Previous studies have profiled breast cancer compared to normal breast tissue and identified differentially expressed microRNAs (miRNAs). These miRNAs are then assessed in serum of breast cancer patients compared to healthy volunteers. MiRNAs in serum however do not always reflect what is in tissue and important serum miRNAs may be missed. PCR arrays were therefore performed on serum samples from breast cancer patients compared to healthy volunteers with the aim of identifying circulating miRNAs that are more highly expressed in serum from early breast cancer patients compared to controls. Taqman low density array (TLDA) cards were used to profile serum miRNAs in a discovery cohort of serum from 39 early breast cancer patients compared to 10 healthy volunteers. The results were confirmed in a validation cohort of serum from 98 early breast cancer patients compared to 25 healthy volunteers using customized qPCR plates. Seventeen miRNAs were found to have significantly higher levels in breast cancer serum compared to serum of healthy volunteers in the discovery cohort. Fourteen of these miRNAs were studied in the validation cohort and serum miR-484 was found to be at a significantly higher level in breast cancer serum compared to healthy volunteers. In this study, we found that miR-484 is significantly differentially expressed in serum of early breast cancer patients compared to healthy volunteers. We did not however find any correlation between miR-484 levels with histopathological parameters of the breast cancers. With further studies, miR-484 may prove useful as an adjunct to mammography for detection of early breast cancer.

Therapy of hormone receptor positive breast cancer (BCa) generally targets estrogen receptor (ER) function and signaling by reducing estrogen production or by blocking its interaction with the ER. Despite good long-term responses, resistance to treatment remains a significant issue, with approximately 40% of BCa patients developing resistance to ET. Mutations in the gene encoding ERα, ESR1, have been identified in BCa patients and are implicated as drivers of resistance and disease recurrence. Understanding the molecular consequences of these mutations on ER protein levels and its activity, which is tightly regulated, is vital. ER activity is in part controlled via its short protein half-life and therefore changes to its stability, either through mutations or alterations in pathways involved in protein stability, may play a role in therapy resistance. Understanding these connections and how ESR1 alterations could affect protein stability may identify novel biomarkers of resistance. This review explores the current reported data regarding posttranslational modifications (PTMs) of the ER and the potential impact of known resistance associated ESR1 mutations on ER regulation by affecting these PTMs in the context of ET resistance.

Objective: Little is known about the experience of women of culturally and linguistically diverse (CALD) backgrounds in relation to breast reconstruction following mastectomy as treatment for their breast cancer. The aim of this study was to explore the factors that influenced Vietnamese- and English-speaking women’s decisions about breast reconstruction post-mastectomy for their breast cancer, in Australia. Design: The participants in this study comprised of Vietnamese-speaking women of Vietnamese heritage, and English-speaking women from mixed ethnicities (Vietnamese included). In this qualitative study, Vietnamese-speaking and English-speaking women who had breast cancer treated by mastectomy with or without breast reconstruction participated in in-depth interviews. Interviews were undertaken in the woman’s chosen language (Vietnamese or English), audio-recorded, transcribed/translated and analysed using thematic analysis. Results: Fourteen Vietnamese-speaking and 13 English-speaking patients were recruited. Participants identified age, lack of information, concerns regarding surgical procedure, fears about complications and cancer recurrence as barriers to breast reconstruction. Many more Vietnamese-speaking participants identified lack of information about breast reconstruction as a barrier compared to English-speaking participants. Both groups described the ability to wear clothing of their choice, partner influence, and the need to feel ‘normal’ as facilitators to having breast reconstruction. Vietnamese-speaking participants in particular identified doctor recommendation of breast reconstruction as a major facilitator. Conclusion: Lack of information about reconstruction was a persistent theme, though it was identified by more Vietnamese women as a barrier to having breast reconstruction. The results reinforce the importance of doctors’ recommendations in helping particularly the Vietnamese women make an informed decision about reconstruction following mastectomy as treatment for their breast cancer.

Cancer-associated fibroblasts (CAFs) represent an important component of the tumour microenvironment and are implicated in disease progression. Two outstanding questions in cancer biology are how CAFs arise and how they might be targeted therapeutically. The calcium signal also has an important role in tumorigenesis. To date, the role of calcium signalling pathways in the induction of the CAF phenotype remains unexplored. A CAF model was generated through exogenous transforming growth factor beta 1 (TGFβ1) stimulation of the normal human mammary fibroblast cell line, HMF3S (HMF3S-CAF), and changes in calcium signalling were investigated. Functional changes in HMF3S-CAF calcium signalling pathways were assessed using a fluorescent indicator, gene expression, gene-silencing and pharmacological approaches. HMF3S-CAF cells demonstrated functionally altered calcium influx pathways with reduced store-operated calcium entry. In support of a calcium signalling switch, two voltage-gated calcium channel (VGCC) family members, Ca_V1.2 and Ca_V3.2, were upregulated in HMF3S-CAFs and a subset of patient-derived breast CAFs. Both siRNA-mediated silencing and pharmacological inhibition of Ca_V1.2 or Ca_V3.2 significantly impaired CAF activation in HMF3S cells. Our findings show that VGCCs contribute to TGFβ1-mediated induction of HMF3S-CAF cells and both transcriptional interference and pharmacological antagonism of Ca_V1.2 and Ca_V3.2 inhibit CAF induction. This suggests a potential therapeutic role for targeting calcium signalling in breast CAFs.