Value of ultrasound in assessing response to neoadjuvant chemotherapy in breast cancer.

AIM: To analyse the utility of ultrasound in assessing response to neoadjuvant chemotherapy (NAC) and predicting residual cancer burden (RCB) index and pathological complete response (pCR) MATERIALS AND METHODS: This was a retrospective study with 417 patients over 7 years. The difference in longest diameter (LD) of the index lesion from baseline to end, baseline to mid, and mid to end was evaluated with respect to RCB class using logistic regression and ordered logistic regression. RESULTS: Change in LD measurements from baseline to end, baseline to mid, and mid to end of chemotherapy as a predictor of RCB class show a negative relationship with a statistically significant association. This would suggest that a smaller change in LD measurements would be associated with an eventual higher RCB class. Change in LD measurements from baseline to end and baseline to mid chemotherapy as a predictor of pCR class show a negative relationship with a statistically significant association (p<0.05). This similarly indicates an inversely proportional relationship between changes in LD measurements and RCB class 0 for baseline to end and baseline to mid. CONCLUSION: This study has shown significance in reducing LD measurements on ultrasound as a predictor of PCR and RCB class. This adds weight to the current practice of using ultrasound at the start, mid and end of chemotherapy cycles to monitor NACT responses.

Oncosis and apoptosis induction by activation of an overexpressed ion channel in breast cancer cells.

The critical role of calcium signalling in processes related to cancer cell proliferation and invasion has seen a focus on pharmacological inhibition of overexpressed ion channels in specific cancer subtypes as a potential therapeutic approach. However, despite the critical role of calcium in cell death pathways, pharmacological activation of overexpressed ion channels has not been extensively evaluated in breast cancer. Here we define the overexpression of transient receptor potential vanilloid 4 (TRPV4) in a subgroup of breast cancers of the basal molecular subtype. We also report that pharmacological activation of TRPV4 with GSK1016790A reduced viability of two basal breast cancer cell lines with pronounced endogenous overexpression of TRPV4, MDA-MB-468 and HCC1569. Pharmacological activation of TRPV4 produced pronounced cell death through two mechanisms: apoptosis and oncosis in MDA-MB-468 cells. Apoptosis was associated with PARP-1 cleavage and oncosis was associated with a rapid decline in intracellular ATP levels, which was a consequence of, rather than the cause of, the intracellular ion increase. TRPV4 activation also resulted in reduced tumour growth in vivo. These studies define a novel therapeutic strategy for breast cancers that overexpress specific calcium permeable plasmalemmal ion channels with available selective pharmacological activators.