No abstract

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 ten 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.

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 induced 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. This preclinical data provides a new understanding of the mechanisms by which MLN8237 mediates its anti-metastatic effects and advocates for its combination with eribulin in future clinical trials for metastatic breast cancer and early stage solid tumors.

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.

No abstract