0.001. Furthermore, each breast tumor's shape and size were estimated in vivo using 3-D elastography, and were enhanced using interactive segmentation. Segmentation with level sets was used to isolate the stiff tumor from the surrounding soft tissue. Segmentation also provided a reliable means to estimate tumors volumes. Four volumetric strains were investigated: the traditional normal axial strain, the first principal strain, von Mises strain and maximum shear strain. It was noted that these strains can provide varying degrees of boundary enhancement to the stiff tumor in the constructed elastograms. The enhanced boundary improved the performance of the segmentation process. In summary, the proposed methods can be employed as a 3-D non-invasive tool for characterization of breast tumors, and may provide early prognosis with minimal pain, as well as diminish the risk of late-stage breast cancer.

Nonlinear characterization of breast cancer using multi-compression 3D ultrasound elastography in vivo.

The main objective of this article is to introduce a new nonlinear elastography based classification method for human breast masses. Multi-compression elastography imaging is elucidated in this study to differentiate malignant from benign lesions, based on their nonlinear mechanical behavior under compression. Three classification parameters were used and compared in this work: a new nonlinear parameter based on a power-law behavior of the strain difference between breast masses and healthy tissues, mass-soft tissue strain ratio and the mass relative volume between B-mode and elastography imaging. Using 3D elastography, these parameters were tested in vivo. A pilot study on 10 patients was performed, and results were compared with biopsy diagnosis as a gold standard. Initial elastography results showed a good agreement with biopsy outcomes. The new estimated nonlinear parameter had an average value of 0.163±0.063 and 1.642±0.261 for benign and malignant masses, respectively. Strain ratio values for the benign and malignant masses had an average value of 2.135±0.707 and 4.21±2.108, respectively. Relative mass volume was 0.848±0.237 and 2.18±0.522 for benign and malignant masses. In addition to the traditional normal axial strain, new strain types were used for elastography and constructed in 3D, including the first principal, maximum shear and Von Mises strains. The new strains provided an enhanced distinction of the stiff lesion from the soft tissue. In summary, the proposed elastographic techniques can be used as a noninvasive quantitative characterization tool for breast cancer, with the capability of visualizing and separating the masses in a three dimensional space. This may reduce the number of unnecessary painful breast biopsies.