Quality of life in women with early-stage and metastatic hormone receptor-positive, HER2-negative breast cancer receiving endocrine therapy.

INTRODUCTION: Early discontinuation of endocrine therapy (ET) is higher among patients with early breast cancer (EBC) compared to patients with metastatic hormone receptor-positive (HR+) breast cancer (MBC). In our clinical experience the reasons for this may include a significant burden of ET side effects impacting quality of life (QOL) in patients with EBC.  We hypothesized that QOL is lower in patients with HR + EBC compared to patients with HR + MBC on ET. METHODS: We conducted a cross-sectional observational study to assess QOL utilizing FACT-ES & EORTC QLQ C30 tools among patients with EBC and MBC receiving ET across 5 Irish hospitals. RESULTS: A total of 417 patients were enrolled-EBC (79% n = 331) and MBC 21% (n = 86). Using the FACT-ES, we found no difference in overall QOL by stage (139.2 vs 141, P  = .33). Patients with HR + MBC had a lower symptom burden from ET compared to HR + EBC (61.4 vs 54, P < .01). In adjusted multivariate linear regression models, there was no difference in QOL for patients with EBC and MBC receiving ET. CONCLUSIONS: There was no significant difference in overall QOL for patients with EBC and MBC. However, patients with EBC experienced more endocrine symptoms. In adjusted multivariate linear regression models, the stage did not predict QOL. Our results suggest that endocrine symptoms are significant contributors to impaired QOL for patients with EBC but the role of other determinants of QOL (eg, stage) is less clear. Future work could include the development of stage-specific QOL tools and utilization of electronic patient-reported outcomes (ePROs) to identify and manage emergent toxicities.

Immune privilege: failure of immunotherapy in controlling metastatic cutaneous melanoma to the eye.

This report concerns a 49-year-old female with cutaneous malignant melanoma and systemic metastases. These resolved following combination immunotherapy with ipilimumab and nivolumab. She subsequently experienced unilateral floaters, an increase in iris pigmentation and pigmentary glaucoma. The eye progressively lost vision and became painful due to iris neovascularization. The clinical diagnosis was of cutaneous melanoma metastatic to the vitreous, ciliary body and iris. Enucleation was performed for symptom control, with histopathology confirming the clinical diagnosis. The immune privilege of the eye may preclude ocular metastasis control with immunotherapy. Ocular symptoms in such patients merit referral to an ophthalmologist.

Characterisation of the androgen regulation of glycine N-methyltransferase in prostate cancer cells.

The development and growth of prostate cancer is dependent on androgens; thus, the identification of androgen-regulated genes in prostate cancer cells is vital for defining the mechanisms of prostate cancer development and progression and developing new markers and targets for prostate cancer treatment. Glycine N-methyltransferase (GNMT) is a S-adenosylmethionine-dependent methyltransferase that has been recently identified as a novel androgen-regulated gene in prostate cancer cells. Although the importance of this protein in prostate cancer progression has been extensively addressed, little is known about the mechanism of its androgen regulation. Here, we show that GNMT expression is stimulated by androgen in androgen receptor (AR) expressing cells and that the stimulation occurs at the mRNA and protein levels. We have identified an androgen response element within the first exon of the GNMT gene and demonstrated that AR binds to this element in vitro and in vivo. Together, these studies identify GNMT as a direct transcriptional target of the AR. As this is an evolutionarily conserved regulatory element, this highlights androgen regulation as an important feature of GNMT regulation.

New drugs for prostate cancer.

UNLABELLED: What's known on the subject? and What does the study add? Recent studies have demonstrated the efficacy of various new treatments. These have been in diverse areas of therapeutics research, including immunology and targeted biological therapy, as well as in new ways of approaching hormone refractory disease. The present paper seeks to review all of the key advances that have been reported in late-stage clinical studies and place them into the context of managing patients with advanced prostate cancer. OBJECTIVE: • To describe some of the most exciting late stage clinical developments in the field of new therapies for advanced prostate cancer. METHODS: • Pubmed was searched for articles pertaining to prostate cancer therapeutics clinical trials in the last 3 years. RESULTS: • Key positive trials in the areas of androgen resistance, tumour immunology, molecularly targeted agents and cytotoxics were reviewed and discussed in the context of metastatic prostate cancer. CONCLUSION: • Treatments emerging from these areas of scientific endeavour are progressing into clinical trials and are both good cause for hope in patients, and excellent examples of mechanism based drug discovery.