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Background It is unclear whether diabetes and glycemic control affects the outcomes of breast cancer, especially among those with metastatic disease. This study aims to determine the impact of diabetes and hyperglycemia on cancer progression and mortality in individuals with metastatic breast cancer (MBC). Methods Patients with a diagnosis of MBC between 2010 and 2021 were identified using the MBC database at 2 academic institutions. We evaluated the effects of diabetes and glycemic control on overall survival (OS) and time to next treatment (TTNT). Results We compared 244 patients with diabetes (median age 57.6 years) to 244 patients without diabetes (matched for age, sex, ethnicity, and receptor subtype). OS at 5 years [diabetes: 54% (95% CI 47-62%) vs controls: 56% (95% CI 49-63%), P = 0.65] and TTNT at 1 year [diabetes: 43% (95% CI 36-50%) vs controls: 44% (95% CI 36-51%), P = 0.33] were similar between groups. A subgroup analysis comparing those with good glycemic control and those with poor glycemic control among patients with specific receptor subtype profiles showed no differences in OS at 5 years or TTNT at 1 year. In an 8-year landmark subgroup analysis, there was worse OS among individuals with diabetes compared to controls, and OS was found to be better among those with good glycemic control compared to those with poor control. Conclusions Diabetes was not associated with increased mortality in individuals with MBC at 5 years. However, diabetes and hyperglycemia were associated with worse OS among a cohort of longer-term survivors. These findings suggest that individualized diabetes and glycemic goals should be considered in patients with MBC.

Immune checkpoint inhibitors (ICIs) are a rapidly expanding class of targeted therapies effective in the treatment of various cancers. However, while efficacious, ICIs have been associated with treatment complications, namely immune-related adverse events (irAEs). IrAEs of the endocrine system are among the most commonly reported irAEs, but despite their high incidence, standardized disease definitions and endocrine IrAE-specific International Classification of Diseases (ICD) codes remain lacking. This dearth of standardized nomenclature and ICD codes has in many ways impeded both the clinical care of patients and the progress of endocrine irAE-related research. ICD codes are used internationally and are essential for medical claims reporting in the health care setting, and they provide a universal language system for recording, reporting, and monitoring diseases. These codes are also a well-accepted form of electronic health record data capture that facilitates the collection, storage, and sharing of data. Therefore, the lack of standardized disease definitions and ICD codes has been associated with misclassification and suboptimal management of individuals with endocrine irAEs and has also been associated with reduced data availability, comparability, and quality. Harmonized and clinically relevant disease definitions along with the subsequent development of endocrine-irAE-specific ICD codes will provide a systematic approach to understanding the spectrum and burden of endocrine irAE diseases, and will have a positive effect across clinical, public health, and research settings.

Aromatase inhibitor (AI) therapy provides oncological benefits in postmenopausal women with oestrogen receptor-positive breast cancer. However, AI treatment has been associated with increased cardiovascular risk. In nonbreast cancer populations, experimentally induced low oestrogen states and natural transition to menopause have been associated with increases in visceral adipose tissue (VAT), a known surrogate marker for cardiometabolic risk. Given that AI treatment blocks oestradiol production, we hypothesized that AI treatment would increase VAT.We conducted a prospective 12-month cohort study of 52 postmenopausal women newly initiating AI treatment (median age: 64.5 years) and 52 women with breast pathology not requiring endocrine therapy (median age: 63.5 years). VAT area and other body composition parameters were measured at baseline, 6 months and 12 months using dual X-ray absorptiometry. Other risk markers of cardiometabolic health were also assessed.In women initiating AI treatment, there was no statistically significant difference in VAT area after 12 months when compared to controls, with a mean adjusted difference of -5.00 cmThese data provide reassurance that over the initial 12 months of AI therapy, AI treatment is not associated with metabolically adverse changes in body composition, hepatic steatosis or vascular reactivity. The impact of extended AI therapy on cardiometabolic health requires further study.

In patients with breast cancer (BCa) and diabetes (DM) , diabetes distress (DD) and treatment satisfaction (DTS) can influence cancer management and outcomes, yet there is limited data on how important these factors are in the BCa DM population. In this pilot study we assessed the impact of implementing a personalized DM care model on DD and DTS in patients with BCa. Patients in active treatment or surveillance for BCa who had uncontrolled DM (A1c > 7% or random blood glucose > 200 mg/dL) were included. All participants were offered continuous glucose monitoring (CGM) , virtual care and a dedicated diabetes provider with monthly visits for six months. The primary outcomes were change in DD measured by the Diabetes Distress Survey (DDS) and DTS measured by the Diabetes Treatment Satisfaction Questionnaire (DTSQ) . Questionnaires were conducted at 0, 3 and 6 months and changes were assessed using paired T test. Thirty-one women were enrolled (median age 61) . When each participant was assessed for changes in DD, a significant decrease in mean DD was observed at both 3 (baseline: 2.2 vs. 3 months: 1.8, p=0.004) and 6 months (baseline: 2.4 vs. 6 months: 1.9, p= 0.010) . Participants with high DD, DDS score ≥ 3, N=6 (19%) , had a significant decrease in DD at both 3 (baseline: 3.8 vs. 3 months: 2.7, p=0.016) and 6 months (baseline: 3.8 vs. 6 months: 2.7, p=0.018) . Those with low to moderate DD (DDS Disclosure J.Harrod: None. Y.M.Cheung: None. K.M.Fowler: n/a. M.E.Hughes: None. L.Min: Research Support; Bristol-Myers Squibb Company, Lilly. S.Tolaney: Consultant; 4D Pharma PLC, AstraZeneca, Athenex, BeyondSpring Pharmaceuticals, Bristol-Myers Squibb Company, Certara, Inc., Chugai Pharmaceutical Co., Ltd., CytomX, Daiichi Sankyo, Eisai Co., Ltd., Eli Lilly and Company, Ellipses Pharmaceuticals, Genentech, Inc., Gilead Sciences, Inc., Kyowa Kirin Co., Ltd., Merck & Co., Inc., Mersana Therapeutics, Novartis AG, Odonate, OncoPep, OncoSec Medical Inc, OncXerna, Pfizer Inc., Puma, Sanofi, Seattle Genetics, Inc., Zentalis, Zymeworks, Research Support; AstraZeneca, Bristol-Myers Squibb Company, Cyclacel, Eisai Co., Ltd., Eli Lilly and Company, Exelixis, Genentech, Inc., Gilead Sciences, Inc., Merck & Co., Inc., Nanostring, Nektar, Novartis AG, Odonate, Pfizer Inc., Sanofi, Seattle Genetics, Inc. M.E.Mcdonnell: Advisory Panel; Everlywell, Inc., Research Support; Lilly, Stock/Shareholder; Abbott Diabetes. Funding Lilly USA, LLC

