EZH2 and BMI1 inversely correlate with prognosis and TP53 mutation in breast cancer

Introduction PolycombGroup (PcG) proteins maintain gene repression through histone modifications and have been implicated in stem cell regulation and cancer. EZH2 is part of Polycomb Repressive Complex 2 (PRC2) and trimethylates H3K27. This histone mark recruits the BMI1-containing PRC1 that silences the genes marked by PRC2. Based on their role in stem cells, EZH2 and BMI1 have been predicted to contribute to a poor outcome for cancer patients. Methods We have analysed the expression of EZH2 and BMI1 in a well-characterised dataset of 295 human breast cancer samples. Results Interestingly, although EZH2 overexpression correlates with a poor prognosis in breast cancer, BMI1 overexpression correlates with a good outcome. Although this may reflect transformation of different cell types, we also observed a functional difference. The PcG-target genes INK4A and ARF are not expressed in tumours with high BMI1, but they are expressed in tumours with EZH2 overexpression. ARF expression results in tumour protein P53 (TP53) activation, and we found a significantly higher proportion of TP53 mutations in tumours with high EZH2. This may explain why tumours with high EZH2 respond poorly to therapy, in contrast to tumours with high BMI1. Conclusions Overall, our data highlight that whereas EZH2 and BMI1 may function in a 'linear' pathway in normal development, their overexpression has different functional consequences for breast tumourigenesi

Why do hospital mastectomy rates vary? Differences in the decision-making experiences of women with breast cancer

BACKGROUND: Hospital mastectomy rates vary. This study explores the relationship between mastectomy rates and breast cancer patients’ consultation and decision-making experiences with specialist clinicians. METHODS: Qualitative semi-structured interviews were conducted with 65 patients from three purposively selected breast units from a single UK region. Patients provided with a choice of breast cancer surgery (breast conservation therapy (BCT) or mastectomy) were purposively recruited from high, medium and low case-mix-adjusted mastectomy rate units. RESULTS: Low mastectomy rate unit patients’ consultation and decision-making experiences were markedly different to those of the medium and high mastectomy rate breast units. Treatment variation was associated with patients’ perception of the most reassuring and least disruptive treatment; the content and style of information provision (equipoise or directed); level of patient participation in decision making; the time and process of decision making and patient autonomy in decision making. The provision of more comprehensive less directive information and greater autonomy, time and support of independent decision making were associated with a lower uptake of BCT. CONCLUSION: Variation in hospital mastectomy rates was associated with differences in the consultation and decision-making experiences of breast cancer patients. Higher mastectomy rates were associated with the facilitation of more informed autonomous patient decision making

Information needs of older women faced with a choice of primary endocrine therapy or surgery for early-stage breast cancer: a literature review

Primary endocrine therapy (PET) as an alternative to surgery is widely used in the UK for the treatment of older women with operable breast cancer. For women over 70 it has equivalent overall survival to surgery, although local control rates may be inferior. There are trade-offs to be made in deciding between surgery and PET. There has been little research to investigate the information needs of older women or the involvement in decision making they wish to have when faced with this breast-cancer treatment decision. This review examines the information needs of older women (>65 years) regarding the use of surgery or PET for treating operable primary breast cancer, and identifies their preferred format and media for the presentation of this information. The preference for involvement in treatment decision-making among this group will also be considered. © 2014 Springer Science+Business Media

Utilization of neoadjuvant chemotherapy varies in the treatment of women with invasive breast cancer

Background: Treatment with neoadjuvant chemotherapy (NAC) has made it possible for some women to be successfully treated with breast conservation therapy (BCT ) who were initially considered ineligible. Factors related to current practice patterns of NAC use are important to understand particularly as the surgical treatment of invasive breast cancer has changed. The goal of this study was to determine variations in neoadjuvant chemotherapy use in a large multi-center national database of patients with breast cancer. Methods: We evaluated NAC use in patients with initially operable invasive breast cancer and potential impact on breast conservation rates. Records of 2871 women ages 18-years and older diagnosed with 2907 invasive breast cancers from January 2003 to December 2008 at four institutions across the United States were examined using the Breast Cancer Surgical Outcomes (BRCASO) database. Main outcome measures included NAC use and association with pre-operatively identified clinical factors, surgical approach (partial mastectomy [PM] or total mastectomy [TM]), and BCT failure (initial PM followed by subsequent TM). Results: Overall, NAC utilization was 3.8%l. Factors associated with NAC use included younger age, pre-operatively known positive nodal status, and increasing clinical tumor size. NAC use and BCT failure rates increased with clinical tumor size, and there was significant variation in NAC use across institutions. Initial TM frequency approached initial PM frequency for tumors >30-40mm; BCT failure rate was 22.7% for tumors >40mm. Only 2.7% of patients undergoing initial PM and 7.2% undergoing initial TM received NAC. Conclusions: NAC use in this study was infrequent and varied among institutions. Infrequent NAC use in patients suggests that NAC may be underutilized in eligible patients desiring breast conservation