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Background: Detailed toxicity data are routinely collected in breast cancer (BC) clinical trials. However, ovarian toxicity is infrequently assessed, despite the adverse impacts on fertility and long-term health from treatment-induced ovarian insufficiency., Objectives: To determine the barriers to and facilitators of ovarian toxicity assessment in BC trials of anti-cancer drugs., Methods: Semi-structured interviews were conducted with purposively selected stakeholders from multiple countries involved in BC clinical trials (clinicians, consumers, pharmaceutical company representatives, members of drug-regulatory agencies). Participants were asked to describe the perceived benefits and barriers to evaluating ovarian toxicity. Interviews were transcribed verbatim, coded in NVivo software and analysed using inductive thematic analysis., Results: Saturation of the main themes was reached and the final sample size included 25 participants from 14 countries (9 clinicians, 7 consumers, 5 members of regulatory agencies, 4 pharmaceutical company representatives); half were female. The main reported barrier to ovarian toxicity assessment was that the issue was rarely considered. Reasons included that these data are less important than survival data and are not required for regulatory approval. Overall, most participants believed evaluating the impact of BC treatments on ovarian function is valuable. Suggested strategies to increase ovarian toxicity assessment were to include it in clinical trial design guidelines and stakeholder advocacy., Conclusion: Lack of consideration about measuring ovarian toxicity in BC clinical trials that include premenopausal women suggest that guidelines and stronger advocacy from stakeholders, including regulators, would facilitate its more frequent inclusion in future trials, allowing women to make better informed treatment decisions., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Women with breast cancer experience a significantly higher prevalence of sleep disturbance and insomnia than the general population. The experience of persistent sleep disturbance places these women at a higher risk of psychological and physical morbidity and a reduced quality of life. Treatment for sleep in this population is not part of routine care and is often managed inadequately. This randomised controlled trial will examine the combined effects of cognitive behavioural therapy (CBT) and bright light therapy (BLT) on the symptoms of insomnia, fatigue and mental health., Method/design: Women diagnosed with breast cancer who receive intravenous chemotherapy treatment at a quaternary referral metropolitan cancer centre in Melbourne, Australia, will be recruited. Recruitment will occur after diagnosis and prior to completion of chemotherapy. Eligible women will be randomised to the combined CBT and BLT intervention (CBT+) or relaxation audio-enhanced treatment as usual (TAU+). The CBT+ group will receive one face-to-face session on sleep strategies, one subsequent telephone call, and seven email packages containing CBT-based information and strategies. CBT+ participants will also wear Luminette® light glasses for 20 min each morning for the 6-week duration of the intervention. Women in TAU+ will receive two relaxation audio tracks via email. Outcomes will be measured at multiple points throughout the 6 weeks. Primary outcomes will be symptoms of insomnia and sleep efficiency, measured using the Insomnia Severity Index and a self-reported sleep diary. Secondary outcomes include objective measures of sleep assessed using the ActiGraph wGT3X-BT, and sleep-related complaints, fatigue and mental health, all assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS). Data will also be collected on potential treatment moderators and mechanisms and adherence to treatment. There will be 3-month follow-up measurements of insomnia symptoms, fatigue, sleep-related impairment, sleep disturbance, depression and anxiety., Discussion: This is the first randomised controlled trial to combine CBT and BLT for the treatment of sleep disturbance in women with breast cancer. This novel design addresses the multiple causal factors for sleep complaints in this population. Results from this trial will advance knowledge in this field and may have important clinical implications for how best to treat sleep disturbance and insomnia in this population. If effective, the largely email-based format of the intervention would allow for relatively easy translation., Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12618001255279. Retrospectively registered on 25 July 2018.