Alpelisib is a phosphoinositide-3-kinase inhibitor approved for hormone-receptor-positive, PIK3CA-mutated metastatic breast cancer. However, length of drug exposure, maximum-tolerated dose, and therefore clinical response can vary significantly outside of the trial setting. This study evaluates our center's "real world" experience with alpelisib and focuses on duration of therapy and factors associated with cancer progression.Patients receiving alpelisib at our center between 2019 and 2021 were identified. We evaluated duration of alpelisib therapy and the causative reasons for drug discontinuation. The association of drug duration and dose with subsequent cancer progression were assessed, along with the association between hyperglycemia during alpelisib therapy and cancer progression.Sixty-two women prescribed alpelisib were included (mean age 61 years). Disease progression was the most common reason for drug discontinuation, while discontinuation within 30 days was primarily attributed to adverse events (AEs). Among those who progressed, median time to progression was longer in those on alpelisib for 90 days compared with those on alpelisib for ≤ 90 days (187 vs. 77 days, p 0.001). At 200 days, freedom from progression was greater for those on alpelisib for 90 days compared to those receiving therapy for ≤ 90 days (59% vs. 19%, p = 0.001). Median blood glucose as a continuous variable was associated with disease progression (HR 1.01, 95% CI 1.00-1.02, p = 0.02).While progression of disease is the largest contributor to alpelisib discontinuation, AEs are the leading cause for early drug cessation. Shorter alpelisib exposure is associated with greater cancer progression. Further studies are needed to determine the impact of sustained hyperglycemia on cancer progression.

Background Reports from resource-poor countries have associated thionamide- and para-aminosalicylate sodium (PAS)-based treatment of multi-drug-resistant tuberculosis (MDR-TB) with the development of hypothyroidism. Aim To identify predictors and assess the cumulative proportions of hypothyroidism in patients treated for MDR-TB with these agents in Australia. Methods Retrospective multicentre study of MDR-TB patients from five academic centres covering tuberculosis (TB) services in Victoria, Australia. Patients were identified using each centre's pharmacy department and cross checked with the Victorian Tuberculosis Program. Hypothyroidism was categorised as subclinical if the thyroid-stimulating hormone was elevated and as overt if free thyroxine (fT4) was additionally reduced on two separate occasions. Our main outcome measured was the cumulative proportion of hypothyroidism (at 5 years from treatment initiation). Results Of the 29 cases available for analysis, the cumulative proportion of hypothyroidism at 5 years was 37% (95% confidence interval (CI): 0-57.8%). Eight of the nine affected cases developed hypothyroidism within the first 12 months of treatment. Hypothyroidism was marginally (P = 0.06) associated with higher prothionamide/PAS dosing and was reversible with cessation of the anti-tuberculosis medication. Conclusions Prothionamide/PAS treatment-associated hypothyroidism is common in MDR-TB patients in Australia, emphasising the importance of regular thyroid function monitoring during this treatment. Thyroid hormone replacement, if initiated, may not need to be continued after MDR-TB treatment is completed.

Objective: To confirm prior findings that the larger the maximum monthly increase in solar insolation in springtime, the younger the age of onset of bipolar disorder. Method: Data were collected from 5536 patients at 50 sites in 32 countries on six continents. Onset occurred at 456 locations in 57 countries. Variables included solar insolation, birth-cohort, family history, polarity of first episode and country physician density. Results: There was a significant, inverse association between the maximum monthly increase in solar insolation at the onset location, and the age of onset. This effect was reduced in those without a family history of mood disorders and with a first episode of mania rather than depression. The maximum monthly increase occurred in springtime. The youngest birth-cohort had the youngest age of onset. All prior relationships were confirmed using both the entire sample, and only the youngest birth-cohort (all estimated coefficients P < 0.001). Conclusion: A large increase in springtime solar insolation may impact the onset of bipolar disorder, especially with a family history of mood disorders. Recent societal changes that affect light exposure (LED lighting, mobile devices backlit with LEDs) may influence adaptability to a springtime circadian challenge. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd