Overexpression of BQ323636.1 contributes to anastrozole resistance in AR+ve/ER+ve breast cancer.

Aromatase inhibitors (Ais) are used as adjuvant endocrine therapy for oestrogen receptor-positive (ER+ve) post-menopausal breast cancer patients. Ais, by inhibiting the enzyme aromatase, block the conversion of androgen to oestrogen, reducing oestrogen levels. Resistance to Ais limits their clinical utilisation. Here, we show that overexpression of BQ323636.1 (BQ), a novel splice variant of nuclear co-repressor NCOR2, is associated with resistance to the non-steroidal aromatase inhibitor anastrozole in ER+ve post-menopausal breast cancer. Mechanistic study indicates that BQ overexpression enhances androgen receptor (AR) activity and in the presence of anastrozole, causes hyper-activation of AR signalling, which unexpectedly enhanced cell proliferation, through increased expression of CDK2, CDK4, and CCNE1. BQ overexpression reverses the effect of anastrozole in ER+ve breast cancer in an AR-dependent manner, whilst co-treatment with the AR antagonist bicalutamide recovered its therapeutic effect both in vitro and in vivo. Thus, for BQ-overexpressing breast cancer, targeting AR can combat anastrozole resistance. Clinical study of 268 primary breast cancer samples of ER+ve patients who had been treated with non-steroidal Ais showed 32.5% (38/117) of cases with combined high nuclear expression of BQ and AR, which were found to be significantly associated with Ai resistance. Non-steroidal Ai-treated patients with high nuclear expression of both BQ and AR had poorer overall, disease-specific, and disease-free survival. These findings suggest the importance of assessing BQ and AR expression status in the primary ER+ve breast tumour prior to Ai treatment. This may save patients from inappropriate treatment and enable effective therapy to be given at an early stage. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

A cross-sectional study on the attitudes and perceptions of outpatients towards palliative care at the Hong Kong Queen Mary Hospital Hospice Centre.

BACKGROUND: Palliative care aims to improve the quality of life for patients and their families, by helping them to cope with problems associated with illness. It targets four aspects of health: physical, psychological, social, and spiritual. Most of the current literature on palliative care is limited to the perspectives of health professionals. This study aims to investigate the views of outpatients receiving palliative care at the Hong Kong Queen Mary Hospital Hospice Centre (HKQMHHC), which offers palliative care services to cancer patients. METHODS: This observational cross-sectional study was performed with the completion of a single paper- based original questionnaire over 18 afternoon clinic sessions on Thursdays and Fridays from December 2017 to February 2018 at the HKQMHHC. The questionnaire was designed to examine patients' perspectives; in particular, the Edmonton Symptom Assessment Scale (ESAS) was used to assess their symptoms. Descriptive and univariate analyses were performed. RESULTS: One hundred patients attending HKQMHHC were included in the study. The study revealed that all the mean scores for aspects of care offered at the centre were above 8, on a scale of 0-10 with 0 being extremely inadequate and 10 being extremely adequate. Each respondent was able to identify an average of 1.82 of the 4 aspects of palliative care. Eighty-seven percent of respondents perceived the physical aspect of this care to be of the highest priority. A negative correlation (P<0.05) was found between the extent of symptoms experienced by the patient and their satisfaction towards the services offered. CONCLUSIONS: Patients generally held very positive attitudes, reflecting that the services sufficiently met their needs. However, owing to their rather limited knowledge, this may have restricted their perspectives to a largely superficial level, as many discerned palliative care to be simply targeting physical health with medical consultations. Considering the implications of the results, the addition of accessibility and education components to Hong Kong's current system of palliative care is crucial in the betterment of such services for patients. There should also be increased local coverage of palliative care services to facilitate convenience of access. With reference to the World Health Organisation (WHO) palliative care model, the inclusion of a continued spectrum of services, such as physical and mental health activities and psychosocial counselling, should be reinforced throughout the progression of disease so as to better help patients to cope with illness. The discovery of the relationship between extent of symptoms experienced and patients' satisfaction towards services provided is a new direction for further study.