Optimal adjuvant endocrine therapy for premenopausal women with hormone-receptor positive breast cancer has long been debated. In particular, the role of ovarian function suppression in addition to standard tamoxifen divided oncologists worldwide, and more recently, the role of aromatase inhibitors as an alternative to tamoxifen in the setting of ovarian suppression became a key question. In 2014, the long awaited results of the International Breast Cancer Study Group (IBCSG) led randomized, phase 3 trials, Suppression of Ovarian Function Trial (SOFT) and Tamoxifen and Exemestane Trial (TEXT), provided additional evidence to inform the discussion. The interpretation of the SOFT and TEXT trial data can facilitate better selection of appropriate endocrine therapy according to individual disease characteristics, recognizing the complexity of the puzzle, which is still not complete., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: 'Taste' changes are commonly reported during chemotherapy. It is unclear to what extent this relates to actual changes in taste function or to changes in appetite and food liking and how these changes affect dietary intake and nutritional status., Patients and Methods: This prospective, repeated measures cohort study recruited participants from three oncology clinics. Women (n = 52) prescribed adjuvant chemotherapy underwent standardised testing of taste perception, appetite and food liking at six time points to measure change from baseline. Associations between taste and hedonic changes and nutritional outcomes were examined., Results: Taste function was significantly reduced early in chemotherapy cycles (p<0.05) but showed recovery by late in the cycle. Ability to correctly identify salty, sour and umami tastants was reduced. Liking of sweet food decreased early and mid-cycle (p<0.01) but not late cycle. Liking of savory food was not significantly affected. Appetite decreased early in the cycle (p<0.001). Reduced taste function was associated with lowest kilojoule intake (r = 0.31; p = 0.008) as was appetite loss with reduced kilojoule (r = 0.34; p = 0.002) and protein intake (r = 0.36; p = 0.001) early in the third chemotherapy cycle. Decreased appetite early in the third and final chemotherapy cycles was associated with a decline in BMI (p = <0.0005) over the study period. Resolution of taste function, food liking and appetite was observed 8 weeks after chemotherapy completion. There was no association between taste change and dry mouth, oral mucositis or nausea., Conclusion: The results reveal, for the first time, the cyclical yet transient effects of adjuvant chemotherapy on taste function and the link between taste and hedonic changes, dietary intake and nutritional outcomes. The results should be used to inform reliable pre-chemotherapy education.

Background: Acquired and de novo endocrine resistance in breast cancer (BC) may be associated with overexpression of epidermal growth factor receptor (EGFR). Gefinitib is an orally active selective EGFR inhibitor which might benefit advanced breast cancer (ABC) patients either with acquired hormone resistance or with hormone receptor (HR)-negative tumors., Patients and Methods: A two-arm multicenter phase II trial of oral gefitinib 500 mg/day was planned in two groups of 45 patients with ABC for whom chemotherapy was not currently indicated. Group 1 had hormone-resistant BC defined as HR-positive BC with progression after treatment with tamoxifen and an aromatase inhibitor. Group 2 had HR-negative BC. Tumor response was assessed every 8 weeks. The primary end point was the clinical benefit rate (CBR)., Results: Forty patients with hormone-resistant BC had a CBR of 0%. Two of 25 HR-negative BC patients showed stable disease (less than a 50% reduction and less than a 25% increase in the sum of the products of two perpendicular diameters of all measured lesions and the appearance of no new lesions) at 24 weeks resulting in a CBR of 7.7% (95% CI 0.9% to 25.1%). Enrollment ceased due to the low CBR. Toxicity resulted in treatment interruption (46%), dose reduction (20%) and withdrawal (11%) of patients., Conclusion: At a dose of 500 mg/day, gefitinib monotherapy resulted in a low CBR and no tumor response was identified.

The in vitro human tumor colony-forming assay identified chloroquinoxaline sulfonamide (CQS) as an active agent at human plasma concentrations of > 100 micrograms/ml. In the initial phase I trial of CQS given every 28 days, peak plasma concentrations > 500 micrograms/ml were associated with reversible dose-limiting hypoglycemia and occasional cardiac arrhythmias. Therefore, we evaluated whether a weekly schedule of treatment might minimize the drug-associated toxicity while maintaining potential therapeutic concentrations. CQS was given intravenously over 1 h once per week for 4 weeks to 12 patients, beginning at a dose of 2,000 mg/m2. All patients underwent monitoring for cardiac arrhythmias and hypoglycemia. Plasma drug levels were measured following each dose. Mild hypoglycemia was the most common adverse effect. A median nadir plasma glucose concentration of 56 mg/dl was observed at a weekly dose of 2,500 mg/m2. Two patients experienced cardiac dysrhythmia while on study. Continuous electrocardiographic monitoring failed to identify any significant infusion-related arrhythmia. The median CQS plasma concentration measured 24 h following a 2,000-mg/m2 dose of CQS was > 100 micrograms/ml, and the cumulative area under the concentration x time curve (AUC) determined at concentrations of > or = 100 micrograms/ml was similar to that observed with the every-28-day schedule. The weekly schedule described herein appears to maximize the plasma AUC with an acceptable margin of safety. The recommended phase II dose and schedule for CQS is 2,000 mg/m2 given once per week. Although severe hypoglycemia is unlikely, glucose monitoring is appropriate for 6 h following CQS administration.